SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) - MichaelTutt, MD
BASICS
DESCRIPTION
Multisystem, autoimmune inflammatory condition characterized by fluctuating, chronic course; varies from mild to severe and may be lethal (CNS and renal forms)
• System(s) Affected: Endocrine/Metabolic; Gastrointestinal; Hemic/Lymphatic/Immunologic; Musculoskeletal; Nervous; Renal/Urologic; Skin/Exocrine
• Synonym(s): SLE; Disseminated lupus erythematosus
ALERT
Stroke syndromes frequently seen in children
Pregnancy Considerations
• The onset of lupus and lupus flares more common during pregnancy.
• Fetal loss increased for mothers with lupus
• Newborns of mothers who have lupus are more likely to have cardiac arrhythmias.
• Specialists' collaboration during pregnancy is indicated.
GENERAL PREVENTION
• Avoiding sun exposure is only necessary for ~1/6 of SLE patients (those who report such sensitivity).
• Routine vaccinations are safe and appropriate for SLE patients.
• Drugs known to induce SLE in normal individuals are not necessarily contraindicated in patients who have idiopathic SLE.
EPIDEMIOLOGY
• Predominant age: All ages, but 30-50 most common
• Predominant sex: Female > Male (10:1)
• Higher percentage of males involved among elderly
Prevalence
20/100,000
RISK FACTORS
• Race: African Americans, Hispanics, Asians, and Native Americans have a higher prevalence than whites.
• Genetic markers (see "Genetics")
• Hereditary complement deficiency, especially C1q, C1r, C1s, C4, and C2
• Polymorphisms in the FCGR2A and FCGR3A genes may be important.
Genetics
Markers: HLA-B8, HLA-DR2, HLA-DR3
ETIOLOGY
• Most cases are idiopathic.
• Drugs: Drug-induced lupus is clinically different from idiopathic SLE.
ASSOCIATED CONDITIONS
Other autoimmune diseases
• Rheumatoid arthritis
• Hypothyroidism
• Diabetes
DIAGNOSIS
SIGNS AND SYMPTOMS
• Arthritis
• Fever
• Anorexia
• Malaise
• Weight loss
• Skin lesions
• Oral ulcers
• Eye pain and/or redness
• Chest pain and/or shortness of breath
• Pallor
• Nausea, vomiting, diarrhea
• Muscles: Tenderness, aching, and stiffness
• Headaches and visual problems
• Psychosis/delirium
TESTS
Special tests
• Complement levels, immune complex assays (cryoglobulins, Raji cell test, C1q precipitins)
• Coagulation studies (lupus anticoagulant)
• Biopsy of skin, kidney, and peripheral nerves may reveal typical histopathology.
Lab
• Positive antinuclear antibody
- "False-positive ANA" occurs in 15% of the elderly tested, so caution is required when interpreting the lab results for patients in this age group.
• Anti-double standard DNA (dsDNA), anti-Sm, false-positive VDRL, or positive LE preparation. These tests have either high sensitivity (ANA, false-positive VDRL) or specificity (anti-dsDNA, anti-Sm, and LE preparation) and are included as American Rheumatology Association criteria for diagnosis along with clinical features.
• Sedimentation rate nonspecific, but valuable in assessing SLE activity
• Anemia
• Anticardiolipin antibody
• Leukopenia
• Lymphopenia
• Abnormal urinary sediment
• Proteinuria
• Increased prothrombin time
• Hypoalbuminuria
• Thrombocytopenia
• Increased serum creatinine
• Positive Coombs test
Imaging
• Cerebral angiography in CNS lupus
• Chest x-ray for pulmonary infiltration, pleural effusion
• MRI to detect CNS lupus
• ECG for pericardial effusion
Diagnostic Procedures/Surgery
The American Rheumatology Association criteria (any 4 manifestations of the 11 listed)
• Malar (butterfly) rash
• Discoid rash
• Photosensitivity
• Oral/nasopharyngeal ulcers
• Nonerosive arthritis
• Pleuritis or pericarditis
• Renal disorder: Proteinuria or cylindruria
• Neurologic disorder: Psychosis or seizures
• Hematologic disorder: Hemolytic anemia, leukopenia (4000), lymphopenia (1500), thrombocytopenia (100,000)
• Immunologic disorder
• Positive ANA in absence of drugs known to cause positive ANA
Note: Although the above criteria are required for proper epidemiologic classification of SLE, in practical situations, a combination of a multisystem inflammatory illness, a positive ANA, and the absence of a better diagnosis often represents the most practical way to make a clinical diagnosis.
Pathological Findings
Connective-tissue disorders affecting skin, blood vessels, and serous and synovial membranes
• Collagenous swelling
• Fibrinoid change
• Cellular necrosis
• Periarterial sclerosis
• Granulomatous reaction
• Infiltration of polymorphonuclear leukocytes, plasma cells, lymphocytes in walls of small vessels, arterioles of skin, spleen, glomeruli, endocardium pericardium, brain
• Hematoxylin bodies resembling those in LE cells
• Vegetation on heart valves
DIFFERENTIAL DIAGNOSIS
• SLE mimics numerous systemic conditions, especially those involving inflammation.
• Many other disorders mimic SLE: Rheumatoid arthritis, mixed connective tissue disease, scleroderma, metastatic malignancy, fever of unknown origin, psychogenic rheumatism, and many cutaneous rashes. No one test or biopsy is pathognomonic.
TREATMENT
GENERAL MEASURES
• Outpatient with regular monitoring
• Avoidance of, or protection from, ultraviolet light by using sunscreens, hats, and so on
• Early intervention when infections occur
• Energy conservation
• Stress avoidance/management
Diet
No special diet unless for complications, such as renal failure
Activity
• As active as possible
• Those with arthritis may be limited by pain, but active exercises are to be encouraged.
MEDICATION (DRUGS)
Treatment is symptomatic with certain exceptions. No 1 drug of choice is available. Local steroids for cutaneous manifestations, NSAIDs for minor arthritis symptoms, low-dose steroids for minor discomfort, and high-dose steroids for major inflammatory disease
• Renal disease and severe disease in other organs: Immunosuppressants
• Minor arthritis: NSAIDs
• Cutaneous lupus: Sunscreen and topical steroids
• More significant arthritis or dermal lupus: Hydroxychloroquine 310 mg/d (400 mg/d of the sulfate salt)
• Major symptoms in one or more organ systems: Prednisone 30-60 mg/d
• Glomerulonephritis: Cyclophosphamide 0.5 g/m2 IV on a monthly basis together with prednisone 60 mg/d PO tapering to 10 mg every other day after 4 months
• Arthritis, rash, serositis, or fever: Methotrexate 5-25 mg PO or SC weekly in a single dose has been effective as a "steroid sparer."
• SLE thrombocytopenia: Immune globulin IV pulse has been effective in temporary treatment.
• Obvious thrombotic disease and/or CNS symptoms, when associated with a positive "lupus anticoagulant" test or anticardiolipin antibody: Heparin or warfarin (Coumadin)
• Contraindications: Refer to the manufacturer's profile of each drug.
• Precautions: Ensure good hydration when administering cyclophosphamide, due to possibility of hemorrhagic cystitis.
• Significant possible interactions: Refer to the manufacturer's profile of each drug.
FOLLOW-UP
PROGNOSIS
• Most patients with lupus follow a course of remissions and exacerbations. Many experience spontaneous permanent remission.
• Treatment of renal lupus (the most serious form) with immunosuppressors, renal dialysis, and renal transplantation has increased the 5-year life expectancy to >90%. For those patients surviving the 1st 2 years of the disease, life expectancy is essentially normal.
• In patients with drug-induced lupus, symptoms should gradually decrease upon the discontinuation of the suspected agent.
COMPLICATIONS
• Fever
• Vasculitis
• Panniculitis
• Myositis
• Avascular necrosis of bone
• Endocarditis
• Pulmonary fibrosis
• Renal failure
• Organic brain syndromes
• Peripheral neuropathy
• Stroke syndromes
• Pancreatitis and elevated liver enzymes
• Infertility
• Ascites
• Venous thrombosis
• Seizures
PATIENT MONITORING
• Follow acute flares frequently (weekly to monthly) in order to adjust the medication based on the clinical impression.
- Laboratory parameters are of limited value.
- CBC useful in hematologic lupus
- Serum creatinine or renal clearance tests of value in renal lupus
- The sedimentation rate often helps determine adequate suppression of the symptoms or the development of remission.
• Confirming tests for lupus (e.g., ANA titers, anti-DNA titers, complement levels) are usually not helpful in the follow-up assessment.
• The value of continuing the medication depends upon the symptoms. The exception is in the case of renal lupus, for which it has been shown that a defined course of monthly IV cyclophosphamide has been of value.
• Baseline ophthalmological exam and yearly exam while on hydroxychloroquine
REFERENCES
1. Kelley WN, Harris ED, Ruddy S, Sledge CB. Textbook of Rheumatology. 4th ed. Philadelphia, PA: WB Saunders Co.1993.
2. Kippel JH, Dippe PA, eds. Rheumatology. St. Louis, Mo: Mosby; 1994.
3. Tan FK, Arnett FC. The genetics of lupus. Curr Opin Rheumatol. 1998;10:399-408.
4. Godfrey T, et al. Therapeutic advances in SLE. Curr Opin Rheumatol. 1998;10:435-441.
MISCELLANEOUS
See also: Anemia, autoimmune hemolytic
Tuesday, January 6, 2009
SYPHILIS
SYPHILIS - Milisa K. Rizer, MD, MPH
BASICS
DESCRIPTION
• Infectious disease caused by the spirochete, Treponema pallidum. Transmitted sexually, maternal-fetal, and via blood transfusions
• Primary
- Painless ulcer at site of infection (chancre)
• Secondary
- Rash, usually palms and soles, can be whole body.
• Latent
- Seroreactive without evidence of disease.
- Early latent: Acquired within the past year
- Late latent or latent of unknown duration
Exposure >12 months prior
• Tertiary (late)
- Serology may be negative
- Damage to multiple systems
Cardiovascular
CNS
Musculoskeletal
- May result in death
- Mental status may be altered
• Neurosyphilis
- May occur at any stage of syphilis
• Congenital
- Syphilis acquired in utero
ALERT
Pediatric Considerations
In noncongenital cases, must consider possibility of child abuse
Pregnancy Considerations
• All expectant mothers should have VDRL or RPR at 1st prenatal visit. If high exposure risk, repeat the tests at 28 weeks and at delivery.
• Jarisch-Herxheimer reaction (acute febrile reaction of headache, myalgia, rash, and hypotension) may induce preterm labor or fetal distress, but is not a reason to delay treatment.
GENERAL PREVENTION
Safe sex; use of condoms
EPIDEMIOLOGY
Predominant age: Sexually active years
Predominant sex: Male > Female (5.9:1)
Incidence
In 2004: 2.7/100,000 population
• White, non-Hispanic: 1.6/100,000
• Black: 9.0/100,000
• Hispanic: 3.2/100,000
• Asian/Pacific Islander: 1.2/100,000
• American Indian/Alaska Native: 3.2/100,000
RISK FACTORS
• Men having sex with men
• Multiple sexual partners
• Exposure to infected body fluids
• IV drug use
• Transplacental transmission
ETIOLOGY
Treponema pallidum
ASSOCIATED CONDITIONS
• HIV infection
• Hepatitis B
• Other sexually transmitted diseases
DIAGNOSIS
SIGNS AND SYMPTOMS
• Primary
- Small, round, firm ulcer at the place where the bacteria enter (chancre). Typically on penis, vulva, or vagina but can be lips, tongue, and cervix. Occurs 9-90 days after exposure (mean of 21-28 days).
- Lymphadenopathy often present locally.
- Chancre heals spontaneously within 28 days.
- ~3/4 of the patients have no further symptoms; 1/4 progress.
• Secondary
- Occurs ~28-70 days after the chancre
- May have fever, lymphadenopathy, malaise, myalgias, and arthralgias
- Patchy alopecia: Scalp, eyebrows, and beard
- Nickel and dime lesions: Hyperpigmented annular lesions with raised depigmented border.
- Often characterized by generalized body rash: Polymorphic, nonpruritic; usually not bullous or vesicular.
- Papules may coalesce to form highly infectious lesions called condylomata lata; these start as red, vesicular, and painful, and progress to gray. Often in perineal region.
- Active spirochetes are present in lesions; contact with broken skin or mucous membrane can spread infection.
- Rash resolves spontaneously in 49 days.
• Latent syphilis
- Characterized by positive serology but no signs or symptoms
- Early latent: Acquired within the past year; within the past year patient had to have
4-fold seroconversion in nontreponemal test titer, or
Unequivocal symptoms of primary or secondary syphilis, or
Sex partner with primary, secondary, or early latent syphilis, or
Reactive nontreponemal and treponemal tests with only possible exposure within the last 12 months.
- Late latent or latent of unknown duration
Exposure >12 months prior
• Tertiary syphilis
- Serologies often are negative.
- Gummatous lesions that usually affect skin, bone, and mucous membranes, but may involve any organ and cause local destruction of the affected organ system.
- Cardiovascular symptoms result from endarteritis of the aorta resulting in aortitis and aneurysm formation
Asymptomatic murmur, aortic insufficiency, left heart failure, aneurysms of ascending thoracic aorta, aortic-valve regurgitation
- Orthopedic complications
Rare with antibiotics
Charcot joints, osteomyelitis
• Neurosyphilis
- May be symptomatic or asymptomatic
- Personality change, ataxia, stroke
- Blurred vision, photophobia
- Urinary incontinence, meningitis
- Headache, nausea, and vomiting
- Cranial nerve involvement, paresthesias
- Loss of position, vibratory, pain, and temperature sensation
• Congenital syphilis
- Young infants
Rash: Hallmark similar to secondary syphilis in adults, may be bullous or vesicular
Snuffles (mucopurulent rhinitis)
Failure to thrive
Nonimmune hydrops
Osteochondritis
Lymphadenopathy
Jaundice
Anemia
Hepatosplenomegaly
Nephrosis
Meningitis
Saddle nose
Iritis
Pseudoparalysis of a limb
- Children
Hutchinson teeth
Saber shins
Charcot joints
Deafness
Interstitial keratitis
History
Exposure
TESTS
• Dark-field microscopy demonstrating T. pallidum spirochetes is gold standard for definitive diagnosis.
• Direct florescent antibody test
• Skin biopsy to demonstrate Treponema pallidum in tissue
Lab
• Nontreponemal tests: VDRL or RPR
- Primary screening test
- Relatively inexpensive
- Positive within 7 days of exposure
- Positive test should be quantified and titers followed at regular intervals after treatment.
- Titers usually correlate with disease activity.
- Titer decreases with time or treatment; following adequate treatment for primary or secondary a 4-fold decline should be noted by 4 months and an 8-fold decline by 8 months. Titer eventually should be negative (see "Serofast Reaction"). Titers of patients treated in latent stages will decline more gradually.
- Failure of nontreponemal test titers to decline 4-fold within 6 months after therapy for primary or secondary might indicate treatment failure.
- Nonspecific; must confirm diagnosis with treponemal test (false-positive common)
- Prozone phenomenon: Negative results due to very high titers of antibody; test diluted serum sample
- Serofast reaction: Persistently positive results years after successful treatment; new infection is diagnosed by 4-fold rise in titer
- Drugs that may alter lab results
Recent immunization (e.g., smallpox)
Many reported to cause false positive, but uncommon with a good history
- Disorders that may alter lab results
Pregnancy
Autoimmune disease
Systemic lupus erythematosus
Mononucleosis
Malaria
Leprosy
Viral pneumonia
Presence of cardiolipin antigens
Drug addiction
Acute febrile illness
HIV infection
Elderly can be false positive
• Treponemal tests: FTA-ABS, TP-PA
- Confirmatory test, not used for screening
- More expensive
- Usually positive for life after treatment
- Titers of no benefit
- 15-20% of patients treated during the primary stage revert to being serologically nonreactive after 2-3 years.
- Drugs that may alter lab results: See "Nontreponemal Tests"
- Disorders that may alter lab results: See "Nontreponemal Tests"
• Lumbar puncture
- Indicated for any patient who has clinical evidence of neurologic involvement or has syphilitic ocular or auditory manifestations
- Some experts advise in all secondary and early latent cases without neuro symptoms
- In HIV-positive patients with late latent or latent of unknown duration
- In cases of late latent or latent of unknown duration, or when nonpenicillin therapy is planned
- In treatment failures
- If other evidence of active syphilis is present (aortitis, gumma, iritis)
- In children with syphilis, after the newborn period, to rule out neurosyphilis
- VDRL, not RPR, used on CSF; may be negative in neurosyphilis; highly specific but insensitive
- Send fluid for protein, glucose and cell count
- Monitor resolution by cell count at 6 months along with serologies as recommended (see Patient Monitoring)
- Negative FTA-ABS or MHA-TP on CSF excludes neurosyphilis, highly sensitive
- Positive FTA-ABS or MHA-TP on CSF not diagnostic because high false-positive rate
- Bloody tap, tuberculosis, pyogenic or aseptic meningitis can result in false-positive VDRL
Imaging
Only in late cases as indicated
Pathological Findings
• Aneurysm
• Osteomyelitis
• Gummas in late cases
DIFFERENTIAL DIAGNOSIS
• Primary
- Chancroid
- Lymphogranuloma venereum
- Granuloma inguinale
- Condyloma Acuminata
- Herpes Simplex
- Behcet syndrome
- Trauma
- Carcinoma
- Mycotic infection
- Lichen planus
- Psoriasis
- Fungal infection
• Secondary
- Pityriasis rosea
- Drug eruption
- Psoriasis
- Lichen planus
- Viral exanthema
- Stevens-Johnson syndrome
• Positive serology, asymptomatic
- Previously treated syphilis
- Other spirochetal disease (yaws, pinta)
- Biological false positive: See "Disorders that May Alter Lab Results"
TREATMENT
GENERAL MEASURES
• Outpatient, except for initiating IV penicillin or desensitization
• Baseline serologies prior to treatment
Diet
No special diet
Activity
Full activity, but no sexual contacts until 4-fold drop in nontreponemal test titer
MEDICATION (DRUGS)
First Line
Parenteral penicillin G is drug of choice for all stages. (2)[A] Choice of penicillin formulation is determined by the disease stage and clinical manifestations.
ALERT
Bicillin L-A should be used and not Bicillin C-R when penicillin G benzathine is indicated. (4)[A]
• Primary, secondary, and early latent 1 year
- Benzathine penicillin G 2.4 million units IM for 1 dose (2)[A]
- Penicillin-allergic patients: Doxycycline 100 mg PO b.i.d. for 2 weeks or tetracycline 500 mg PO q.i.d. for 2 weeks; Ceftriaxone 1 g IM or IV daily for 8-10 days is used by some
• Late latent or latent of unknown duration and tertiary without evidence of neurosyphilis
- Benzathine penicillin G 2.4 million units IM weekly for 3 doses (2)[A]
- Penicillin-allergic patients: Attempt desensitization and treatment with penicillin; doxycycline 100 mg PO 2 b.i.d. for 28 days or tetracycline 500 mg PO for 28 days; compliance may be an issue
• Neurosyphilis
- Aqueous crystalline penicillin G 3-4 million units IV q4h, or continuous infusion for 10-14 days, or procaine penicillin G 2.4 million units IM daily and probenecid 500 mg PO q.i.d. for 10-14 days (if compliance can be ensured) (2)[A]
- Penicillin-allergic patients: Attempt desensitization and treatment with penicillin; Ceftriaxone 2 g daily IM or IV for 10-14 days
- If late latent, latent of unknown duration, or tertiary in addition to neurosyphilis, consider also treating as recommended for late latent after completion of neurosyphilis treatment
• Congenital
- Aqueous crystalline penicillin G 50,000 units/kg/dose IV q12h for 1st 7 days of life and q8hs thereafter for a total of 10 days, or procaine penicillin G 50,000 units/kg/dose IM daily for 10 days (2)[A]
- If negative CSF serologies, normal physical exam, and titer maternal titer then 50,000 units/kg benzathine penicillin G IM in single dose is also alternative (2)[A]
- If >1 day of therapy is missed, restart entire course.
• Children (after newborn period)
- Aqueous crystalline penicillin G 50,000 units/kg/dose IV q4-6h for 10 days; late latent: 50,000 units/kg IM as 3 doses at 1-week intervals (2)[A]
• Pregnancy
- Treatment same as for nonpregnant patients;
- Some specialists recommend 2nd dose of 2.4 million units benzathine penicillin G 1 week after initial dose, especially in 3rd trimester or with primary, secondary, or early latent syphilis.
- Penicillin sensitivity: No proven alternatives to penicillin exist for treatment during pregnancy; consider desensitization and treat with penicillin (2)[A]
• Epidemiologic treatment for contacts without symptoms, treat as primary after baseline serologies obtained
• Contraindications: Allergy to penicillin
• Precautions
- HIV-infected and pregnant patients may show poor response to recommended IM doses. Use IV therapy for all treatment failures in these patients.
- Do not give benzathine or procaine penicillins IV.
• Significant possible interactions: Refer to manufacturer's literature.
FOLLOW-UP
Follow-up is very important
DISPOSITION
Issues for Referral
Sonographic signs of fetal or placental syphilis indicate a greater risk for treatment failure and should be managed in consult with obstetric specialist.
PROGNOSIS
• Excellent in all cases except patients with late-syphilis complications and a few with HIV infection
• Syphilis in HIV-infected patient
- Test for HIV in any patient with syphilis.
- Treatment recommendations are same as HIV negative.
- More often false-negative treponemal and nontreponemal tests or unusually high titers (see "Prozone Phenomenon")
- Serologic response to therapy sometimes less predictable
- Early syphilis: Increased risk of neurosyphilis and might have higher rates of treatment failure
- Neurosyphilis: Harder to treat; can occur up to 20 years after infection
COMPLICATIONS
• Cardiovascular disease
• CNS disease
• Membranous glomerulonephritis
• Paroxysmal cold hemoglobinemia
• Meningitis
• Tabes dorsalis
• Irreversible organ damage
• Jarisch-Herxheimer reaction
- Marked by fever, chills, headache, myalgias, new rash
- Common on starting treatment (of primary or secondary disease; less common with tertiary) due to lysis of treponemes
- Should not be confused with reaction to antibiotics
- Managed with analgesics and antipyretics
PATIENT MONITORING
• Use VDRL or RPR to monitor therapy: 4-fold rise in titer indicates new infection, whereas failure to decrease 4-fold within 6 months is treatment failure (although definitive criteria for cure not established); always use same test (VDRL or RPR).
• Re-treat for persistent clinical signs or recurrence, 4-fold rise in titers, or failure of initially high titer to decrease 4-fold by 6 months.
• Labs must titer tests to final end point (e.g., not report as ">1:512") to make best use of results in monitoring therapy response.
• Repeat serologies at 3, 6, 9, and 12 months after treatment; if >1 year's duration, check at 24 months also.
REFERENCES
1. CDC. Sexually transmitted disease surveillance, 2004. Atlanta, GA: US Department of Health and Human Services.
2. CDC Sexually Transmitted Diseases Treatment Guidelines, 2006. MMWR Weekly. 2006;55(RR-11):22-34.
3. Drugs for sexually transmitted infections. Med Lett. 2004;2(26).
4. Palacioz K. Syphilis treatment errors. Prescriber's Letter. 2004;11(5):200513.
5. CDC. Primary and Secondary SyphilisUnited States, 2003-2004. MMWR Weekly. 2006;55(10):269-273.
6. McGregor T. Syphilis. www.emedicine.com/ emerg/topic563.htm. Accessed 8/26/2006.
7. Knudsen R. Neurosyphilis. www.emedicine.com/ neuro/topic684.htm Accessed 8/28/2006.
8. Larson S. A Manual of Tests for Syphilis. Washington, DC: American Public Health Association, 1990.
MISCELLANEOUS
• See also: Chlamydial sexually transmitted diseases; Gonococcal infections
• Many experts urge more aggressive treatment than standard regimens in all patients especially HIV-positive and pregnant patients, and strongly advocate use of penicillin rather than any alternative antibiotic.
• Penicillin-allergic patients, particularly with neurosyphilis, HIV infection, and pregnancy, should undergo desensitization.
BASICS
DESCRIPTION
• Infectious disease caused by the spirochete, Treponema pallidum. Transmitted sexually, maternal-fetal, and via blood transfusions
• Primary
- Painless ulcer at site of infection (chancre)
• Secondary
- Rash, usually palms and soles, can be whole body.
• Latent
- Seroreactive without evidence of disease.
- Early latent: Acquired within the past year
- Late latent or latent of unknown duration
Exposure >12 months prior
• Tertiary (late)
- Serology may be negative
- Damage to multiple systems
Cardiovascular
CNS
Musculoskeletal
- May result in death
- Mental status may be altered
• Neurosyphilis
- May occur at any stage of syphilis
• Congenital
- Syphilis acquired in utero
ALERT
Pediatric Considerations
In noncongenital cases, must consider possibility of child abuse
Pregnancy Considerations
• All expectant mothers should have VDRL or RPR at 1st prenatal visit. If high exposure risk, repeat the tests at 28 weeks and at delivery.
• Jarisch-Herxheimer reaction (acute febrile reaction of headache, myalgia, rash, and hypotension) may induce preterm labor or fetal distress, but is not a reason to delay treatment.
GENERAL PREVENTION
Safe sex; use of condoms
EPIDEMIOLOGY
Predominant age: Sexually active years
Predominant sex: Male > Female (5.9:1)
Incidence
In 2004: 2.7/100,000 population
• White, non-Hispanic: 1.6/100,000
• Black: 9.0/100,000
• Hispanic: 3.2/100,000
• Asian/Pacific Islander: 1.2/100,000
• American Indian/Alaska Native: 3.2/100,000
RISK FACTORS
• Men having sex with men
• Multiple sexual partners
• Exposure to infected body fluids
• IV drug use
• Transplacental transmission
ETIOLOGY
Treponema pallidum
ASSOCIATED CONDITIONS
• HIV infection
• Hepatitis B
• Other sexually transmitted diseases
DIAGNOSIS
SIGNS AND SYMPTOMS
• Primary
- Small, round, firm ulcer at the place where the bacteria enter (chancre). Typically on penis, vulva, or vagina but can be lips, tongue, and cervix. Occurs 9-90 days after exposure (mean of 21-28 days).
- Lymphadenopathy often present locally.
- Chancre heals spontaneously within 28 days.
- ~3/4 of the patients have no further symptoms; 1/4 progress.
• Secondary
- Occurs ~28-70 days after the chancre
- May have fever, lymphadenopathy, malaise, myalgias, and arthralgias
- Patchy alopecia: Scalp, eyebrows, and beard
- Nickel and dime lesions: Hyperpigmented annular lesions with raised depigmented border.
- Often characterized by generalized body rash: Polymorphic, nonpruritic; usually not bullous or vesicular.
- Papules may coalesce to form highly infectious lesions called condylomata lata; these start as red, vesicular, and painful, and progress to gray. Often in perineal region.
- Active spirochetes are present in lesions; contact with broken skin or mucous membrane can spread infection.
- Rash resolves spontaneously in 49 days.
• Latent syphilis
- Characterized by positive serology but no signs or symptoms
- Early latent: Acquired within the past year; within the past year patient had to have
4-fold seroconversion in nontreponemal test titer, or
Unequivocal symptoms of primary or secondary syphilis, or
Sex partner with primary, secondary, or early latent syphilis, or
Reactive nontreponemal and treponemal tests with only possible exposure within the last 12 months.
- Late latent or latent of unknown duration
Exposure >12 months prior
• Tertiary syphilis
- Serologies often are negative.
- Gummatous lesions that usually affect skin, bone, and mucous membranes, but may involve any organ and cause local destruction of the affected organ system.
- Cardiovascular symptoms result from endarteritis of the aorta resulting in aortitis and aneurysm formation
Asymptomatic murmur, aortic insufficiency, left heart failure, aneurysms of ascending thoracic aorta, aortic-valve regurgitation
- Orthopedic complications
Rare with antibiotics
Charcot joints, osteomyelitis
• Neurosyphilis
- May be symptomatic or asymptomatic
- Personality change, ataxia, stroke
- Blurred vision, photophobia
- Urinary incontinence, meningitis
- Headache, nausea, and vomiting
- Cranial nerve involvement, paresthesias
- Loss of position, vibratory, pain, and temperature sensation
• Congenital syphilis
- Young infants
Rash: Hallmark similar to secondary syphilis in adults, may be bullous or vesicular
Snuffles (mucopurulent rhinitis)
Failure to thrive
Nonimmune hydrops
Osteochondritis
Lymphadenopathy
Jaundice
Anemia
Hepatosplenomegaly
Nephrosis
Meningitis
Saddle nose
Iritis
Pseudoparalysis of a limb
- Children
Hutchinson teeth
Saber shins
Charcot joints
Deafness
Interstitial keratitis
History
Exposure
TESTS
• Dark-field microscopy demonstrating T. pallidum spirochetes is gold standard for definitive diagnosis.
• Direct florescent antibody test
• Skin biopsy to demonstrate Treponema pallidum in tissue
Lab
• Nontreponemal tests: VDRL or RPR
- Primary screening test
- Relatively inexpensive
- Positive within 7 days of exposure
- Positive test should be quantified and titers followed at regular intervals after treatment.
- Titers usually correlate with disease activity.
- Titer decreases with time or treatment; following adequate treatment for primary or secondary a 4-fold decline should be noted by 4 months and an 8-fold decline by 8 months. Titer eventually should be negative (see "Serofast Reaction"). Titers of patients treated in latent stages will decline more gradually.
- Failure of nontreponemal test titers to decline 4-fold within 6 months after therapy for primary or secondary might indicate treatment failure.
- Nonspecific; must confirm diagnosis with treponemal test (false-positive common)
- Prozone phenomenon: Negative results due to very high titers of antibody; test diluted serum sample
- Serofast reaction: Persistently positive results years after successful treatment; new infection is diagnosed by 4-fold rise in titer
- Drugs that may alter lab results
Recent immunization (e.g., smallpox)
Many reported to cause false positive, but uncommon with a good history
- Disorders that may alter lab results
Pregnancy
Autoimmune disease
Systemic lupus erythematosus
Mononucleosis
Malaria
Leprosy
Viral pneumonia
Presence of cardiolipin antigens
Drug addiction
Acute febrile illness
HIV infection
Elderly can be false positive
• Treponemal tests: FTA-ABS, TP-PA
- Confirmatory test, not used for screening
- More expensive
- Usually positive for life after treatment
- Titers of no benefit
- 15-20% of patients treated during the primary stage revert to being serologically nonreactive after 2-3 years.
- Drugs that may alter lab results: See "Nontreponemal Tests"
- Disorders that may alter lab results: See "Nontreponemal Tests"
• Lumbar puncture
- Indicated for any patient who has clinical evidence of neurologic involvement or has syphilitic ocular or auditory manifestations
- Some experts advise in all secondary and early latent cases without neuro symptoms
- In HIV-positive patients with late latent or latent of unknown duration
- In cases of late latent or latent of unknown duration, or when nonpenicillin therapy is planned
- In treatment failures
- If other evidence of active syphilis is present (aortitis, gumma, iritis)
- In children with syphilis, after the newborn period, to rule out neurosyphilis
- VDRL, not RPR, used on CSF; may be negative in neurosyphilis; highly specific but insensitive
- Send fluid for protein, glucose and cell count
- Monitor resolution by cell count at 6 months along with serologies as recommended (see Patient Monitoring)
- Negative FTA-ABS or MHA-TP on CSF excludes neurosyphilis, highly sensitive
- Positive FTA-ABS or MHA-TP on CSF not diagnostic because high false-positive rate
- Bloody tap, tuberculosis, pyogenic or aseptic meningitis can result in false-positive VDRL
Imaging
Only in late cases as indicated
Pathological Findings
• Aneurysm
• Osteomyelitis
• Gummas in late cases
DIFFERENTIAL DIAGNOSIS
• Primary
- Chancroid
- Lymphogranuloma venereum
- Granuloma inguinale
- Condyloma Acuminata
- Herpes Simplex
- Behcet syndrome
- Trauma
- Carcinoma
- Mycotic infection
- Lichen planus
- Psoriasis
- Fungal infection
• Secondary
- Pityriasis rosea
- Drug eruption
- Psoriasis
- Lichen planus
- Viral exanthema
- Stevens-Johnson syndrome
• Positive serology, asymptomatic
- Previously treated syphilis
- Other spirochetal disease (yaws, pinta)
- Biological false positive: See "Disorders that May Alter Lab Results"
TREATMENT
GENERAL MEASURES
• Outpatient, except for initiating IV penicillin or desensitization
• Baseline serologies prior to treatment
Diet
No special diet
Activity
Full activity, but no sexual contacts until 4-fold drop in nontreponemal test titer
MEDICATION (DRUGS)
First Line
Parenteral penicillin G is drug of choice for all stages. (2)[A] Choice of penicillin formulation is determined by the disease stage and clinical manifestations.
ALERT
Bicillin L-A should be used and not Bicillin C-R when penicillin G benzathine is indicated. (4)[A]
• Primary, secondary, and early latent 1 year
- Benzathine penicillin G 2.4 million units IM for 1 dose (2)[A]
- Penicillin-allergic patients: Doxycycline 100 mg PO b.i.d. for 2 weeks or tetracycline 500 mg PO q.i.d. for 2 weeks; Ceftriaxone 1 g IM or IV daily for 8-10 days is used by some
• Late latent or latent of unknown duration and tertiary without evidence of neurosyphilis
- Benzathine penicillin G 2.4 million units IM weekly for 3 doses (2)[A]
- Penicillin-allergic patients: Attempt desensitization and treatment with penicillin; doxycycline 100 mg PO 2 b.i.d. for 28 days or tetracycline 500 mg PO for 28 days; compliance may be an issue
• Neurosyphilis
- Aqueous crystalline penicillin G 3-4 million units IV q4h, or continuous infusion for 10-14 days, or procaine penicillin G 2.4 million units IM daily and probenecid 500 mg PO q.i.d. for 10-14 days (if compliance can be ensured) (2)[A]
- Penicillin-allergic patients: Attempt desensitization and treatment with penicillin; Ceftriaxone 2 g daily IM or IV for 10-14 days
- If late latent, latent of unknown duration, or tertiary in addition to neurosyphilis, consider also treating as recommended for late latent after completion of neurosyphilis treatment
• Congenital
- Aqueous crystalline penicillin G 50,000 units/kg/dose IV q12h for 1st 7 days of life and q8hs thereafter for a total of 10 days, or procaine penicillin G 50,000 units/kg/dose IM daily for 10 days (2)[A]
- If negative CSF serologies, normal physical exam, and titer maternal titer then 50,000 units/kg benzathine penicillin G IM in single dose is also alternative (2)[A]
- If >1 day of therapy is missed, restart entire course.
• Children (after newborn period)
- Aqueous crystalline penicillin G 50,000 units/kg/dose IV q4-6h for 10 days; late latent: 50,000 units/kg IM as 3 doses at 1-week intervals (2)[A]
• Pregnancy
- Treatment same as for nonpregnant patients;
- Some specialists recommend 2nd dose of 2.4 million units benzathine penicillin G 1 week after initial dose, especially in 3rd trimester or with primary, secondary, or early latent syphilis.
- Penicillin sensitivity: No proven alternatives to penicillin exist for treatment during pregnancy; consider desensitization and treat with penicillin (2)[A]
• Epidemiologic treatment for contacts without symptoms, treat as primary after baseline serologies obtained
• Contraindications: Allergy to penicillin
• Precautions
- HIV-infected and pregnant patients may show poor response to recommended IM doses. Use IV therapy for all treatment failures in these patients.
- Do not give benzathine or procaine penicillins IV.
• Significant possible interactions: Refer to manufacturer's literature.
FOLLOW-UP
Follow-up is very important
DISPOSITION
Issues for Referral
Sonographic signs of fetal or placental syphilis indicate a greater risk for treatment failure and should be managed in consult with obstetric specialist.
PROGNOSIS
• Excellent in all cases except patients with late-syphilis complications and a few with HIV infection
• Syphilis in HIV-infected patient
- Test for HIV in any patient with syphilis.
- Treatment recommendations are same as HIV negative.
- More often false-negative treponemal and nontreponemal tests or unusually high titers (see "Prozone Phenomenon")
- Serologic response to therapy sometimes less predictable
- Early syphilis: Increased risk of neurosyphilis and might have higher rates of treatment failure
- Neurosyphilis: Harder to treat; can occur up to 20 years after infection
COMPLICATIONS
• Cardiovascular disease
• CNS disease
• Membranous glomerulonephritis
• Paroxysmal cold hemoglobinemia
• Meningitis
• Tabes dorsalis
• Irreversible organ damage
• Jarisch-Herxheimer reaction
- Marked by fever, chills, headache, myalgias, new rash
- Common on starting treatment (of primary or secondary disease; less common with tertiary) due to lysis of treponemes
- Should not be confused with reaction to antibiotics
- Managed with analgesics and antipyretics
PATIENT MONITORING
• Use VDRL or RPR to monitor therapy: 4-fold rise in titer indicates new infection, whereas failure to decrease 4-fold within 6 months is treatment failure (although definitive criteria for cure not established); always use same test (VDRL or RPR).
• Re-treat for persistent clinical signs or recurrence, 4-fold rise in titers, or failure of initially high titer to decrease 4-fold by 6 months.
• Labs must titer tests to final end point (e.g., not report as ">1:512") to make best use of results in monitoring therapy response.
• Repeat serologies at 3, 6, 9, and 12 months after treatment; if >1 year's duration, check at 24 months also.
REFERENCES
1. CDC. Sexually transmitted disease surveillance, 2004. Atlanta, GA: US Department of Health and Human Services.
2. CDC Sexually Transmitted Diseases Treatment Guidelines, 2006. MMWR Weekly. 2006;55(RR-11):22-34.
3. Drugs for sexually transmitted infections. Med Lett. 2004;2(26).
4. Palacioz K. Syphilis treatment errors. Prescriber's Letter. 2004;11(5):200513.
5. CDC. Primary and Secondary SyphilisUnited States, 2003-2004. MMWR Weekly. 2006;55(10):269-273.
6. McGregor T. Syphilis. www.emedicine.com/ emerg/topic563.htm. Accessed 8/26/2006.
7. Knudsen R. Neurosyphilis. www.emedicine.com/ neuro/topic684.htm Accessed 8/28/2006.
8. Larson S. A Manual of Tests for Syphilis. Washington, DC: American Public Health Association, 1990.
MISCELLANEOUS
• See also: Chlamydial sexually transmitted diseases; Gonococcal infections
• Many experts urge more aggressive treatment than standard regimens in all patients especially HIV-positive and pregnant patients, and strongly advocate use of penicillin rather than any alternative antibiotic.
• Penicillin-allergic patients, particularly with neurosyphilis, HIV infection, and pregnancy, should undergo desensitization.
SYNOVITIS PIGMENTED VILLONODULAR
SYNOVITIS PIGMENTED VILLONODULAR - Brian Busconi, MD; Adam Harner, MD
BASICS
DESCRIPTION
• Pigmented villonodular synovitis (PVNS) is a condition of the synovial membrane that is characterized by the presence of inflammation and hemosiderin deposition in the synovium.
• 2 forms of PVNS exist: Diffuse (DPVNS) and localized (LPVNS).
EPIDEMIOLOGY
• Predominant age: 3rd and 4th decades
• Predominant sex: Male = Female
Incidence
1.8 per million
PATHOPHYSIOLOGY
• Histologically, LPVNS and DPVNS are similar
- Lipid-laden macrophages
- Multinucleated giant cells
- Hemosiderin deposition in the synovium
- Stromal and fibroblast cell proliferation
• DPVNS and LPVNS differ in their disease course
- DPVNS
Characterized by involvement of most or all of the joint synovium
More common
More rapidly destructive course with poorer prognosis
Can encroach on major neurovascular structures
Higher occurrence rate
Continued inflammation and joint erosions lead to articular cartilage destruction and subsequent osteoarthritis
- LPVNS
Characterized by a pedunculated, lobular lesion localized to one area of the synovium
Favorable prognosis secondary to its localized nature
Low recurrence rate following surgical intervention
ETIOLOGY
• Still largely unknown
• Possibly the result of trauma and subsequent recurrent local hemorrhage in the affected joint
- 1/3 of patients report a history of trauma.
• Possibly secondary to abnormal local metabolic activity
• Possibly a neoplastic process with rare reports of malignant transformation and metastasis
- Demonstrates neither cellular atypia nor abnormal mitotic activity
- Exhibits some cytogenetic abnormalities
• Possibly a chronic inflammation process
DIAGNOSIS
SIGNS AND SYMPTOMS
• Typically a monoarticular process that often involves the large joints.
• Knee is most commonly involved.
• Hip, ankle, shoulder, and elbow also are possibilities.
History
• Slow and insidious onset of pain, swelling, and stillness
• History of locking, catching, or instability is more common with LPVNS.
• Symptoms are often intermittent
Physical Exam
• Tenderness to palpation of involved joint
• Joint effusion
• Loss of range of motion
Imaging
• Plain radiographs
- Periarticular erosions with thin rim of reactive bone
- Reciprocal bony lesions on opposite sides of the joint
- Joint space narrowing is a late finding.
- Majority of cases have no findings.
• CT
- Appears as a soft tissue mass of high density
- Underlying bone erosions or cysts
• MRI
- Modality of choice
- Helpful for determining the extent of disease and differentiation DPVNS from LPVNS
- DPVNS
Poorly localized mass or synovial thickening with varying degrees of periarticular erosions
Low signal on T1 and T2 weighted images
Joint effusion
- LPVNS
Periarticular or synovial nodular mass with varying degrees of bond erosion
High hemosiderin content causes low signal on T1- and T2-weighted images
Joint effusion
Diagnostic Procedures/Surgery
Synovial fluid aspiration
• Brownish-stained bloody fluid is indicative of PVNS.
• Lacks sensitivity and specificity
DIFFERENTIAL DIAGNOSIS
• Rheumatoid arthritis
• Osteoarthritis
• Synovial sarcoma
• Hemophilia
• Lipoma arborescens
• Hematoma
• Hemangioma
• Giant cell tumor of the tendon sheath
TREATMENT
GENERAL MEASURES
• The goal is to eradicate all abnormal synovial tissue, thus removing the source of pain and reducing the risk of joint destruction and recurrence.
• The treatment of PVNS is largely surgical.
Activity
As tolerated
Radiotherapy
• An alternative to surgical synovectomy
• Serious potential complications
- Skin reactions
- Poor wound healing
- Joint stiffness
- Sarcomatous transformation
• Highly useful in managing refractory cases or in those with extensive extra-articular involvement
• May be used as an adjuvant to surgical synovectomy, especially in challenging cases with persistently recurrent disease and involvement of critical anatomic structures.
SURGERY
• The mainstay of treatment
• Arthroscopy has been associated with better functional results and lower rates of postoperative stiffness than have open techniques.
• Arthroscopic partial synovectomy is the standard care for LPVNS.
- Recurrence is rare after limited local treatment of LPVNS.
• Arthroscopic treatment of DPVNS is associated with a significantly higher recurrence rate.
• Patients with large popliteal masses or extra-articular involvement generally are not candidates for an exclusively arthroscopic approach.
• A thorough, complete synovectomy is the treatment of choice for DPVNS.
- This is most easily accomplished through an open surgical procedure.
- A combined arthroscopic and open approach is also a commonly utilized alternative.
• Joint replacement is indicated in cases with significant joint destruction.
FOLLOW-UP
PROGNOSIS
• Patients presenting with recurrent disease have much more extensive involvement and a poorer likelihood of successful treatment.
• DPVNS is more rapidly destructive and has a poorer prognosis.
• Recurrence rates after adequate synovectomy are in the range of 5-20%.
- Rates are higher with DPVNS.
- Rates are also increased with extra-articular involvement.
• Articular cartilage destruction and the development of osteoarthritis requires joint replacement surgery.
• Malignant transformation has been reported but is exceedingly rare.
• Extensive joint involvement and extra-articular spread may result after failed arthroscopic management.
• Postoperative stiffness occurs in ~25% of patients treated with an open procedure.
REFERENCES
1. Tyler WK, Vidal AF, Williams RJ, Healey JM. Pigmented villonodular synovitis. J Am Acad Orthopaed Surg. 2006;14:376-385.
2. Al-Nakshabandi NA, Ryan AG, Choudur H, Al-Ismail K. Pigmented villonodular synovitis. Clin Radiol. 2004;59:414-420.
ADDITIONAL READING
Flandry F, Hughston JC. Pigmented villonodular synovitis. J Bone Joint Surg Am. 1987;69:942-949.
PATIENT TEACHING
Resources and education are important when dealing with patients with PVNS
BASICS
DESCRIPTION
• Pigmented villonodular synovitis (PVNS) is a condition of the synovial membrane that is characterized by the presence of inflammation and hemosiderin deposition in the synovium.
• 2 forms of PVNS exist: Diffuse (DPVNS) and localized (LPVNS).
EPIDEMIOLOGY
• Predominant age: 3rd and 4th decades
• Predominant sex: Male = Female
Incidence
1.8 per million
PATHOPHYSIOLOGY
• Histologically, LPVNS and DPVNS are similar
- Lipid-laden macrophages
- Multinucleated giant cells
- Hemosiderin deposition in the synovium
- Stromal and fibroblast cell proliferation
• DPVNS and LPVNS differ in their disease course
- DPVNS
Characterized by involvement of most or all of the joint synovium
More common
More rapidly destructive course with poorer prognosis
Can encroach on major neurovascular structures
Higher occurrence rate
Continued inflammation and joint erosions lead to articular cartilage destruction and subsequent osteoarthritis
- LPVNS
Characterized by a pedunculated, lobular lesion localized to one area of the synovium
Favorable prognosis secondary to its localized nature
Low recurrence rate following surgical intervention
ETIOLOGY
• Still largely unknown
• Possibly the result of trauma and subsequent recurrent local hemorrhage in the affected joint
- 1/3 of patients report a history of trauma.
• Possibly secondary to abnormal local metabolic activity
• Possibly a neoplastic process with rare reports of malignant transformation and metastasis
- Demonstrates neither cellular atypia nor abnormal mitotic activity
- Exhibits some cytogenetic abnormalities
• Possibly a chronic inflammation process
DIAGNOSIS
SIGNS AND SYMPTOMS
• Typically a monoarticular process that often involves the large joints.
• Knee is most commonly involved.
• Hip, ankle, shoulder, and elbow also are possibilities.
History
• Slow and insidious onset of pain, swelling, and stillness
• History of locking, catching, or instability is more common with LPVNS.
• Symptoms are often intermittent
Physical Exam
• Tenderness to palpation of involved joint
• Joint effusion
• Loss of range of motion
Imaging
• Plain radiographs
- Periarticular erosions with thin rim of reactive bone
- Reciprocal bony lesions on opposite sides of the joint
- Joint space narrowing is a late finding.
- Majority of cases have no findings.
• CT
- Appears as a soft tissue mass of high density
- Underlying bone erosions or cysts
• MRI
- Modality of choice
- Helpful for determining the extent of disease and differentiation DPVNS from LPVNS
- DPVNS
Poorly localized mass or synovial thickening with varying degrees of periarticular erosions
Low signal on T1 and T2 weighted images
Joint effusion
- LPVNS
Periarticular or synovial nodular mass with varying degrees of bond erosion
High hemosiderin content causes low signal on T1- and T2-weighted images
Joint effusion
Diagnostic Procedures/Surgery
Synovial fluid aspiration
• Brownish-stained bloody fluid is indicative of PVNS.
• Lacks sensitivity and specificity
DIFFERENTIAL DIAGNOSIS
• Rheumatoid arthritis
• Osteoarthritis
• Synovial sarcoma
• Hemophilia
• Lipoma arborescens
• Hematoma
• Hemangioma
• Giant cell tumor of the tendon sheath
TREATMENT
GENERAL MEASURES
• The goal is to eradicate all abnormal synovial tissue, thus removing the source of pain and reducing the risk of joint destruction and recurrence.
• The treatment of PVNS is largely surgical.
Activity
As tolerated
Radiotherapy
• An alternative to surgical synovectomy
• Serious potential complications
- Skin reactions
- Poor wound healing
- Joint stiffness
- Sarcomatous transformation
• Highly useful in managing refractory cases or in those with extensive extra-articular involvement
• May be used as an adjuvant to surgical synovectomy, especially in challenging cases with persistently recurrent disease and involvement of critical anatomic structures.
SURGERY
• The mainstay of treatment
• Arthroscopy has been associated with better functional results and lower rates of postoperative stiffness than have open techniques.
• Arthroscopic partial synovectomy is the standard care for LPVNS.
- Recurrence is rare after limited local treatment of LPVNS.
• Arthroscopic treatment of DPVNS is associated with a significantly higher recurrence rate.
• Patients with large popliteal masses or extra-articular involvement generally are not candidates for an exclusively arthroscopic approach.
• A thorough, complete synovectomy is the treatment of choice for DPVNS.
- This is most easily accomplished through an open surgical procedure.
- A combined arthroscopic and open approach is also a commonly utilized alternative.
• Joint replacement is indicated in cases with significant joint destruction.
FOLLOW-UP
PROGNOSIS
• Patients presenting with recurrent disease have much more extensive involvement and a poorer likelihood of successful treatment.
• DPVNS is more rapidly destructive and has a poorer prognosis.
• Recurrence rates after adequate synovectomy are in the range of 5-20%.
- Rates are higher with DPVNS.
- Rates are also increased with extra-articular involvement.
• Articular cartilage destruction and the development of osteoarthritis requires joint replacement surgery.
• Malignant transformation has been reported but is exceedingly rare.
• Extensive joint involvement and extra-articular spread may result after failed arthroscopic management.
• Postoperative stiffness occurs in ~25% of patients treated with an open procedure.
REFERENCES
1. Tyler WK, Vidal AF, Williams RJ, Healey JM. Pigmented villonodular synovitis. J Am Acad Orthopaed Surg. 2006;14:376-385.
2. Al-Nakshabandi NA, Ryan AG, Choudur H, Al-Ismail K. Pigmented villonodular synovitis. Clin Radiol. 2004;59:414-420.
ADDITIONAL READING
Flandry F, Hughston JC. Pigmented villonodular synovitis. J Bone Joint Surg Am. 1987;69:942-949.
PATIENT TEACHING
Resources and education are important when dealing with patients with PVNS
SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE (SIADH)
SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE (SIADH) - Ruben Peralta, MD, FACS; Jacqueline J. Wu, MD
BASICS
DESCRIPTION
• Form of hyponatremia with decreased serum sodium, low serum osmolality, and inappropriately elevated urine osmolality
- The resulting abnormal urinary water retention and normal sodium excretion lead to dilutional hyponatremia. Total body sodium levels may be normal or near normal. The patient's total body water usually is increased.
- Associated with an underlying disorder such as neoplasm, pulmonary disorder, or CNS system disease
• Synonym(s): Syndrome of inappropriate secretion of ADH
GENERAL PREVENTION
• Search for cause, if unknown
• Monitor electrolytes in postoperative patients to determine if fluid intake needs restriction
• Reduce or change medications, if caused by drug
• Life-long restriction of fluid intake
EPIDEMIOLOGY
Predominant age: Elderly
Predominate sex: Females > Males
Incidence
Usually found in the hospital setting, where incidence can be as high as 35%
RISK FACTORS
• Use of predisposing drugs
• Advanced age
• Postoperative status
• Institutionalization
Genetics
No known genetic pattern
ETIOLOGY
• Drugs (1)[B]
- Antidepressants (MAOIs, tricyclics, SSRIs)
- Oral hypoglycemics (chlorpropamide, metformin)
- Antineoplastic drugs (vincristine, vinblastine, cisplatin, cyclophosphamide)
- Antipsychotic agents (phenothiazines, thioridazine, haloperidol)
- Analgesics (NSAIDs)
- Antiepileptics (carbamazepine, valproic acid)
- Diuretics (thiazides and loop)
- Others (vasopressin, DDAVP, Ecstasy, oxytocin, alpha interferon)
• Neoplasms (ectopic ADH production)
- Small cell carcinoma of the lung
- Oat-cell carcinoma of the lung
- Hodgkin disease
- Pancreatic carcinoma
- Thymoma
- Mesothelioma
- Bronchogenic carcinoma
• Infectious diseases
- Meningitis
- Encephalitis
- Pneumonia
- Pulmonary tuberculosis
- Rocky Mountain spotted fever
- HIV
• Miscellaneous cardiopulmonary conditions
- Asthma
- Atelectasis
- Myocardial infarction
- Vascular diseases
• Other
- CNS injury
- Mechanical ventilation
- Multiple sclerosis
- Guillain-Barre syndrome
- Lupus erythematosus
- Porphyria
- Hypothyroidism, myxedema
- Idiopathic
ASSOCIATED CONDITIONS
See "Etiology."
DIAGNOSIS
SIGNS AND SYMPTOMS
• Early symptoms
- Fatigue
- Anorexia
- Nausea
- Vomiting
- Diarrhea
- Headaches
- Myalgias
- Increased thirst
• Late/severe hyponatremia (serum sodium 100-115 mEq/L)
- Altered mental status
- Confusion
- Lethargy
- Seizures
- Psychosis
- Coma
- Death
TESTS
Oral water-loading test
• May be helpful in diagnosing some patients.
• Response to water-load will be impaired in SIADH.
• May be unsafe and often not necessary to establish diagnosis.
Lab
• Serum sodium level (low)
• Serum osmolality (low 280)
• BUN
• Creatinine
• Urine osmolality (100+ mOsm/kg)
• Urinary sodium concentration >40 mEq/L (>40 mmol/L)
• Serum glucose
• Thyroid function
• Morning cortisol
• Elevated serum ADH level
• Uric acid
Imaging
Not usually required for diagnosis
DIFFERENTIAL DIAGNOSIS
• Postoperative complication
- Usually after major abdominal or thoracic surgery
- Caused by nonosmotic release of ADH, probably mediated by pain afferents
- ADH increased by pain and narcotics
• Postprostatectomy syndrome
- Irrigating solution must be nonconducting (i.e., electrolyte free)
- D5W absorbed
• Psychogenic polydipsia
- Active therapy rarely is needed.
- Diuresis occurs when intake is stopped.
- Intake usually over 10 L/d
- Interaction with other psychotropic drugs
• Acute (usually in children)
- Swallowing water during swimming
- Diluted formula
- Tap-water enemas
• Endocrine
- Addison disease
- Hypothyroidism
• Factitious hyponatremia: Caused by increased serum glucose, cholesterol, or proteins
• "Appropriate" ADH secretion and hyponatremia with decreased effective arterial blood volume (e.g., CHF, nephrotic syndrome, cirrhosis)
TREATMENT
GENERAL MEASURES
• Fluid restriction: 800-1000 mL/d. This is the main form of treatment.
• Mildly symptomatic (serum sodium >125 mEq/L [>125 mmol/L]): Restrict fluid to 800-1000 mL/d (1)[B]
• Acute (48 h duration) or symptomatic (altered mental status, seizure, coma)
- Hypertonic saline (3% normal saline) bolus
- Diuresis with loop diuretics
- Decrease oral free water to 2/3 maintenance
- Increase oral salt
- Correct serum sodium deficit (mEq sodium deficit = [desired sodium - actual sodium] 0.5 times body weight [kg])
- Increase serum sodium slowly with hypertonic saline by 0.5 mEq/L/h until it reaches 120 mEq/L
ALERT
Increase sodium levels slowly, no greater than 0.5-1 mEq/L/h to prevent complications such as central pontine myelinosis (CPM)
Diet
May need increased salt or decreased water intake, depending on cause
Activity
As tolerated
MEDICATION (DRUGS)
First Line
• Diuretics: Furosemide (Lasix) plus hourly sodium chloride and potassium chloride replacement
- Requires frequent monitoring (see "Patient Monitoring")
- Treatment of choice for acute management
• Hypertonic (3%) saline; to cautiously increase serum sodium (2)[B]
- By 10-12 mEq/L (10-12 mmol/L) q24h (in chronic hyponatremia)
- 5% over 1st few hours
- To only 120 mEq/L (120 mmol/L), acutely
- By 0.5 mEq/h (0.5 mmol/h)
• Contraindications: Avoid fluids in CHF, nephrotic syndrome, or cirrhosis
• Precautions: Overly rapid correction (>12m Eq/L/d [>12 mmol/d]) can cause
- CHF
- Subdural and intracerebral hemorrhage
- Permanent CNS damage, especially with serum sodium 120 mEq/L (120 mmol/L)
- Demyelination syndrome
• Demeclocycline
- Blocks ADH at renal tubule, produces nephrogenic diabetes insipidus
- Dosage for long-term management: 600-1,200 mg/d
- Onset of action within 1 week, therefore not best for acute management
• Lithium
- Blocks ADH at renal tubule
- Use with caution to avoid lithium toxicity.
FOLLOW-UP
PROGNOSIS
• Depends on underlying cause
• If symptomatic (seizure, coma): High mortality due to cerebral edema if serum sodium 120 mEq/L (120 mmol/L)
COMPLICATIONS
• Central pontine myelinosis
• Chronic hyponatremia: Usually 120 mEq/L (120 mmol/L)
• Complications of overly rapid correction (see "Treatment, Precautions")
PATIENT MONITORING
• Careful, continuous clinical and laboratory monitoring of hyponatremic state during acute phase
- Hourly urine output
- Urine sodium
- Serum sodium and potassium
• Chronic management: Monitor underlying cause as needed.
REFERENCES
1. Yeates KE, Singer M, Morton AR. Salt and water: A simple approach to hyponatremia. CMAJ 2004;170(3):365-369.
2. Arvanitis ML, Pasquale JL. External causes of metabolic disorders. Emerg Med Clin North Amer 2005:827-841.
3. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med 2000;342:1581-1589.
MISCELLANEOUS
See also: Hyponatremia
BASICS
DESCRIPTION
• Form of hyponatremia with decreased serum sodium, low serum osmolality, and inappropriately elevated urine osmolality
- The resulting abnormal urinary water retention and normal sodium excretion lead to dilutional hyponatremia. Total body sodium levels may be normal or near normal. The patient's total body water usually is increased.
- Associated with an underlying disorder such as neoplasm, pulmonary disorder, or CNS system disease
• Synonym(s): Syndrome of inappropriate secretion of ADH
GENERAL PREVENTION
• Search for cause, if unknown
• Monitor electrolytes in postoperative patients to determine if fluid intake needs restriction
• Reduce or change medications, if caused by drug
• Life-long restriction of fluid intake
EPIDEMIOLOGY
Predominant age: Elderly
Predominate sex: Females > Males
Incidence
Usually found in the hospital setting, where incidence can be as high as 35%
RISK FACTORS
• Use of predisposing drugs
• Advanced age
• Postoperative status
• Institutionalization
Genetics
No known genetic pattern
ETIOLOGY
• Drugs (1)[B]
- Antidepressants (MAOIs, tricyclics, SSRIs)
- Oral hypoglycemics (chlorpropamide, metformin)
- Antineoplastic drugs (vincristine, vinblastine, cisplatin, cyclophosphamide)
- Antipsychotic agents (phenothiazines, thioridazine, haloperidol)
- Analgesics (NSAIDs)
- Antiepileptics (carbamazepine, valproic acid)
- Diuretics (thiazides and loop)
- Others (vasopressin, DDAVP, Ecstasy, oxytocin, alpha interferon)
• Neoplasms (ectopic ADH production)
- Small cell carcinoma of the lung
- Oat-cell carcinoma of the lung
- Hodgkin disease
- Pancreatic carcinoma
- Thymoma
- Mesothelioma
- Bronchogenic carcinoma
• Infectious diseases
- Meningitis
- Encephalitis
- Pneumonia
- Pulmonary tuberculosis
- Rocky Mountain spotted fever
- HIV
• Miscellaneous cardiopulmonary conditions
- Asthma
- Atelectasis
- Myocardial infarction
- Vascular diseases
• Other
- CNS injury
- Mechanical ventilation
- Multiple sclerosis
- Guillain-Barre syndrome
- Lupus erythematosus
- Porphyria
- Hypothyroidism, myxedema
- Idiopathic
ASSOCIATED CONDITIONS
See "Etiology."
DIAGNOSIS
SIGNS AND SYMPTOMS
• Early symptoms
- Fatigue
- Anorexia
- Nausea
- Vomiting
- Diarrhea
- Headaches
- Myalgias
- Increased thirst
• Late/severe hyponatremia (serum sodium 100-115 mEq/L)
- Altered mental status
- Confusion
- Lethargy
- Seizures
- Psychosis
- Coma
- Death
TESTS
Oral water-loading test
• May be helpful in diagnosing some patients.
• Response to water-load will be impaired in SIADH.
• May be unsafe and often not necessary to establish diagnosis.
Lab
• Serum sodium level (low)
• Serum osmolality (low 280)
• BUN
• Creatinine
• Urine osmolality (100+ mOsm/kg)
• Urinary sodium concentration >40 mEq/L (>40 mmol/L)
• Serum glucose
• Thyroid function
• Morning cortisol
• Elevated serum ADH level
• Uric acid
Imaging
Not usually required for diagnosis
DIFFERENTIAL DIAGNOSIS
• Postoperative complication
- Usually after major abdominal or thoracic surgery
- Caused by nonosmotic release of ADH, probably mediated by pain afferents
- ADH increased by pain and narcotics
• Postprostatectomy syndrome
- Irrigating solution must be nonconducting (i.e., electrolyte free)
- D5W absorbed
• Psychogenic polydipsia
- Active therapy rarely is needed.
- Diuresis occurs when intake is stopped.
- Intake usually over 10 L/d
- Interaction with other psychotropic drugs
• Acute (usually in children)
- Swallowing water during swimming
- Diluted formula
- Tap-water enemas
• Endocrine
- Addison disease
- Hypothyroidism
• Factitious hyponatremia: Caused by increased serum glucose, cholesterol, or proteins
• "Appropriate" ADH secretion and hyponatremia with decreased effective arterial blood volume (e.g., CHF, nephrotic syndrome, cirrhosis)
TREATMENT
GENERAL MEASURES
• Fluid restriction: 800-1000 mL/d. This is the main form of treatment.
• Mildly symptomatic (serum sodium >125 mEq/L [>125 mmol/L]): Restrict fluid to 800-1000 mL/d (1)[B]
• Acute (48 h duration) or symptomatic (altered mental status, seizure, coma)
- Hypertonic saline (3% normal saline) bolus
- Diuresis with loop diuretics
- Decrease oral free water to 2/3 maintenance
- Increase oral salt
- Correct serum sodium deficit (mEq sodium deficit = [desired sodium - actual sodium] 0.5 times body weight [kg])
- Increase serum sodium slowly with hypertonic saline by 0.5 mEq/L/h until it reaches 120 mEq/L
ALERT
Increase sodium levels slowly, no greater than 0.5-1 mEq/L/h to prevent complications such as central pontine myelinosis (CPM)
Diet
May need increased salt or decreased water intake, depending on cause
Activity
As tolerated
MEDICATION (DRUGS)
First Line
• Diuretics: Furosemide (Lasix) plus hourly sodium chloride and potassium chloride replacement
- Requires frequent monitoring (see "Patient Monitoring")
- Treatment of choice for acute management
• Hypertonic (3%) saline; to cautiously increase serum sodium (2)[B]
- By 10-12 mEq/L (10-12 mmol/L) q24h (in chronic hyponatremia)
- 5% over 1st few hours
- To only 120 mEq/L (120 mmol/L), acutely
- By 0.5 mEq/h (0.5 mmol/h)
• Contraindications: Avoid fluids in CHF, nephrotic syndrome, or cirrhosis
• Precautions: Overly rapid correction (>12m Eq/L/d [>12 mmol/d]) can cause
- CHF
- Subdural and intracerebral hemorrhage
- Permanent CNS damage, especially with serum sodium 120 mEq/L (120 mmol/L)
- Demyelination syndrome
• Demeclocycline
- Blocks ADH at renal tubule, produces nephrogenic diabetes insipidus
- Dosage for long-term management: 600-1,200 mg/d
- Onset of action within 1 week, therefore not best for acute management
• Lithium
- Blocks ADH at renal tubule
- Use with caution to avoid lithium toxicity.
FOLLOW-UP
PROGNOSIS
• Depends on underlying cause
• If symptomatic (seizure, coma): High mortality due to cerebral edema if serum sodium 120 mEq/L (120 mmol/L)
COMPLICATIONS
• Central pontine myelinosis
• Chronic hyponatremia: Usually 120 mEq/L (120 mmol/L)
• Complications of overly rapid correction (see "Treatment, Precautions")
PATIENT MONITORING
• Careful, continuous clinical and laboratory monitoring of hyponatremic state during acute phase
- Hourly urine output
- Urine sodium
- Serum sodium and potassium
• Chronic management: Monitor underlying cause as needed.
REFERENCES
1. Yeates KE, Singer M, Morton AR. Salt and water: A simple approach to hyponatremia. CMAJ 2004;170(3):365-369.
2. Arvanitis ML, Pasquale JL. External causes of metabolic disorders. Emerg Med Clin North Amer 2005:827-841.
3. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med 2000;342:1581-1589.
MISCELLANEOUS
See also: Hyponatremia
SURGICAL COMPLICATIONS
SURGICAL COMPLICATIONS - Michael Ford, MD; Mitchell Cahan, MD
BASICS
DESCRIPTION
• When defined broadly, most patients have some form of complication.
• Most common complications are fever and infection.
• Rarely, death or other morbidity occurs.
GENERAL PREVENTION
Operative complications are prevented during the entire perioperative period.
• Imaging to delineate anatomy/recognize aberrancy
• Appropriate resuscitation
• Assessment of underlying risk factors
• Sterile technique
• Preoperative antibiotics
Incidence
• Fever is seen in 27-58% of post-op patients.
• Infection occurs in 3.3-28.3% of operations depending on level of bacterial contamination.
• Dehiscence occurs in 0.5-5% of abdominal operations.
• Renal failure can occur in up to 10% of patients when contrast is used, 4% for all patients.
• Respiratory complications occur in >50% of patients (mostly self-limited atelectasis), and are responsible for 35% of deaths.
• Perioperative myocardial infarction (MI) occurs in between 0.1% and 27%, based on risk factors including age, date of prior MI, and coronary artery disease; 9% risk exists for all patients.
• Fistula/intestinal leaks occur in ~1% of cases.
• Urinary retention occurs in 4-5%.
RISK FACTORS
• Poorly controlled diabetes
• Heart disease (especially recent MI)
• Bleeding disorders
• Malnutrition
• Renal failure
• Liver disease
• Pulmonary disease
Genetics
Malignant hyperthermia; 1 in 100,000, treated with dantrolene
PATHOPHYSIOLOGY
• Fever is caused by pyrogens (bacteria, viruses, antigen-antibody complexes) mediated by interleukin-1.
• Local infection at wound
• Hematoma: Inadequate hemostasis/bleeding disorder
• Seroma: Disruption of lymphatics
• Wound dehiscence: Poor wound healing (malnutrition) or increased abdominal pressure
• Renal failure: Drug toxicity (commonly antibiotics) or inadequate resuscitation leads to poor perfusion (catecholamine release at operation and renin-angiotensin-aldosterone system activation) results in acute tubular necrosis (ATN).
• Respiratory: Decreased vital capacity leads to atelectasis, pneumonitis, and adult respiratory distress syndrome. Aspiration can occur at induction of anesthesia, if stomach acid/particulate matter cause an inflammatory reaction leading to cyanosis, or death. Pulmonary edema is due to fluid transudation to the alveolus, from fluid overload, or heart failure.
• Cardiac: MI generally occurs within 3 days of operation and is caused by anesthetics and blood loss (shock, as little as 500 cc). Arrhythmia is due to destabilization of cardiac membranes or prolongation of conduction.
• Small bowel obstruction: Adhesive bands (scar tissue) form intra-abdominally and can constrict the bowel.
• Urinary retention: Males are affected much more commonly than females; impaired coordination between a-receptors in the bladder neck and parasympathetic stimulation to the bladder.
ETIOLOGY
• Fever in the 1st 24 hours is due to atelectasis.
• Staphylococcus aureus is the most common cause of wound infection. Others include Pseudomonas, Proteus, and Klebsiella.
• Hematoma: Inadequate hemostasis
• Dehiscence: Increased abdominal pressure, interrupted fascial closure, malnutrition, contamination, and chemotherapy
• Renal failure: Hypovolemia, drug toxicity (commonly due to antibiotics)
• Respiratory: Many causes including volume overload, aspiration, and decreased vital capacity, leading to decreased diffusion capacity
• Cardiac: Arrhythmia occurs due to electrolyte abnormalities, catecholamine release (due to pain), hypercapnia, and digitalis
• Small bowel obstruction: Occurs remotely after abdominal operation
• Fistula/intestinal leak: Generally occur at site of bowel anastomosis due to suture line breakdown. Can follow local abscess.
• Stomal complications: Increased in obese patients, include fibrosis of bowel at stoma, necrosis, retraction, skin breakdown, and stomal stricture. Most complications are due to technical errors at time of operation.
• Urinary retention: Due to anesthetics
ASSOCIATED CONDITIONS
• Adrenal insufficiency if steroids used
• Liver failure in patients with pre-existing disease
• Delirium tremens in alcoholics
• Thyroid storm in patients with undiagnosed hyperthyroidism
• Parotitis in elderly, under-resuscitated patients
• Depression can occur
• "Sundowning" in the elderly
ALERT
Pediatric Considerations
Operative procedures can lead to severe anxiety in children, with lasting emotional disturbance in 20%, most pronounced between 1 and 2 years old.
Geriatric Considerations
Ninety percent of patients >65 experience depression after surgery, with activities of daily living impaired in 50%. Increased human contact to prevent withdrawal can reduce these symptoms.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Low fevers are not significant until 48 hours post-op. Wound infection is the most common cause of fever after 72 hours.
• High fever, mental status changes, hypotension, and rigors are associated with severe wound complications or intestinal leak.
• Dolor, tumor, rubor, and calor indicate a wound infection.
• Hematoma is an expanding, tender mass. Seroma is a slowly expanding, nontender mass.
• Dehiscence is indicated by "salmon" colored drainage post-op day 4-5, evisceration, or later as ventral hernia. Some patients feel sutures "pop." Complain of palpable bulge.
• Renal failure is indicated by persisting oliguria, FENA >1.
• Pulmonary complications are indicated by dyspnea, cough, fever may be present.
• Cardiac complications present with chest pain (seen in 27% of perioperative MI); ST depression and T-wave flattening; elevated CPK-MB; arrhythmia on telemetry/EKG.
• Small bowel obstruction is heralded by nausea, bilious vomiting, abdominal pain, cessation of flatus.
• Fistula/intestinal leak present with feces protruding from skin opening, acute abdomen, pain, fever, nausea, vomiting.
- Stomal complications are evident when the ostomy appliance is removed.
- Urinary retention is indicated by suprapubic pain, inability to void.
History
• Pain is a common complaint
• Wound infection: Operation several days ago, pain, redness at incision
• Expanding mass is consistent with seroma/ hematoma. Surgery within 2-3 days is more likely hematoma, further out is likely seroma.
• Dehiscence/hernia: Some patients feel sutures "pop"; caused by lifting within 6 weeks of operation, or increased abdominal operation (i.e., coughing).
• Renal failure: Oliguria, or anuria, fatigue
• Pulmonary: Witnessed aspiration, no incentive spirometry use, narcotic use, fluid retention, advanced age
• Cardiac: Elderly, prior cardiac dysfunction
• Ileus/small bowel obstruction: Progressive nausea/vomiting, inability to tolerate PO, abdominal pain
• Fistula/intestinal leak: Severe abdominal pain (leak), fever, nausea/vomiting
• Stomal complications: Pain at stoma site, change in color of stoma
• Urinary retention: Inability to void, suprapubic pain
Physical Exam
• Wound infection: Dolor, rubor, calor, and tumor at incision, pus or foul-smelling discharge, may be febrile
• Expanding mass is consistent with seroma/ hematoma, may have tenderness at site.
• Dehiscence/hernia: Open incision or palpable fascial edge, rarely tender
• Renal failure: Can have pericardial rub, bleeding/hematoma if uremic
• Pulmonary: Basilar crackles, poor inspiratory effort, egophony, dullness to percussion at bases
• Cardiac: Peripheral edema, irregularly irregular heartbeat
• Ileus/small bowel obstruction: "Tinkling" vs. absent bowel sounds, tympanitic abdomen, tenderness to palpation, guarding
• Fistula/intestinal leak: Firm abdomen, guarding, peritoneal signs, possible feculent discharge from site at skin, fever, hypotension
• Stomal complications: Skin irritation, black/discolored intestinal mucosa, retracted ostomy
• Urinary retention: Suprapubic tenderness, palpable bladder
TESTS
Lab
• Elevated WBC count is seen in wound infections, atelectasis, pneumonia, infected hematoma/seroma, bowel leak, and stomal complications.
• BUN and creatinine, along with urine chemistries, are used to diagnose renal failure.
• Pulmonary: Hypoxia, hypercarbia on ABG
• Cardiac: Elevated troponins, CK, CK-MB
Imaging
• SC gas can be seen in necrotizing fasciitis on radiographs or CT.
• CT or ultrasound can be used to diagnose hernia or fascial disruption.
• Small bowel obstruction/ileus: Upright abdominal film shows air fluid levels, dilated small bowel. Transition point may be seen on CT.
• Fistula: Fistulogram aids in diagnosis and is critical for treatment planning.
• Intestinal leak: Chest radiograph reveals free air under the diaphragm.
• Bladder scan can help diagnose urinary retention if the diagnosis is in doubt.
Diagnostic Procedures/Surgery
Exploratory laparotomy/laparoscopy if the patient is extremely ill/septic and diagnosis is unknown, but abdominal cause is suspected
TREATMENT
STABILIZATION
• Fluid resuscitate as needed
• Broad spectrum antibiotics, if septic
• IV antibiotics for infections
GENERAL MEASURES
• Surgical site infections are decreased by using clipping to remove hair vs. shaving. Appropriate antibacterial prep should be utilized to decrease bacterial counts. (2)[A]
• Identify the complication.
• Appropriate antibiotics as needed
• Nasogastric tube for bowel obstruction/leak
Diet
• NPO for fistula, intestinal leak, or small bowel obstruction
• Diet as tolerated for other listed complications
Activity
Patients should be out of bed as tolerated.
Nursing
• Monitor vital signs at least every 4 hours
• Strict I Os
• DVT prophylaxis
IV Fluids
Use D5 1/2 normal saline or lactated Ringer's at a fluid replacement rate.
MEDICATION (DRUGS)
First Line
• Opiates for pain control
• Broad-spectrum antibiotics for sepsis/severe infection (piperacillin/tazobactam and vancomycin)
• Simple wound infections and stomal complications: 1st- or 2nd-generation cephalosporins
• Intestinal leak: Gram-negative and Gram-positive coverage (Levaquin and metronidazole)
• Pneumonia should be treated empirically with antibiotics to cover local flora
• Cardiac complications: Avoided/treated with -blockade for rate control; angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers also useful.
- Urinary retention: -Blockers (tamsulosin)
SURGERY
• Wound infections may need surgical debridement if no response to antibiotics.
• Hematomas may need re-exploration and hemostasis if large and progressing.
• Dehiscence/hernia should be repaired. Evisceration is a surgical emergency.
• Small bowel obstruction that fails to resolve with nasogastric decompression should be explored with lysis of adhesions.
• Intestinal leak is a surgical emergency and needs exploration and repair immediately. Fistulas generally need surgical intervention to resolve.
• Some stomal complications (necrosis, retraction) need surgical revision.
FOLLOW-UP
All complications should be seen by the surgeon responsible for the procedure when they are identified.
DISPOSITION
Admission Criteria
• Need for IV antibiotics
• Need for surgical procedure
• Need for NG decompression
Discharge Criteria
• Infection resolved/responding to antibiotics
• Able to tolerate PO intake
• Pain controlled
• Patient has bowel function
• Recovered adequately from operation
Issues for Referral
All complications should be seen by the physician performing the operation.
PROGNOSIS
With prompt and appropriate treatment, most patients with complications recover well.
REFERENCES
1. Schwartz S, Shires G, Spencer F, eds. Principles of Surgery, 7th ed. New York: McGraw-Hill; 1999:441-483.
2. Tanner J, Woodings D, Moncaster K. Preoperative hair removal to reduce surgical site infection. Cochrane Database Sys Rev. Cochrane Wound Group. 2006;3:.
BASICS
DESCRIPTION
• When defined broadly, most patients have some form of complication.
• Most common complications are fever and infection.
• Rarely, death or other morbidity occurs.
GENERAL PREVENTION
Operative complications are prevented during the entire perioperative period.
• Imaging to delineate anatomy/recognize aberrancy
• Appropriate resuscitation
• Assessment of underlying risk factors
• Sterile technique
• Preoperative antibiotics
Incidence
• Fever is seen in 27-58% of post-op patients.
• Infection occurs in 3.3-28.3% of operations depending on level of bacterial contamination.
• Dehiscence occurs in 0.5-5% of abdominal operations.
• Renal failure can occur in up to 10% of patients when contrast is used, 4% for all patients.
• Respiratory complications occur in >50% of patients (mostly self-limited atelectasis), and are responsible for 35% of deaths.
• Perioperative myocardial infarction (MI) occurs in between 0.1% and 27%, based on risk factors including age, date of prior MI, and coronary artery disease; 9% risk exists for all patients.
• Fistula/intestinal leaks occur in ~1% of cases.
• Urinary retention occurs in 4-5%.
RISK FACTORS
• Poorly controlled diabetes
• Heart disease (especially recent MI)
• Bleeding disorders
• Malnutrition
• Renal failure
• Liver disease
• Pulmonary disease
Genetics
Malignant hyperthermia; 1 in 100,000, treated with dantrolene
PATHOPHYSIOLOGY
• Fever is caused by pyrogens (bacteria, viruses, antigen-antibody complexes) mediated by interleukin-1.
• Local infection at wound
• Hematoma: Inadequate hemostasis/bleeding disorder
• Seroma: Disruption of lymphatics
• Wound dehiscence: Poor wound healing (malnutrition) or increased abdominal pressure
• Renal failure: Drug toxicity (commonly antibiotics) or inadequate resuscitation leads to poor perfusion (catecholamine release at operation and renin-angiotensin-aldosterone system activation) results in acute tubular necrosis (ATN).
• Respiratory: Decreased vital capacity leads to atelectasis, pneumonitis, and adult respiratory distress syndrome. Aspiration can occur at induction of anesthesia, if stomach acid/particulate matter cause an inflammatory reaction leading to cyanosis, or death. Pulmonary edema is due to fluid transudation to the alveolus, from fluid overload, or heart failure.
• Cardiac: MI generally occurs within 3 days of operation and is caused by anesthetics and blood loss (shock, as little as 500 cc). Arrhythmia is due to destabilization of cardiac membranes or prolongation of conduction.
• Small bowel obstruction: Adhesive bands (scar tissue) form intra-abdominally and can constrict the bowel.
• Urinary retention: Males are affected much more commonly than females; impaired coordination between a-receptors in the bladder neck and parasympathetic stimulation to the bladder.
ETIOLOGY
• Fever in the 1st 24 hours is due to atelectasis.
• Staphylococcus aureus is the most common cause of wound infection. Others include Pseudomonas, Proteus, and Klebsiella.
• Hematoma: Inadequate hemostasis
• Dehiscence: Increased abdominal pressure, interrupted fascial closure, malnutrition, contamination, and chemotherapy
• Renal failure: Hypovolemia, drug toxicity (commonly due to antibiotics)
• Respiratory: Many causes including volume overload, aspiration, and decreased vital capacity, leading to decreased diffusion capacity
• Cardiac: Arrhythmia occurs due to electrolyte abnormalities, catecholamine release (due to pain), hypercapnia, and digitalis
• Small bowel obstruction: Occurs remotely after abdominal operation
• Fistula/intestinal leak: Generally occur at site of bowel anastomosis due to suture line breakdown. Can follow local abscess.
• Stomal complications: Increased in obese patients, include fibrosis of bowel at stoma, necrosis, retraction, skin breakdown, and stomal stricture. Most complications are due to technical errors at time of operation.
• Urinary retention: Due to anesthetics
ASSOCIATED CONDITIONS
• Adrenal insufficiency if steroids used
• Liver failure in patients with pre-existing disease
• Delirium tremens in alcoholics
• Thyroid storm in patients with undiagnosed hyperthyroidism
• Parotitis in elderly, under-resuscitated patients
• Depression can occur
• "Sundowning" in the elderly
ALERT
Pediatric Considerations
Operative procedures can lead to severe anxiety in children, with lasting emotional disturbance in 20%, most pronounced between 1 and 2 years old.
Geriatric Considerations
Ninety percent of patients >65 experience depression after surgery, with activities of daily living impaired in 50%. Increased human contact to prevent withdrawal can reduce these symptoms.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Low fevers are not significant until 48 hours post-op. Wound infection is the most common cause of fever after 72 hours.
• High fever, mental status changes, hypotension, and rigors are associated with severe wound complications or intestinal leak.
• Dolor, tumor, rubor, and calor indicate a wound infection.
• Hematoma is an expanding, tender mass. Seroma is a slowly expanding, nontender mass.
• Dehiscence is indicated by "salmon" colored drainage post-op day 4-5, evisceration, or later as ventral hernia. Some patients feel sutures "pop." Complain of palpable bulge.
• Renal failure is indicated by persisting oliguria, FENA >1.
• Pulmonary complications are indicated by dyspnea, cough, fever may be present.
• Cardiac complications present with chest pain (seen in 27% of perioperative MI); ST depression and T-wave flattening; elevated CPK-MB; arrhythmia on telemetry/EKG.
• Small bowel obstruction is heralded by nausea, bilious vomiting, abdominal pain, cessation of flatus.
• Fistula/intestinal leak present with feces protruding from skin opening, acute abdomen, pain, fever, nausea, vomiting.
- Stomal complications are evident when the ostomy appliance is removed.
- Urinary retention is indicated by suprapubic pain, inability to void.
History
• Pain is a common complaint
• Wound infection: Operation several days ago, pain, redness at incision
• Expanding mass is consistent with seroma/ hematoma. Surgery within 2-3 days is more likely hematoma, further out is likely seroma.
• Dehiscence/hernia: Some patients feel sutures "pop"; caused by lifting within 6 weeks of operation, or increased abdominal operation (i.e., coughing).
• Renal failure: Oliguria, or anuria, fatigue
• Pulmonary: Witnessed aspiration, no incentive spirometry use, narcotic use, fluid retention, advanced age
• Cardiac: Elderly, prior cardiac dysfunction
• Ileus/small bowel obstruction: Progressive nausea/vomiting, inability to tolerate PO, abdominal pain
• Fistula/intestinal leak: Severe abdominal pain (leak), fever, nausea/vomiting
• Stomal complications: Pain at stoma site, change in color of stoma
• Urinary retention: Inability to void, suprapubic pain
Physical Exam
• Wound infection: Dolor, rubor, calor, and tumor at incision, pus or foul-smelling discharge, may be febrile
• Expanding mass is consistent with seroma/ hematoma, may have tenderness at site.
• Dehiscence/hernia: Open incision or palpable fascial edge, rarely tender
• Renal failure: Can have pericardial rub, bleeding/hematoma if uremic
• Pulmonary: Basilar crackles, poor inspiratory effort, egophony, dullness to percussion at bases
• Cardiac: Peripheral edema, irregularly irregular heartbeat
• Ileus/small bowel obstruction: "Tinkling" vs. absent bowel sounds, tympanitic abdomen, tenderness to palpation, guarding
• Fistula/intestinal leak: Firm abdomen, guarding, peritoneal signs, possible feculent discharge from site at skin, fever, hypotension
• Stomal complications: Skin irritation, black/discolored intestinal mucosa, retracted ostomy
• Urinary retention: Suprapubic tenderness, palpable bladder
TESTS
Lab
• Elevated WBC count is seen in wound infections, atelectasis, pneumonia, infected hematoma/seroma, bowel leak, and stomal complications.
• BUN and creatinine, along with urine chemistries, are used to diagnose renal failure.
• Pulmonary: Hypoxia, hypercarbia on ABG
• Cardiac: Elevated troponins, CK, CK-MB
Imaging
• SC gas can be seen in necrotizing fasciitis on radiographs or CT.
• CT or ultrasound can be used to diagnose hernia or fascial disruption.
• Small bowel obstruction/ileus: Upright abdominal film shows air fluid levels, dilated small bowel. Transition point may be seen on CT.
• Fistula: Fistulogram aids in diagnosis and is critical for treatment planning.
• Intestinal leak: Chest radiograph reveals free air under the diaphragm.
• Bladder scan can help diagnose urinary retention if the diagnosis is in doubt.
Diagnostic Procedures/Surgery
Exploratory laparotomy/laparoscopy if the patient is extremely ill/septic and diagnosis is unknown, but abdominal cause is suspected
TREATMENT
STABILIZATION
• Fluid resuscitate as needed
• Broad spectrum antibiotics, if septic
• IV antibiotics for infections
GENERAL MEASURES
• Surgical site infections are decreased by using clipping to remove hair vs. shaving. Appropriate antibacterial prep should be utilized to decrease bacterial counts. (2)[A]
• Identify the complication.
• Appropriate antibiotics as needed
• Nasogastric tube for bowel obstruction/leak
Diet
• NPO for fistula, intestinal leak, or small bowel obstruction
• Diet as tolerated for other listed complications
Activity
Patients should be out of bed as tolerated.
Nursing
• Monitor vital signs at least every 4 hours
• Strict I Os
• DVT prophylaxis
IV Fluids
Use D5 1/2 normal saline or lactated Ringer's at a fluid replacement rate.
MEDICATION (DRUGS)
First Line
• Opiates for pain control
• Broad-spectrum antibiotics for sepsis/severe infection (piperacillin/tazobactam and vancomycin)
• Simple wound infections and stomal complications: 1st- or 2nd-generation cephalosporins
• Intestinal leak: Gram-negative and Gram-positive coverage (Levaquin and metronidazole)
• Pneumonia should be treated empirically with antibiotics to cover local flora
• Cardiac complications: Avoided/treated with -blockade for rate control; angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers also useful.
- Urinary retention: -Blockers (tamsulosin)
SURGERY
• Wound infections may need surgical debridement if no response to antibiotics.
• Hematomas may need re-exploration and hemostasis if large and progressing.
• Dehiscence/hernia should be repaired. Evisceration is a surgical emergency.
• Small bowel obstruction that fails to resolve with nasogastric decompression should be explored with lysis of adhesions.
• Intestinal leak is a surgical emergency and needs exploration and repair immediately. Fistulas generally need surgical intervention to resolve.
• Some stomal complications (necrosis, retraction) need surgical revision.
FOLLOW-UP
All complications should be seen by the surgeon responsible for the procedure when they are identified.
DISPOSITION
Admission Criteria
• Need for IV antibiotics
• Need for surgical procedure
• Need for NG decompression
Discharge Criteria
• Infection resolved/responding to antibiotics
• Able to tolerate PO intake
• Pain controlled
• Patient has bowel function
• Recovered adequately from operation
Issues for Referral
All complications should be seen by the physician performing the operation.
PROGNOSIS
With prompt and appropriate treatment, most patients with complications recover well.
REFERENCES
1. Schwartz S, Shires G, Spencer F, eds. Principles of Surgery, 7th ed. New York: McGraw-Hill; 1999:441-483.
2. Tanner J, Woodings D, Moncaster K. Preoperative hair removal to reduce surgical site infection. Cochrane Database Sys Rev. Cochrane Wound Group. 2006;3:.
SUPERIOR VENA CAVA SYNDROME
SUPERIOR VENA CAVA SYNDROME - Ruben Peralta, MD, FACS; Sarah Guzofski, MD
BASICS
DESCRIPTION
• Partial or complete obstruction of the superior vena cava
- 90% extrinsic
- 90% from neoplasm (most frequently bronchogenic carcinoma)
• Usual course: Acute; usually 28 days from onset of symptoms to diagnosis
• Synonym(s): Superior mediastinal syndrome; Superior vena cava obstruction
GENERAL PREVENTION
No preventive measures known
EPIDEMIOLOGY
• Predominant age: Young adult (16-40 years old); middle age (40-60 years old)
• Predominant sex: Male > Female
RISK FACTORS
• HIV infection
• History of mediastinal tumor
PATHOPHYSIOLOGY
Increased pressure in the venous system draining into the superior vena cava
ETIOLOGY
• Obstruction of venous drainage of upper part of chest and neck. Sudden occlusion may cause rapid development of cerebral edema, intracranial thrombosis, and death.
• In adults, may be primary tumor or lymph node metastasis; most frequent cause is bronchogenic carcinoma; lymph node metastasis most common from breast and testicular cancer
• In children, most common after cardiac surgical procedures
• Lymphoma
• Thymoma
• Germ cell tumors
• Fungal infections
• Other malignancies
• Iatrogenic (including catheter induced)
• Thyroid goiter
• Primary superior vena caval thrombosis
• Pericardial constriction
• Idiopathic sclerosing mediastinitis
ASSOCIATED CONDITIONS
• Breast cancer
• Lung cancer
• HIV infection
• Hyperthyroidism
• Tuberculosis
• Histoplasmosis
• Lymphoma
DIAGNOSIS
Made on clinical grounds in almost all cases
SIGNS AND SYMPTOMS
• Neck and anterior chest wall venous distension
• Tachypnea, dyspnea
• Cyanosis and edema of upper extremities and face
• Feeling of fullness in the head (ears and eyes)
• Jugular venous distention
• Prominent veins over chest
• Cough
• Dilated retinal vessels, conjunctival edema, proptosis
• Horner syndrome
• Stridor, paralyzed vocal cord
• Nonpitting edema in neck (Stoke's collar)
• Truncal swelling
• Altered consciousness
• Dysphagia, hoarseness
• Easy fatigability
• Chest pain
• Orthopnea
TESTS
Increased central venous pressure; usually 20-50 mm Hg
Lab
Sputum cytology: Malignant cells
Imaging
• Abnormal chest x-ray
• Contrast-enhanced CT or MRI usually adequate to establish diagnosis.
• Venography: Superior vena cava obstruction
Diagnostic Procedures/Surgery
• Percutaneous needle biopsy used to establish histological diagnosis; should be prior to initiation of therapy
• Open biopsy may be necessary; however, these patients are at increased risk for cardiorespiratory compromise under generalized anesthesia.
• Bronchoscopy
• Thoracentesis, thoracotomy, lymph node biopsy, as indicated
Pathological Findings
Sputum cytology, occasionally thoracentesis, bone marrow, lymph node biopsy, bronchoscopy, or thoracotomy confirms malignant cells.
DIFFERENTIAL DIAGNOSIS
• Aortic aneurysm
• Tuberculosis
• Histoplasmosis
• Fungal infections
TREATMENT
STABILIZATION
• Inpatient, intensive care
• Institute supportive therapy.
GENERAL MEASURES
• Depending on etiology (1)[B]
• Chemotherapy (treatment of choice for high-grade lymphomas, and small cell lung cancer)
• Percutaneous stenting
• Radiotherapy
• Corticosteroids
• Neoadjuvant chemoradiotherapy and then resection
• Anticoagulation or fibrinolytic therapy
• Benign causes usually respond to medical therapy including diuretics, upright positioning, and fluid restriction until adequate collateral circulation is established and clinical regression is noted.
• In pregnancy: Must treat underlying condition despite pregnancy
Diet
As tolerated; possibly, salt restriction
Activity
Bed rest (head of bed elevated)
MEDICATION (DRUGS)
First Line
Determined by underlying cause
SURGERY
• Superior vena cava reconstruction for benign processes may be considered, but is rarely done.
• Spiral saphenous vein bypass grafting may also be useful in some patients.
FOLLOW-UP
PROGNOSIS
• High probability of response
• Linked to cause
- Lung cancer: 1-year survival in 20%
- Lymphoma: 2-year survival in 50%
- Neoplastic cases: 85% better in 3 weeks with radiation therapy, but symptoms usually recur
COMPLICATIONS
Complications of underlying disease
PATIENT MONITORING
Linked to cause
• If infection, monitor for evaluation of antimicrobial treatment
• If malignant, monitor response to radiotherapy or chemotherapy
REFERENCES
1. Rowell NP, Gleeson FV. Steroids, radiotherapy, chemotherapy and stents for superior vena caval obstruction in carcinoma of the bronchus: A systematic review. Clin Oncol. 2002;14:338-351.
2. Hochrein J, et al. Percutaneous stenting of superior vena cava syndrome: A case report and review of the literature. Am J Med. 1998;104:78-84.
3. Thirlwell C, Brock CS. Emergencies in oncology. Clin Med. 2003;3:306-310.
BASICS
DESCRIPTION
• Partial or complete obstruction of the superior vena cava
- 90% extrinsic
- 90% from neoplasm (most frequently bronchogenic carcinoma)
• Usual course: Acute; usually 28 days from onset of symptoms to diagnosis
• Synonym(s): Superior mediastinal syndrome; Superior vena cava obstruction
GENERAL PREVENTION
No preventive measures known
EPIDEMIOLOGY
• Predominant age: Young adult (16-40 years old); middle age (40-60 years old)
• Predominant sex: Male > Female
RISK FACTORS
• HIV infection
• History of mediastinal tumor
PATHOPHYSIOLOGY
Increased pressure in the venous system draining into the superior vena cava
ETIOLOGY
• Obstruction of venous drainage of upper part of chest and neck. Sudden occlusion may cause rapid development of cerebral edema, intracranial thrombosis, and death.
• In adults, may be primary tumor or lymph node metastasis; most frequent cause is bronchogenic carcinoma; lymph node metastasis most common from breast and testicular cancer
• In children, most common after cardiac surgical procedures
• Lymphoma
• Thymoma
• Germ cell tumors
• Fungal infections
• Other malignancies
• Iatrogenic (including catheter induced)
• Thyroid goiter
• Primary superior vena caval thrombosis
• Pericardial constriction
• Idiopathic sclerosing mediastinitis
ASSOCIATED CONDITIONS
• Breast cancer
• Lung cancer
• HIV infection
• Hyperthyroidism
• Tuberculosis
• Histoplasmosis
• Lymphoma
DIAGNOSIS
Made on clinical grounds in almost all cases
SIGNS AND SYMPTOMS
• Neck and anterior chest wall venous distension
• Tachypnea, dyspnea
• Cyanosis and edema of upper extremities and face
• Feeling of fullness in the head (ears and eyes)
• Jugular venous distention
• Prominent veins over chest
• Cough
• Dilated retinal vessels, conjunctival edema, proptosis
• Horner syndrome
• Stridor, paralyzed vocal cord
• Nonpitting edema in neck (Stoke's collar)
• Truncal swelling
• Altered consciousness
• Dysphagia, hoarseness
• Easy fatigability
• Chest pain
• Orthopnea
TESTS
Increased central venous pressure; usually 20-50 mm Hg
Lab
Sputum cytology: Malignant cells
Imaging
• Abnormal chest x-ray
• Contrast-enhanced CT or MRI usually adequate to establish diagnosis.
• Venography: Superior vena cava obstruction
Diagnostic Procedures/Surgery
• Percutaneous needle biopsy used to establish histological diagnosis; should be prior to initiation of therapy
• Open biopsy may be necessary; however, these patients are at increased risk for cardiorespiratory compromise under generalized anesthesia.
• Bronchoscopy
• Thoracentesis, thoracotomy, lymph node biopsy, as indicated
Pathological Findings
Sputum cytology, occasionally thoracentesis, bone marrow, lymph node biopsy, bronchoscopy, or thoracotomy confirms malignant cells.
DIFFERENTIAL DIAGNOSIS
• Aortic aneurysm
• Tuberculosis
• Histoplasmosis
• Fungal infections
TREATMENT
STABILIZATION
• Inpatient, intensive care
• Institute supportive therapy.
GENERAL MEASURES
• Depending on etiology (1)[B]
• Chemotherapy (treatment of choice for high-grade lymphomas, and small cell lung cancer)
• Percutaneous stenting
• Radiotherapy
• Corticosteroids
• Neoadjuvant chemoradiotherapy and then resection
• Anticoagulation or fibrinolytic therapy
• Benign causes usually respond to medical therapy including diuretics, upright positioning, and fluid restriction until adequate collateral circulation is established and clinical regression is noted.
• In pregnancy: Must treat underlying condition despite pregnancy
Diet
As tolerated; possibly, salt restriction
Activity
Bed rest (head of bed elevated)
MEDICATION (DRUGS)
First Line
Determined by underlying cause
SURGERY
• Superior vena cava reconstruction for benign processes may be considered, but is rarely done.
• Spiral saphenous vein bypass grafting may also be useful in some patients.
FOLLOW-UP
PROGNOSIS
• High probability of response
• Linked to cause
- Lung cancer: 1-year survival in 20%
- Lymphoma: 2-year survival in 50%
- Neoplastic cases: 85% better in 3 weeks with radiation therapy, but symptoms usually recur
COMPLICATIONS
Complications of underlying disease
PATIENT MONITORING
Linked to cause
• If infection, monitor for evaluation of antimicrobial treatment
• If malignant, monitor response to radiotherapy or chemotherapy
REFERENCES
1. Rowell NP, Gleeson FV. Steroids, radiotherapy, chemotherapy and stents for superior vena caval obstruction in carcinoma of the bronchus: A systematic review. Clin Oncol. 2002;14:338-351.
2. Hochrein J, et al. Percutaneous stenting of superior vena cava syndrome: A case report and review of the literature. Am J Med. 1998;104:78-84.
3. Thirlwell C, Brock CS. Emergencies in oncology. Clin Med. 2003;3:306-310.
SYNCOPE
SYNCOPE - Ricardo A. Samson, MD
BASICS
DESCRIPTION
• Transient loss of consciousness characterized by unresponsiveness, loss of postural tone, and spontaneous recovery
• System(s) Affected: Cardiovascular; Nervous
GENERAL PREVENTION
Avoid risk factors (see "Risk Factors").
EPIDEMIOLOGY
• Predominant age: Elderly
• Rare in infancy, though increasing occurrence during adolescence
Incidence
• Up to 20% of adults will have 1 episode by age 75; 15% of children 18 years of age
• Accounts for 1-6% of hospital admissions and about 3% of emergency room visits
Prevalence
In institutionalized elderly (>75 years), 6%
RISK FACTORS
• Heart disease
• Drugs
- Antihypertensives
- Vasodilators (including calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and nitrates)
- Phenothiazines
- Antidepressants
- Antiarrhythmics
- Diuretics
Genetics
Specific cardiomyopathies and arrhythmias may be familiial.
PATHOPHYSIOLOGY
Systemic hypotension secondary to decreased cardiac output and/or systemic vasodilation leads to a drop in cerebral perfusion and resultant loss of consciousness.
ETIOLOGY
• Cardiac: Obstruction to outflow
- Aortic stenosis
- Hypertrophic cardiomyopathy
- Pulmonary embolus
• Cardiac: Arrhythmias
- Sustained ventricular tachycardia (probable cause)
- Sick-sinus syndrome
- Sinus node recovery time 3 seconds (probable cause)
- 2nd-degree and 3rd-degree AV block
- Pacing-induced infranodal block (probable cause)
- H-V interval >100 m (probable cause)
• Noncardiac
- Reflex-mediated vasovagal ("drop atttack") (neurocardiogenic/neurally mediated), situational (micturition, defecation, cough)
- Orthostatic hypotension
- Drug induced
- Neurologic: Seizures, transient ischemic attack
- Carotid sinus
- Psychogenic
ASSOCIATED CONDITIONS
See "Etiology."
DIAGNOSIS
• Careful history, physical examination, and an ECG are more important than other investigations in determining the diagnosis.
• Make sure patient or witness (if present) is not talking about vertigo, coma, or drop attacks.
• After careful evaluation, including diagnostic procedures and special tests, the cause of syncope will be found in only 50-60% of the patients.
PRE HOSPITAL
Support ABCs.
SIGNS AND SYMPTOMS
• Transient loss of consciousness is characterized by unresponsiveness, loss of postural tone, and spontaneous recovery.
• Vasovagal
- Prodromal manifestations of sudden weakness, nausea, and sweating, especially in circumstances provoking strong emotion
- Does not occur when patient is horizontal
• Cardiac
- Suggested by: (a) syncope of sudden onset with no prodrome or brief premonitory symptoms and (b) occurrence with exertion
- Can occur in any position
History
Onset of syncope is usually rapid, and recovery is spontaneous, rapid, and complete. Duration of episodes are typically brief (60 s). Presence of underlying cardiac or neurologic conditions provides key to diagnosis.
Physical Exam
• Direct to BP and pulse, both lying and standing.
• Check for cardiac murmur or focal neurologic abnormality.
TESTS
• If history and physical suggest ischemic, valvular, or congenital heart disease
- ECG
- Cardiac catheterization
• If CNS disease suspected
- EEG
- Head CT
- Head MRI
- Do not order these tests unless hints of CNS disease on history or physical examination
• ECG monitoring, either in hospital or ambulatory (Holter)
- Useful in 4-15% of patients
- Should be done in patients with heart disease or recurrent syncope
- Arrhythmias frequently documented, but rarely associated with syncope
• Electrophysiologic studies
- Have been positive in 18-75% of patients
- Induction of ventricular tachycardia and dysfunction of His-Purkinje system are the 2 most common abnormalities.
- Should be done in patients with heart disease or recurrent syncope, although problem exists of knowing whether arrhythmia noted or induced during study is cause of syncope
• Carotid hypersensitivity evaluation
- Carotid hypersensitivity should be considered in patients with syncope during head turning, especially with head turning while wearing tight collar, and in patients with neck tumors and neck-tissue scars.
- The technique is not standardized; 1 side should be massaged at a time for 20 seconds with constant monitoring of pulse and BP.
- Atropine should be readily available.
• Tilt table testing, with and without isoproterenol infusion
- Provocative test for vasovagal syncope
- Should be done only if cardiac causes have been excluded; role of test in workup of patients with syncope of unknown origin is not known
- Not standardized, but has been reported positive (symptomatic hypotension and bradycardia) in 26-87% of patients; however, also reported positive in 0-45% of control subjects
• Psychiatric evaluation
- Anxiety, depression, alcohol, and drug abuse can be associated with syncope.
Lab
Rarely helpful; 2% have hyponatremia, hypocalcemia, hypoglycemia, or renal failure causing seizures.
Imaging
Lung scan or helical CT of thorax if history and physical examination suggest pulmonary embolism
Diagnostic Procedures/Surgery
Patient-activated implantable loop recorders, which patient activates after regaining consciousness, can record 4-5 minutes of retrograde ECG rhythm. Helpful in patients with recurrent syncope, with diagnostic yield of 24-47%.
Pathological Findings
Depends on etiology and presence of underlying cardiac or neurologic conditions
DIFFERENTIAL DIAGNOSIS
• Drop attacks
• Coma
• Vertigo
TREATMENT
PRE-HOSPITAL
Support ABCs.
STABILIZATION
Aimed at stabilization of heart rate and blood pressure, typically with IV fluids
GENERAL MEASURES
• Patients with heart disease should be admitted to the hospital for evaluation.
• Elderly patients without previously recognized heart disease should be admitted if the physician thinks that the cause of syncope is likely cardiac.
• Patients without heart disease, especially young patients (60 years old), can be safely worked up as outpatients.
• Prescribe antiarrhythmic drugs for documented arrhythmias occurring simultaneously with syncope or symptoms of presyncope. Asymptomatic arrhythmias do not require treatment.
• The decision to treat patients on basis of arrhythmias or conduction abnormalities provoked or detected during EPS is even more problematic: Does the arrhythmia or conduction abnormality have anything to do with patient's symptoms?
• Most would treat patient with provoked sustained ventricular tachycardia with antiarrhythmic drug that suppressed arrhythmia during study.
• Many recommend pacemaker implantation in patients with
- H-V intervals >100 m
- Pacing-induced infranodal block
- Sinus node recovery time of 3 s
• Rationale for such treatment: Recurrent syncope less frequent in patients with positive EPS who are treated than it is in those who have negative EPS
Diet
• No specific diet unless heart disease
• Increased fluid and salt intake to maintain intravascular volume in cases of recurrent vasovagal syncope
Activity
Full activity unless severe cardiac disease, with avoidance of specific triggers or stimuli
Nursing
Close monitoring of BP, HR during initial presentation
SPECIAL THERAPY
IV Fluids
Use isotonic crystalloids fluids for fluid resuscitation if needed.
MEDICATION (DRUGS)
• Geared towards specific underlying cardiac or neurologic abnormalities
• In cases of recurrent vasovagal/neurocardiogenic/neurally-mediated syncope, the following have been shown to be effective in various placebo-controlled trials
- Beta-adrenergic blockers
- Mineralocorticoids (fludrocortisone)
- Vagolytics (disopyramide)
- Alpha-adrenergic agonsists (midodrine)
- Serotonin-reuptake inhibitors (paroxetine, sertraline, fluoxetine)
FOLLOW-UP
DISPOSITION
Admission Criteria
See "General Measures."
Discharge Criteria
• Attainment of hemodynamic stability
• Satisfactory completion of workup for etiology
• Adequate control of specific arrhythmia or seizure, if present
Issues for Referral
Where cardiac or neurologic etiologies are suspected, appropriate expert consultation is indicated.
PROGNOSIS
Cumulative mortality at 2 years
• Low (25%): Young patients (60) with noncardiac or unknown cause of syncope
• Intermediate (20%): Older patients (>60) with noncardiac or unknown cause of syncope
• High (32-38%): Patients with cardiac cause of syncope
COMPLICATIONS
• Trauma from falling
• Death (see "Prognosis")
PATIENT MONITORING
• Frequent follow-up visits for patients with cardiac causes of syncope, especially patients on antiarrhythmic drugs
• Patients with an unknown cause of syncope rarely (5%) are diagnosed during the follow-up.
REFERENCES
1. Schnipper JL, Kapoor WN. Diagnostic evaluation and management of patients with syncope. Med Clin North Am. 2001;85:423-456.
2. Brignole M, et al. Task Force Report: Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J. 2001;22:1256-1306.
3. Goldschlager N, et al. Etiologic considerations in the patient with syncope and an apparently normal heart. Arch Intern Med. 2003;163:151-162.
MISCELLANEOUS
See also: Aortic valvular stenosis; Atrial septal defect (ASD); Carotid sinus syndrome; Idiopathic hypertrophic subaortic stenosis (IHSS); Patent ductus arteriosus; Primary pulmonary hypertension; Pulmonary embolism; Seizure disorders; Stokes-Adams attacks
BASICS
DESCRIPTION
• Transient loss of consciousness characterized by unresponsiveness, loss of postural tone, and spontaneous recovery
• System(s) Affected: Cardiovascular; Nervous
GENERAL PREVENTION
Avoid risk factors (see "Risk Factors").
EPIDEMIOLOGY
• Predominant age: Elderly
• Rare in infancy, though increasing occurrence during adolescence
Incidence
• Up to 20% of adults will have 1 episode by age 75; 15% of children 18 years of age
• Accounts for 1-6% of hospital admissions and about 3% of emergency room visits
Prevalence
In institutionalized elderly (>75 years), 6%
RISK FACTORS
• Heart disease
• Drugs
- Antihypertensives
- Vasodilators (including calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and nitrates)
- Phenothiazines
- Antidepressants
- Antiarrhythmics
- Diuretics
Genetics
Specific cardiomyopathies and arrhythmias may be familiial.
PATHOPHYSIOLOGY
Systemic hypotension secondary to decreased cardiac output and/or systemic vasodilation leads to a drop in cerebral perfusion and resultant loss of consciousness.
ETIOLOGY
• Cardiac: Obstruction to outflow
- Aortic stenosis
- Hypertrophic cardiomyopathy
- Pulmonary embolus
• Cardiac: Arrhythmias
- Sustained ventricular tachycardia (probable cause)
- Sick-sinus syndrome
- Sinus node recovery time 3 seconds (probable cause)
- 2nd-degree and 3rd-degree AV block
- Pacing-induced infranodal block (probable cause)
- H-V interval >100 m (probable cause)
• Noncardiac
- Reflex-mediated vasovagal ("drop atttack") (neurocardiogenic/neurally mediated), situational (micturition, defecation, cough)
- Orthostatic hypotension
- Drug induced
- Neurologic: Seizures, transient ischemic attack
- Carotid sinus
- Psychogenic
ASSOCIATED CONDITIONS
See "Etiology."
DIAGNOSIS
• Careful history, physical examination, and an ECG are more important than other investigations in determining the diagnosis.
• Make sure patient or witness (if present) is not talking about vertigo, coma, or drop attacks.
• After careful evaluation, including diagnostic procedures and special tests, the cause of syncope will be found in only 50-60% of the patients.
PRE HOSPITAL
Support ABCs.
SIGNS AND SYMPTOMS
• Transient loss of consciousness is characterized by unresponsiveness, loss of postural tone, and spontaneous recovery.
• Vasovagal
- Prodromal manifestations of sudden weakness, nausea, and sweating, especially in circumstances provoking strong emotion
- Does not occur when patient is horizontal
• Cardiac
- Suggested by: (a) syncope of sudden onset with no prodrome or brief premonitory symptoms and (b) occurrence with exertion
- Can occur in any position
History
Onset of syncope is usually rapid, and recovery is spontaneous, rapid, and complete. Duration of episodes are typically brief (60 s). Presence of underlying cardiac or neurologic conditions provides key to diagnosis.
Physical Exam
• Direct to BP and pulse, both lying and standing.
• Check for cardiac murmur or focal neurologic abnormality.
TESTS
• If history and physical suggest ischemic, valvular, or congenital heart disease
- ECG
- Cardiac catheterization
• If CNS disease suspected
- EEG
- Head CT
- Head MRI
- Do not order these tests unless hints of CNS disease on history or physical examination
• ECG monitoring, either in hospital or ambulatory (Holter)
- Useful in 4-15% of patients
- Should be done in patients with heart disease or recurrent syncope
- Arrhythmias frequently documented, but rarely associated with syncope
• Electrophysiologic studies
- Have been positive in 18-75% of patients
- Induction of ventricular tachycardia and dysfunction of His-Purkinje system are the 2 most common abnormalities.
- Should be done in patients with heart disease or recurrent syncope, although problem exists of knowing whether arrhythmia noted or induced during study is cause of syncope
• Carotid hypersensitivity evaluation
- Carotid hypersensitivity should be considered in patients with syncope during head turning, especially with head turning while wearing tight collar, and in patients with neck tumors and neck-tissue scars.
- The technique is not standardized; 1 side should be massaged at a time for 20 seconds with constant monitoring of pulse and BP.
- Atropine should be readily available.
• Tilt table testing, with and without isoproterenol infusion
- Provocative test for vasovagal syncope
- Should be done only if cardiac causes have been excluded; role of test in workup of patients with syncope of unknown origin is not known
- Not standardized, but has been reported positive (symptomatic hypotension and bradycardia) in 26-87% of patients; however, also reported positive in 0-45% of control subjects
• Psychiatric evaluation
- Anxiety, depression, alcohol, and drug abuse can be associated with syncope.
Lab
Rarely helpful; 2% have hyponatremia, hypocalcemia, hypoglycemia, or renal failure causing seizures.
Imaging
Lung scan or helical CT of thorax if history and physical examination suggest pulmonary embolism
Diagnostic Procedures/Surgery
Patient-activated implantable loop recorders, which patient activates after regaining consciousness, can record 4-5 minutes of retrograde ECG rhythm. Helpful in patients with recurrent syncope, with diagnostic yield of 24-47%.
Pathological Findings
Depends on etiology and presence of underlying cardiac or neurologic conditions
DIFFERENTIAL DIAGNOSIS
• Drop attacks
• Coma
• Vertigo
TREATMENT
PRE-HOSPITAL
Support ABCs.
STABILIZATION
Aimed at stabilization of heart rate and blood pressure, typically with IV fluids
GENERAL MEASURES
• Patients with heart disease should be admitted to the hospital for evaluation.
• Elderly patients without previously recognized heart disease should be admitted if the physician thinks that the cause of syncope is likely cardiac.
• Patients without heart disease, especially young patients (60 years old), can be safely worked up as outpatients.
• Prescribe antiarrhythmic drugs for documented arrhythmias occurring simultaneously with syncope or symptoms of presyncope. Asymptomatic arrhythmias do not require treatment.
• The decision to treat patients on basis of arrhythmias or conduction abnormalities provoked or detected during EPS is even more problematic: Does the arrhythmia or conduction abnormality have anything to do with patient's symptoms?
• Most would treat patient with provoked sustained ventricular tachycardia with antiarrhythmic drug that suppressed arrhythmia during study.
• Many recommend pacemaker implantation in patients with
- H-V intervals >100 m
- Pacing-induced infranodal block
- Sinus node recovery time of 3 s
• Rationale for such treatment: Recurrent syncope less frequent in patients with positive EPS who are treated than it is in those who have negative EPS
Diet
• No specific diet unless heart disease
• Increased fluid and salt intake to maintain intravascular volume in cases of recurrent vasovagal syncope
Activity
Full activity unless severe cardiac disease, with avoidance of specific triggers or stimuli
Nursing
Close monitoring of BP, HR during initial presentation
SPECIAL THERAPY
IV Fluids
Use isotonic crystalloids fluids for fluid resuscitation if needed.
MEDICATION (DRUGS)
• Geared towards specific underlying cardiac or neurologic abnormalities
• In cases of recurrent vasovagal/neurocardiogenic/neurally-mediated syncope, the following have been shown to be effective in various placebo-controlled trials
- Beta-adrenergic blockers
- Mineralocorticoids (fludrocortisone)
- Vagolytics (disopyramide)
- Alpha-adrenergic agonsists (midodrine)
- Serotonin-reuptake inhibitors (paroxetine, sertraline, fluoxetine)
FOLLOW-UP
DISPOSITION
Admission Criteria
See "General Measures."
Discharge Criteria
• Attainment of hemodynamic stability
• Satisfactory completion of workup for etiology
• Adequate control of specific arrhythmia or seizure, if present
Issues for Referral
Where cardiac or neurologic etiologies are suspected, appropriate expert consultation is indicated.
PROGNOSIS
Cumulative mortality at 2 years
• Low (25%): Young patients (60) with noncardiac or unknown cause of syncope
• Intermediate (20%): Older patients (>60) with noncardiac or unknown cause of syncope
• High (32-38%): Patients with cardiac cause of syncope
COMPLICATIONS
• Trauma from falling
• Death (see "Prognosis")
PATIENT MONITORING
• Frequent follow-up visits for patients with cardiac causes of syncope, especially patients on antiarrhythmic drugs
• Patients with an unknown cause of syncope rarely (5%) are diagnosed during the follow-up.
REFERENCES
1. Schnipper JL, Kapoor WN. Diagnostic evaluation and management of patients with syncope. Med Clin North Am. 2001;85:423-456.
2. Brignole M, et al. Task Force Report: Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J. 2001;22:1256-1306.
3. Goldschlager N, et al. Etiologic considerations in the patient with syncope and an apparently normal heart. Arch Intern Med. 2003;163:151-162.
MISCELLANEOUS
See also: Aortic valvular stenosis; Atrial septal defect (ASD); Carotid sinus syndrome; Idiopathic hypertrophic subaortic stenosis (IHSS); Patent ductus arteriosus; Primary pulmonary hypertension; Pulmonary embolism; Seizure disorders; Stokes-Adams attacks
SUPERFICIAL THROMBOPHLEBITIS
SUPERFICIAL THROMBOPHLEBITIS - Abdulrazak Abyad, MD, PhD, MBA, MPH, AGSF
BASICS
DESCRIPTION
• Superficial thrombophlebitis is an inflammatory condition of the veins with secondary thrombosis.
• Septic (suppurative) thrombophlebitis types
- Iatrogenic
- Infectious, mainly syphilis and psittacosis
• Aseptic thrombophlebitis types
- Primary hypercoagulable statesdisorders with measurable defects in the proteins of the coagulation and/or fibrinolytic systems
- Secondary hypercoagulable statesclinical conditions with a risk of thrombosis
• System(s) Affected: Cardiovascular
• Synonym(s): Phlebitis; Phlebothrombosis
ALERT
Geriatric Considerations
Septic thrombophlebitis is more common, prognosis is poorer.
Pediatric Considerations
Subperiosteal abscesses of adjacent long bone may complicate.
Pregnancy Considerations
• Associated with increased risk of aseptic superficial thrombophlebitis
• Warfarin and NSAIDs are contraindicated.
GENERAL PREVENTION
• Use of scalp vein cannulae
• Avoidance of lower-extremity cannulations
• Insertion under aseptic conditions
• Secure anchoring of the cannulae.
• Replacement of cannulae, connecting tubing, and IV fluid q48-72h
• Neomycin-polymyxin B-bacitracin ointment in cutdown
EPIDEMIOLOGY
• Predominant age
- Septic: More common in childhood
- Aseptic primary hypercoagulable state
Antithrombin III and heparin cofactor II deficiencyneonatal period, but 1st episode usually at age 20-30 years
Proteins C and S30 years of age
- Aseptic secondary hypercoagulable state
Mondor disease: women, ages 21-55 years
Thromboangiitis obliterans onset: ages 20-50 years
• Predominant sex
- Suppurative: Male = Female
- Aseptic
Mondor: Female > Male (2:1)
Thromboangiitis obliterans: Female > Male (1-19% of clinical cases)
Incidence
• Septic
- Up to 10% of all nosocomial infections
- Incidence of catheter-related thrombophlebitis is 88/100,000
- Develops in 4-8% if cutdown is performed.
• Aseptic primary hypercoagulable state: Antithrombin III and heparin cofactor II deficiency incidence is 50/100,000.
• Aseptic secondary hypercoagulable state
- Trousseau incidence in malignancy 5-15%
- Trousseau in pancreatic carcinoma 50%
- In pregnancy, 49-fold increased incidence of phlebitis
- Superficial migratory thrombophlebitis in 27% of patients with thromboangiitis obliterans
RISK FACTORS
• Nonspecific
- Immobilization
- Obesity
- Advanced age
- Postoperative states
• Septic
- IV catheter
- Duration of IV catheterization (68% of cannulae have been left in place for 2 days)
- Cutdowns
- Cancer, debilitating diseases
- Steroid
- Incidence is 40 times higher with plastic cannula (8%) than with steel or scalp cannulas (0.2%).
- Thrombosis
- Dermal infection
- Burned patients
- Lower-extremities IV catheter
- IV antibiotics
- AIDS
- Varicose veins
• Antithrombin II and heparin cofactor II deficiency
- Pregnancy
- Oral contraceptives
- Surgery; trauma; infection
• In pregnancy
- Increased age
- Hypertension
- Eclampsia
- Increased parity
• Thromboangiitis obliterans: Persistent smoking
• Mondor disease
- Breast abscess
- Antecedent breast surgery
- Breast augmentation
- Reduction mammoplasty
Genetics
• Septic: No known genetic pattern
• Antithrombin III deficiencies: Autosomal dominant
• Proteins C and S deficiency: Autosomal dominant with variable penetrance
• Disorders of fibrinolytic system: Congenital defects inheritance variable
• Dysfibrinogenemia: Autosomal dominant
• Factor XII deficiency: Autosomal recessive
ETIOLOGY
• Septic
- Staphylococcus aureus in 65-78%
- Enterobacteriaceae, especially Klebsiella
- Multiple organisms in 14%
- Anaerobic isolate rare
- Candida spp.
- Cytomegalovirus in AIDS patients
• Aseptic primary hypercoagulable state
- Antithrombin III and heparin II deficiency
- Protein C and protein S deficiency
- Disorder of tissue plasminogen activator
- Abnormal plasminogen and co-plasminogen
- Dysfibrinogenemia
- Factor XII deficiency
- Lupus anticoagulant and anticardiolipin antibody syndrome
• Aseptic secondary hypercoagulable states
- Malignancy (Trousseau syndrome: Recurrent migratory thrombophlebitis): Most commonly seen in metastatic mucin or adenocarcinomas of the gastrointestinal tract (pancreas, stomach, colon, and gall bladder), lung, prostate, ovary
- Pregnancy
- Oral contraceptive
- Infusion of prothrombin complex concentrates
- Behcet disease
- Buerger disease
- Mondor disease
DIAGNOSIS
SIGNS AND SYMPTOMS
• Swelling, tenderness, redness along the course of the veins
• May look like cellulitis or erythema nodosa
• Fever in 70% of patients
• Warmth, erythema, tenderness, or lymphangitis in 32%
• Sign of systemic sepsis in 84% in suppurative
• Red, tender cord
• Pain
TESTS
Leukocyte imaging
Lab
• Septic
- Bacteremia in 80-90%
- Culture of IV fluid bag
- Leukocytosis
• Aseptic
- Acute-phase reactant
- Factor levels
- Thrombin activity
- Platelet function test
• Drugs that may alter lab results
- In septic, broad-spectrum antibiotics
Imaging
Septic and aseptic
• Ultrasound of veins reveals an increase in the diameter of the lumen.
• Chest x-ray: Multiple peripheral densities or a pleural effusion consistent with pulmonary embolism, abscess, or empyema
• Bone and gallium scan: For associated subperiosteal abscess in septic thrombophlebitis
• Evaluation of complications (deep vein thrombosis and others)
Diagnostic Procedures/Surgery
Skin biopsy
Pathological Findings
• The affected vein is enlarged, tortuous, and thickened.
• Associated perivascular suppuration and/or hemorrhage
• Vein lumen may contain pus and thrombus.
• Endothelial damage, fibrinoid necrosis, and thickening of the vein wall
DIFFERENTIAL DIAGNOSIS
• Cellulitis
• Erythema nodosa
• Cutaneous polyarteritis nodosa
• Sarcoid
• Kaposi sarcoma
• Hyperalgesic pseudothrombophlebitis
TREATMENT
STABILIZATION
• Septic: Inpatient
• Aseptic: Outpatient
GENERAL MEASURES
• Heat application
• Extremity elevation
Diet
No restrictions
Activity
Bed rest
MEDICATION (DRUGS)
First Line
• Septic
- Initially: semisynthetic penicillin (e.g., nafcillin 2 g IV q6h) plus an aminoglycoside (e.g., gentamicin, 1.0-1.7 mg/kg IV)
- Duration of therapy is empiric.
- If due to Candida albicans, consider a short course of amphotericin B, ~200 mg cumulative dose
- If osteomyelitis documented, antibiotic therapy for at least 6 weeks
• Aseptic general
- NSAIDs
- Oral anticoagulant warfarin
- Systemic anticoagulant heparin
- Low-molecular-weight heparin
• Antithrombin III and heparin cofactor II deficiency
- IV heparin
- Antithrombin III concentrate
- Prophylaxis: Warfarin, oxymetholone
• Proteins C and S: Long-term warfarin, lower dose, no loading
• Disorder of tissue plasminogen activator
- Phenformin and ethylestrenol
- Stanozolol and phenformin
- Stanozolol alone
- Ethylestrenol alone
• Dysfibrinogenemia
- Acute attack: Anticoagulation
- Prophylaxis: Stanozolol
• Abnormal plasminogen and plasminogenemia
- Acute attack: Anticoagulation
- Prophylaxis: Warfarin
• Factor XII deficiency: Standard therapy
• Lupus anticardiolipin: Prophylaxis: Warfarin
• Trousseau syndrome: Heparin
• For pregnancy: Heparin
• Behcet disease
- Phenformin
- Ethylestrenol
- Stanozolol
• Thromboangiitis obliterans
- Stop smoking.
- Pentoxifylline
• Contraindications: Refer to the manufacturer's literature.
• Precautions: Refer to the manufacturer's literature.
• Significant possible interactions: Refer to the manufacturer's literature.
Second Line
• Factor XII deficiencystreptokinase or alteplase (tissue plasminogen activator [tPA])
• Behcetoral anticoagulants plus cyclosporine
• Thromboangiitis obliteranscorticosteroid, antiplatelets, and vasodilating drugs
SURGERY
• Septic
- Excision of the involved vein segment and all involved tributaries
- Excision from ankle to groin may be required in some burn patients.
- If systemic symptoms persist after vein excision, re-exploration is necessary, with removal of all involved veins.
- Drainage of contiguous abscesses
- Remove all cannulae.
• Aseptic
- Mondor disease, consider surgical transection of the phlebitic cord
- Management of underlying conditions
FOLLOW-UP
PROGNOSIS
• Septic: High mortality (50%) if untreated
• Aseptic
- Usually benign course; recovery in 7-10 days
- Antithrombin III and heparin cofactor deficiency: recurrence rate 60%
- Proteins C and S: Recurrence rate 70%
- Prognosis depends on development of deep vein thrombosis and early detection of complications.
- Aseptic thrombophlebitis can be isolated, recurrent, or migratory.
COMPLICATIONS
• Septic: Systemic sepsis, bacteremia (84%); septic pulmonary emboli (44%); metastatic abscess formation; pneumonia (44%); subperiosteal abscess of adjacent long bones in children
• Aseptic: Deep vein thrombosis; thromboembolic phenomena
PATIENT MONITORING
• Septic
- Routine WBC and differential and culture
- Repeat culture from the phlebitic vein.
• Aseptic
- Clinical follow-up to rule out secondary complications
- Repeat of blood studies for fibrinolytic system, platelets, and factors
REFERENCES
1. Mandell GL, ed. Principles and Practice of Infectious Diseases. 4th ed. New York, NY: Churchill Livingstone; 1995.
2. Samlaskie CP, James WD. Superficial thrombophlebitis I. Primary hypercoagulable states. J Am Acad Dermatol. 1990;22:975-989.
3. Samlaskie CP, James WD. Superficial thrombophlebitis II. Secondary hypercoagulable states. J Am Acad Dermatol. 1990;23:1-18.
MISCELLANEOUS
See also: Thrombosis, deep vein
BASICS
DESCRIPTION
• Superficial thrombophlebitis is an inflammatory condition of the veins with secondary thrombosis.
• Septic (suppurative) thrombophlebitis types
- Iatrogenic
- Infectious, mainly syphilis and psittacosis
• Aseptic thrombophlebitis types
- Primary hypercoagulable statesdisorders with measurable defects in the proteins of the coagulation and/or fibrinolytic systems
- Secondary hypercoagulable statesclinical conditions with a risk of thrombosis
• System(s) Affected: Cardiovascular
• Synonym(s): Phlebitis; Phlebothrombosis
ALERT
Geriatric Considerations
Septic thrombophlebitis is more common, prognosis is poorer.
Pediatric Considerations
Subperiosteal abscesses of adjacent long bone may complicate.
Pregnancy Considerations
• Associated with increased risk of aseptic superficial thrombophlebitis
• Warfarin and NSAIDs are contraindicated.
GENERAL PREVENTION
• Use of scalp vein cannulae
• Avoidance of lower-extremity cannulations
• Insertion under aseptic conditions
• Secure anchoring of the cannulae.
• Replacement of cannulae, connecting tubing, and IV fluid q48-72h
• Neomycin-polymyxin B-bacitracin ointment in cutdown
EPIDEMIOLOGY
• Predominant age
- Septic: More common in childhood
- Aseptic primary hypercoagulable state
Antithrombin III and heparin cofactor II deficiencyneonatal period, but 1st episode usually at age 20-30 years
Proteins C and S30 years of age
- Aseptic secondary hypercoagulable state
Mondor disease: women, ages 21-55 years
Thromboangiitis obliterans onset: ages 20-50 years
• Predominant sex
- Suppurative: Male = Female
- Aseptic
Mondor: Female > Male (2:1)
Thromboangiitis obliterans: Female > Male (1-19% of clinical cases)
Incidence
• Septic
- Up to 10% of all nosocomial infections
- Incidence of catheter-related thrombophlebitis is 88/100,000
- Develops in 4-8% if cutdown is performed.
• Aseptic primary hypercoagulable state: Antithrombin III and heparin cofactor II deficiency incidence is 50/100,000.
• Aseptic secondary hypercoagulable state
- Trousseau incidence in malignancy 5-15%
- Trousseau in pancreatic carcinoma 50%
- In pregnancy, 49-fold increased incidence of phlebitis
- Superficial migratory thrombophlebitis in 27% of patients with thromboangiitis obliterans
RISK FACTORS
• Nonspecific
- Immobilization
- Obesity
- Advanced age
- Postoperative states
• Septic
- IV catheter
- Duration of IV catheterization (68% of cannulae have been left in place for 2 days)
- Cutdowns
- Cancer, debilitating diseases
- Steroid
- Incidence is 40 times higher with plastic cannula (8%) than with steel or scalp cannulas (0.2%).
- Thrombosis
- Dermal infection
- Burned patients
- Lower-extremities IV catheter
- IV antibiotics
- AIDS
- Varicose veins
• Antithrombin II and heparin cofactor II deficiency
- Pregnancy
- Oral contraceptives
- Surgery; trauma; infection
• In pregnancy
- Increased age
- Hypertension
- Eclampsia
- Increased parity
• Thromboangiitis obliterans: Persistent smoking
• Mondor disease
- Breast abscess
- Antecedent breast surgery
- Breast augmentation
- Reduction mammoplasty
Genetics
• Septic: No known genetic pattern
• Antithrombin III deficiencies: Autosomal dominant
• Proteins C and S deficiency: Autosomal dominant with variable penetrance
• Disorders of fibrinolytic system: Congenital defects inheritance variable
• Dysfibrinogenemia: Autosomal dominant
• Factor XII deficiency: Autosomal recessive
ETIOLOGY
• Septic
- Staphylococcus aureus in 65-78%
- Enterobacteriaceae, especially Klebsiella
- Multiple organisms in 14%
- Anaerobic isolate rare
- Candida spp.
- Cytomegalovirus in AIDS patients
• Aseptic primary hypercoagulable state
- Antithrombin III and heparin II deficiency
- Protein C and protein S deficiency
- Disorder of tissue plasminogen activator
- Abnormal plasminogen and co-plasminogen
- Dysfibrinogenemia
- Factor XII deficiency
- Lupus anticoagulant and anticardiolipin antibody syndrome
• Aseptic secondary hypercoagulable states
- Malignancy (Trousseau syndrome: Recurrent migratory thrombophlebitis): Most commonly seen in metastatic mucin or adenocarcinomas of the gastrointestinal tract (pancreas, stomach, colon, and gall bladder), lung, prostate, ovary
- Pregnancy
- Oral contraceptive
- Infusion of prothrombin complex concentrates
- Behcet disease
- Buerger disease
- Mondor disease
DIAGNOSIS
SIGNS AND SYMPTOMS
• Swelling, tenderness, redness along the course of the veins
• May look like cellulitis or erythema nodosa
• Fever in 70% of patients
• Warmth, erythema, tenderness, or lymphangitis in 32%
• Sign of systemic sepsis in 84% in suppurative
• Red, tender cord
• Pain
TESTS
Leukocyte imaging
Lab
• Septic
- Bacteremia in 80-90%
- Culture of IV fluid bag
- Leukocytosis
• Aseptic
- Acute-phase reactant
- Factor levels
- Thrombin activity
- Platelet function test
• Drugs that may alter lab results
- In septic, broad-spectrum antibiotics
Imaging
Septic and aseptic
• Ultrasound of veins reveals an increase in the diameter of the lumen.
• Chest x-ray: Multiple peripheral densities or a pleural effusion consistent with pulmonary embolism, abscess, or empyema
• Bone and gallium scan: For associated subperiosteal abscess in septic thrombophlebitis
• Evaluation of complications (deep vein thrombosis and others)
Diagnostic Procedures/Surgery
Skin biopsy
Pathological Findings
• The affected vein is enlarged, tortuous, and thickened.
• Associated perivascular suppuration and/or hemorrhage
• Vein lumen may contain pus and thrombus.
• Endothelial damage, fibrinoid necrosis, and thickening of the vein wall
DIFFERENTIAL DIAGNOSIS
• Cellulitis
• Erythema nodosa
• Cutaneous polyarteritis nodosa
• Sarcoid
• Kaposi sarcoma
• Hyperalgesic pseudothrombophlebitis
TREATMENT
STABILIZATION
• Septic: Inpatient
• Aseptic: Outpatient
GENERAL MEASURES
• Heat application
• Extremity elevation
Diet
No restrictions
Activity
Bed rest
MEDICATION (DRUGS)
First Line
• Septic
- Initially: semisynthetic penicillin (e.g., nafcillin 2 g IV q6h) plus an aminoglycoside (e.g., gentamicin, 1.0-1.7 mg/kg IV)
- Duration of therapy is empiric.
- If due to Candida albicans, consider a short course of amphotericin B, ~200 mg cumulative dose
- If osteomyelitis documented, antibiotic therapy for at least 6 weeks
• Aseptic general
- NSAIDs
- Oral anticoagulant warfarin
- Systemic anticoagulant heparin
- Low-molecular-weight heparin
• Antithrombin III and heparin cofactor II deficiency
- IV heparin
- Antithrombin III concentrate
- Prophylaxis: Warfarin, oxymetholone
• Proteins C and S: Long-term warfarin, lower dose, no loading
• Disorder of tissue plasminogen activator
- Phenformin and ethylestrenol
- Stanozolol and phenformin
- Stanozolol alone
- Ethylestrenol alone
• Dysfibrinogenemia
- Acute attack: Anticoagulation
- Prophylaxis: Stanozolol
• Abnormal plasminogen and plasminogenemia
- Acute attack: Anticoagulation
- Prophylaxis: Warfarin
• Factor XII deficiency: Standard therapy
• Lupus anticardiolipin: Prophylaxis: Warfarin
• Trousseau syndrome: Heparin
• For pregnancy: Heparin
• Behcet disease
- Phenformin
- Ethylestrenol
- Stanozolol
• Thromboangiitis obliterans
- Stop smoking.
- Pentoxifylline
• Contraindications: Refer to the manufacturer's literature.
• Precautions: Refer to the manufacturer's literature.
• Significant possible interactions: Refer to the manufacturer's literature.
Second Line
• Factor XII deficiencystreptokinase or alteplase (tissue plasminogen activator [tPA])
• Behcetoral anticoagulants plus cyclosporine
• Thromboangiitis obliteranscorticosteroid, antiplatelets, and vasodilating drugs
SURGERY
• Septic
- Excision of the involved vein segment and all involved tributaries
- Excision from ankle to groin may be required in some burn patients.
- If systemic symptoms persist after vein excision, re-exploration is necessary, with removal of all involved veins.
- Drainage of contiguous abscesses
- Remove all cannulae.
• Aseptic
- Mondor disease, consider surgical transection of the phlebitic cord
- Management of underlying conditions
FOLLOW-UP
PROGNOSIS
• Septic: High mortality (50%) if untreated
• Aseptic
- Usually benign course; recovery in 7-10 days
- Antithrombin III and heparin cofactor deficiency: recurrence rate 60%
- Proteins C and S: Recurrence rate 70%
- Prognosis depends on development of deep vein thrombosis and early detection of complications.
- Aseptic thrombophlebitis can be isolated, recurrent, or migratory.
COMPLICATIONS
• Septic: Systemic sepsis, bacteremia (84%); septic pulmonary emboli (44%); metastatic abscess formation; pneumonia (44%); subperiosteal abscess of adjacent long bones in children
• Aseptic: Deep vein thrombosis; thromboembolic phenomena
PATIENT MONITORING
• Septic
- Routine WBC and differential and culture
- Repeat culture from the phlebitic vein.
• Aseptic
- Clinical follow-up to rule out secondary complications
- Repeat of blood studies for fibrinolytic system, platelets, and factors
REFERENCES
1. Mandell GL, ed. Principles and Practice of Infectious Diseases. 4th ed. New York, NY: Churchill Livingstone; 1995.
2. Samlaskie CP, James WD. Superficial thrombophlebitis I. Primary hypercoagulable states. J Am Acad Dermatol. 1990;22:975-989.
3. Samlaskie CP, James WD. Superficial thrombophlebitis II. Secondary hypercoagulable states. J Am Acad Dermatol. 1990;23:1-18.
MISCELLANEOUS
See also: Thrombosis, deep vein
SUDDEN INFANT DEATH SYNDROME (SIDS)
SUDDEN INFANT DEATH SYNDROME (SIDS) - Fern R. Hauck, MD, MS
BASICS
DESCRIPTION
• The sudden death of an infant 1 year of age that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history. Sudden infant death syndrome (SIDS) was 1st formally defined in 1969, and the definition was revised in 1989.
• System(s) Affected: Cardiovascular; Endocrine/Metabolic; Nervous; Pulmonary
• Synonym(s): Crib death; Cot death
GENERAL PREVENTION
Because a SIDS death is sudden and the cause is unknown, SIDS cannot be "treated." However, there are some measures that may be effective in reducing the risk of SIDS. (1)[B]
• Maternal avoidance of cigarette smoking and illicit drug use during pregnancy
• Avoidance of the prone and side sleep positions, excessive bed clothing, and soft bedding such as pillows and comforters or a soft mattress
• Avoidance of overheating
• A crib, bassinet, or cradle conforming to federal safety standards is the recommended sleeping location.
• Avoidance of bed sharing with the infant, particularly by adults other than the parent(s) or by other children. Bed sharing should be avoided if mother or father has used cigarettes, drugs, or alcohol. Bed sharing on couches is very dangerous and should never be done.
• Infants who sleep in the same room as their parents (without bed sharing) have a lower risk of SIDS. It is recommended that infants sleep in a crib or bassinet in their parents' bedroom, which when placed close to their bed will allow for more convenient breastfeeding and contact.
• Pacifier use is associated with reduced risk of SIDS. Consider offering a pacifier at bedtime and nap time. Delay introduction of the pacifier among breastfed infants until 1 month of age. (2)[B]
• Avoidance of commercial devices marketed to reduce the risk of SIDS
• Avoidance of passive cigarette smoke exposure
• It is critical that all people caring for infants, including day care providers, be instructed in these risk-reduction measures.
• Newborn nurseries should implement these recommendations well before discharge.
EPIDEMIOLOGY
• Predominant age: Uncommon in 1st month of life; peak occurs in infants between 2 and 4 months of age; 80% of deaths occur by 6 months of age
• Predominant sex: Males > Females (52-60% of SIDS cases are boys)
Incidence
For 2002
• All races: 0.57 in 1,000 live births (2,295 cases/year)
• White non-Hispanic: 0.55 in 1,000 live births (1,269 cases/year)
• Black non-Hispanic: 1.11 in 1,000 live births (642 cases/year)
• Hispanic: 0.30 in 1,000 live births (260 cases/year)
• Native American: 1.23 in 1,000 live births (52 cases/year)
ALERT
Pediatric Considerations
Occurs in infants only
RISK FACTORS
• Most SIDS deaths occur in children who are "low risk." However, there are several risk factors associated with SIDS
- Race: Native Americans and African Americans have highest incidence.
- Season: Late fall and winter months
- Time of day: Between midnight and 6 a.m.
- Activity: During sleep
- Low birth weight; intrauterine growth retardation (IUGR)
- Poverty
• Maternal factors
- Decreased age
- Decreased education
- Maternal use of cigarettes or drugs (cocaine, opiates) during pregnancy
- Higher parity
- Inadequate prenatal care
• Respiratory or gastrointestinal infection in recent past
• Sleep practices
- Prone and side sleep position
- Overheating from heavy clothing and bedding, and/or elevated room temperature
- Soft bedding
- Bed sharing
• Passive cigarette smoke exposure after birth
• No pacifier use
Genetics
Emerging evidence for genetic risk factors, especially related to impaired brainstem regulation of breathing or other autonomic control
ETIOLOGY
• There are many theories about the cause of SIDS. There may be subtle developmental abnormalities resulting from pre- and/or perinatal brain injury.
• Possible causes
- Abnormalities in respiratory control and arousal responsiveness
- Central and peripheral nervous system abnormalities
- Cardiac arrhythmias
- Rebreathing in face-down position on soft surface, leading to hypoxia and hypercarbia
- SIDS may occur when 1 or more environmental risk factors interact with one or more genetic risk factors.
DIAGNOSIS
SIGNS AND SYMPTOMS
These babies generally appear healthy or may have had a minor upper respiratory or gastrointestinal infection in the last 2 weeks of life.
History
Infant usually found unresponsive by parent or other caregiver without any warning
TESTS
Lab
• Pneumocardiograms have been abandoned in the workup.
• Postmortem laboratory tests are done to rule out other cause of death (e.g., electrolytes to rule out dehydration and electrolyte imbalance). In SIDS, there are no consistently abnormal laboratory tests.
Imaging
X-rays to rule out possible child abuse
Diagnostic Procedures/Surgery
Because the diagnosis of SIDS is often one of "exclusion," it is crucial to do a thorough death-scene investigation and case review in addition to the autopsy and laboratory tests.
Pathological Findings
Characteristic findings on postmortem examination
• Frothy discharge, sometimes blood tinged, from nostrils and mouth in majority
• Petechiae on surface of lungs, heart, and thymus gland in 50-85% (but not unique to SIDS)
• Pulmonary congestion and edema often present
• Morphologic markers of hypoxia: Increased gliosis in brainstem, retention of periadrenal brown fat, and hematopoiesis in the liverpresent to varying degrees; not confirmed by all studies
DIFFERENTIAL DIAGNOSIS
• Suffocation/accidental asphyxia
• Abnormalities of fatty acid metabolism (e.g., deficiency of medium-chain acyl-coenzyme A dehydrogenase or of carnitine)
• Homicide
• Dehydration/electrolyte disturbance
FOLLOW-UP
PROGNOSIS
• SIDS deaths have a powerful impact on families and their functioning. Physicians play an important role in providing immediate information about SIDS and sensitive counseling to limit parents' misinformation and feelings of guilt.
• Counseling needs of families vary from short term to long term; support groups are helpful to many couples. Physicians need to be familiar with resources available in their communities to help families mourning a SIDS death. Parents need to be counseled about subsequent pregnancies. Genetic testing and counseling may be indicated to rule out a metabolic or other genetically acquired disorder. They need to be advised of the most current recommendations regarding sleep position and other infant care practices during subsequent pregnancies.
• Follow-up counseling, including review of the autopsy report with the family after some time has passed, is important to help with understanding this condition and to alleviate the tremendous guilt these families experience.
PATIENT MONITORING
Some authorities recommend cardiopulmonary monitoring in siblings of prior SIDS victims. There is no evidence that use of monitors prevents SIDS, and they should not be prescribed for that purpose. (3)[B]
REFERENCES
1. American Academy of Pediatrics, Task Force on Sudden Infant Death Syndrome. The changing concept of sudden infant death syndrome: Diagnostic coding shifts, controversies regarding the sleeping environment, and new variables to consider in reducing risk. Pediatrics. 2005;116:1245-1255.
2. Hauck FR, Omojokun OO, Siadaty MS. Do pacifiers reduce the risk of sudden infant death syndrome? A meta-analysis. Pediatrics. 2005;116. Available at: www.pediatrics.org/cgi/content/full/116/5/e716.
3. American Academy of Pediatrics, Committee on Fetus and Newborn. Apnea, sudden infant death syndrome, and home monitoring. Pediatrics. 2003;111:914-917.
ADDITIONAL READING
Horchler JN, Morris RR. The SIDS and Infant Death Survival Guide. Information and Comfort for Grieving Family and Friends and Professionals Who Seek to Help Them. Hyattsville, MD: SIDS Educational Services; 2003.
BASICS
DESCRIPTION
• The sudden death of an infant 1 year of age that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history. Sudden infant death syndrome (SIDS) was 1st formally defined in 1969, and the definition was revised in 1989.
• System(s) Affected: Cardiovascular; Endocrine/Metabolic; Nervous; Pulmonary
• Synonym(s): Crib death; Cot death
GENERAL PREVENTION
Because a SIDS death is sudden and the cause is unknown, SIDS cannot be "treated." However, there are some measures that may be effective in reducing the risk of SIDS. (1)[B]
• Maternal avoidance of cigarette smoking and illicit drug use during pregnancy
• Avoidance of the prone and side sleep positions, excessive bed clothing, and soft bedding such as pillows and comforters or a soft mattress
• Avoidance of overheating
• A crib, bassinet, or cradle conforming to federal safety standards is the recommended sleeping location.
• Avoidance of bed sharing with the infant, particularly by adults other than the parent(s) or by other children. Bed sharing should be avoided if mother or father has used cigarettes, drugs, or alcohol. Bed sharing on couches is very dangerous and should never be done.
• Infants who sleep in the same room as their parents (without bed sharing) have a lower risk of SIDS. It is recommended that infants sleep in a crib or bassinet in their parents' bedroom, which when placed close to their bed will allow for more convenient breastfeeding and contact.
• Pacifier use is associated with reduced risk of SIDS. Consider offering a pacifier at bedtime and nap time. Delay introduction of the pacifier among breastfed infants until 1 month of age. (2)[B]
• Avoidance of commercial devices marketed to reduce the risk of SIDS
• Avoidance of passive cigarette smoke exposure
• It is critical that all people caring for infants, including day care providers, be instructed in these risk-reduction measures.
• Newborn nurseries should implement these recommendations well before discharge.
EPIDEMIOLOGY
• Predominant age: Uncommon in 1st month of life; peak occurs in infants between 2 and 4 months of age; 80% of deaths occur by 6 months of age
• Predominant sex: Males > Females (52-60% of SIDS cases are boys)
Incidence
For 2002
• All races: 0.57 in 1,000 live births (2,295 cases/year)
• White non-Hispanic: 0.55 in 1,000 live births (1,269 cases/year)
• Black non-Hispanic: 1.11 in 1,000 live births (642 cases/year)
• Hispanic: 0.30 in 1,000 live births (260 cases/year)
• Native American: 1.23 in 1,000 live births (52 cases/year)
ALERT
Pediatric Considerations
Occurs in infants only
RISK FACTORS
• Most SIDS deaths occur in children who are "low risk." However, there are several risk factors associated with SIDS
- Race: Native Americans and African Americans have highest incidence.
- Season: Late fall and winter months
- Time of day: Between midnight and 6 a.m.
- Activity: During sleep
- Low birth weight; intrauterine growth retardation (IUGR)
- Poverty
• Maternal factors
- Decreased age
- Decreased education
- Maternal use of cigarettes or drugs (cocaine, opiates) during pregnancy
- Higher parity
- Inadequate prenatal care
• Respiratory or gastrointestinal infection in recent past
• Sleep practices
- Prone and side sleep position
- Overheating from heavy clothing and bedding, and/or elevated room temperature
- Soft bedding
- Bed sharing
• Passive cigarette smoke exposure after birth
• No pacifier use
Genetics
Emerging evidence for genetic risk factors, especially related to impaired brainstem regulation of breathing or other autonomic control
ETIOLOGY
• There are many theories about the cause of SIDS. There may be subtle developmental abnormalities resulting from pre- and/or perinatal brain injury.
• Possible causes
- Abnormalities in respiratory control and arousal responsiveness
- Central and peripheral nervous system abnormalities
- Cardiac arrhythmias
- Rebreathing in face-down position on soft surface, leading to hypoxia and hypercarbia
- SIDS may occur when 1 or more environmental risk factors interact with one or more genetic risk factors.
DIAGNOSIS
SIGNS AND SYMPTOMS
These babies generally appear healthy or may have had a minor upper respiratory or gastrointestinal infection in the last 2 weeks of life.
History
Infant usually found unresponsive by parent or other caregiver without any warning
TESTS
Lab
• Pneumocardiograms have been abandoned in the workup.
• Postmortem laboratory tests are done to rule out other cause of death (e.g., electrolytes to rule out dehydration and electrolyte imbalance). In SIDS, there are no consistently abnormal laboratory tests.
Imaging
X-rays to rule out possible child abuse
Diagnostic Procedures/Surgery
Because the diagnosis of SIDS is often one of "exclusion," it is crucial to do a thorough death-scene investigation and case review in addition to the autopsy and laboratory tests.
Pathological Findings
Characteristic findings on postmortem examination
• Frothy discharge, sometimes blood tinged, from nostrils and mouth in majority
• Petechiae on surface of lungs, heart, and thymus gland in 50-85% (but not unique to SIDS)
• Pulmonary congestion and edema often present
• Morphologic markers of hypoxia: Increased gliosis in brainstem, retention of periadrenal brown fat, and hematopoiesis in the liverpresent to varying degrees; not confirmed by all studies
DIFFERENTIAL DIAGNOSIS
• Suffocation/accidental asphyxia
• Abnormalities of fatty acid metabolism (e.g., deficiency of medium-chain acyl-coenzyme A dehydrogenase or of carnitine)
• Homicide
• Dehydration/electrolyte disturbance
FOLLOW-UP
PROGNOSIS
• SIDS deaths have a powerful impact on families and their functioning. Physicians play an important role in providing immediate information about SIDS and sensitive counseling to limit parents' misinformation and feelings of guilt.
• Counseling needs of families vary from short term to long term; support groups are helpful to many couples. Physicians need to be familiar with resources available in their communities to help families mourning a SIDS death. Parents need to be counseled about subsequent pregnancies. Genetic testing and counseling may be indicated to rule out a metabolic or other genetically acquired disorder. They need to be advised of the most current recommendations regarding sleep position and other infant care practices during subsequent pregnancies.
• Follow-up counseling, including review of the autopsy report with the family after some time has passed, is important to help with understanding this condition and to alleviate the tremendous guilt these families experience.
PATIENT MONITORING
Some authorities recommend cardiopulmonary monitoring in siblings of prior SIDS victims. There is no evidence that use of monitors prevents SIDS, and they should not be prescribed for that purpose. (3)[B]
REFERENCES
1. American Academy of Pediatrics, Task Force on Sudden Infant Death Syndrome. The changing concept of sudden infant death syndrome: Diagnostic coding shifts, controversies regarding the sleeping environment, and new variables to consider in reducing risk. Pediatrics. 2005;116:1245-1255.
2. Hauck FR, Omojokun OO, Siadaty MS. Do pacifiers reduce the risk of sudden infant death syndrome? A meta-analysis. Pediatrics. 2005;116. Available at: www.pediatrics.org/cgi/content/full/116/5/e716.
3. American Academy of Pediatrics, Committee on Fetus and Newborn. Apnea, sudden infant death syndrome, and home monitoring. Pediatrics. 2003;111:914-917.
ADDITIONAL READING
Horchler JN, Morris RR. The SIDS and Infant Death Survival Guide. Information and Comfort for Grieving Family and Friends and Professionals Who Seek to Help Them. Hyattsville, MD: SIDS Educational Services; 2003.
SUICIDE
SUICIDE - Sarah Guzofski, MD; Ruben Peralta, MD, FACS
BASICS
DESCRIPTION
Suicide, or death due to self-injury and attempted suicide are significant causes of morbidity and mortality. There are ~30,000 completed suicides in the US annually, and 10 suicide attempts for every completed suicide.
GENERAL PREVENTION
• >50% of those who commit suicide saw PCP in month prior to death. Insufficient evidence that routine screening in primary care reduces suicide. (1)[A]
• Look for and treat underlying mental illness.
• Provide risk reduction counseling for alcohol and other drug use.
• For those at risk for suicide, create a safety plan with patient and family, including education about how to access emergency care.
• Screen at-risk patients for gun ownership; encourage these patients to remove guns from their homes and to relinquish gun license.
EPIDEMIOLOGY
• Predominant age: Highest in older people (>65 years old) and adolescent age period (15-24 years old)
• Predominant sex
- Complete suicide: Male > Female (3:1)
- Attempted suicide: Female > Male (3:1)
• Rates vary globally; higher rates in Eastern Europe, lower rates in Latin American and Muslim countries.
Incidence
• 10-12 in 100,000.
• In 2000, 11th leading cause of death in adults in the US.
ALERT
Geriatric Considerations
Increasing rate with increasing age (women peak at 55 years of age, men peak at 75 years of age)
Prevalence
In the US, 80 suicide deaths per day and US 10-20 attempts for every death
RISK FACTORS
• Past suicide attempt
• Axis I or II Psychiatric Disorders: 90% who complete suicide meet DSM criteria for Axis I or II disorder
- Mood disorders: 60% of suicide completers have depression or bipolar disorder. 15-20% with mood disorder die from suicide.
- Substance use (especially alcohol): 25% of all completed suicides
- Schizophrenia: 10% die from suicide, especially, young males who recognize a loss of functioning
- Personality disorders: Especially borderline and antisocial personality disorders
- Anorexia nervosa
- Panic disorder
• Family history of suicide
• Physical illness: Multiple sclerosis, brain and spinal cord injury, seizure disorder, stroke, Huntington disease, cancer, HIV/AIDS, COPD, chronic hemodialysis-dependent renal failure, chronic pain
• Hopelessness
• Epidemiologic
- Sex: Men complete suicide 3 more often than women, women attempt suicide 3 more often than men. Women more likely to choose ingestions which have higher rescue potential than higher lethality methods chosen by males.
- Age: Adolescent and geriatric population (males peaking at 75 years old, females peaking at 55 years old)
- Race: 75% of completed suicides are by white males. Native Americans have highest rate in US. Caucasians have twice greater risk than African Americans.
- Immigration: In 1st generation, mirrors country of origin
- Marital status: Single > divorced, widowed > married
• Psychologic
- Recent loss (e.g., loved one, job)
- Social isolation
- Anniversaries, holidays
• Access to lethal means
• Mnemonic: SAD PERSONS. If 5 risk factors are present, high suicide risk
- Ssex (male)
- Aage
- Ddepression
- Pprevious attempt
- Eethanol abuse
- Rrational thinking loss
- Ssocial support loss
- Oorganized plan
- Nno spouse
- Ssickness
ETIOLOGY
Combination of psychiatric illness, social circumstances, and other stressors
ASSOCIATED CONDITIONS
• Axis I and II psychiatric illness
• Medical illnesses as above
DIAGNOSIS
SIGNS AND SYMPTOMS
• Hopelessness about the future
• Suicidal thoughts with organized plan and intent to act
• Major depression (screen for symptoms)
- Change in sleep
- Loss of interest
- Loss of energy
- Loss of concentration
- Loss of appetite
- Diminished psychomotor activity
- Guilt
- Suicidal ideation
• Psychosis: Ask about command auditory hallucinations to kill oneself, delusional guilt, and persecutory delusions.
History
• Suicide is a statistically rare event, and no reliable method of predicting who will or will not attempt suicide has been devised. Screen for risk factors, and consider overall clinical picture.
• Detailed history of current suicide plans
• Intention to act on plans
• Availability and lethality of means
• Prior attempts: Lethality, intent to die, precipitants, substance use, precautions taken to avoid being rescued
• After an attempt, patient's feelings about surviving
• Detailed history of psychiatric symptoms, especially high risk disorders above
• Substance use history
• Reasons to live, hope for future
• Social supports
• Review risk factors.
• Collateral history is often essential (from friends, family, physicians); it may be appropriate to break confidentiality if patient is at imminent risk of suicide.
TESTS
Lab
• There are no laboratory tests to determine who will commit suicide.
• Patients who have completed violent suicides found to have low levels of 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, in the CSF and brainstem
DIFFERENTIAL DIAGNOSIS
• Psychiatric
- Look for high risk disorders: Mood disorders, schizophrenia, panic, axis II, substance abuse and dependence, anorexia nervosa.
- Consider presence of delirium or dementia.
• Medical illness presenting with depression, mania, psychosis (e.g., hypothyroid, delirium)
• Medication effects causing psychiatric symptoms, (e.g., beta blockers and depression)
• Substance intoxication and substance-induced mood, psychotic and anxiety disorders
TREATMENT
STABILIZATION
• Determine appropriate level of care.
• After a suicide attempt, consider need for medical care before psychiatric care.
• Inpatient if suicidal with a plan to act or otherwise at high risk. If immediate risk for self-harm, may be hospitalized involuntarily
• Intensive outpatient follow-up may be appropriate if not at immediate risk to harm self, adequate social supports, able to seek help when needed
GENERAL MEASURES
• Patients expressing active suicidal thoughts or who made an attempt should be screened for suicide risk factors and have a full mental status examination and psychiatric consultation.
• Ensure patient safety by least restrictive method (i.e., remove potentially dangerous objects, provide one-to-one constant observation, medication, four-point restraints, chemical restraint).
• Search patient for dangerous objects.
• Diagnose and treat underlying psychiatric and medical disorders using standard algorithms.
• Electroconvulsive therapy provides rapid, safe, and effective treatment option for severely depressed, acutely suicidal patients.
• Therapy for suicidal patients
- Insufficient evidence to recommend, but Dialectical Behavioral Therapy for Borderline Personality Disorder may reduce suicide risk (1,2)[A]
- Cognitive therapy decreased re-attempt rate in prior suicide attempters by 1/2. (3)[B]
Activity
Assess for less restrictive, yet safe suicide precautions; every-15-minute checks; one-to-one observation; 4-point restraints
MEDICATION (DRUGS)
• Use standard algorithms to treat underlying psychiatric conditions.
• Anxiety and agitation are risk factors for suicide and should be treated aggressively (e.g., benzodiazepines).
• No evidence that SSRIs decrease suicide risk, although they are proven to decrease depression, a major risk factor for suicide (4)[B]
ALERT
Pediatric Considerations
• FDA has issued a black box warning for SSRIs in pediatric population after increased suicidality noted. If risk of untreated depression is sufficient to warrant treatment with SSRIs, children must be very closely monitored for suicidality.
• Lithium and clozapine have some efficacy in reducing rate of suicide.
- In patients with mood disorders, a meta-analysis of randomized controlled trials found that lithium reduced risk of death by suicide by 60%. (5)
- Long-term treatment for psychosis with clozapine shows some benefit for reducing rate of suicide. (6)[A]
• Agitated or combative, patients
- May require sedation with benzodiazepines (e.g., lorazepam 2 mg IM/IV) and/or antipsychotics (e.g., haloperidol 2-5 mg IM/IV)
- Clinical response typically seen within 20-30 minutes if given IM/IV
• Precautions
- Use smaller doses in older patients.
- Monitor for drug toxicities.
Lithium intoxication (includes delirium, ataxia, dysarthria, hyperreflexia)
Serotonin syndrome (delirium, diarrhea, myoclonus, autonomic instability)
Neuroleptic malignant syndrome (delirium, autonomic instability, rigidity, tremor)
• Significant possible interactions
- Monoamine oxidase inhibitors (antidepressants) interact with tyramine-containing foods and sympathomimetic medications to cause hypertensive crisis. Washout period required before using other psychoactive medications.
- Check for cytochrome P450 interactions.
- Medications such as NSAIDs and diuretics increase lithium levels, and can cause toxicity.
First Line
• Choose medication based on underlying disorder.
• Consider toxicity of medication in overdose (e.g., cardiac toxicity of TCA overdose, compared to safer SSRIs) versus therapeutic benefit.
FOLLOW-UP
DISPOSITION
Discharge Criteria
• No longer considered a danger to self/others
• At discharge, patient must be provided with contact information for emergency mental health services in their community.
PROGNOSIS
The key to a favorable course and prognosis is early recognition of risk factors, early diagnosis and treatment of a psychiatric disorder, and appropriate intervention and follow-up.
PATIENT MONITORING
• Brief period of increased suicide risk as depression resolves and patient's energy and initiative return
• Increased rate of suicide attempts in period following psychiatric hospitalization
• Frequent outpatient follow-up appointments
• Prescribe only a small supply of antidepressants or other psychotropic medications at each appointment.
REFERENCES
1. Gaynes BN, et al. Screening for suicide risk in adults: A summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2004;140:822-835.
2. Mann JJ, Apter A, Bertolote J. Suicide prevention strategies: A systematic review. JAMA. 2005;294:2061-2074.
3. Brown GK, et al. Cognitive therapy for the prevention of suicide attempts: A randomized controlled trial. JAMA. 2005;295:563-570.
4. Mann J, et al. The neurobiology of suicide risk: A review for the clinician. J Clin Psychiatry. 1999;60(suppl 2):7-11.
5. Cipriani A, et al. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: A systematic review of randomized trials. Am J Psychiatry. 2005;162:1805-1819.
6. Hennen J, Baldessarinin RJ. Suicide risk during treatment with clozapine: A meta-analysis. Schizophrenia Res. 2004;73:139-145.
7. Patterson WM, et al. Evaluation of suicidal patients: The SAD PERSONS scale. Psychosomatics. 1983;24:348-349.
ADDITIONAL READING
American Psychiatric Association Practice Guidelines for the Assessment and Treatment of Patients with Suicidal Behaviors
MISCELLANEOUS
Other notes
• Overdose is the most common method for suicide attempts.
• Most common method for completed suicide is self-inflicted gunshot.
• Decrease in suicide rates have been noted where access to lethal means (i.e., firearms, toxic gas) is restricted.
BASICS
DESCRIPTION
Suicide, or death due to self-injury and attempted suicide are significant causes of morbidity and mortality. There are ~30,000 completed suicides in the US annually, and 10 suicide attempts for every completed suicide.
GENERAL PREVENTION
• >50% of those who commit suicide saw PCP in month prior to death. Insufficient evidence that routine screening in primary care reduces suicide. (1)[A]
• Look for and treat underlying mental illness.
• Provide risk reduction counseling for alcohol and other drug use.
• For those at risk for suicide, create a safety plan with patient and family, including education about how to access emergency care.
• Screen at-risk patients for gun ownership; encourage these patients to remove guns from their homes and to relinquish gun license.
EPIDEMIOLOGY
• Predominant age: Highest in older people (>65 years old) and adolescent age period (15-24 years old)
• Predominant sex
- Complete suicide: Male > Female (3:1)
- Attempted suicide: Female > Male (3:1)
• Rates vary globally; higher rates in Eastern Europe, lower rates in Latin American and Muslim countries.
Incidence
• 10-12 in 100,000.
• In 2000, 11th leading cause of death in adults in the US.
ALERT
Geriatric Considerations
Increasing rate with increasing age (women peak at 55 years of age, men peak at 75 years of age)
Prevalence
In the US, 80 suicide deaths per day and US 10-20 attempts for every death
RISK FACTORS
• Past suicide attempt
• Axis I or II Psychiatric Disorders: 90% who complete suicide meet DSM criteria for Axis I or II disorder
- Mood disorders: 60% of suicide completers have depression or bipolar disorder. 15-20% with mood disorder die from suicide.
- Substance use (especially alcohol): 25% of all completed suicides
- Schizophrenia: 10% die from suicide, especially, young males who recognize a loss of functioning
- Personality disorders: Especially borderline and antisocial personality disorders
- Anorexia nervosa
- Panic disorder
• Family history of suicide
• Physical illness: Multiple sclerosis, brain and spinal cord injury, seizure disorder, stroke, Huntington disease, cancer, HIV/AIDS, COPD, chronic hemodialysis-dependent renal failure, chronic pain
• Hopelessness
• Epidemiologic
- Sex: Men complete suicide 3 more often than women, women attempt suicide 3 more often than men. Women more likely to choose ingestions which have higher rescue potential than higher lethality methods chosen by males.
- Age: Adolescent and geriatric population (males peaking at 75 years old, females peaking at 55 years old)
- Race: 75% of completed suicides are by white males. Native Americans have highest rate in US. Caucasians have twice greater risk than African Americans.
- Immigration: In 1st generation, mirrors country of origin
- Marital status: Single > divorced, widowed > married
• Psychologic
- Recent loss (e.g., loved one, job)
- Social isolation
- Anniversaries, holidays
• Access to lethal means
• Mnemonic: SAD PERSONS. If 5 risk factors are present, high suicide risk
- Ssex (male)
- Aage
- Ddepression
- Pprevious attempt
- Eethanol abuse
- Rrational thinking loss
- Ssocial support loss
- Oorganized plan
- Nno spouse
- Ssickness
ETIOLOGY
Combination of psychiatric illness, social circumstances, and other stressors
ASSOCIATED CONDITIONS
• Axis I and II psychiatric illness
• Medical illnesses as above
DIAGNOSIS
SIGNS AND SYMPTOMS
• Hopelessness about the future
• Suicidal thoughts with organized plan and intent to act
• Major depression (screen for symptoms)
- Change in sleep
- Loss of interest
- Loss of energy
- Loss of concentration
- Loss of appetite
- Diminished psychomotor activity
- Guilt
- Suicidal ideation
• Psychosis: Ask about command auditory hallucinations to kill oneself, delusional guilt, and persecutory delusions.
History
• Suicide is a statistically rare event, and no reliable method of predicting who will or will not attempt suicide has been devised. Screen for risk factors, and consider overall clinical picture.
• Detailed history of current suicide plans
• Intention to act on plans
• Availability and lethality of means
• Prior attempts: Lethality, intent to die, precipitants, substance use, precautions taken to avoid being rescued
• After an attempt, patient's feelings about surviving
• Detailed history of psychiatric symptoms, especially high risk disorders above
• Substance use history
• Reasons to live, hope for future
• Social supports
• Review risk factors.
• Collateral history is often essential (from friends, family, physicians); it may be appropriate to break confidentiality if patient is at imminent risk of suicide.
TESTS
Lab
• There are no laboratory tests to determine who will commit suicide.
• Patients who have completed violent suicides found to have low levels of 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, in the CSF and brainstem
DIFFERENTIAL DIAGNOSIS
• Psychiatric
- Look for high risk disorders: Mood disorders, schizophrenia, panic, axis II, substance abuse and dependence, anorexia nervosa.
- Consider presence of delirium or dementia.
• Medical illness presenting with depression, mania, psychosis (e.g., hypothyroid, delirium)
• Medication effects causing psychiatric symptoms, (e.g., beta blockers and depression)
• Substance intoxication and substance-induced mood, psychotic and anxiety disorders
TREATMENT
STABILIZATION
• Determine appropriate level of care.
• After a suicide attempt, consider need for medical care before psychiatric care.
• Inpatient if suicidal with a plan to act or otherwise at high risk. If immediate risk for self-harm, may be hospitalized involuntarily
• Intensive outpatient follow-up may be appropriate if not at immediate risk to harm self, adequate social supports, able to seek help when needed
GENERAL MEASURES
• Patients expressing active suicidal thoughts or who made an attempt should be screened for suicide risk factors and have a full mental status examination and psychiatric consultation.
• Ensure patient safety by least restrictive method (i.e., remove potentially dangerous objects, provide one-to-one constant observation, medication, four-point restraints, chemical restraint).
• Search patient for dangerous objects.
• Diagnose and treat underlying psychiatric and medical disorders using standard algorithms.
• Electroconvulsive therapy provides rapid, safe, and effective treatment option for severely depressed, acutely suicidal patients.
• Therapy for suicidal patients
- Insufficient evidence to recommend, but Dialectical Behavioral Therapy for Borderline Personality Disorder may reduce suicide risk (1,2)[A]
- Cognitive therapy decreased re-attempt rate in prior suicide attempters by 1/2. (3)[B]
Activity
Assess for less restrictive, yet safe suicide precautions; every-15-minute checks; one-to-one observation; 4-point restraints
MEDICATION (DRUGS)
• Use standard algorithms to treat underlying psychiatric conditions.
• Anxiety and agitation are risk factors for suicide and should be treated aggressively (e.g., benzodiazepines).
• No evidence that SSRIs decrease suicide risk, although they are proven to decrease depression, a major risk factor for suicide (4)[B]
ALERT
Pediatric Considerations
• FDA has issued a black box warning for SSRIs in pediatric population after increased suicidality noted. If risk of untreated depression is sufficient to warrant treatment with SSRIs, children must be very closely monitored for suicidality.
• Lithium and clozapine have some efficacy in reducing rate of suicide.
- In patients with mood disorders, a meta-analysis of randomized controlled trials found that lithium reduced risk of death by suicide by 60%. (5)
- Long-term treatment for psychosis with clozapine shows some benefit for reducing rate of suicide. (6)[A]
• Agitated or combative, patients
- May require sedation with benzodiazepines (e.g., lorazepam 2 mg IM/IV) and/or antipsychotics (e.g., haloperidol 2-5 mg IM/IV)
- Clinical response typically seen within 20-30 minutes if given IM/IV
• Precautions
- Use smaller doses in older patients.
- Monitor for drug toxicities.
Lithium intoxication (includes delirium, ataxia, dysarthria, hyperreflexia)
Serotonin syndrome (delirium, diarrhea, myoclonus, autonomic instability)
Neuroleptic malignant syndrome (delirium, autonomic instability, rigidity, tremor)
• Significant possible interactions
- Monoamine oxidase inhibitors (antidepressants) interact with tyramine-containing foods and sympathomimetic medications to cause hypertensive crisis. Washout period required before using other psychoactive medications.
- Check for cytochrome P450 interactions.
- Medications such as NSAIDs and diuretics increase lithium levels, and can cause toxicity.
First Line
• Choose medication based on underlying disorder.
• Consider toxicity of medication in overdose (e.g., cardiac toxicity of TCA overdose, compared to safer SSRIs) versus therapeutic benefit.
FOLLOW-UP
DISPOSITION
Discharge Criteria
• No longer considered a danger to self/others
• At discharge, patient must be provided with contact information for emergency mental health services in their community.
PROGNOSIS
The key to a favorable course and prognosis is early recognition of risk factors, early diagnosis and treatment of a psychiatric disorder, and appropriate intervention and follow-up.
PATIENT MONITORING
• Brief period of increased suicide risk as depression resolves and patient's energy and initiative return
• Increased rate of suicide attempts in period following psychiatric hospitalization
• Frequent outpatient follow-up appointments
• Prescribe only a small supply of antidepressants or other psychotropic medications at each appointment.
REFERENCES
1. Gaynes BN, et al. Screening for suicide risk in adults: A summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2004;140:822-835.
2. Mann JJ, Apter A, Bertolote J. Suicide prevention strategies: A systematic review. JAMA. 2005;294:2061-2074.
3. Brown GK, et al. Cognitive therapy for the prevention of suicide attempts: A randomized controlled trial. JAMA. 2005;295:563-570.
4. Mann J, et al. The neurobiology of suicide risk: A review for the clinician. J Clin Psychiatry. 1999;60(suppl 2):7-11.
5. Cipriani A, et al. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: A systematic review of randomized trials. Am J Psychiatry. 2005;162:1805-1819.
6. Hennen J, Baldessarinin RJ. Suicide risk during treatment with clozapine: A meta-analysis. Schizophrenia Res. 2004;73:139-145.
7. Patterson WM, et al. Evaluation of suicidal patients: The SAD PERSONS scale. Psychosomatics. 1983;24:348-349.
ADDITIONAL READING
American Psychiatric Association Practice Guidelines for the Assessment and Treatment of Patients with Suicidal Behaviors
MISCELLANEOUS
Other notes
• Overdose is the most common method for suicide attempts.
• Most common method for completed suicide is self-inflicted gunshot.
• Decrease in suicide rates have been noted where access to lethal means (i.e., firearms, toxic gas) is restricted.
SUBPHRENIC ABSCESS
SUBPHRENIC ABSCESS - Ruben Peralta, MD, FACS; Sarah Guzofski, MD
BASICS
DESCRIPTION
Any localized collection of pus below the diaphragm.
• Synonym(s): Subdiaphragmatic abscess
RISK FACTORS
• Operative procedure with significant contamination
• Patients with chronic disease: Diabetes, cirrhosis, renal failure, malnutrition
• Patients receiving corticosteroids, chemotherapy, radiotherapy
• Immunosuppression
ETIOLOGY
• Complications of abdominal surgery cause 50% of cases.
• Abdominal trauma
• Gastrointestinal perforations: Appendicitis, diverticulitis, duodenal or gastric ulcer
• Neoplastic disease
• Iatrogenic, for example, after cholecystectomy, retained stone
• Organisms: Ptolymicrobial, mixed aerobic and anaerobic
- Aerobic
Escherichia
Enterococcus
- Anaerobic
Bacteroides fragilis
Peptostreptococcus
Clostridium
ASSOCIATED CONDITIONS
• Multisystem organ failure
• Sepsis
• Fistula
DIAGNOSIS
SIGNS AND SYMPTOMS
• High-spiking fever with chills and diaphoresis
• Ileus
• Abdominal pain
• Nausea
• Tachycardia
• Hypotension
• Chest pain
• Dyspnea
• Shoulder pain
• Hiccups
Physical Exam
• Localized abdominal tenderness with or without rebound
• Anterior abdominal wall erythema
• Rales at lung base
TESTS
Lab
• WBC
• Blood cultures
• Serum chemistry
Imaging
• CT scan
• Ultrasound
• Plain films of chest and abdomen display elevation and immobility of right diaphragm and fluid in right costophrenic sulcus; air-fluid level in subphrenic space, pleural effusion
Diagnostic Procedures/Surgery
CT- or ultrasound-guided percutaneous drainage (1)[B]
DIFFERENTIAL DIAGNOSIS
• Other intra-abdominal abscesses
• Empyema
TREATMENT
Inpatient care
GENERAL MEASURES
• IV fluid resuscitation
• Drainage of abscess
• Antibiotics
• Supportive care: nutrition, monitoring, oxygenation, hydration
• Swan-Ganz catheter if condition unstable
• Mechanical ventilation if necessary
• Vasopressors if indicated
Diet
NPO until intestinal function returns
Activity
As tolerated
MEDICATION (DRUGS)
First Line
Broad-spectrum antibiotics based on culture and sensitivity (2)[B]
SURGERY
• Adequate drainage of abscess: Percutaneous and/or surgical
• Percutaneous drainage is not advised if
- Abscess is multiloculated.
- Drainage route would traverse bowel or uncontaminated peritoneal or pleural space.
- Source of continued contamination is still present.
- Fungal infection
- Pus is too viscous.
• Surgical drainage is mandated if patient fails to respond to percutaneous drainage in 24-48 hours.
FOLLOW-UP
PROGNOSIS
Simple abscess, i.e., perforated appendicitis treated with drainage and antibiotics has a low mortality rate. High mortality rate should be expected in elderly patients with complex abscess who develop multiorgan failure.
COMPLICATIONS
• Mortality with treatment: Range 5-65%
• Multisystem organ failure
• Recurrent abscess
• Hemorrhage
• Bowel obstruction
• Wound dehiscence
• Continuing sepsis
• Pneumonia
• Pleural effusion
• Suppurative pylephlebitis
PATIENT MONITORING
Follow labs and radiographic studies as clinically indicated.
REFERENCES
1. Cinat ME, Wilson SE, Din AM. Determinants for successful percutaneous image-guided drainage of intra-abdominal abscess. Arch Surg. 2002;137:845-849.
2. Solomkin JS, et al. Guidelines for the selection of antiinfective agents for complicated intraabdominal infection. CID. 2003;37:997-1005.
3. Men S, et al. Percutaneous drainage of abdominal abscess, 2002. Euro J Radiol. 2002;43:204-215.
BASICS
DESCRIPTION
Any localized collection of pus below the diaphragm.
• Synonym(s): Subdiaphragmatic abscess
RISK FACTORS
• Operative procedure with significant contamination
• Patients with chronic disease: Diabetes, cirrhosis, renal failure, malnutrition
• Patients receiving corticosteroids, chemotherapy, radiotherapy
• Immunosuppression
ETIOLOGY
• Complications of abdominal surgery cause 50% of cases.
• Abdominal trauma
• Gastrointestinal perforations: Appendicitis, diverticulitis, duodenal or gastric ulcer
• Neoplastic disease
• Iatrogenic, for example, after cholecystectomy, retained stone
• Organisms: Ptolymicrobial, mixed aerobic and anaerobic
- Aerobic
Escherichia
Enterococcus
- Anaerobic
Bacteroides fragilis
Peptostreptococcus
Clostridium
ASSOCIATED CONDITIONS
• Multisystem organ failure
• Sepsis
• Fistula
DIAGNOSIS
SIGNS AND SYMPTOMS
• High-spiking fever with chills and diaphoresis
• Ileus
• Abdominal pain
• Nausea
• Tachycardia
• Hypotension
• Chest pain
• Dyspnea
• Shoulder pain
• Hiccups
Physical Exam
• Localized abdominal tenderness with or without rebound
• Anterior abdominal wall erythema
• Rales at lung base
TESTS
Lab
• WBC
• Blood cultures
• Serum chemistry
Imaging
• CT scan
• Ultrasound
• Plain films of chest and abdomen display elevation and immobility of right diaphragm and fluid in right costophrenic sulcus; air-fluid level in subphrenic space, pleural effusion
Diagnostic Procedures/Surgery
CT- or ultrasound-guided percutaneous drainage (1)[B]
DIFFERENTIAL DIAGNOSIS
• Other intra-abdominal abscesses
• Empyema
TREATMENT
Inpatient care
GENERAL MEASURES
• IV fluid resuscitation
• Drainage of abscess
• Antibiotics
• Supportive care: nutrition, monitoring, oxygenation, hydration
• Swan-Ganz catheter if condition unstable
• Mechanical ventilation if necessary
• Vasopressors if indicated
Diet
NPO until intestinal function returns
Activity
As tolerated
MEDICATION (DRUGS)
First Line
Broad-spectrum antibiotics based on culture and sensitivity (2)[B]
SURGERY
• Adequate drainage of abscess: Percutaneous and/or surgical
• Percutaneous drainage is not advised if
- Abscess is multiloculated.
- Drainage route would traverse bowel or uncontaminated peritoneal or pleural space.
- Source of continued contamination is still present.
- Fungal infection
- Pus is too viscous.
• Surgical drainage is mandated if patient fails to respond to percutaneous drainage in 24-48 hours.
FOLLOW-UP
PROGNOSIS
Simple abscess, i.e., perforated appendicitis treated with drainage and antibiotics has a low mortality rate. High mortality rate should be expected in elderly patients with complex abscess who develop multiorgan failure.
COMPLICATIONS
• Mortality with treatment: Range 5-65%
• Multisystem organ failure
• Recurrent abscess
• Hemorrhage
• Bowel obstruction
• Wound dehiscence
• Continuing sepsis
• Pneumonia
• Pleural effusion
• Suppurative pylephlebitis
PATIENT MONITORING
Follow labs and radiographic studies as clinically indicated.
REFERENCES
1. Cinat ME, Wilson SE, Din AM. Determinants for successful percutaneous image-guided drainage of intra-abdominal abscess. Arch Surg. 2002;137:845-849.
2. Solomkin JS, et al. Guidelines for the selection of antiinfective agents for complicated intraabdominal infection. CID. 2003;37:997-1005.
3. Men S, et al. Percutaneous drainage of abdominal abscess, 2002. Euro J Radiol. 2002;43:204-215.
SUBDURAL HEMATOMA
SUBDURAL HEMATOMA - Oren N.Gottfried, MD; Martin E.Weinand, MD
BASICS
DESCRIPTION
• Accumulation of blood in subdural space
- Acute: Most severe form, usually result of trauma involving acceleration or deceleration head injury and commonly associated with parenchymal brain injury. Hematoma age is 3 days.
- Chronic: Often result of trivial head injury in older patients; 25-50% have no history of head trauma. Hematoma is classically >3 weeks and associated with encapsulating membrane.
- Subacute: Appearing 4-21 days from maturation of acute subdural hematoma
• System(s) Affected: Cardiovascular; Nervous
• Synonym(s): Subdural hemorrhage
GENERAL PREVENTION
• Acute: Trauma-prevention programs
• Chronic
- Alcoholism prevention
- Medical and surgical management of epilepsy
- Conservative use of anticoagulation therapy
- Medium-pressure or high-pressure ventriculoperitoneal shunt valves in at-risk patients with hydrocephalus
EPIDEMIOLOGY
• Predominant age
- Acute: 60 years. Relatively infrequent in newborns and children, occurring 25% as often as in adults.
- Chronic: >50 years. Occurs in children of all ages
• Predominant sex: Male > Female
Incidence
Chronic: Peak incidence at ~6 months and rarely after 1 year of age
Prevalence
• Acute
- 1-2/100,000
- Present with 5-22% of episodes of severe head trauma
• Chronic: 1-2/100,000
RISK FACTORS
• Acute
- Severe head trauma
- High-velocity acceleration or deceleration head injury (motor vehicle accidents, falls, blunt head trauma)
- Suspected nonaccidental trauma in infants
• Chronic
- Chronic alcoholism
- Epilepsy
- Coagulopathy/anticoagulation therapy
- CSF shunt for hydrocephalus
- Rarely, metastatic carcinoma to subdural space
ALERT
Cerebral atrophy common and predisposes to subdural hematomas
ETIOLOGY
• Acute
- High-velocity acceleration or deceleration head injury resulting in tearing of bridging veins between cerebral cortex and dural venous sinuses
- Injury to surface of brain with bleeding from injured cortical vessels
• Chronic
- Adults: Often from trivial head injury
- Children: May be caused by unrecognized/unreported trauma, abuse, or, rarely, birth trauma
- Balance between recurrent bleeding from hematoma membrane and resorption determines ultimate size of hematoma.
ASSOCIATED CONDITIONS
• Acute
- Multisystem trauma
- Cervical spinal cord injury
- Injury to the thoracic, lumbar, or sacral spine
- Disseminated intravascular coagulation
- Epilepsy
• Chronic
- Alcoholism
- Epilepsy
- Coagulopathy
- CSF shunt
- Birth trauma
- Child abuse
- Rarely, metastatic carcinoma
DIAGNOSIS
SIGNS AND SYMPTOMS
• Acute
- Altered level of consciousness: 99%
- Pupillary irregularity (usually unilateral to hematoma): 47-53%
- Hemiparesis (usually contralateral to hematoma): 34-47%
- Decerebrate posturing or flaccid motor exam: 47%
- Papilledema: 16%
- Cranial nerve VI palsy: 5%
• Chronic
- Impaired consciousness: 53%
- Hemiparesis: 45%
- Papilledema: 24%
- Cranial nerve III abnormality: 11%
- Hemianopsia: 7%
- Infants often present with accelerated increase in head size with or without irritability, poor feeding, occasional vomiting, or tension of anterior fontanelle (60% of cases).
- Infants may present with seizures.
TESTS
• EEG for seizures
• ICU: Continuous cardiac monitoring often in conjunction with continuous monitoring of intra-arterial pressure and intracranial pressure (ventriculostomy or intraparenchymal or subdural pressure-monitoring probe)
Lab
• Acute: Consumptive coagulopathy due to underlying parenchymal injury diagnosed with
- Elevated PT and PTT
- Elevated fibrin degradation products
- Decreased fibrinogen
- Decreased platelet level
- Extended bleeding time
• Chronic
- Bleeding time or coagulation parameters: Appropriate abnormalities produced by predisposing factors such as coagulopathy or anticoagulation therapy
- Subtherapeutic anticonvulsant levels in patients with epilepsy
- Serum ethanol level in alcoholics
• Drugs that may alter lab results: Anticoagulants (e.g., warfarin)
• Disorders that may alter lab results: DIC and other coagulopathies (e.g., hemophilia)
Imaging
• Acute
- Imaging study of choice: CT head scan (with intravascular contrast if hemoglobin 9 g/d)
- Axial view demonstrates hyperdense, cresenteric, extra-axial collection usually adjacent to inner table
• Chronic
- Imaging study of choice: CT head scan
- Hematomas usually evolve from isodense to hypodense by 3 weeks.
- MRI head scan: Often necessary for hematomas isodense with brain due to mixture of chronic hematoma with recurrent hemorrhage
Pathological Findings
• Acute: Fresh hemorrhage
• Chronic
- Liquefied hematoma
- Outer membrane beneath dura after 1 week
- Inner membrane between hematoma and arachnoid after 3 weeks
- On rare occasions, cytology examination may reveal association between metastatic carcinoma cells and hemorrhage
DIFFERENTIAL DIAGNOSIS
• Acute versus chronic
• Other forms of intracranial hematoma (e.g., epidural hematoma, cerebral contusion/hematoma)
• Dementia
• Stroke
• Transient ischemic attack
• Brain tumor
• Subdural empyema
• Meningitis
ALERT
The insidious onset of symptoms may lead to misdiagnosis of dementia, tumor, or depression.
TREATMENT
GENERAL MEASURES
• Inpatient
• Acute: medical management
- Control of elevated intracranial pressure with osmotic and loop diuretics
- Hyperventilation to induce hypocapnia (PaCO2 of 22-28 mm Hg [2.9-3.7 kPa])
- Elevate head of bed to reduce intracranial pressure.
- Avoid flexion of lower body until thoracic, lumbar, or sacral spine injuries are ruled out.
- Maintain patient in rigid cervical collar until cervical spine is cleared radiographically.
• Subacute
- Maintenance of adequate airway and ventilation and support of cardiovascular system to promote normal cerebral perfusion
- Treatment of multisystem trauma and precautions for cervical and other spine injury
• Chronic
- Keep head of bed flat.
- Take appropriate precautions if spinal injury is present.
Diet
• Acute: Most patients require enteral or total parenteral nutrition initially.
• Chronic: Depending on level of consciousness, patients can usually have diet advanced to regular food as tolerated.
First Line
• Acute
- Prior to surgery, management of cerebral edema and elevated intracranial pressure may require mannitol 20% solution 0.5-1.0 g/kg followed by 0.25-0.75 g/kg q4-6h. If loop diuretic used in conjunction with mannitol, administer furosemide (Lasix) 0.5 mg/kg IV. Check serum osmolality q8h and serum electrolytes at least daily. A 5% or 25% albumin preparation (Plasmanate) may be used either as continuous or intermittent infusion to augment osmotherapy as needed.
- Seizure prophylaxis includes phenytoin (Dilantin) 1000 mg load (50 mg/min IV) with ECG monitoring, followed by 100 mg IV q8h or as needed to maintain therapeutic blood levels (10-20 ug/mL [40-79 umol/L]). Convert Dilantin therapy to oral route as soon as possible to avoid cardiovascular complications of IV Dilantin administration.
• Chronic
- Medical management alone is frequently unsuccessful and entails risks of neurological deterioration.
- However, when small and asymptomatic, may be appropriate to treat conservatively with observation, as some chronic subdural hematomas have been known to resolve spontaneously.
- Steroids may be helpful in some patients, if not otherwise contraindicated.
• Contraindications, precautions, and significant possible interactions: Refer to the manufacturer's literature.
SURGERY
• Acute: Emergent craniotomy indicated for evacuation of hematomas causing significant mass effect
• Subacute
- If patient is neurologically stable, surgery may be delayed until hematoma matures and becomes chronic, at which time a burr hole drainage can be performed.
- If causing significant mass effect and neurological deficit, may require craniotomy for evacuation
• Chronic: Burr hole drainage; some neurosurgeons leave a catheter in subdural space for 24 hours after operation
FOLLOW-UP
PROGNOSIS
Outcome highly dependent on presurgical neurological status
• Acute
- Mortality >50%; lower in patients 40 years old than in those >40 years old
- Significant neurological disability and impairment of function seen in most surviving patients
- Seizure prophylaxis usually required for 1 year
• Chronic
- Mortality 10%
- Most patients resume preoperative functional status.
COMPLICATIONS
• Acute: Immediate postoperative complications include
- Elevated intracranial pressure and brain edema
- New or recurrent hematoma
- Infection
- Seizures (in ~1/3 of cases)
• Chronic:
- Recurrent hematoma in up to 50% of cases (can be alleviated by use of subdural drainage catheters)
- Infection (subdural empyema, wound)
- Seizures in up to 10% of cases
PATIENT MONITORING
• Anticonvulsant levels should be checked approximately every 3-6 months after initiation.
• Consider discontinuing anticonvulsant if patient has no seizures for 1 year.
• EEG may complement decision-making process for discontinuation of anticonvulsants.
REFERENCES
1. Francel et al. Diagnosis and treatment of moderate and severe head injuries in infants and children. In: Youmans JR, ed. Neurological Surgery. 4th ed. Philadelphia, PA: WB Saunders; 1996: 1730-1766.
2. Greenberg MS. Handbook of Neurosurgery. 4th ed. Lakeland, FL: Greenberg Graphics; 1997.
3. Samudrala S, Cooper PR. Traumatic intracranial hematomas. In: Wilkins RH, Rengachary SS, eds. Neurosurgery. 2nd ed. New York, NY: McGraw-Hill; 1996: 2797-2807.
BASICS
DESCRIPTION
• Accumulation of blood in subdural space
- Acute: Most severe form, usually result of trauma involving acceleration or deceleration head injury and commonly associated with parenchymal brain injury. Hematoma age is 3 days.
- Chronic: Often result of trivial head injury in older patients; 25-50% have no history of head trauma. Hematoma is classically >3 weeks and associated with encapsulating membrane.
- Subacute: Appearing 4-21 days from maturation of acute subdural hematoma
• System(s) Affected: Cardiovascular; Nervous
• Synonym(s): Subdural hemorrhage
GENERAL PREVENTION
• Acute: Trauma-prevention programs
• Chronic
- Alcoholism prevention
- Medical and surgical management of epilepsy
- Conservative use of anticoagulation therapy
- Medium-pressure or high-pressure ventriculoperitoneal shunt valves in at-risk patients with hydrocephalus
EPIDEMIOLOGY
• Predominant age
- Acute: 60 years. Relatively infrequent in newborns and children, occurring 25% as often as in adults.
- Chronic: >50 years. Occurs in children of all ages
• Predominant sex: Male > Female
Incidence
Chronic: Peak incidence at ~6 months and rarely after 1 year of age
Prevalence
• Acute
- 1-2/100,000
- Present with 5-22% of episodes of severe head trauma
• Chronic: 1-2/100,000
RISK FACTORS
• Acute
- Severe head trauma
- High-velocity acceleration or deceleration head injury (motor vehicle accidents, falls, blunt head trauma)
- Suspected nonaccidental trauma in infants
• Chronic
- Chronic alcoholism
- Epilepsy
- Coagulopathy/anticoagulation therapy
- CSF shunt for hydrocephalus
- Rarely, metastatic carcinoma to subdural space
ALERT
Cerebral atrophy common and predisposes to subdural hematomas
ETIOLOGY
• Acute
- High-velocity acceleration or deceleration head injury resulting in tearing of bridging veins between cerebral cortex and dural venous sinuses
- Injury to surface of brain with bleeding from injured cortical vessels
• Chronic
- Adults: Often from trivial head injury
- Children: May be caused by unrecognized/unreported trauma, abuse, or, rarely, birth trauma
- Balance between recurrent bleeding from hematoma membrane and resorption determines ultimate size of hematoma.
ASSOCIATED CONDITIONS
• Acute
- Multisystem trauma
- Cervical spinal cord injury
- Injury to the thoracic, lumbar, or sacral spine
- Disseminated intravascular coagulation
- Epilepsy
• Chronic
- Alcoholism
- Epilepsy
- Coagulopathy
- CSF shunt
- Birth trauma
- Child abuse
- Rarely, metastatic carcinoma
DIAGNOSIS
SIGNS AND SYMPTOMS
• Acute
- Altered level of consciousness: 99%
- Pupillary irregularity (usually unilateral to hematoma): 47-53%
- Hemiparesis (usually contralateral to hematoma): 34-47%
- Decerebrate posturing or flaccid motor exam: 47%
- Papilledema: 16%
- Cranial nerve VI palsy: 5%
• Chronic
- Impaired consciousness: 53%
- Hemiparesis: 45%
- Papilledema: 24%
- Cranial nerve III abnormality: 11%
- Hemianopsia: 7%
- Infants often present with accelerated increase in head size with or without irritability, poor feeding, occasional vomiting, or tension of anterior fontanelle (60% of cases).
- Infants may present with seizures.
TESTS
• EEG for seizures
• ICU: Continuous cardiac monitoring often in conjunction with continuous monitoring of intra-arterial pressure and intracranial pressure (ventriculostomy or intraparenchymal or subdural pressure-monitoring probe)
Lab
• Acute: Consumptive coagulopathy due to underlying parenchymal injury diagnosed with
- Elevated PT and PTT
- Elevated fibrin degradation products
- Decreased fibrinogen
- Decreased platelet level
- Extended bleeding time
• Chronic
- Bleeding time or coagulation parameters: Appropriate abnormalities produced by predisposing factors such as coagulopathy or anticoagulation therapy
- Subtherapeutic anticonvulsant levels in patients with epilepsy
- Serum ethanol level in alcoholics
• Drugs that may alter lab results: Anticoagulants (e.g., warfarin)
• Disorders that may alter lab results: DIC and other coagulopathies (e.g., hemophilia)
Imaging
• Acute
- Imaging study of choice: CT head scan (with intravascular contrast if hemoglobin 9 g/d)
- Axial view demonstrates hyperdense, cresenteric, extra-axial collection usually adjacent to inner table
• Chronic
- Imaging study of choice: CT head scan
- Hematomas usually evolve from isodense to hypodense by 3 weeks.
- MRI head scan: Often necessary for hematomas isodense with brain due to mixture of chronic hematoma with recurrent hemorrhage
Pathological Findings
• Acute: Fresh hemorrhage
• Chronic
- Liquefied hematoma
- Outer membrane beneath dura after 1 week
- Inner membrane between hematoma and arachnoid after 3 weeks
- On rare occasions, cytology examination may reveal association between metastatic carcinoma cells and hemorrhage
DIFFERENTIAL DIAGNOSIS
• Acute versus chronic
• Other forms of intracranial hematoma (e.g., epidural hematoma, cerebral contusion/hematoma)
• Dementia
• Stroke
• Transient ischemic attack
• Brain tumor
• Subdural empyema
• Meningitis
ALERT
The insidious onset of symptoms may lead to misdiagnosis of dementia, tumor, or depression.
TREATMENT
GENERAL MEASURES
• Inpatient
• Acute: medical management
- Control of elevated intracranial pressure with osmotic and loop diuretics
- Hyperventilation to induce hypocapnia (PaCO2 of 22-28 mm Hg [2.9-3.7 kPa])
- Elevate head of bed to reduce intracranial pressure.
- Avoid flexion of lower body until thoracic, lumbar, or sacral spine injuries are ruled out.
- Maintain patient in rigid cervical collar until cervical spine is cleared radiographically.
• Subacute
- Maintenance of adequate airway and ventilation and support of cardiovascular system to promote normal cerebral perfusion
- Treatment of multisystem trauma and precautions for cervical and other spine injury
• Chronic
- Keep head of bed flat.
- Take appropriate precautions if spinal injury is present.
Diet
• Acute: Most patients require enteral or total parenteral nutrition initially.
• Chronic: Depending on level of consciousness, patients can usually have diet advanced to regular food as tolerated.
First Line
• Acute
- Prior to surgery, management of cerebral edema and elevated intracranial pressure may require mannitol 20% solution 0.5-1.0 g/kg followed by 0.25-0.75 g/kg q4-6h. If loop diuretic used in conjunction with mannitol, administer furosemide (Lasix) 0.5 mg/kg IV. Check serum osmolality q8h and serum electrolytes at least daily. A 5% or 25% albumin preparation (Plasmanate) may be used either as continuous or intermittent infusion to augment osmotherapy as needed.
- Seizure prophylaxis includes phenytoin (Dilantin) 1000 mg load (50 mg/min IV) with ECG monitoring, followed by 100 mg IV q8h or as needed to maintain therapeutic blood levels (10-20 ug/mL [40-79 umol/L]). Convert Dilantin therapy to oral route as soon as possible to avoid cardiovascular complications of IV Dilantin administration.
• Chronic
- Medical management alone is frequently unsuccessful and entails risks of neurological deterioration.
- However, when small and asymptomatic, may be appropriate to treat conservatively with observation, as some chronic subdural hematomas have been known to resolve spontaneously.
- Steroids may be helpful in some patients, if not otherwise contraindicated.
• Contraindications, precautions, and significant possible interactions: Refer to the manufacturer's literature.
SURGERY
• Acute: Emergent craniotomy indicated for evacuation of hematomas causing significant mass effect
• Subacute
- If patient is neurologically stable, surgery may be delayed until hematoma matures and becomes chronic, at which time a burr hole drainage can be performed.
- If causing significant mass effect and neurological deficit, may require craniotomy for evacuation
• Chronic: Burr hole drainage; some neurosurgeons leave a catheter in subdural space for 24 hours after operation
FOLLOW-UP
PROGNOSIS
Outcome highly dependent on presurgical neurological status
• Acute
- Mortality >50%; lower in patients 40 years old than in those >40 years old
- Significant neurological disability and impairment of function seen in most surviving patients
- Seizure prophylaxis usually required for 1 year
• Chronic
- Mortality 10%
- Most patients resume preoperative functional status.
COMPLICATIONS
• Acute: Immediate postoperative complications include
- Elevated intracranial pressure and brain edema
- New or recurrent hematoma
- Infection
- Seizures (in ~1/3 of cases)
• Chronic:
- Recurrent hematoma in up to 50% of cases (can be alleviated by use of subdural drainage catheters)
- Infection (subdural empyema, wound)
- Seizures in up to 10% of cases
PATIENT MONITORING
• Anticonvulsant levels should be checked approximately every 3-6 months after initiation.
• Consider discontinuing anticonvulsant if patient has no seizures for 1 year.
• EEG may complement decision-making process for discontinuation of anticonvulsants.
REFERENCES
1. Francel et al. Diagnosis and treatment of moderate and severe head injuries in infants and children. In: Youmans JR, ed. Neurological Surgery. 4th ed. Philadelphia, PA: WB Saunders; 1996: 1730-1766.
2. Greenberg MS. Handbook of Neurosurgery. 4th ed. Lakeland, FL: Greenberg Graphics; 1997.
3. Samudrala S, Cooper PR. Traumatic intracranial hematomas. In: Wilkins RH, Rengachary SS, eds. Neurosurgery. 2nd ed. New York, NY: McGraw-Hill; 1996: 2797-2807.
SUBCLAVIAN STEAL SYNDROME
SUBCLAVIAN STEAL SYNDROME - Frederico Milla, MD; Ruben Peralta, MD, FACS
BASICS
DESCRIPTION
Origin of the subclavian artery becomes occluded, compromising blood flow to the ipsilateral upper extremity. To supplement this perfusion, blood flow from the vertebral artery reverses, leading to vertebral-basilar insufficiency. Symptoms may be especially prominent when demand increases, for example during upper extremity exercise.
EPIDEMIOLOGY
• Predominant age
- Age >55 yearsatherosclerotic etiology
- Age 30 years90% of patients with Takayasu arteritis
• Predominant sex: Male > Female (2:1)
Incidence
Unknown
RISK FACTORS
• Smoking
• Hypertension
• Diabetes
• Hyperlipidemia
ETIOLOGY
• Arteriosclerosis obliterans of the proximal subclavian artery in 95% of cases
• Less common causes of obstruction
- Dissecting aneurysm of aortic arch
- Trauma
- Embolus
- Takayasu arteritis
ASSOCIATED CONDITIONS
• Carotid artery disease
• Heart disease
• Arteriosclerosis
ALERT
Geriatric Considerations
Older patients are more likely to have arteriosclerosis.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Most common: Vertigo or presyncope following upper extremity exercise. The reversal of flow down the ipsilateral vertebral artery results in a relative vertebral-basilar insufficiency.
• Less common: Weakness and clumsiness of an extremity, loss of vision, homonymous hemianopsia, ataxia, and drop attacks
• Arm claudication following minimal exercise
• Reduced blood pressure of >20 mm Hg in involved arm
• Symptoms should be reproducible by exercising the arm
Physical Exam
• Absent or diminished pulses in ipsilateral arm
• Reduced blood pressure (>20 mm Hg) when compared to the contralateral arm
TESTS
• Noninvasive measurement of BP in upper extremities
• Pulse volume recording of upper extremities
Lab
• No labs findings are pathognomonic for subclavian steal syndrome.
• If Takayasu arteritis is suspected
- Erythrocyte sedimentation rate (elevated)
- Complete blood count (thrombocytosis)
- Electrocardiogram (ischemic pattern)
- Chest radiograph (widening of thoracic aorta)
Imaging
• Duplex scanning of extracranial vessels
• Magnetic Resonance Angiography (1)[B]
• Arteriogram of arch vessels with delayed films of vertebral arteries
Diagnostic Procedures/Surgery
Arteriography
DIFFERENTIAL DIAGNOSIS
• Vascular: Intracranial vascular disease, carotid artery disease, vertebral artery disease
• Neurogenic: Brain tumor, seizures, subdural hematoma
• Cardiac arrhythmias
TREATMENT
STABILIZATION
Outpatient care unless vascular surgery is anticipated
GENERAL MEASURES
Reduce cholesterol levels, if appropriate, using diet or medication.
Diet
Low-cholesterol diet, if appropriate
Activity
Reduced exercise of arms
MEDICATION (DRUGS)
None
SURGERY
Treatment options include
• Balloon angioplasty. Stent insertion may increase long-term patency rates. (2,3)[B]
• Carotid-subclavian bypass
FOLLOW-UP
PROGNOSIS
Good
COMPLICATIONS
Completed stroke
PATIENT MONITORING
Annual physical examination including BP reading in both arms
REFERENCES
1. Wu C, Zhang J, Ladner CJ, et al. Subclavian steal syndrome: Diagnosis with perfusion metrics from contrast-enhanced MR angiographic bolus-timing examination-initial experience. Radiology 2005;235:927-933.
2. Taylor CL, Selman WR, Ratcheson RA. Steal affecting the central nervous system. Neurosurgery. 2002;51:856-857.
3. White CJ. Non-surgical treatment of patients with peripheral vascular disease. Br Med Bull 2001;59:173-192.
4. Valadez ER, Martinez PH, Peralta SO, et al. Imaging diagnosis of subclavian steal syndrome secondary to Takayasu arteritis affecting a left-side subclavian artery. Arch Med Res 2003;34:433-438.
MISCELLANEOUS
See also: Arteriosclerosis obliterans, Takayasu syndrome
BASICS
DESCRIPTION
Origin of the subclavian artery becomes occluded, compromising blood flow to the ipsilateral upper extremity. To supplement this perfusion, blood flow from the vertebral artery reverses, leading to vertebral-basilar insufficiency. Symptoms may be especially prominent when demand increases, for example during upper extremity exercise.
EPIDEMIOLOGY
• Predominant age
- Age >55 yearsatherosclerotic etiology
- Age 30 years90% of patients with Takayasu arteritis
• Predominant sex: Male > Female (2:1)
Incidence
Unknown
RISK FACTORS
• Smoking
• Hypertension
• Diabetes
• Hyperlipidemia
ETIOLOGY
• Arteriosclerosis obliterans of the proximal subclavian artery in 95% of cases
• Less common causes of obstruction
- Dissecting aneurysm of aortic arch
- Trauma
- Embolus
- Takayasu arteritis
ASSOCIATED CONDITIONS
• Carotid artery disease
• Heart disease
• Arteriosclerosis
ALERT
Geriatric Considerations
Older patients are more likely to have arteriosclerosis.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Most common: Vertigo or presyncope following upper extremity exercise. The reversal of flow down the ipsilateral vertebral artery results in a relative vertebral-basilar insufficiency.
• Less common: Weakness and clumsiness of an extremity, loss of vision, homonymous hemianopsia, ataxia, and drop attacks
• Arm claudication following minimal exercise
• Reduced blood pressure of >20 mm Hg in involved arm
• Symptoms should be reproducible by exercising the arm
Physical Exam
• Absent or diminished pulses in ipsilateral arm
• Reduced blood pressure (>20 mm Hg) when compared to the contralateral arm
TESTS
• Noninvasive measurement of BP in upper extremities
• Pulse volume recording of upper extremities
Lab
• No labs findings are pathognomonic for subclavian steal syndrome.
• If Takayasu arteritis is suspected
- Erythrocyte sedimentation rate (elevated)
- Complete blood count (thrombocytosis)
- Electrocardiogram (ischemic pattern)
- Chest radiograph (widening of thoracic aorta)
Imaging
• Duplex scanning of extracranial vessels
• Magnetic Resonance Angiography (1)[B]
• Arteriogram of arch vessels with delayed films of vertebral arteries
Diagnostic Procedures/Surgery
Arteriography
DIFFERENTIAL DIAGNOSIS
• Vascular: Intracranial vascular disease, carotid artery disease, vertebral artery disease
• Neurogenic: Brain tumor, seizures, subdural hematoma
• Cardiac arrhythmias
TREATMENT
STABILIZATION
Outpatient care unless vascular surgery is anticipated
GENERAL MEASURES
Reduce cholesterol levels, if appropriate, using diet or medication.
Diet
Low-cholesterol diet, if appropriate
Activity
Reduced exercise of arms
MEDICATION (DRUGS)
None
SURGERY
Treatment options include
• Balloon angioplasty. Stent insertion may increase long-term patency rates. (2,3)[B]
• Carotid-subclavian bypass
FOLLOW-UP
PROGNOSIS
Good
COMPLICATIONS
Completed stroke
PATIENT MONITORING
Annual physical examination including BP reading in both arms
REFERENCES
1. Wu C, Zhang J, Ladner CJ, et al. Subclavian steal syndrome: Diagnosis with perfusion metrics from contrast-enhanced MR angiographic bolus-timing examination-initial experience. Radiology 2005;235:927-933.
2. Taylor CL, Selman WR, Ratcheson RA. Steal affecting the central nervous system. Neurosurgery. 2002;51:856-857.
3. White CJ. Non-surgical treatment of patients with peripheral vascular disease. Br Med Bull 2001;59:173-192.
4. Valadez ER, Martinez PH, Peralta SO, et al. Imaging diagnosis of subclavian steal syndrome secondary to Takayasu arteritis affecting a left-side subclavian artery. Arch Med Res 2003;34:433-438.
MISCELLANEOUS
See also: Arteriosclerosis obliterans, Takayasu syndrome
SUBARACHNOID HEMORRHAGE
SUBARACHNOID HEMORRHAGE - Michael Previti, MD
BASICS
DESCRIPTION
• Extravasation of blood into subarachnoid space, particularly of basal cisterns, and into CSF pathways including ventricles.
• Accounts for 2-5% of new strokes.
• Traumatic: More common; related to head trauma
• Spontaneous: 80% due to ruptured intracranial saccular aneurysms and have a much worse prognosis than nonaneurysmal subarachnoid hemorrhages (SAHs).
• May also occur from rupture of arteriovenous malformations (AVMs).
• System(s) Affected: Nervous
ALERT
Pregnancy Considerations
Increased BP and blood volume may predispose pregnant women to hemorrhages.
GENERAL PREVENTION
• Incidental aneurysms have risk of hemorrhage according to size; therefore, endovascular coiling or surgical clipping may be indicated.
• The 5-year cumulative rate of aneurysmal rupture in the internal carotid artery, anterior cerebral artery, middle cerebral artery, or anterior communicating artery based on size
- 7 mm: 0%
- 7-12 mm: 2.6%
- 13-24 mm: 14.5%
- >25 mm: 40%
• The 5-year cumulative rate of aneurysmal rupture in the vertebral, basilar, posterior communicating arteries by size
- 7 mm: 2.5%
- 7-12 mm: 14.5%
- 13-24 mm: 18.4%
- >25 mm: 50%
• In younger age groups, incidentally found AVMs have a 2% risk of rupture per year.
EPIDEMIOLOGY
• Mean age of presentation is 55 years.
• Majority occur in 4th-7th decades.
• SAHs due to AVMs occur in 2nd-4th decades.
• Female > Male (1.6:1)
• Blacks > Whites (2.1:1)
Incidence
Spontaneous: 10.5/100,000 person years
Prevalence
In the US: 21,000-33,000 new cases each year
RISK FACTORS
• Cigarette smoking
• Cocaine use
• Heavy alcohol use
• Hypertension associated with rupture of aneurysm, but not with saccular aneurysms
• 1st-degree relatives with SAH
• AVMs
ETIOLOGY
• Trauma
• Intracranial saccular aneurysm
• Intracranial AVM
• Hypertension
• Rarely, tumors and blood dyscrasias
ASSOCIATED CONDITIONS
• Morbidity and mortality of SAH are determined by complications that develop after the initial bleed.
• Outcome predicted by the World Federation of Neurological Surgeons clinical grading.
• Blood volume on initial CT is predictive of vasospasm.
• The following complications are common
- Cerebral vasospasm occurs within 4-12 days of initial bleed, and is seen angiographically in 67%.
- Cardiac arrhythmias occur in 35% of patients.
- Seizures occur in up to 33% of patients.
- Electrolyte disturbances (including SIADH and cerebral salt wasting) occur in 28% of patients.
- Pulmonary edema occurs in 23% of patients.
- Hydrocephalus occurs in 20% of patients.
- Rebleeding occurs in 7% of patients and has a 50% risk of permanent neurologic damage.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Abrupt onset of headache ("worst headache of life") associated with stiff neck, nausea, vomiting, photophobia, and/or LOC.
• Headache may be the only presenting symptom in up to 40% of patients and may disappear within hours (so called thunderclap headaches, sentinel bleeds, or warning leaks).
History
Assess for recent head trauma, perimesencephalic hemorrhage of SAH, hypertension, nicotine/EtOH/cocaine use, AVMs, family history of SAH, and current use of anticoagulants.
Physical Exam
• Retinal hemorrhages
• Meningismus
• Diminished consciousness, calculate Glasgow Coma Scale on all patients
• Focal neurologic signs, such as 3rd-nerve palsy (p. comm. aneurysm), 6th-nerve palsy (increased intracranial pressure [ICP]), bilateral leg weakness and/or abulia (a. comm. aneurysm), hemiparesis and/or aphasia and/or visuospatial neglect (MCA aneurysm).
• Perform lumbar puncture if CT is negative and suspicion is high. Elevated opening pressure, xanthochromia (takes 12 hours to develop), or RBCs unchanged in tubes 1-4 are consistent with SAH.
TESTS
Imaging
• Noncontrast head CT with thin cuts through the base of the brain. Sensitivity drops to 50% at 7 days, but is 100 at 12 hours and 93% at 24 hours.
• CT may show hydrocephalus, cerebral edema, intraparenchymal bleeds, and can predict the site of rupture (particularly in the anterior circulation).
• CT is the most reliable prediction of vasospasm and poor outcome using Fisher Scale.
• CT can rule out mass effect in order to safely perform a necessary lumbar puncture.
• If CT or LP are positive, check cerebral angiography (gold standard) or CT angiography; they have similar sensitivity and specificity.
• If 2nd study is negative, high-definition MRI should be performed. MRA can be used but is not the standard for surgical planning.
• Important: If no source of SAH is found intracranially, obtain MRI spinal or myelography.
DIFFERENTIAL DIAGNOSIS
• Traumatic SAH
• Aneurysmal rupture (including mycotic aneurysms associated with bacterial endocarditis)
• AVM
• Arterial dissection with intracranial extension
• Pituitary apoplexy
• Drug abuse (e.g. cocaine) with or without aneurysm as a result of vasculitis
• Coagulopathies
• Migraine (especially with aura)
TREATMENT
PRE-HOSPITAL
• Stabilize ABCs, IV, O2 monitor
• After stabilized, consider transfer to neurovascular center
GENERAL MANAGEMENT
• Initial therapy in ICU. Treatment is directed to prevent complications, including rebleeding, hydrocephalus, and cerebral vasospasm.
• BP is maintained within normal limits with IV labetalol and nicardipine.
• Maintain euvolemia (CVP 5-8 mm Hg) unless cerebral vasospasm is present (see below).
• Evaluate and treat myocardial injury and/or arrhythmias.
• Distinguish cardiogenic vs. neurogenic pulmonary edema and treat appropriately.
• Control pain with morphine sulfate 2-4 mg IV q2-4h.
• Maintain serum glucose at 80-120 mg/dL with insulin sliding scale or continuous infusion.
• Maintain core body temperature 37.2C.
• DVT prophylaxis with thigh-high stockings and compressive devices; after aneurysm is secured; subcutaneous heparin 5,000 U SC t.i.d.
• GI prophylaxis with ranitidine 150 mg PO b.i.d. (50 mg IV q8-12h) or lansoprazole 30 mg/d PO
• Stool softeners may also be used.
Diet
If swallow evaluation allows, give PO diet.
Activity
Strict bed rest, reduced noise level, and limited visitors until source of bleeding is secured.
SPECIAL THERAPY
Perform neuropsychological testing before discharge, and schedule cognitive rehabilitation
Physical Therapy
Aggressive physical, occupational and, speech evaluation.
MEDICATION (DRUGS)
• Nimodipine 60 mg PO (via nasogastric tube if necessary) q4h for 21 days for prevention of cerebral vasospasm; start immediately.
• Antifibrinolytic agents may be used before aneurysm treatment (aminocaproic acid 5 g IV in the 1st 24-48 hours with a 1.5 g/h infusion thereafter).
• Phenytoin 3-5 mg/kg/d PO or IV, valproic acid 15-45 mg/kg/d PO or IV, or phenobarbital 4 mg/kg IV may be used as seizure prophylaxis.
• Treat seizures with lorazepam 0.1 mg/kg IV at a 2 mg/min rate followed by phenytoin 20 mg/kg IV bolus at 50 mg/min up to 30 mg/kg.
• SIADH vs. cerebral salt wasting must be distinguished with serum and urine electrolytes.
• Symptomatic vasospasm is currently treated with hypervolemia (CVP 8-12 mm Hg, PCWP 12-16 mm Hg) and/or induced hypertension
SURGERY
• Endovascular coiling and surgical clipping are options for securing aneurysms. Aneurysmal securing should be performed within 1st 72 hours.
• Rebleeding should be dealt with immediately by treatment of aneurysm.
• 25-30% of aneurysms will be multiple.
• Hydrocephalus should be treated with external ventricular drain (EVD), lumbar drain, or permanent CSF drainage.
• Arteriovenous malformations may be obliterated with embolization and surgery.
PROGNOSIS
• Average case fatality rate is 51% overall: 10% before receiving care, 25% within the 1st 24 hours
• 25-30% of patients die from spontaneous SAH due to aneurysm. Highest morbidity secondary to cerebral vasospasm.
• If aneurysm can be successfully obliterated and vasospasm treated effectively, satisfactory outcome occurs in 50-65% of patients.
• 45-50% of survivors report long-term cognitive impairment of varying degrees.
• 50-75% of survivors return to work after 1 year.
COMPLICATIONS
• Temporary and permanent neurologic deficits and/or disorders (e.g., seizures, headache, SIADH)
• Death
PATIENT MONITORING
As needed
REFERENCES
1. Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl J Med. 2006;354:387-396.
2. Whitfield PC, Kirkpatrick PJ. Timing of surgery for aneurysmal subarachnoid haemorrhage. Cochrane Database Sys Rev. 2006;1.
3. Lapointe M, Haines S. Fibrinolytic therapy for intraventricular hemorrhage in adults. Cochrane Database Sys Rev. 2006;1.
4. van der Schaaf I, Algra A, Wermer M, et al. Endovascular coiling versus neurosurgical clipping for patients with aneurysmal subarachnoid haemorrhage. Cochrane Database Sys Rev. 2006;1.
5. Rinkel GJE, Feigin VL, Algra A, et al. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Sys Rev. 2006;1.
6. Roos YBWEM, Rinkel GJE, Vermeulen M, et al. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Sys Rev. 2006;1.
7. Intensive insulin therapy reduced the incidence of neurologic complications in critically ill patients. ACP Journal Club. 2006;144(1):20.
8. Review: Computed tomographic angiography and magnetic resonance angiography accurately detect intracranial aneurysms. ACP Journal Club. 2001;134(3):113.
9. Mustonen T, Koivisto T, Vanninen E, et al. Cerebral perfusion heterogeneity and complexity in patients with acute subarachnoid haemorrhage. Nucl Med Commun. 2006;27(2):157-164.
10. Wijdicks EF. Induced hypothermia in neurocatastrophes: Feeling the chill. Rev Neurol Dis. 2004;1(1):10-15. Review.
ADDITIONAL READING
Rinkel GJE, Feigin VL, Algra A, van Gijn J. Circulatory volume expansion therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Sys Rev. 2006;1.
BASICS
DESCRIPTION
• Extravasation of blood into subarachnoid space, particularly of basal cisterns, and into CSF pathways including ventricles.
• Accounts for 2-5% of new strokes.
• Traumatic: More common; related to head trauma
• Spontaneous: 80% due to ruptured intracranial saccular aneurysms and have a much worse prognosis than nonaneurysmal subarachnoid hemorrhages (SAHs).
• May also occur from rupture of arteriovenous malformations (AVMs).
• System(s) Affected: Nervous
ALERT
Pregnancy Considerations
Increased BP and blood volume may predispose pregnant women to hemorrhages.
GENERAL PREVENTION
• Incidental aneurysms have risk of hemorrhage according to size; therefore, endovascular coiling or surgical clipping may be indicated.
• The 5-year cumulative rate of aneurysmal rupture in the internal carotid artery, anterior cerebral artery, middle cerebral artery, or anterior communicating artery based on size
- 7 mm: 0%
- 7-12 mm: 2.6%
- 13-24 mm: 14.5%
- >25 mm: 40%
• The 5-year cumulative rate of aneurysmal rupture in the vertebral, basilar, posterior communicating arteries by size
- 7 mm: 2.5%
- 7-12 mm: 14.5%
- 13-24 mm: 18.4%
- >25 mm: 50%
• In younger age groups, incidentally found AVMs have a 2% risk of rupture per year.
EPIDEMIOLOGY
• Mean age of presentation is 55 years.
• Majority occur in 4th-7th decades.
• SAHs due to AVMs occur in 2nd-4th decades.
• Female > Male (1.6:1)
• Blacks > Whites (2.1:1)
Incidence
Spontaneous: 10.5/100,000 person years
Prevalence
In the US: 21,000-33,000 new cases each year
RISK FACTORS
• Cigarette smoking
• Cocaine use
• Heavy alcohol use
• Hypertension associated with rupture of aneurysm, but not with saccular aneurysms
• 1st-degree relatives with SAH
• AVMs
ETIOLOGY
• Trauma
• Intracranial saccular aneurysm
• Intracranial AVM
• Hypertension
• Rarely, tumors and blood dyscrasias
ASSOCIATED CONDITIONS
• Morbidity and mortality of SAH are determined by complications that develop after the initial bleed.
• Outcome predicted by the World Federation of Neurological Surgeons clinical grading.
• Blood volume on initial CT is predictive of vasospasm.
• The following complications are common
- Cerebral vasospasm occurs within 4-12 days of initial bleed, and is seen angiographically in 67%.
- Cardiac arrhythmias occur in 35% of patients.
- Seizures occur in up to 33% of patients.
- Electrolyte disturbances (including SIADH and cerebral salt wasting) occur in 28% of patients.
- Pulmonary edema occurs in 23% of patients.
- Hydrocephalus occurs in 20% of patients.
- Rebleeding occurs in 7% of patients and has a 50% risk of permanent neurologic damage.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Abrupt onset of headache ("worst headache of life") associated with stiff neck, nausea, vomiting, photophobia, and/or LOC.
• Headache may be the only presenting symptom in up to 40% of patients and may disappear within hours (so called thunderclap headaches, sentinel bleeds, or warning leaks).
History
Assess for recent head trauma, perimesencephalic hemorrhage of SAH, hypertension, nicotine/EtOH/cocaine use, AVMs, family history of SAH, and current use of anticoagulants.
Physical Exam
• Retinal hemorrhages
• Meningismus
• Diminished consciousness, calculate Glasgow Coma Scale on all patients
• Focal neurologic signs, such as 3rd-nerve palsy (p. comm. aneurysm), 6th-nerve palsy (increased intracranial pressure [ICP]), bilateral leg weakness and/or abulia (a. comm. aneurysm), hemiparesis and/or aphasia and/or visuospatial neglect (MCA aneurysm).
• Perform lumbar puncture if CT is negative and suspicion is high. Elevated opening pressure, xanthochromia (takes 12 hours to develop), or RBCs unchanged in tubes 1-4 are consistent with SAH.
TESTS
Imaging
• Noncontrast head CT with thin cuts through the base of the brain. Sensitivity drops to 50% at 7 days, but is 100 at 12 hours and 93% at 24 hours.
• CT may show hydrocephalus, cerebral edema, intraparenchymal bleeds, and can predict the site of rupture (particularly in the anterior circulation).
• CT is the most reliable prediction of vasospasm and poor outcome using Fisher Scale.
• CT can rule out mass effect in order to safely perform a necessary lumbar puncture.
• If CT or LP are positive, check cerebral angiography (gold standard) or CT angiography; they have similar sensitivity and specificity.
• If 2nd study is negative, high-definition MRI should be performed. MRA can be used but is not the standard for surgical planning.
• Important: If no source of SAH is found intracranially, obtain MRI spinal or myelography.
DIFFERENTIAL DIAGNOSIS
• Traumatic SAH
• Aneurysmal rupture (including mycotic aneurysms associated with bacterial endocarditis)
• AVM
• Arterial dissection with intracranial extension
• Pituitary apoplexy
• Drug abuse (e.g. cocaine) with or without aneurysm as a result of vasculitis
• Coagulopathies
• Migraine (especially with aura)
TREATMENT
PRE-HOSPITAL
• Stabilize ABCs, IV, O2 monitor
• After stabilized, consider transfer to neurovascular center
GENERAL MANAGEMENT
• Initial therapy in ICU. Treatment is directed to prevent complications, including rebleeding, hydrocephalus, and cerebral vasospasm.
• BP is maintained within normal limits with IV labetalol and nicardipine.
• Maintain euvolemia (CVP 5-8 mm Hg) unless cerebral vasospasm is present (see below).
• Evaluate and treat myocardial injury and/or arrhythmias.
• Distinguish cardiogenic vs. neurogenic pulmonary edema and treat appropriately.
• Control pain with morphine sulfate 2-4 mg IV q2-4h.
• Maintain serum glucose at 80-120 mg/dL with insulin sliding scale or continuous infusion.
• Maintain core body temperature 37.2C.
• DVT prophylaxis with thigh-high stockings and compressive devices; after aneurysm is secured; subcutaneous heparin 5,000 U SC t.i.d.
• GI prophylaxis with ranitidine 150 mg PO b.i.d. (50 mg IV q8-12h) or lansoprazole 30 mg/d PO
• Stool softeners may also be used.
Diet
If swallow evaluation allows, give PO diet.
Activity
Strict bed rest, reduced noise level, and limited visitors until source of bleeding is secured.
SPECIAL THERAPY
Perform neuropsychological testing before discharge, and schedule cognitive rehabilitation
Physical Therapy
Aggressive physical, occupational and, speech evaluation.
MEDICATION (DRUGS)
• Nimodipine 60 mg PO (via nasogastric tube if necessary) q4h for 21 days for prevention of cerebral vasospasm; start immediately.
• Antifibrinolytic agents may be used before aneurysm treatment (aminocaproic acid 5 g IV in the 1st 24-48 hours with a 1.5 g/h infusion thereafter).
• Phenytoin 3-5 mg/kg/d PO or IV, valproic acid 15-45 mg/kg/d PO or IV, or phenobarbital 4 mg/kg IV may be used as seizure prophylaxis.
• Treat seizures with lorazepam 0.1 mg/kg IV at a 2 mg/min rate followed by phenytoin 20 mg/kg IV bolus at 50 mg/min up to 30 mg/kg.
• SIADH vs. cerebral salt wasting must be distinguished with serum and urine electrolytes.
• Symptomatic vasospasm is currently treated with hypervolemia (CVP 8-12 mm Hg, PCWP 12-16 mm Hg) and/or induced hypertension
SURGERY
• Endovascular coiling and surgical clipping are options for securing aneurysms. Aneurysmal securing should be performed within 1st 72 hours.
• Rebleeding should be dealt with immediately by treatment of aneurysm.
• 25-30% of aneurysms will be multiple.
• Hydrocephalus should be treated with external ventricular drain (EVD), lumbar drain, or permanent CSF drainage.
• Arteriovenous malformations may be obliterated with embolization and surgery.
PROGNOSIS
• Average case fatality rate is 51% overall: 10% before receiving care, 25% within the 1st 24 hours
• 25-30% of patients die from spontaneous SAH due to aneurysm. Highest morbidity secondary to cerebral vasospasm.
• If aneurysm can be successfully obliterated and vasospasm treated effectively, satisfactory outcome occurs in 50-65% of patients.
• 45-50% of survivors report long-term cognitive impairment of varying degrees.
• 50-75% of survivors return to work after 1 year.
COMPLICATIONS
• Temporary and permanent neurologic deficits and/or disorders (e.g., seizures, headache, SIADH)
• Death
PATIENT MONITORING
As needed
REFERENCES
1. Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl J Med. 2006;354:387-396.
2. Whitfield PC, Kirkpatrick PJ. Timing of surgery for aneurysmal subarachnoid haemorrhage. Cochrane Database Sys Rev. 2006;1.
3. Lapointe M, Haines S. Fibrinolytic therapy for intraventricular hemorrhage in adults. Cochrane Database Sys Rev. 2006;1.
4. van der Schaaf I, Algra A, Wermer M, et al. Endovascular coiling versus neurosurgical clipping for patients with aneurysmal subarachnoid haemorrhage. Cochrane Database Sys Rev. 2006;1.
5. Rinkel GJE, Feigin VL, Algra A, et al. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Sys Rev. 2006;1.
6. Roos YBWEM, Rinkel GJE, Vermeulen M, et al. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Sys Rev. 2006;1.
7. Intensive insulin therapy reduced the incidence of neurologic complications in critically ill patients. ACP Journal Club. 2006;144(1):20.
8. Review: Computed tomographic angiography and magnetic resonance angiography accurately detect intracranial aneurysms. ACP Journal Club. 2001;134(3):113.
9. Mustonen T, Koivisto T, Vanninen E, et al. Cerebral perfusion heterogeneity and complexity in patients with acute subarachnoid haemorrhage. Nucl Med Commun. 2006;27(2):157-164.
10. Wijdicks EF. Induced hypothermia in neurocatastrophes: Feeling the chill. Rev Neurol Dis. 2004;1(1):10-15. Review.
ADDITIONAL READING
Rinkel GJE, Feigin VL, Algra A, van Gijn J. Circulatory volume expansion therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Sys Rev. 2006;1.
STROKE REHABILITATION
STROKE REHABILITATION - Jeremy Collins, MD; Frank J. Domino, MD
BASICS
DESCRIPTION
• Restoration of function after medical and neurologic stability have been achieved following cerebral compromise.
• Cerebrovascular diseases or disorders that affect CNS compromise delivery of blood or cause hemorrhage, resulting in ischemia, necrosis, and gliosis.
• Anterior lesions in the cerebrovascular system affect the arteries that supply the cerebral hemispheres and cause thrombotic strokes.
• Posterior lesions affect arteries that supply the brainstem and yield the crossed motor and/or sensory signs and symptoms of hemorrhagic strokes.
• Both anterior and posterior lesions can cause sudden death, but the lower in the CNS the lesion, or the more incomplete the lesion, or the more hemorrhagic the lesion, the higher the chance for neurologic return and also for 2nd and subsequent strokes.
• System(s) Affected: Cardiovascular; Nervous
ALERT
Geriatric Considerations
Heart disease, vascular disease, hypertension can lead to stroke.
Pediatric Considerations
Aneurysms, hypertension, tumors, trauma can lead to stroke.
Pregnancy Considerations
Hypertension in pregnancy can lead to stroke.
EPIDEMIOLOGY
• Predominant age: >45
• Predominant sex: Male > Female
Incidence
Annually: 150/100,000
Prevalence
Annually: 550/100,000
RISK FACTORS
• Many are lifestyle-oriented and preventable. Factors include: Coffee ingestion, cigarette smoking, obesity, inactivity, hyperactivity to the point of exhaustion, emotional lability, sexual hyperactivity, starvation, antidepressant or diet reduction medication, alcohol or recreational drug habituation, unusual stress states
• Ethnicity may be a risk factor, but relationships to factors above 1st must be clarified.
• Overly aggressive treatment of diabetes with insulin, hypoglycemia
• Vasculitis; immune, infections, associated with malignancy
Genetics
Similar to the probability of developing hypertension or coronary artery disease
ETIOLOGY
• Coronary artery disease
• Hypertension
• Cerebral arteriosclerosis
• Cardiac thrombus embolus
• Foreign body embolus
• Combination of gout, diabetes, hypertension untreated for 5-10 years before onset of stroke disorder
• Aneurysms and arteriovenous malformations
ASSOCIATED CONDITIONS
• Hypertension
• Coronary artery disease
• Diabetes mellitus
• Gout
• Atherosclerosis
• Smoking
• Alcoholism
DIAGNOSIS
SIGNS AND SYMPTOMS
• Variable: Depends on the arterial system affected
• Hemiparesis
• Hemianesthesia
• Unilateral central facial palsy
• Homonymous hemianopsia
• Aphasia, apraxia (if the dominant cerebral hemisphere is involved)
TESTS
• Somatosensory, auditory, and visual evoked potential technology can monitor neurologic recovery.
• EEG sometimes useful in evaluating seizure disorders
• Cardiovascular stress testing to evaluate the extent of coronary artery disease
• Serum glucose level
Lab
• CBC
• Blood alcohol level
• Spinal fluid for routine studies (only if indicated)
• Urinalysis
• Rapid plasma reagent test
• Antinuclear antibody for collagen vascular disorders
• Consider quantitative immunoelectrophoresis with the combination of stroke disorders, anemia, hypertension
• Carotid flow studies
Imaging
• CT, MRI, and PET scanning give good data about anatomy, blood flow, and metabolic activity.
• Serial exams can delineate the course of this disease and reveal hydrocephalus or brain tumors.
• Total body bone scans can help diagnose reflex sympathetic dystrophy (hand-shoulder syndrome).
Diagnostic Procedures/Surgery
• Spinal taps, myelography, pneumoencephalography, angiography all have special indications and contraindications at this time. None is routinely used.
• Electrodiagnosis for neuritis, radiculitis in specialized centers if available
• Endovascular procedures have great diagnostic implications.
Pathological Findings
Thrombotic, hemorrhagic, mixed combinations can be present.
DIFFERENTIAL DIAGNOSIS
• Infection, tumor, bleeding disorders, endocrinologic, metabolic, gastrointestinal, toxic
• Different types of stroke disorders can occur in 1 patient.
• Liver failure with or without transplantation can be associated with cognitive deficits that persist even after transplantation.
• Brain tumors often present as stroke syndromes with significant personality and/or aphasic disorders and relatively less obvious weakness or spasticity on examination.
TREATMENT
STABILIZATION
• Referral to a full-service rehabilitation centera rehabilitation medicine team can make the difference between independence and dependency.
• Refer when medically and neurologically stable.
GENERAL MEASURES
• Full-service rehabilitation center characteristics
- Comparison with national standards for admission, process, discharge, and follow-up care
- Closed units
- Regular team meetings to discuss long- and short-term objectives
- Quality-assurance system in place
- Accreditation by Commission on Accreditation of Rehabilitation Facilities
• Use deep heat (e.g., ultrasound, prolonged hydrotherapy) with caution in patients with reduced sensation and/or taking anticoagulants.
• Use hydrotherapy and/or isometric exercise cautiously in patients with limited cardiopulmonary reserve.
• In patients able to respond to the protocols after surgery, restorative, tendon transplant, or nerve transplants may be of value.
• Cardiac precautions and a CPR team may be required during exercise programs, because patients who are obese, hypertensive, or have coronary artery disease are at increased risk. Real-time monitoring might be required.
• Open units, especially in investor-owned, private rehabilitation centers, must be closely monitored for outcome and cost/benefit ratio type productivity quality.
• Inpatient rehab in acute rehab units is probably not necessary for stable, uncomplicated strokes (can be done as outpatient).
• Check and adjust serum glucose level if necessary.
Diet
Depends on other medical conditions, but control of hypertension and diabetes is important.
Activity
• Physical therapy, occupational therapy, speech pathology, psychology, and nursing therapy should be delivered to the patient for 3 hours/d throughout the inpatient stay.
• Patient must be able to tolerate this vigorous activity level.
- If patient becomes medically or neurologically unstable during the inpatient stay, 48-hour leeway is usually built into the system. After that period, therapy must resume or the patient must be returned to an acute hospital bed.
- Most stroke acute rehabilitation units can deliver this type of functional return within 1 month of inpatient stay, although length of stay is individually determined.
• Although most rehabilitative efforts take place within a very short time after ictus, successful rehabilitative efforts have taken place as long as 5 years later. This delayed response is frequent but partial.
MEDICATION (DRUGS)
First Line
• Use only what is absolutely necessary. Sleeping medications, such as flurazepam, can accumulate over time in stroke patients.
• As needed for underlying disorders (e.g., hypertension, heart disease) or for complications (e.g., seizures, deep vein thrombosis, pneumonitis)
• When neurologic and medical stability have been achieved, depression can be treated with a serotonin inhibitor antidepressant, for example, sertraline HCl 50 mg every morning.
• For thrombotic strokes or for patients with a high risk of this type of stroke, anticoagulant medications are important.
• Contraindications: Refer to the manufacturer's profile of each drug.
• Precautions
- 4 or more medications will often have interactions; polypharmacy is frequent.
- Antihypertensive medication can generate orthostatic hypotension.
- Antidepressant medication can lower seizure threshold and interact with antihypertensive medications.
- Muscle relaxants, tranquilizers, and major neuroleptic medication can confuse, delay return of memory and cognition, sedate, occasionally agitate, and obliterate spontaneous thought.
- Unnecessary medications, such as antihistamines, should be withdrawn owing to risk of hypertension.
- Elderly patients regularly require lower dosages of the above medications.
- Most common cause of resistance to hypertensive medication is patient's failure to take medicine.
• Significant possible interactions
- NSAIDs can adversely interact with psychotropic medication and can generate hypertension/GI bleeding.
- Some NSAIDs contain sulfa drugs that will cause allergic reactions.
- COX-2 NSAIDs should not be used.
- Overly aggressive treatment of hypertension can yield hypotension and extend the stroke.
Second Line
• Reflex sympathetic dystrophy (shoulder-hand syndrome) can be treated with tizanidine (Zanaflex) 4-8 mg at bedtime and botulinum (Myobloc) injections.
• Flexor spasms in spasticity: To help control, tizanidine 4-8 mg at bedtime, diazepam 5 mg b.i.d. and/or baclofen 10 mg t.i.d.
• For spasticity in those not tolerating systemic medication: Either intrathecal baclofen by pump or botulinum toxin IM administration
SURGERY
• Microcatheter and microsurgical technology have been used to clip, embolize, or reset aneurysms and other lesions.
• Applied cardioangiographic technology has generated new endovascular treatment procedures.
FOLLOW-UP
PROGNOSIS
• Generally good, although pneumonia, respiratory failure, heart failure, and myocardial infarction occur more frequently after stroke
• Outcome studies: Acute rehab center programs generate 33% more functional improvement than comparable skilled nursing facilities, but tend to cost more.
• Premature discharges can often be associated with suboptimal functional recovery.
COMPLICATIONS
• Reflex sympathetic dystrophy syndromessuch as hand-shoulder syndromeare nonspecific complications and last for 12 weeks before subsiding to adhesive capsulitis.
• Tendonitis-bursitis-capsulitis may coexist with prolonged paralysis
- Prolonged range-of-motion and neuromuscular re-education exercises help retard functional deterioration of the limb.
- Electrical stimulation and biofeedback for control and relaxation have also been used, but the treatment of choice is restoration of function.
• Diabetes and alcohol intake will add peripheral neuritis. Diabetes could also be associated (especially in males) with gout and hypertension.
• Many patients develop osteoporosisespecially on side of paresis. The normal side can develop osteoarthritis.
• Repeat strokes from lack of hypertension and/or artery disease control
PATIENT MONITORING
• Within the month following discharge, patient and family should be seen in outpatient group "alumni" day coordinated with an interdisciplinary outpatient clinic appointment.
• If outpatient therapy is rendered, team therapist(s) should meet with the physician regularly to rate progress and discuss long- and short-term objectives.
• For 1st uncomplicated stroke patients: When the acute rehab is completed, the rest of the rehab can be accomplished as an outpatient or in a day care program.
REFERENCES
1. Clinchot DM, Bogner JA, Kaplan PE. Cerebral aneurysms. Arch Phys Med Rehabil. 1997;78:346-349.
2. Clinchot DM, et al. Cerebral aneurysms and arteriovenous malformations. Arch Phys Med Rehabil. 1994;75:1342-1351.
3. Kaplan PE, Cailliet R, Kaplan C. Stroke Rehabilitation. Boston: Butterworth, 2002.
4. Kaplan PE, Clinchot DM, Firnett JA. Cognitive deficits after hepatic transplantation. Brain Inj. 1996;10:599-607.
MISCELLANEOUS
See also: Brain injury-post acute care issues; Stroke (brain attack)
BASICS
DESCRIPTION
• Restoration of function after medical and neurologic stability have been achieved following cerebral compromise.
• Cerebrovascular diseases or disorders that affect CNS compromise delivery of blood or cause hemorrhage, resulting in ischemia, necrosis, and gliosis.
• Anterior lesions in the cerebrovascular system affect the arteries that supply the cerebral hemispheres and cause thrombotic strokes.
• Posterior lesions affect arteries that supply the brainstem and yield the crossed motor and/or sensory signs and symptoms of hemorrhagic strokes.
• Both anterior and posterior lesions can cause sudden death, but the lower in the CNS the lesion, or the more incomplete the lesion, or the more hemorrhagic the lesion, the higher the chance for neurologic return and also for 2nd and subsequent strokes.
• System(s) Affected: Cardiovascular; Nervous
ALERT
Geriatric Considerations
Heart disease, vascular disease, hypertension can lead to stroke.
Pediatric Considerations
Aneurysms, hypertension, tumors, trauma can lead to stroke.
Pregnancy Considerations
Hypertension in pregnancy can lead to stroke.
EPIDEMIOLOGY
• Predominant age: >45
• Predominant sex: Male > Female
Incidence
Annually: 150/100,000
Prevalence
Annually: 550/100,000
RISK FACTORS
• Many are lifestyle-oriented and preventable. Factors include: Coffee ingestion, cigarette smoking, obesity, inactivity, hyperactivity to the point of exhaustion, emotional lability, sexual hyperactivity, starvation, antidepressant or diet reduction medication, alcohol or recreational drug habituation, unusual stress states
• Ethnicity may be a risk factor, but relationships to factors above 1st must be clarified.
• Overly aggressive treatment of diabetes with insulin, hypoglycemia
• Vasculitis; immune, infections, associated with malignancy
Genetics
Similar to the probability of developing hypertension or coronary artery disease
ETIOLOGY
• Coronary artery disease
• Hypertension
• Cerebral arteriosclerosis
• Cardiac thrombus embolus
• Foreign body embolus
• Combination of gout, diabetes, hypertension untreated for 5-10 years before onset of stroke disorder
• Aneurysms and arteriovenous malformations
ASSOCIATED CONDITIONS
• Hypertension
• Coronary artery disease
• Diabetes mellitus
• Gout
• Atherosclerosis
• Smoking
• Alcoholism
DIAGNOSIS
SIGNS AND SYMPTOMS
• Variable: Depends on the arterial system affected
• Hemiparesis
• Hemianesthesia
• Unilateral central facial palsy
• Homonymous hemianopsia
• Aphasia, apraxia (if the dominant cerebral hemisphere is involved)
TESTS
• Somatosensory, auditory, and visual evoked potential technology can monitor neurologic recovery.
• EEG sometimes useful in evaluating seizure disorders
• Cardiovascular stress testing to evaluate the extent of coronary artery disease
• Serum glucose level
Lab
• CBC
• Blood alcohol level
• Spinal fluid for routine studies (only if indicated)
• Urinalysis
• Rapid plasma reagent test
• Antinuclear antibody for collagen vascular disorders
• Consider quantitative immunoelectrophoresis with the combination of stroke disorders, anemia, hypertension
• Carotid flow studies
Imaging
• CT, MRI, and PET scanning give good data about anatomy, blood flow, and metabolic activity.
• Serial exams can delineate the course of this disease and reveal hydrocephalus or brain tumors.
• Total body bone scans can help diagnose reflex sympathetic dystrophy (hand-shoulder syndrome).
Diagnostic Procedures/Surgery
• Spinal taps, myelography, pneumoencephalography, angiography all have special indications and contraindications at this time. None is routinely used.
• Electrodiagnosis for neuritis, radiculitis in specialized centers if available
• Endovascular procedures have great diagnostic implications.
Pathological Findings
Thrombotic, hemorrhagic, mixed combinations can be present.
DIFFERENTIAL DIAGNOSIS
• Infection, tumor, bleeding disorders, endocrinologic, metabolic, gastrointestinal, toxic
• Different types of stroke disorders can occur in 1 patient.
• Liver failure with or without transplantation can be associated with cognitive deficits that persist even after transplantation.
• Brain tumors often present as stroke syndromes with significant personality and/or aphasic disorders and relatively less obvious weakness or spasticity on examination.
TREATMENT
STABILIZATION
• Referral to a full-service rehabilitation centera rehabilitation medicine team can make the difference between independence and dependency.
• Refer when medically and neurologically stable.
GENERAL MEASURES
• Full-service rehabilitation center characteristics
- Comparison with national standards for admission, process, discharge, and follow-up care
- Closed units
- Regular team meetings to discuss long- and short-term objectives
- Quality-assurance system in place
- Accreditation by Commission on Accreditation of Rehabilitation Facilities
• Use deep heat (e.g., ultrasound, prolonged hydrotherapy) with caution in patients with reduced sensation and/or taking anticoagulants.
• Use hydrotherapy and/or isometric exercise cautiously in patients with limited cardiopulmonary reserve.
• In patients able to respond to the protocols after surgery, restorative, tendon transplant, or nerve transplants may be of value.
• Cardiac precautions and a CPR team may be required during exercise programs, because patients who are obese, hypertensive, or have coronary artery disease are at increased risk. Real-time monitoring might be required.
• Open units, especially in investor-owned, private rehabilitation centers, must be closely monitored for outcome and cost/benefit ratio type productivity quality.
• Inpatient rehab in acute rehab units is probably not necessary for stable, uncomplicated strokes (can be done as outpatient).
• Check and adjust serum glucose level if necessary.
Diet
Depends on other medical conditions, but control of hypertension and diabetes is important.
Activity
• Physical therapy, occupational therapy, speech pathology, psychology, and nursing therapy should be delivered to the patient for 3 hours/d throughout the inpatient stay.
• Patient must be able to tolerate this vigorous activity level.
- If patient becomes medically or neurologically unstable during the inpatient stay, 48-hour leeway is usually built into the system. After that period, therapy must resume or the patient must be returned to an acute hospital bed.
- Most stroke acute rehabilitation units can deliver this type of functional return within 1 month of inpatient stay, although length of stay is individually determined.
• Although most rehabilitative efforts take place within a very short time after ictus, successful rehabilitative efforts have taken place as long as 5 years later. This delayed response is frequent but partial.
MEDICATION (DRUGS)
First Line
• Use only what is absolutely necessary. Sleeping medications, such as flurazepam, can accumulate over time in stroke patients.
• As needed for underlying disorders (e.g., hypertension, heart disease) or for complications (e.g., seizures, deep vein thrombosis, pneumonitis)
• When neurologic and medical stability have been achieved, depression can be treated with a serotonin inhibitor antidepressant, for example, sertraline HCl 50 mg every morning.
• For thrombotic strokes or for patients with a high risk of this type of stroke, anticoagulant medications are important.
• Contraindications: Refer to the manufacturer's profile of each drug.
• Precautions
- 4 or more medications will often have interactions; polypharmacy is frequent.
- Antihypertensive medication can generate orthostatic hypotension.
- Antidepressant medication can lower seizure threshold and interact with antihypertensive medications.
- Muscle relaxants, tranquilizers, and major neuroleptic medication can confuse, delay return of memory and cognition, sedate, occasionally agitate, and obliterate spontaneous thought.
- Unnecessary medications, such as antihistamines, should be withdrawn owing to risk of hypertension.
- Elderly patients regularly require lower dosages of the above medications.
- Most common cause of resistance to hypertensive medication is patient's failure to take medicine.
• Significant possible interactions
- NSAIDs can adversely interact with psychotropic medication and can generate hypertension/GI bleeding.
- Some NSAIDs contain sulfa drugs that will cause allergic reactions.
- COX-2 NSAIDs should not be used.
- Overly aggressive treatment of hypertension can yield hypotension and extend the stroke.
Second Line
• Reflex sympathetic dystrophy (shoulder-hand syndrome) can be treated with tizanidine (Zanaflex) 4-8 mg at bedtime and botulinum (Myobloc) injections.
• Flexor spasms in spasticity: To help control, tizanidine 4-8 mg at bedtime, diazepam 5 mg b.i.d. and/or baclofen 10 mg t.i.d.
• For spasticity in those not tolerating systemic medication: Either intrathecal baclofen by pump or botulinum toxin IM administration
SURGERY
• Microcatheter and microsurgical technology have been used to clip, embolize, or reset aneurysms and other lesions.
• Applied cardioangiographic technology has generated new endovascular treatment procedures.
FOLLOW-UP
PROGNOSIS
• Generally good, although pneumonia, respiratory failure, heart failure, and myocardial infarction occur more frequently after stroke
• Outcome studies: Acute rehab center programs generate 33% more functional improvement than comparable skilled nursing facilities, but tend to cost more.
• Premature discharges can often be associated with suboptimal functional recovery.
COMPLICATIONS
• Reflex sympathetic dystrophy syndromessuch as hand-shoulder syndromeare nonspecific complications and last for 12 weeks before subsiding to adhesive capsulitis.
• Tendonitis-bursitis-capsulitis may coexist with prolonged paralysis
- Prolonged range-of-motion and neuromuscular re-education exercises help retard functional deterioration of the limb.
- Electrical stimulation and biofeedback for control and relaxation have also been used, but the treatment of choice is restoration of function.
• Diabetes and alcohol intake will add peripheral neuritis. Diabetes could also be associated (especially in males) with gout and hypertension.
• Many patients develop osteoporosisespecially on side of paresis. The normal side can develop osteoarthritis.
• Repeat strokes from lack of hypertension and/or artery disease control
PATIENT MONITORING
• Within the month following discharge, patient and family should be seen in outpatient group "alumni" day coordinated with an interdisciplinary outpatient clinic appointment.
• If outpatient therapy is rendered, team therapist(s) should meet with the physician regularly to rate progress and discuss long- and short-term objectives.
• For 1st uncomplicated stroke patients: When the acute rehab is completed, the rest of the rehab can be accomplished as an outpatient or in a day care program.
REFERENCES
1. Clinchot DM, Bogner JA, Kaplan PE. Cerebral aneurysms. Arch Phys Med Rehabil. 1997;78:346-349.
2. Clinchot DM, et al. Cerebral aneurysms and arteriovenous malformations. Arch Phys Med Rehabil. 1994;75:1342-1351.
3. Kaplan PE, Cailliet R, Kaplan C. Stroke Rehabilitation. Boston: Butterworth, 2002.
4. Kaplan PE, Clinchot DM, Firnett JA. Cognitive deficits after hepatic transplantation. Brain Inj. 1996;10:599-607.
MISCELLANEOUS
See also: Brain injury-post acute care issues; Stroke (brain attack)
STROKE (BRAIN ATTACK)
STROKE (BRAIN ATTACK) - William A. Tosches, MD; Michael Previti, MD
BASICS
DESCRIPTION
• The sudden onset of a focal neurologic deficit resulting from either infarction or hemorrhage within the brain.
• Adults 45 years old are most likely to have a cardiac source of embolism.
• 2 broad categories: Hemorrhagic and ischemic
• System(s) Affected: Cardiovascular; Nervous
• Synonym(s): Cerebrovascular accident; Reversible ischemic neurologic accident
ALERT
Geriatric Considerations
Amyloid (congophilic) angiopathy is most prevalent in the elderly, especially if the patient also has dementia.
Pediatric Considerations
• Cardiac (especially developmental abnormalities)
• Metabolic: Homocystinuria, Fabry disease
Pregnancy Considerations
• Parturition may increase the risk of rupture for aneurysm; amniotic fluid embolism may cause stroke at the time of delivery.
• The postpartum period is associated with an increased risk for cerebral venous thrombosis.
GENERAL PREVENTION
• Stop smoking.
• Control BP, diabetes, hyperlipidemia.
• Use alcohol in moderation, if at all.
• Exercise regularly.
• Maintain positive psychologic outlook.
• Seek professional dietary advice on weight control.
• Antiplatelet drugs
• Angiotensin-converting enzyme (ACE) inhibitors
• Statins
• Treat homocystinemia with vitamin B6, vitamin B12, and folic acid.
• Nonvalvular atrial fibrillation should be treated with dose-adjusted heparin to achieve an INR of 2-3 to prevent stroke. (1)[A]
• Women >45 years on ASA 100 mg/d have decreased risk of ischemic stroke and TIA but increased risk of GI bleed needing transfusion. (2)[B]
EPIDEMIOLOGY
Incidence
Incidence in the US: 150/100,000
Prevalence
• Prevalence in the US: 550/100,000
• Predominant age: Risk increases >45, and is highest in the 7th and 8th decades.
• Predominant sex: Male > Female (3:1), but equalizes after menopause
RISK FACTORS
• Uncontrollable
- Age
- Sex
- Race
- Family history
• Controllable
- Hypertension
- Diabetes mellitus
- Hypercholesterolemia
- Cardiac disease
- History of stroke or TIA
- Atrial fibrillation
- Valvular heart disease
- Severe carotid stenosis
- Intracranial arterial stenosis
- Hypercoagulable states (antiphospholipid antibodies)
- Homocystinemia
- Obesity
- Smoking
Genetics
Inheritance is polygenic, with a tendency to clustering of risk factors within families.
ETIOLOGY
• Ischemic: Carotid atherosclerotic disease with artery-to-artery thromboembolism
• Cardiac
- Cardioembolism secondary to valvular (mitral valve) pathology
- Mural hypokinesias or akinesias with thrombosis (acute anterior myocardial infarctions (MIs) or congestive cardiomyopathies)
- Cardiac arrhythmia (atrial fibrillation)
• Hypercoagulable states
- Antiphospholipid antibodies, factor V Leiden deficiency, deficiency of protein S, protein C, antithrombin III deficiency
- Estrogen use (HRT, OCP, etc.)
• Other causes
- Spontaneous and posttraumatic (i.e., chiropractic manipulation) artery dissection
- Fibromuscular dysplasia
- Vasculitis
- Drugs (cocaine, amphetamines)
• Hemorrhagic
• Hypertension: May cause damage to putamen, internal capsule, cerebellum, brainstem, corona radiata
• Amyloid (congophilic) angiopathy: Lobar (cortical) hemorrhages in the elderly
• Vascular malformations: Arteriovenous malformation, cavernous angioma, venous angioma and capillary angioma
ASSOCIATED CONDITIONS
Cardiac disease is the major cause of death in the 1st 5 years after a stroke.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Carotid circulation (hemispheric): Hemiplegia, hemianesthesia, neglect, aphasia, visual field defects; less often headaches, seizures, amnesia, confusion
• Vertebrobasilar (brainstem or cerebellar): Diplopia, vertigo, ataxia, facial paresis, Horner syndrome, dysphagia, dysarthria
• Impaired level of consciousness
• Cerebellar lesion in patients with headache, nausea, vomiting, and ataxia
Physical Exam
• Early mortality increases among those with any combination of impaired consciousness, hemiplegia, and conjugate gaze palsy
• Symptoms associated with the diagnosis of stroke or transient ischemic attack (TIA) are a sudden change in speech, visual loss, diplopia, numbness or tingling, paralysis or weakness, and nonorthostatic dizziness
TESTS
• Duplex carotid ultrasonography
• Cerebral angiography
• ECG
• Transthoracic ECG; if normal and a cardiac source is suspected, follow-up with transesophageal ECG.
• Holter monitoring
• EEG for suspected seizure
• Prothrombin time (PT) and partial thromboplastin time (PTT)
- Coumadin prolongs PT.
• Antiphospholipid antibodies
• Cardiac enzymes
Imaging
Acute phase
• Multimodal CT of head
• MRI scan of brain with diffusion weighted imaging (DWI) remains the most powerful and accurate method for stroke identification.
• Arterial occlusions are seen with CTA as well as with MRA.
• Both CTA and MRA are highly reliable, noninvasive methods to verify the results of thrombolytic therapy.
• Quantitative CT perfusion and DWI/PWI (perfusion-weighted imaging) can rapidly provide functional information about brain perfusion and thus guide antithrombotic and neuroprotective strategies.
• Quantitative CTP is limited to a single slab of tissue per bolus, whereas MRI can provide whole-brain cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT).
• The goal of perfusion imaging is to reliably identify and distinguish brain tissue that is ischemic and will develop infarction without a specific intervention from brain tissue that is already damaged and cannot escape infarction.
DIFFERENTIAL DIAGNOSIS
• Migraine
• Focal seizure
• Tumor
• Subdural hematoma
• Hypoglycemia; hyperglycemia; hypercalcemia
TREATMENT
• Acute phase: Inpatient care
• Surgical therapy
- In medically fit patients with nondisabling stroke, carotid endarterectomy is indicated for stenosis of >70% on side ipsilateral to stroke.
- Medical therapy for 50% stenosis, 50-69% depends on risk factors
GENERAL MEASURES
• Maintain oxygenation.
• Monitor cardiac rhythm for 48 hours.
• Control hyperglycemia (keep glucose 220 mg/dL [12.1 mmol/L]).
• Treat blood pressure >185/110 if patient will be or has been treated with IV tissue plasminogen activator.
• Do not treat elevated BP unless acute end-organ dysfunction (encephalopathy, myocardial ischemia, aortic dissection, acute renal failure) is suspected.
• Prevent hyperthermia.
• Introduce physiotherapy and ambulation early.
• Subcutaneous heparin 5,000 units SC q12h
Diet
• Alert with no dysphagia: Diet as tolerated (no added salt if hypertensive)
• Alert with dysphagia: Pureed dysphagia diet or nasogastric feeding tube if indicated
Activity
Ambulate as soon as possible.
MEDICATION (DRUGS)
First Line
• IV tissue plasminogen activator (tPA) 0.9 mg/kg in highly selected cases within 3 hours of ischemic stroke symptom onset
• Enteric-coated aspirin 50-325 mg/d or
• Dipyridamole-aspirin (Aggrenox): Extended release, 200 mg/25 mg capsule PO b.i.d.; more efficacious than aspirin or dipyridamole alone. (3)[A]
• Clopidogrel (Plavix): 75 mg/d; fewer side effects, but shows only slight advantage over aspirin
• Warfarin: INR adjusted dose 2-4 for patients with atrial fibrillation and cardioembolic stroke has shown decreased risk of recurrent stroke compared to ASA 300 mg/d at 2.3 years. (1)[A]
• Contraindications
- Enteric-coated aspirin: Active peptic ulcer disease, hypersensitivity to aspirin, patients who had bronchospastic reaction to aspirin or other NSAIDs
- Warfarin: Intolerance or allergy, dementia, liver disease, active bleeding, pregnancy, recent head injury
• Precautions
- Enteric-coated aspirin: May aggravate pre-existing peptic ulcer disease, may worsen symptoms in some patients with asthma
- Clopidogrel and ticlopidine: Thrombotic thrombocytopenic purpura can occur.
- Warfarin: Poor balance, alcohol/drug abuse, age >80
• Significant possible interactions
- Enteric-coated aspirin: May potentiate effects of anticoagulants and sulfonylurea, hypoglycemic agents
- Ticlopidine: Digoxin plasma levels decreased 15%, theophylline half-life increased from 8.6-12.2 hours
- Warfarin: Aspirin, NSAIDs, antibiotics, tranquilizers
Second Line
Ticlopidine (Ticlid): The treatment of 250 mg PO b.i.d. has fallen out of favor, because of an unfavorable side-effect profile, risk of neutropenia, and need for CBC monitoring.
• Caution: 2.4% of patients develop neutropenia (0.8% severe neutropenia) that is reversible with cessation of drug; monitor blood counts every 2 weeks for the 1st 3 months
FOLLOW-UP
PROGNOSIS
• Variable depending on severity of stroke
• Posterior circulation strokes have a higher acute mortality rate, but generally make a better functional recovery than do hemispheric strokes.
COMPLICATIONS
• Shoulder subluxation
• Hyperextension knee injury
• Depression
• Sympathetic dystrophy
PATIENT MONITORING
Follow the patient every 3 months for the 1st year, then yearly.
REFERENCES
1. Saxena R, Koudstaal PJ. Cochrane Stroke Group. Anticoagulants versus antiplatelet therapy for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischemic attack. Cochrane Database of Systematic Rev. 1, 2006.
2. ACP Journal Club. Low-dose aspirin lowered stroke risk but not risks for MI or cardiovascular deaths in women. ACP Journal Club. 2005;143(2):33.
3. ACP Journal Club Dipyridamole given with or without aspirin reduces recurrent stroke. ACP Journal Club. 2005;143(1):10.
4. Aguilar MI, Hart R. Cochrane Stroke Group. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database of Systematic Rev. 1, 2006.
MISCELLANEOUS
See also: Stroke rehabilitation, Transient ischemic attack (TIA)
BASICS
DESCRIPTION
• The sudden onset of a focal neurologic deficit resulting from either infarction or hemorrhage within the brain.
• Adults 45 years old are most likely to have a cardiac source of embolism.
• 2 broad categories: Hemorrhagic and ischemic
• System(s) Affected: Cardiovascular; Nervous
• Synonym(s): Cerebrovascular accident; Reversible ischemic neurologic accident
ALERT
Geriatric Considerations
Amyloid (congophilic) angiopathy is most prevalent in the elderly, especially if the patient also has dementia.
Pediatric Considerations
• Cardiac (especially developmental abnormalities)
• Metabolic: Homocystinuria, Fabry disease
Pregnancy Considerations
• Parturition may increase the risk of rupture for aneurysm; amniotic fluid embolism may cause stroke at the time of delivery.
• The postpartum period is associated with an increased risk for cerebral venous thrombosis.
GENERAL PREVENTION
• Stop smoking.
• Control BP, diabetes, hyperlipidemia.
• Use alcohol in moderation, if at all.
• Exercise regularly.
• Maintain positive psychologic outlook.
• Seek professional dietary advice on weight control.
• Antiplatelet drugs
• Angiotensin-converting enzyme (ACE) inhibitors
• Statins
• Treat homocystinemia with vitamin B6, vitamin B12, and folic acid.
• Nonvalvular atrial fibrillation should be treated with dose-adjusted heparin to achieve an INR of 2-3 to prevent stroke. (1)[A]
• Women >45 years on ASA 100 mg/d have decreased risk of ischemic stroke and TIA but increased risk of GI bleed needing transfusion. (2)[B]
EPIDEMIOLOGY
Incidence
Incidence in the US: 150/100,000
Prevalence
• Prevalence in the US: 550/100,000
• Predominant age: Risk increases >45, and is highest in the 7th and 8th decades.
• Predominant sex: Male > Female (3:1), but equalizes after menopause
RISK FACTORS
• Uncontrollable
- Age
- Sex
- Race
- Family history
• Controllable
- Hypertension
- Diabetes mellitus
- Hypercholesterolemia
- Cardiac disease
- History of stroke or TIA
- Atrial fibrillation
- Valvular heart disease
- Severe carotid stenosis
- Intracranial arterial stenosis
- Hypercoagulable states (antiphospholipid antibodies)
- Homocystinemia
- Obesity
- Smoking
Genetics
Inheritance is polygenic, with a tendency to clustering of risk factors within families.
ETIOLOGY
• Ischemic: Carotid atherosclerotic disease with artery-to-artery thromboembolism
• Cardiac
- Cardioembolism secondary to valvular (mitral valve) pathology
- Mural hypokinesias or akinesias with thrombosis (acute anterior myocardial infarctions (MIs) or congestive cardiomyopathies)
- Cardiac arrhythmia (atrial fibrillation)
• Hypercoagulable states
- Antiphospholipid antibodies, factor V Leiden deficiency, deficiency of protein S, protein C, antithrombin III deficiency
- Estrogen use (HRT, OCP, etc.)
• Other causes
- Spontaneous and posttraumatic (i.e., chiropractic manipulation) artery dissection
- Fibromuscular dysplasia
- Vasculitis
- Drugs (cocaine, amphetamines)
• Hemorrhagic
• Hypertension: May cause damage to putamen, internal capsule, cerebellum, brainstem, corona radiata
• Amyloid (congophilic) angiopathy: Lobar (cortical) hemorrhages in the elderly
• Vascular malformations: Arteriovenous malformation, cavernous angioma, venous angioma and capillary angioma
ASSOCIATED CONDITIONS
Cardiac disease is the major cause of death in the 1st 5 years after a stroke.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Carotid circulation (hemispheric): Hemiplegia, hemianesthesia, neglect, aphasia, visual field defects; less often headaches, seizures, amnesia, confusion
• Vertebrobasilar (brainstem or cerebellar): Diplopia, vertigo, ataxia, facial paresis, Horner syndrome, dysphagia, dysarthria
• Impaired level of consciousness
• Cerebellar lesion in patients with headache, nausea, vomiting, and ataxia
Physical Exam
• Early mortality increases among those with any combination of impaired consciousness, hemiplegia, and conjugate gaze palsy
• Symptoms associated with the diagnosis of stroke or transient ischemic attack (TIA) are a sudden change in speech, visual loss, diplopia, numbness or tingling, paralysis or weakness, and nonorthostatic dizziness
TESTS
• Duplex carotid ultrasonography
• Cerebral angiography
• ECG
• Transthoracic ECG; if normal and a cardiac source is suspected, follow-up with transesophageal ECG.
• Holter monitoring
• EEG for suspected seizure
• Prothrombin time (PT) and partial thromboplastin time (PTT)
- Coumadin prolongs PT.
• Antiphospholipid antibodies
• Cardiac enzymes
Imaging
Acute phase
• Multimodal CT of head
• MRI scan of brain with diffusion weighted imaging (DWI) remains the most powerful and accurate method for stroke identification.
• Arterial occlusions are seen with CTA as well as with MRA.
• Both CTA and MRA are highly reliable, noninvasive methods to verify the results of thrombolytic therapy.
• Quantitative CT perfusion and DWI/PWI (perfusion-weighted imaging) can rapidly provide functional information about brain perfusion and thus guide antithrombotic and neuroprotective strategies.
• Quantitative CTP is limited to a single slab of tissue per bolus, whereas MRI can provide whole-brain cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT).
• The goal of perfusion imaging is to reliably identify and distinguish brain tissue that is ischemic and will develop infarction without a specific intervention from brain tissue that is already damaged and cannot escape infarction.
DIFFERENTIAL DIAGNOSIS
• Migraine
• Focal seizure
• Tumor
• Subdural hematoma
• Hypoglycemia; hyperglycemia; hypercalcemia
TREATMENT
• Acute phase: Inpatient care
• Surgical therapy
- In medically fit patients with nondisabling stroke, carotid endarterectomy is indicated for stenosis of >70% on side ipsilateral to stroke.
- Medical therapy for 50% stenosis, 50-69% depends on risk factors
GENERAL MEASURES
• Maintain oxygenation.
• Monitor cardiac rhythm for 48 hours.
• Control hyperglycemia (keep glucose 220 mg/dL [12.1 mmol/L]).
• Treat blood pressure >185/110 if patient will be or has been treated with IV tissue plasminogen activator.
• Do not treat elevated BP unless acute end-organ dysfunction (encephalopathy, myocardial ischemia, aortic dissection, acute renal failure) is suspected.
• Prevent hyperthermia.
• Introduce physiotherapy and ambulation early.
• Subcutaneous heparin 5,000 units SC q12h
Diet
• Alert with no dysphagia: Diet as tolerated (no added salt if hypertensive)
• Alert with dysphagia: Pureed dysphagia diet or nasogastric feeding tube if indicated
Activity
Ambulate as soon as possible.
MEDICATION (DRUGS)
First Line
• IV tissue plasminogen activator (tPA) 0.9 mg/kg in highly selected cases within 3 hours of ischemic stroke symptom onset
• Enteric-coated aspirin 50-325 mg/d or
• Dipyridamole-aspirin (Aggrenox): Extended release, 200 mg/25 mg capsule PO b.i.d.; more efficacious than aspirin or dipyridamole alone. (3)[A]
• Clopidogrel (Plavix): 75 mg/d; fewer side effects, but shows only slight advantage over aspirin
• Warfarin: INR adjusted dose 2-4 for patients with atrial fibrillation and cardioembolic stroke has shown decreased risk of recurrent stroke compared to ASA 300 mg/d at 2.3 years. (1)[A]
• Contraindications
- Enteric-coated aspirin: Active peptic ulcer disease, hypersensitivity to aspirin, patients who had bronchospastic reaction to aspirin or other NSAIDs
- Warfarin: Intolerance or allergy, dementia, liver disease, active bleeding, pregnancy, recent head injury
• Precautions
- Enteric-coated aspirin: May aggravate pre-existing peptic ulcer disease, may worsen symptoms in some patients with asthma
- Clopidogrel and ticlopidine: Thrombotic thrombocytopenic purpura can occur.
- Warfarin: Poor balance, alcohol/drug abuse, age >80
• Significant possible interactions
- Enteric-coated aspirin: May potentiate effects of anticoagulants and sulfonylurea, hypoglycemic agents
- Ticlopidine: Digoxin plasma levels decreased 15%, theophylline half-life increased from 8.6-12.2 hours
- Warfarin: Aspirin, NSAIDs, antibiotics, tranquilizers
Second Line
Ticlopidine (Ticlid): The treatment of 250 mg PO b.i.d. has fallen out of favor, because of an unfavorable side-effect profile, risk of neutropenia, and need for CBC monitoring.
• Caution: 2.4% of patients develop neutropenia (0.8% severe neutropenia) that is reversible with cessation of drug; monitor blood counts every 2 weeks for the 1st 3 months
FOLLOW-UP
PROGNOSIS
• Variable depending on severity of stroke
• Posterior circulation strokes have a higher acute mortality rate, but generally make a better functional recovery than do hemispheric strokes.
COMPLICATIONS
• Shoulder subluxation
• Hyperextension knee injury
• Depression
• Sympathetic dystrophy
PATIENT MONITORING
Follow the patient every 3 months for the 1st year, then yearly.
REFERENCES
1. Saxena R, Koudstaal PJ. Cochrane Stroke Group. Anticoagulants versus antiplatelet therapy for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischemic attack. Cochrane Database of Systematic Rev. 1, 2006.
2. ACP Journal Club. Low-dose aspirin lowered stroke risk but not risks for MI or cardiovascular deaths in women. ACP Journal Club. 2005;143(2):33.
3. ACP Journal Club Dipyridamole given with or without aspirin reduces recurrent stroke. ACP Journal Club. 2005;143(1):10.
4. Aguilar MI, Hart R. Cochrane Stroke Group. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database of Systematic Rev. 1, 2006.
MISCELLANEOUS
See also: Stroke rehabilitation, Transient ischemic attack (TIA)
STOMATITIS
STOMATITIS - Mark R.Dambro, MD
BASICS
DESCRIPTION
• Generalized inflammation of the oral mucosa, of many possible etiologies
• System(s) Affected: Skin/Exocrine
GENERAL PREVENTION
Avoid causative factors.
EPIDEMIOLOGY
• Predominant age
- Primary herpetic infections (children)
- Hand-foot-and-mouth disease (children)
- Vincent stomatitis (also known as Vincent disease or acute necrotizing ulcerative gingivitis) (teenagers and young adults)
- Behet disease (young adults)
- Herpangina (children)
- Other types N/A
• Predominant sex: Male = Female
Prevalence
• Herpetic stomatitis, hand-foot-and-mouth disease, and recurrent aphthous stomatitis are very common.
• Herpangina is fairly common, as are nicotinic and denture-related stomatitis. The remaining causes are uncommon or rare.
ETIOLOGY
• Allergy: Foods, drugs, contact (some erythema multiforme)
• Vitamin deficiency: Riboflavin (angular stomatitis)
• Viral: herpes simplex I and II (herpetic stomatitis), Coxsackie A (herpangina and hand-foot-and-mouth disease)
• Smoking (nicotinic stomatitis)
• Hormonal (possibly recurrent ulcerative stomatitis)
• Uncertain (recurrent aphthous stomatitis, Vincent stomatitis, recurrent scarifying stomatitis, Behcet disease, angular stomatitis, gangrenous stomatitis, erythema multiforme)
• Bacterial (scarlatina)
• Uremic (uremic/nephritic)
• Dentures
ALERT
Pediatric Considerations
Certain etiologies more likely in the pediatric population: Herpetic-primary, hand-foot-and-mouth disease, herpangina
Geriatric Considerations
Certain etiologies more likely in the geriatric population, e.g., dentures
ASSOCIATED CONDITIONS
• AIDS: Associated with severe lesions
• Pregnancy may bring on recurrent ulcerative stomatitis.
DIAGNOSIS
SIGNS AND SYMPTOMS
• General
- Depends on etiology
- Varies from minimal to severe pain
- Many have multiple intraoral ulcers from 1 mm to several centimeters in diameter
- Some with constitutional symptoms: Fever, malaise, headache
• Allergic stomatitis
- Intense shiny erythema
- Slight swelling
- Itching
- Dryness
- Burning
• Vincent infection
- Necrotic ulceration of interdental papillae and mucous membrane
• Thrush (candidiasis)
- White patches, slightly raised (resembling milk curds)
- Distribution: Tongue, buccal mucosa, palate, gums, tonsils, larynx, pharynx, gastrointestinal tract, skin; commonly seen in infants, immunocompromised patients, and patients on long-term antibiotics, corticosteroids, and antineoplastic treatment
• Pseudomembranous stomatitis: Membranelike exudate
• Mucous lesions accompanying systemic disease
- Mucous patches (syphilis)
- Strawberry (measles)
- Koplik spots (measles)
- Ulcers (erythema multiforme)
- Smooth, fire-red, painful (pellagra)
TESTS
Lab
• Hematologic profile
• Tzanck test of historic interest only
• Serologic test for syphilis
Diagnostic Procedures/Surgery
Biopsy if persistent/recurrent/suspicious
Pathological Findings
Biopsy suspicious lesions or lesions that fail to heal or chronically recur, to rule out cancer or vasculitis.
DIFFERENTIAL DIAGNOSIS
• Squamous cell cancer
• Herpetic stomatitis
• Hand-foot-and-mouth disease
• Recurrent aphthous stomatitis
• Vincent stomatitis
• Nicotinic stomatitis
• Denture-related stomatitis
• Erythema multiforme/Stevens-Johnson syndrome
• Recurrent ulcerative stomatitis
• Recurrent scarifying stomatitis
• Behcet disease
• Angular stomatitis
• Noma (gangrenous stomatitis)
• Scarlatina (scarlet fever)
• Herpangina
• Uremic stomatitis
• Pemphigus/pemphigoid
TREATMENT
STABILIZATION
Outpatient care, unless severe
GENERAL MEASURES
• In most cases, treatment of symptoms only
• Severe cases may require parenteral fluids, particularly in children.
• Topical anesthesia
• Analgesics
• Oral rinses such as half-strength hydrogen peroxide
• Mycostatin, if superinfected with Candida
• Smoking cessation
Diet
May need to avoid spicy, sharp, hard, and dry foods
Activity
As tolerated by patient
MEDICATION (DRUGS)
First Line
• Steroids and cytotoxic drugs for Behet disease
• 2% viscous lidocaine (Xylocaine) for local discomfort
• Liquid diphenhydramine (Benadryl) by mouth, or swish and spit
• Antibiotics for gangrenous stomatitis
• Antifungal ointment, e.g., nystatin (Mycostatin) for candidiasis complicating angular stomatitis
• For candidiasis: Nystatin oral suspension 400,000 U (4 mL) q.i.d. for 10 days. Use as oral rinse, then swallow.
• Acyclovir 200-800 mg 5 times a day for 7-14 days for herpetic stomatitis
• Sucralfate (Carafate) suspension 1 tsp, swish in mouth or place on ulcers q.i.d. (helpful)
• Contraindications: Allergy to specific medication
• Precautions
- Toxic dose of topical lidocaine uncertain, but likely only 25-33% of infiltration dose may have significant absorption from open ulcers or mucous membrane
• Significant possible interactions: Refer to manufacturer's literature for each drug.
Second Line
Steroid oral rinses or topical preparations for aphthous ulcers
FOLLOW-UP
PROGNOSIS
• Herpetic: Self-limited, with resolution in 7-14 days
• Hand-foot-and-mouth disease: Same as for herpetic
• Recurrent aphthous ulcers: 7-14-day course per episode
• Vincent: May progress to fascial space infection with airway compromise or sepsis
• Nicotinic: Resolves with cessation of smoking
• Denture: Resolves with careful oral hygiene and daytime-only denture wear
• Erythema multiforme: Resolution in 2-3 weeks
• Stevens-Johnson: Resolution in ~6 weeks with adequate supportive care
• Recurrent ulcerative: As the name implies, recurs over time, but the overall prognosis is good.
• Recurrent scarifying: Occasional patients suffer continuous ulcers, others have recurrence with eventual scarring. The prognosis is otherwise good.
• Behcet disease may recur for several years. Prognosis for vision is poor. Overall prognosis is related to other aspects of the disease.
• Angular: After correction of mechanical problems, allergic disorders, and nutritional deficiencies, the prognosis is good.
• Gangrenous: The most serious stomatitis, requiring aggressive treatment with IV antibiotics and debridement to avoid death
• Scarlatina: The prognosis is related to other manifestations of the disease.
• Herpangina: 7-14-day course, with total resolution
• Uremic: Depends on the underlying renal disease
COMPLICATIONS
• Recurrent scarifying stomatitis may result in intraoral scarring with restriction of oral mobility.
• Behcet disease may result in visual loss, pneumonia, colitis, vasculitis, large artery aneurysms, thrombophlebitis, or encephalitis.
• Gangrenous stomatitis may lead to death.
• Scarlet fever may result in cardiac disease.
• Herpetic stomatitis may be complicated by ocular or CNS involvement.
PATIENT MONITORING
Lesions need to be followed until resolved. If they fail to resolve, continuously recur, or appear suspicious, biopsy may be needed to establish a diagnosis.
REFERENCES
1. Moran WJ. Diseases of the mouth. In: Rakel E, ed. Conn's Current Therapy. Philadelphia, PA: WB Saunders; 1990.
2. Teele DW. Inflammatory diseases of the mouth and pharynx. In: Paparella MM, Shumrick DA, eds. Otolaryngology. Philadelphia, PA: WB Saunders; 1980: 974-1017.
BASICS
DESCRIPTION
• Generalized inflammation of the oral mucosa, of many possible etiologies
• System(s) Affected: Skin/Exocrine
GENERAL PREVENTION
Avoid causative factors.
EPIDEMIOLOGY
• Predominant age
- Primary herpetic infections (children)
- Hand-foot-and-mouth disease (children)
- Vincent stomatitis (also known as Vincent disease or acute necrotizing ulcerative gingivitis) (teenagers and young adults)
- Behet disease (young adults)
- Herpangina (children)
- Other types N/A
• Predominant sex: Male = Female
Prevalence
• Herpetic stomatitis, hand-foot-and-mouth disease, and recurrent aphthous stomatitis are very common.
• Herpangina is fairly common, as are nicotinic and denture-related stomatitis. The remaining causes are uncommon or rare.
ETIOLOGY
• Allergy: Foods, drugs, contact (some erythema multiforme)
• Vitamin deficiency: Riboflavin (angular stomatitis)
• Viral: herpes simplex I and II (herpetic stomatitis), Coxsackie A (herpangina and hand-foot-and-mouth disease)
• Smoking (nicotinic stomatitis)
• Hormonal (possibly recurrent ulcerative stomatitis)
• Uncertain (recurrent aphthous stomatitis, Vincent stomatitis, recurrent scarifying stomatitis, Behcet disease, angular stomatitis, gangrenous stomatitis, erythema multiforme)
• Bacterial (scarlatina)
• Uremic (uremic/nephritic)
• Dentures
ALERT
Pediatric Considerations
Certain etiologies more likely in the pediatric population: Herpetic-primary, hand-foot-and-mouth disease, herpangina
Geriatric Considerations
Certain etiologies more likely in the geriatric population, e.g., dentures
ASSOCIATED CONDITIONS
• AIDS: Associated with severe lesions
• Pregnancy may bring on recurrent ulcerative stomatitis.
DIAGNOSIS
SIGNS AND SYMPTOMS
• General
- Depends on etiology
- Varies from minimal to severe pain
- Many have multiple intraoral ulcers from 1 mm to several centimeters in diameter
- Some with constitutional symptoms: Fever, malaise, headache
• Allergic stomatitis
- Intense shiny erythema
- Slight swelling
- Itching
- Dryness
- Burning
• Vincent infection
- Necrotic ulceration of interdental papillae and mucous membrane
• Thrush (candidiasis)
- White patches, slightly raised (resembling milk curds)
- Distribution: Tongue, buccal mucosa, palate, gums, tonsils, larynx, pharynx, gastrointestinal tract, skin; commonly seen in infants, immunocompromised patients, and patients on long-term antibiotics, corticosteroids, and antineoplastic treatment
• Pseudomembranous stomatitis: Membranelike exudate
• Mucous lesions accompanying systemic disease
- Mucous patches (syphilis)
- Strawberry (measles)
- Koplik spots (measles)
- Ulcers (erythema multiforme)
- Smooth, fire-red, painful (pellagra)
TESTS
Lab
• Hematologic profile
• Tzanck test of historic interest only
• Serologic test for syphilis
Diagnostic Procedures/Surgery
Biopsy if persistent/recurrent/suspicious
Pathological Findings
Biopsy suspicious lesions or lesions that fail to heal or chronically recur, to rule out cancer or vasculitis.
DIFFERENTIAL DIAGNOSIS
• Squamous cell cancer
• Herpetic stomatitis
• Hand-foot-and-mouth disease
• Recurrent aphthous stomatitis
• Vincent stomatitis
• Nicotinic stomatitis
• Denture-related stomatitis
• Erythema multiforme/Stevens-Johnson syndrome
• Recurrent ulcerative stomatitis
• Recurrent scarifying stomatitis
• Behcet disease
• Angular stomatitis
• Noma (gangrenous stomatitis)
• Scarlatina (scarlet fever)
• Herpangina
• Uremic stomatitis
• Pemphigus/pemphigoid
TREATMENT
STABILIZATION
Outpatient care, unless severe
GENERAL MEASURES
• In most cases, treatment of symptoms only
• Severe cases may require parenteral fluids, particularly in children.
• Topical anesthesia
• Analgesics
• Oral rinses such as half-strength hydrogen peroxide
• Mycostatin, if superinfected with Candida
• Smoking cessation
Diet
May need to avoid spicy, sharp, hard, and dry foods
Activity
As tolerated by patient
MEDICATION (DRUGS)
First Line
• Steroids and cytotoxic drugs for Behet disease
• 2% viscous lidocaine (Xylocaine) for local discomfort
• Liquid diphenhydramine (Benadryl) by mouth, or swish and spit
• Antibiotics for gangrenous stomatitis
• Antifungal ointment, e.g., nystatin (Mycostatin) for candidiasis complicating angular stomatitis
• For candidiasis: Nystatin oral suspension 400,000 U (4 mL) q.i.d. for 10 days. Use as oral rinse, then swallow.
• Acyclovir 200-800 mg 5 times a day for 7-14 days for herpetic stomatitis
• Sucralfate (Carafate) suspension 1 tsp, swish in mouth or place on ulcers q.i.d. (helpful)
• Contraindications: Allergy to specific medication
• Precautions
- Toxic dose of topical lidocaine uncertain, but likely only 25-33% of infiltration dose may have significant absorption from open ulcers or mucous membrane
• Significant possible interactions: Refer to manufacturer's literature for each drug.
Second Line
Steroid oral rinses or topical preparations for aphthous ulcers
FOLLOW-UP
PROGNOSIS
• Herpetic: Self-limited, with resolution in 7-14 days
• Hand-foot-and-mouth disease: Same as for herpetic
• Recurrent aphthous ulcers: 7-14-day course per episode
• Vincent: May progress to fascial space infection with airway compromise or sepsis
• Nicotinic: Resolves with cessation of smoking
• Denture: Resolves with careful oral hygiene and daytime-only denture wear
• Erythema multiforme: Resolution in 2-3 weeks
• Stevens-Johnson: Resolution in ~6 weeks with adequate supportive care
• Recurrent ulcerative: As the name implies, recurs over time, but the overall prognosis is good.
• Recurrent scarifying: Occasional patients suffer continuous ulcers, others have recurrence with eventual scarring. The prognosis is otherwise good.
• Behcet disease may recur for several years. Prognosis for vision is poor. Overall prognosis is related to other aspects of the disease.
• Angular: After correction of mechanical problems, allergic disorders, and nutritional deficiencies, the prognosis is good.
• Gangrenous: The most serious stomatitis, requiring aggressive treatment with IV antibiotics and debridement to avoid death
• Scarlatina: The prognosis is related to other manifestations of the disease.
• Herpangina: 7-14-day course, with total resolution
• Uremic: Depends on the underlying renal disease
COMPLICATIONS
• Recurrent scarifying stomatitis may result in intraoral scarring with restriction of oral mobility.
• Behcet disease may result in visual loss, pneumonia, colitis, vasculitis, large artery aneurysms, thrombophlebitis, or encephalitis.
• Gangrenous stomatitis may lead to death.
• Scarlet fever may result in cardiac disease.
• Herpetic stomatitis may be complicated by ocular or CNS involvement.
PATIENT MONITORING
Lesions need to be followed until resolved. If they fail to resolve, continuously recur, or appear suspicious, biopsy may be needed to establish a diagnosis.
REFERENCES
1. Moran WJ. Diseases of the mouth. In: Rakel E, ed. Conn's Current Therapy. Philadelphia, PA: WB Saunders; 1990.
2. Teele DW. Inflammatory diseases of the mouth and pharynx. In: Paparella MM, Shumrick DA, eds. Otolaryngology. Philadelphia, PA: WB Saunders; 1980: 974-1017.
STOKES ADAMS ATTACKS
STOKES-ADAMS ATTACKS - Jeremy Golding, MD
BASICS
DESCRIPTION
• Syncope due to transient complete heart block and resulting severe bradycardia or asystole with hypotension
• System(s) Affected: Cardiovascular; Nervous
• Synonym(s): Drop attacks
GENERAL PREVENTION
Avoid negative chronotropic drugs (e.g., -blockers, calcium channel blockers, digoxin) in at-risk patients.
EPIDEMIOLOGY
• Predominant age: Most common >40 years of age
• Predominant sex: Male = Female
ALERT
Pregnancy Considerations
Rare during pregnancy
Incidence
Undocumented
Prevalence
Undocumented
Geriatric Considerations
Prevalence increases with age
RISK FACTORS
• Use of the medications listed under "Etiology"
• Coronary artery disease
• History of previous atrioventricular nodal dysfunction
• Bundle branch and/or fascicular block
• Acute myocardial infarction (MI) (especially acute right coronary artery occlusion)
• Amyloidosis
• Chagas disease
• Connective tissue diseases involving the heart (e.g., systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis)
Genetics
No known genetic pattern
ETIOLOGY
• Medications
- Calcium channel blockers
- -blockers
- Sotalol
- Digoxin
- Clonidine
- Propafenone (Rythmol); a class IC antiarrhythmic
• Other causes
- Myocardial ischemia involving the atrioventricular node
- Degenerative (fibrosing) and infiltrative diseases involving the heart and its conduction system (e.g., Lenegre)
- Degeneration of the atrioventricular node secondary to aging
- Neuromuscular diseases (e.g., myotonic muscular dystrophy or Kearns-Sayre syndrome)
ASSOCIATED CONDITIONS
• Myocardial ischemia
• Acute MI
• Systemic manifestations of connective tissue disease
• Unreliable self-administration of medications
• Neuromuscular disease
DIAGNOSIS
SIGNS AND SYMPTOMS
• Acute bradycardia
• Hypotension
• Paleness
• Altered sensorium or loss of consciousness, unrelated to position or exertion
• Acute onset of syncopal or near-syncopal symptoms (with or without palpitations)
TESTS
Lab
• Serum digoxin level
• Cardiac enzymes
• Transient or long-standing renal failure may falsely elevate cardiac enzymes (creatine kinase).
Imaging
Transthoracic cardiac 2-D echocardiogram if infiltrative disease is suspected
Diagnostic Procedures/Surgery
• Cardiac coronary catheterization to rule out coronary ischemia
• Electrophysiologic testing to assess status of atrioventricular nodal conduction
• Myocardial biopsy if infiltrative disease is suspected
• ECG, event monitor, or Holter monitor demonstrating (transient) complete heart block with slow or no ventricular escape
• Tilt table testing to rule out a neurogenic etiology for bradycardia and syncope
DIFFERENTIAL DIAGNOSIS
• Seizures
• Transient ischemic attacks
• Orthostatic hypotension
• Vasovagal attacks
• Neurocardiogenic syncope
• Cardiac arrhythmias
- Ventricular tachycardia
- Supraventricular tachycardia
- Reentrant tachycardia
- Wolff-Parkinson-White syndrome
- Sinus arrest
- Sinus exit block
- Sick sinus syndrome
- Transition from normal sinus rhythm to atrial fibrillation or from atrial fibrillation to normal sinus rhythm
TREATMENT
STABILIZATION
• Inpatient assessment in a monitored setting
• Continuing treatment ambulatory
GENERAL MEASURES
• Cardiac monitoring
• Transthoracic pacer availability
• Atropine by the bedside
Diet
Regular
Activity
As tolerated after assessment
MEDICATION (DRUGS)
• For symptomatic bradyarrhythmias
- For acute bradyarrhythmias: Atropine 1 mg IV push, to be given during the complete heart block with hypotension; may be repeated once for a total dosage of 2 mg
- Epinephrine: 1 mg 1:10,000 IV push, to be given during the complete heart block if associated with asystole; may be repeated every 5 minutes
- Isoproterenol: Drip 1 mg in 250 cc D5W or normal saline to be started at 2-20 mcg/min if patient maintains bradycardia and is hypotensive after atropine is given; may titrate drip as necessary
• Contraindications
- Use of epinephrine in a patient with bradycardia and a normal BP may precipitate hypertensive crisis.
• Precautions: Possible tachycardiac response to the above-mentioned medications
SURGERY
• Consider temporary pacemaker placement.
• Permanent pacemaker placement if etiology of transient complete heart block is not reversible.
FOLLOW-UP
PROGNOSIS
After diagnosis is made and appropriate treatment is implemented (e.g., pacemaker insertion), prognosis is excellent and further difficulty is not expected.
COMPLICATIONS
• Protracted bradycardia with hypotension, leading to end-organ damage or death
• Loss of consciousness while operating machinery or at unprotected heights
PATIENT MONITORING
• Routine pacemaker checks if permanent pacemaker has been implanted
• Follow-up Holter and/or event monitoring within 2 weeks after causal medications have been discontinued
• Discontinuation of driving, heavy-machinery operation, and being at unprotected heights pending normal follow-up
REFERENCES
1. Brandenburg RO, et al. Cardiology: Fundamentals and Practice. Chicago: Year Book Medical Publishers, 1987.
2. Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine, 5th ed. Philadelphia: WB Saunders, 1996.
MISCELLANEOUS
See also: Amyloidosis; Myocardial infarction; Seizure disorders
BASICS
DESCRIPTION
• Syncope due to transient complete heart block and resulting severe bradycardia or asystole with hypotension
• System(s) Affected: Cardiovascular; Nervous
• Synonym(s): Drop attacks
GENERAL PREVENTION
Avoid negative chronotropic drugs (e.g., -blockers, calcium channel blockers, digoxin) in at-risk patients.
EPIDEMIOLOGY
• Predominant age: Most common >40 years of age
• Predominant sex: Male = Female
ALERT
Pregnancy Considerations
Rare during pregnancy
Incidence
Undocumented
Prevalence
Undocumented
Geriatric Considerations
Prevalence increases with age
RISK FACTORS
• Use of the medications listed under "Etiology"
• Coronary artery disease
• History of previous atrioventricular nodal dysfunction
• Bundle branch and/or fascicular block
• Acute myocardial infarction (MI) (especially acute right coronary artery occlusion)
• Amyloidosis
• Chagas disease
• Connective tissue diseases involving the heart (e.g., systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis)
Genetics
No known genetic pattern
ETIOLOGY
• Medications
- Calcium channel blockers
- -blockers
- Sotalol
- Digoxin
- Clonidine
- Propafenone (Rythmol); a class IC antiarrhythmic
• Other causes
- Myocardial ischemia involving the atrioventricular node
- Degenerative (fibrosing) and infiltrative diseases involving the heart and its conduction system (e.g., Lenegre)
- Degeneration of the atrioventricular node secondary to aging
- Neuromuscular diseases (e.g., myotonic muscular dystrophy or Kearns-Sayre syndrome)
ASSOCIATED CONDITIONS
• Myocardial ischemia
• Acute MI
• Systemic manifestations of connective tissue disease
• Unreliable self-administration of medications
• Neuromuscular disease
DIAGNOSIS
SIGNS AND SYMPTOMS
• Acute bradycardia
• Hypotension
• Paleness
• Altered sensorium or loss of consciousness, unrelated to position or exertion
• Acute onset of syncopal or near-syncopal symptoms (with or without palpitations)
TESTS
Lab
• Serum digoxin level
• Cardiac enzymes
• Transient or long-standing renal failure may falsely elevate cardiac enzymes (creatine kinase).
Imaging
Transthoracic cardiac 2-D echocardiogram if infiltrative disease is suspected
Diagnostic Procedures/Surgery
• Cardiac coronary catheterization to rule out coronary ischemia
• Electrophysiologic testing to assess status of atrioventricular nodal conduction
• Myocardial biopsy if infiltrative disease is suspected
• ECG, event monitor, or Holter monitor demonstrating (transient) complete heart block with slow or no ventricular escape
• Tilt table testing to rule out a neurogenic etiology for bradycardia and syncope
DIFFERENTIAL DIAGNOSIS
• Seizures
• Transient ischemic attacks
• Orthostatic hypotension
• Vasovagal attacks
• Neurocardiogenic syncope
• Cardiac arrhythmias
- Ventricular tachycardia
- Supraventricular tachycardia
- Reentrant tachycardia
- Wolff-Parkinson-White syndrome
- Sinus arrest
- Sinus exit block
- Sick sinus syndrome
- Transition from normal sinus rhythm to atrial fibrillation or from atrial fibrillation to normal sinus rhythm
TREATMENT
STABILIZATION
• Inpatient assessment in a monitored setting
• Continuing treatment ambulatory
GENERAL MEASURES
• Cardiac monitoring
• Transthoracic pacer availability
• Atropine by the bedside
Diet
Regular
Activity
As tolerated after assessment
MEDICATION (DRUGS)
• For symptomatic bradyarrhythmias
- For acute bradyarrhythmias: Atropine 1 mg IV push, to be given during the complete heart block with hypotension; may be repeated once for a total dosage of 2 mg
- Epinephrine: 1 mg 1:10,000 IV push, to be given during the complete heart block if associated with asystole; may be repeated every 5 minutes
- Isoproterenol: Drip 1 mg in 250 cc D5W or normal saline to be started at 2-20 mcg/min if patient maintains bradycardia and is hypotensive after atropine is given; may titrate drip as necessary
• Contraindications
- Use of epinephrine in a patient with bradycardia and a normal BP may precipitate hypertensive crisis.
• Precautions: Possible tachycardiac response to the above-mentioned medications
SURGERY
• Consider temporary pacemaker placement.
• Permanent pacemaker placement if etiology of transient complete heart block is not reversible.
FOLLOW-UP
PROGNOSIS
After diagnosis is made and appropriate treatment is implemented (e.g., pacemaker insertion), prognosis is excellent and further difficulty is not expected.
COMPLICATIONS
• Protracted bradycardia with hypotension, leading to end-organ damage or death
• Loss of consciousness while operating machinery or at unprotected heights
PATIENT MONITORING
• Routine pacemaker checks if permanent pacemaker has been implanted
• Follow-up Holter and/or event monitoring within 2 weeks after causal medications have been discontinued
• Discontinuation of driving, heavy-machinery operation, and being at unprotected heights pending normal follow-up
REFERENCES
1. Brandenburg RO, et al. Cardiology: Fundamentals and Practice. Chicago: Year Book Medical Publishers, 1987.
2. Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine, 5th ed. Philadelphia: WB Saunders, 1996.
MISCELLANEOUS
See also: Amyloidosis; Myocardial infarction; Seizure disorders
STEVENS-JOHNSON SYNDROME
STEVENS-JOHNSON SYNDROME - Matthew Silva, PharmD, RPh, BCPS; Pablo I. Hernandezz, MD
BASICS
DESCRIPTION
• Stevens-Johnson syndrome (SJS) is a generalized hypersensitivity reaction, usually to a drug, in which skin and mucous membrane lesions are an early manifestation.
• Once considered to be the same as erythema multiforme major, a severe form of erythema multiforme in which >1 mucosal surface was involved.
• Erythema multiforme spectrum is now thought to be a single entity
- Milder form, also known as erythema multiforme-Hebra, either has no mucous membrane involvement, or may involve 1 mucous membrane
- More severe form, erythema multiforme major, involves >1 mucous membrane
- In both variants, it is a self-limited hypersensitivity reaction, usually to a preceding viral infection, and has an excellent prognosis.
• May progress to its more severe form, toxic epidermal necrolysis (TEN), which has a high morbidity and up to 70% mortality (2).
• System(s) Affected: Cardiovascular; Hemic/Lymphatic/Immunologic; Nervous; Renal/Urologic; Skin/Exocrine
• Synonym(s): Ectodermosis erosiva pluriorificialis; Febrile mucocutaneous syndrome; Herpes iris; Erythema polymorphe; Toxic epidermal necrolysis (TEN).
ALERT
Geriatric Considerations
Toxic epidermal necrolysis has a greater mortality in older patients.
Pediatric Considerations
• Rare in children 3 years
• More common in children and young adults
Pregnancy Considerations
Pregnancy is possible predisposing condition
GENERAL PREVENTION
• Rarely possible to anticipate a 1st attack
• Avoid re-exposure to presumed cause.
• Although not FDA approved, IV immune globulin may be beneficial for both treatment and prophylaxis.
EPIDEMIOLOGY
Incidence
• Incidence/prevalence in the US is difficult to estimate because there is no universally accepted definition of SJS.
• 1.1-7.1 and 0.4-1.2 cases per million person-years for SJS and TEN, respectively (2)
Prevalence
• Predominant age: SJS is more common in children and young adults.
• Males > Females (2:1)
• Sex (% range of females): 33-62% for SJS and 61.3-64.3% for TEN (2)
• Age (average range): 25-47 years for SJS and 46-63 years for TEN (2)
RISK FACTORS
• Patients with HIV infection may be predisposed to developing SJS in response to their medications.
- HLA subtypes A, B, and D
- Disease that cause immune compromise (deficiencies, malignancy, etc)
- Possibly radiation therapy or UV light
• Previous history of SJS
Genetics
Possibly associated with HLA-B15, HLA-Bw44, part of HLA-B12, and HLA-DQB1*0601
ETIOLOGY
• 50% of cases are idiopathic.
• Associated with metabolism of parent drugs and metabolites
• Sulfonamides are the drug most strongly associated with SJS and TEN, then
- Cephalosporins
- Quinolones
- Aminopenicillins
- Tetracyclines
- Macrolides
- Imidazole antifungals
- Anticonvulsants
- NSAIDs, especially oxicam
- VaccinesdPT, bCG, oral polio
• Mycoplasma pneumonia infection
• Viruses (HSV, EBV, coxsackie)
ASSOCIATED CONDITIONS
• SJS and toxic epidermal necrolysis are associated conditions.
• Mycoplasma pneumonia may be an infectious precursor.
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Usually a preceding illness for which the medication was given 1-3 weeks before initial cutaneous manifestations
• Sudden onset with rapid progressive pleomorphic rash that includes petechiae, vesicles, bullae.
• Seen in SJS if epidermal detachments affects 10% of the skin
• Seen in TEN if epidermal detachments >30% or if it >10% in the absence of discrete skin lesions
• Cases with discrete skin lesions and 10-30% epidermal detachment are in the overlap between SJS ad TEN
Physical Exam
The condition is classified as follows
• Vesicles and ulcers on the mucous membranes, especially of the mouth and throat
• Burning sensation of the skin and sometimes of the mucous membranes
• Usually no pruritus
• Fever 39-40C (102-104F)
• Headache
• Malaise
• Arthralgias
• Epistaxis
• Crusted nares
• Conjunctivitis
• Corneal ulcerations
• Erosive vulvovaginitis or balanitis
• Cough productive of thick purulent sputum
• Tachypnea/respiratory distress
• Arrhythmias
• Pericarditis
• CHF
• Mental status changes
• Seizures
• Coma
• Sepsis
• Seen in SJS if epidermal detachment affects 10% of the skin
• Seen in TEN, if epidermal detachment exceeds 30% or if it exceeds 10% in the absence of discrete skin lesions
• Cases with discrete skin lesions and 10-30% epidermal detachment are in the overlap between SJS and TEN.
TESTS
Lab
• Culture or serological tests for suspected sources of infection
• Electrolyte disturbance
• Albuminuria/hematuria
Diagnostic Procedures/Surgery
Skin biopsy
Pathological Findings
• Compared with the mainly inflammatory changes in erythema multiforme, necrotic changes predominate in SJS and toxic epidermal necrolysis.
• A cell-poor infiltrate is present, in which macrophages and dendrocytes predominate, with a strong immunoreactivity for tumor necrosis factor (TNF)-.
DIFFERENTIAL DIAGNOSIS
• Exfoliative dermatitis
• Linear IgA bullous dermatosis
• Staphylococcal scalded skin syndrome
• Pemphigus (paraneoplastic)
• Generalized fixed drug eruption
• Erythema multiforme major
• Burns
• Pressure blisters (coma, barbiturates)
TREATMENT
• This disease progresses rapidly, all patients should be admitted.
• Consider admission to a burn unit when sloughed skin >10% of the body surface area.
• ICU for bronchiolitis, ARDS, or multiorgan damage
GENERAL MEASURES
• Withdraw all suspected medication and treat any underlying disease.
• Meticulous care of damaged skin
• Catheter changing and culturing
• Reverse isolation and temperature control with extensive epidermal loss
• Maintenance of fluid, electrolyte, and protein balance
• Plasmapheresis
• Adequate calorie intake; parenteral nutrition, if necessary
• Mouthwashes of warm saline or a solution of diphenhydramine, lidocaine, and kaolin suspension
• Ophthalmologic consultation and monitoring for corneal damage
• Venous thromboembolism prophylaxis with unfractionated heparin or low-molecular-weight heparin
Diet
• Oral fluid intake is recommended.
• Early oral nutrition by nasogastric tube as tolerated
• IV nutritional support with increased protein requirements; may need insulin for glycoregulation in this hypercatabolic state.
Activity
Bed rest until clinically stabilized
Nursing
Avoid administration of topical silver sulfadiazine due to association with sulfonamides and SJS.
SPECIAL THERAPY
IV Fluids
Fluid management with saline and macromolecules are necessary in the 1st 24 hours, with decreasing IV fluid requirements as oral intake proceeds with NG tube.
MEDICATION (DRUGS)
First Line
• Corticosteroids are controversial. Early, high-dose IV steroids may attenuate disease progression, reduce skin detachment, decrease inflammatory cytokine activity, and improve patient comfort. Withdraw if no benefit is seen in the 1st few days.
• Experimental treatments that appear to have been useful include
- Recombinant granulocyte colony stimulating factor
- Cyclophosphamide
- Cyclosporine
- IV immune globulin in HIV-positive patients
IV immune globulin considered beneficial treatment and prophylaxis, although not FDA approved
• Contraindications: Avoid steroids in diabetic or immunosuppressed patients or those with chronic infections.
• Precautions: Refer to the manufacturer's profile for each drug.
• Significant possible interactions: Refer to manufacturer's profile of each drug.
Second Line
• Acyclovir for herpetic infections
• Erythromycin or related antibiotic for Mycoplasma infections (empiric use of antibiotics is not recommended)
SURGERY
• Sterile debridement of areas of extensive epidermal loss
• Application of biosynthetic dressings, such as Biobrane to denuded areas
• Damage to the vulva, vagina, or cornea; consider surgical repair
FOLLOW-UP
PROGNOSIS
• Disease may have a rapid onset or may evolve slowly over 1-2 weeks with resolution over 4-6 weeks.
• Often scarring of the skin or mucous membranes occurs, especially of the vulva.
• Blindness or corneal opacities occur in 7-20% of patients.
• The risk of recurrence as high as 37%.
• Death occurs in 5-15% of the patients with SJS, and up to 40% of patients with TEN.
COMPLICATIONS
• Secondary infections
• Sepsis
• Pneumonia
• ARDS
• Bronchiolitis obliterans in children
• Dehydration/electrolyte disturbance
• Acute tubular necrosis
• Corneal ulceration or iritis
• Arrhythmias
• Venous thromboembolism
• Disseminated intravascular coagulation
• Death in 15% of untreated cases of SJS and up to 40% of TEN
PATIENT MONITORING
• Secondary or concurrent infections
• Dehydration
• Electrolyte imbalance
• Malnutrition
• End-organ damage
REFERENCES
1. French LE, Trent JT, et al. Use of intravenous immunoglobulin in toxic epidermal necrolysis and Stevens-Johnson syndrome: Our current understanding. Int Immunopharmacol. 2006;6:543-549.
2. Letko E, Papaliodis DN, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: A review of the literature. Ann Allergy Asthma Immunol. 2005;94:419-436.
3. Wolf R, et al. Life-threatening acute adverse cutaneous drug reactions. Clin Dermatol. 2005;23:171-181.
MISCELLANEOUS
See also: Burns, Erythema multiforme, Pemphigoid, bullous, Pemphigus vulgaris, Acute respiratory distress syndrome, cutaneous drug reactions, dermatitis herpetiformis
BASICS
DESCRIPTION
• Stevens-Johnson syndrome (SJS) is a generalized hypersensitivity reaction, usually to a drug, in which skin and mucous membrane lesions are an early manifestation.
• Once considered to be the same as erythema multiforme major, a severe form of erythema multiforme in which >1 mucosal surface was involved.
• Erythema multiforme spectrum is now thought to be a single entity
- Milder form, also known as erythema multiforme-Hebra, either has no mucous membrane involvement, or may involve 1 mucous membrane
- More severe form, erythema multiforme major, involves >1 mucous membrane
- In both variants, it is a self-limited hypersensitivity reaction, usually to a preceding viral infection, and has an excellent prognosis.
• May progress to its more severe form, toxic epidermal necrolysis (TEN), which has a high morbidity and up to 70% mortality (2).
• System(s) Affected: Cardiovascular; Hemic/Lymphatic/Immunologic; Nervous; Renal/Urologic; Skin/Exocrine
• Synonym(s): Ectodermosis erosiva pluriorificialis; Febrile mucocutaneous syndrome; Herpes iris; Erythema polymorphe; Toxic epidermal necrolysis (TEN).
ALERT
Geriatric Considerations
Toxic epidermal necrolysis has a greater mortality in older patients.
Pediatric Considerations
• Rare in children 3 years
• More common in children and young adults
Pregnancy Considerations
Pregnancy is possible predisposing condition
GENERAL PREVENTION
• Rarely possible to anticipate a 1st attack
• Avoid re-exposure to presumed cause.
• Although not FDA approved, IV immune globulin may be beneficial for both treatment and prophylaxis.
EPIDEMIOLOGY
Incidence
• Incidence/prevalence in the US is difficult to estimate because there is no universally accepted definition of SJS.
• 1.1-7.1 and 0.4-1.2 cases per million person-years for SJS and TEN, respectively (2)
Prevalence
• Predominant age: SJS is more common in children and young adults.
• Males > Females (2:1)
• Sex (% range of females): 33-62% for SJS and 61.3-64.3% for TEN (2)
• Age (average range): 25-47 years for SJS and 46-63 years for TEN (2)
RISK FACTORS
• Patients with HIV infection may be predisposed to developing SJS in response to their medications.
- HLA subtypes A, B, and D
- Disease that cause immune compromise (deficiencies, malignancy, etc)
- Possibly radiation therapy or UV light
• Previous history of SJS
Genetics
Possibly associated with HLA-B15, HLA-Bw44, part of HLA-B12, and HLA-DQB1*0601
ETIOLOGY
• 50% of cases are idiopathic.
• Associated with metabolism of parent drugs and metabolites
• Sulfonamides are the drug most strongly associated with SJS and TEN, then
- Cephalosporins
- Quinolones
- Aminopenicillins
- Tetracyclines
- Macrolides
- Imidazole antifungals
- Anticonvulsants
- NSAIDs, especially oxicam
- VaccinesdPT, bCG, oral polio
• Mycoplasma pneumonia infection
• Viruses (HSV, EBV, coxsackie)
ASSOCIATED CONDITIONS
• SJS and toxic epidermal necrolysis are associated conditions.
• Mycoplasma pneumonia may be an infectious precursor.
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Usually a preceding illness for which the medication was given 1-3 weeks before initial cutaneous manifestations
• Sudden onset with rapid progressive pleomorphic rash that includes petechiae, vesicles, bullae.
• Seen in SJS if epidermal detachments affects 10% of the skin
• Seen in TEN if epidermal detachments >30% or if it >10% in the absence of discrete skin lesions
• Cases with discrete skin lesions and 10-30% epidermal detachment are in the overlap between SJS ad TEN
Physical Exam
The condition is classified as follows
• Vesicles and ulcers on the mucous membranes, especially of the mouth and throat
• Burning sensation of the skin and sometimes of the mucous membranes
• Usually no pruritus
• Fever 39-40C (102-104F)
• Headache
• Malaise
• Arthralgias
• Epistaxis
• Crusted nares
• Conjunctivitis
• Corneal ulcerations
• Erosive vulvovaginitis or balanitis
• Cough productive of thick purulent sputum
• Tachypnea/respiratory distress
• Arrhythmias
• Pericarditis
• CHF
• Mental status changes
• Seizures
• Coma
• Sepsis
• Seen in SJS if epidermal detachment affects 10% of the skin
• Seen in TEN, if epidermal detachment exceeds 30% or if it exceeds 10% in the absence of discrete skin lesions
• Cases with discrete skin lesions and 10-30% epidermal detachment are in the overlap between SJS and TEN.
TESTS
Lab
• Culture or serological tests for suspected sources of infection
• Electrolyte disturbance
• Albuminuria/hematuria
Diagnostic Procedures/Surgery
Skin biopsy
Pathological Findings
• Compared with the mainly inflammatory changes in erythema multiforme, necrotic changes predominate in SJS and toxic epidermal necrolysis.
• A cell-poor infiltrate is present, in which macrophages and dendrocytes predominate, with a strong immunoreactivity for tumor necrosis factor (TNF)-.
DIFFERENTIAL DIAGNOSIS
• Exfoliative dermatitis
• Linear IgA bullous dermatosis
• Staphylococcal scalded skin syndrome
• Pemphigus (paraneoplastic)
• Generalized fixed drug eruption
• Erythema multiforme major
• Burns
• Pressure blisters (coma, barbiturates)
TREATMENT
• This disease progresses rapidly, all patients should be admitted.
• Consider admission to a burn unit when sloughed skin >10% of the body surface area.
• ICU for bronchiolitis, ARDS, or multiorgan damage
GENERAL MEASURES
• Withdraw all suspected medication and treat any underlying disease.
• Meticulous care of damaged skin
• Catheter changing and culturing
• Reverse isolation and temperature control with extensive epidermal loss
• Maintenance of fluid, electrolyte, and protein balance
• Plasmapheresis
• Adequate calorie intake; parenteral nutrition, if necessary
• Mouthwashes of warm saline or a solution of diphenhydramine, lidocaine, and kaolin suspension
• Ophthalmologic consultation and monitoring for corneal damage
• Venous thromboembolism prophylaxis with unfractionated heparin or low-molecular-weight heparin
Diet
• Oral fluid intake is recommended.
• Early oral nutrition by nasogastric tube as tolerated
• IV nutritional support with increased protein requirements; may need insulin for glycoregulation in this hypercatabolic state.
Activity
Bed rest until clinically stabilized
Nursing
Avoid administration of topical silver sulfadiazine due to association with sulfonamides and SJS.
SPECIAL THERAPY
IV Fluids
Fluid management with saline and macromolecules are necessary in the 1st 24 hours, with decreasing IV fluid requirements as oral intake proceeds with NG tube.
MEDICATION (DRUGS)
First Line
• Corticosteroids are controversial. Early, high-dose IV steroids may attenuate disease progression, reduce skin detachment, decrease inflammatory cytokine activity, and improve patient comfort. Withdraw if no benefit is seen in the 1st few days.
• Experimental treatments that appear to have been useful include
- Recombinant granulocyte colony stimulating factor
- Cyclophosphamide
- Cyclosporine
- IV immune globulin in HIV-positive patients
IV immune globulin considered beneficial treatment and prophylaxis, although not FDA approved
• Contraindications: Avoid steroids in diabetic or immunosuppressed patients or those with chronic infections.
• Precautions: Refer to the manufacturer's profile for each drug.
• Significant possible interactions: Refer to manufacturer's profile of each drug.
Second Line
• Acyclovir for herpetic infections
• Erythromycin or related antibiotic for Mycoplasma infections (empiric use of antibiotics is not recommended)
SURGERY
• Sterile debridement of areas of extensive epidermal loss
• Application of biosynthetic dressings, such as Biobrane to denuded areas
• Damage to the vulva, vagina, or cornea; consider surgical repair
FOLLOW-UP
PROGNOSIS
• Disease may have a rapid onset or may evolve slowly over 1-2 weeks with resolution over 4-6 weeks.
• Often scarring of the skin or mucous membranes occurs, especially of the vulva.
• Blindness or corneal opacities occur in 7-20% of patients.
• The risk of recurrence as high as 37%.
• Death occurs in 5-15% of the patients with SJS, and up to 40% of patients with TEN.
COMPLICATIONS
• Secondary infections
• Sepsis
• Pneumonia
• ARDS
• Bronchiolitis obliterans in children
• Dehydration/electrolyte disturbance
• Acute tubular necrosis
• Corneal ulceration or iritis
• Arrhythmias
• Venous thromboembolism
• Disseminated intravascular coagulation
• Death in 15% of untreated cases of SJS and up to 40% of TEN
PATIENT MONITORING
• Secondary or concurrent infections
• Dehydration
• Electrolyte imbalance
• Malnutrition
• End-organ damage
REFERENCES
1. French LE, Trent JT, et al. Use of intravenous immunoglobulin in toxic epidermal necrolysis and Stevens-Johnson syndrome: Our current understanding. Int Immunopharmacol. 2006;6:543-549.
2. Letko E, Papaliodis DN, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: A review of the literature. Ann Allergy Asthma Immunol. 2005;94:419-436.
3. Wolf R, et al. Life-threatening acute adverse cutaneous drug reactions. Clin Dermatol. 2005;23:171-181.
MISCELLANEOUS
See also: Burns, Erythema multiforme, Pemphigoid, bullous, Pemphigus vulgaris, Acute respiratory distress syndrome, cutaneous drug reactions, dermatitis herpetiformis
STATUS EPILEPTICUS
STATUS EPILEPTICUS - Jeff Ray Gibson Jr., MD
BASICS
DESCRIPTION
Epileptic seizure >30 minutes or absence of full recovery of consciousness between seizures. Tonic/clonic (grand mal or generalized convulsive) status epilepticus is the most common and most serious form. For description and treatment of additional types of status (focal, nonconvulsive, and neonatal) see "References".
• System(s) Affected: Nervous
• Synonym(s): Status convulsivus
ALERT
Status epilepticus is a life-threatening emergency; begin treatment if seizure lasts >5 minutes. Rapid control of seizure is critical to success.
GENERAL PREVENTION
Establish maintenance regimen of anticonvulsant.
EPIDEMIOLOGY
• Predominant age: >50% of new cases of status epilepticus occur in young children.
• Predominant sex: Male > Female
Incidence
• 18-50 cases per 100,000 per year; 1/3 as unprovoked 1st seizure, 1/6 in patients with known epilepsy, 1/2 secondary to acute CNS insult.
• Incidence is 2 times higher in elderly.
RISK FACTORS
• Seizure disorder plus any precipitating insult
• Prior history of status epilepticus (recurrence rate is 17% in children; 50% in those with neurologic abnormality)
• Porphyria
Genetics
Unknown
PATHOPHYSIOLOGY
• Direct neuronal injury: Probably an excitotoxic mechanism related to prolonged depolarization-induced apoptosis or necrotic cell death
• Associated autonomic phenomena: Excess catecholamine secretion resulting in glandular hypersecretion, piloerection, hyperthermia, cyclic pupillary dilation, and prolonged apnea/cyanosis
• Metabolic changes: Lactic acidosis, carbon dioxide narcosis, hyperkalemia, hyperglycemia followed by hypoglycemia
• Cardiac changes: Hypertension (followed by hypotension), arrhythmias, high output failure
• Respiratory changes: Increased secretions, lax tongue, possible airway obstruction, pulmonary edema, aspiration
• Renal complications: Acute tubular necrosis from myoglobinuria after rhabdomyolysis. Cerebrovascular changes: Loss of autoregulation, focal ischemia, cerebral edema; Todd paralysis may occur.
• Postitictal findings: Fever, tachycardia, mydriasis, conjugate deviation of eyes, decreased corneal reflex, positive Babinski sign; fecal and urinary incontinence; tongue, cheek, or lip injury
ETIOLOGY
Etiology varies by age group
• In adults: Usually related to a known condition, for example, established epilepsy, alcohol withdrawal, anticonvulsant withdrawal/noncompliance, or acquired CNS lesion (especially frontal)
• In children: May present in status epilepticus as their 1st seizure owing to febrile seizure, new-onset epilepsy, CNS infection, metabolic derangement
• Neonatal status: Most often related to meningitis or metabolic disorders (deficiencies of calcium, magnesium, or pyridoxine); needs careful workup for cause
• Acute or chronic CNS injury-trauma, infection, stroke, mass/vascular lesion, metabolic disorder, encephalopathy (hypoxic or degenerative type)
• Intoxication: Cocaine, tricyclic antidepressants, isoniazid, chloroquine, cephalosporins, penicillins, ciprofloxacin, cyclosporin, theophylline, tacrolimus, tiagabine, and nerve agent poisoning
• Idiopathic
DIAGNOSIS
SIGNS AND SYMPTOMS
Depends on the duration and type of seizure
• Recurrent generalized (tonic/clonic) convulsions are most common.
- May be preceded by aura
- Tonic phase (stiffening) for 30-45 seconds
- Clonic phase (rhythmic jerking) for 2-5 minutes
- No intervening consciousness; seizure recurs
History
• Pursue available drug history.
• Must search for the primary pathology
Physical Exam
Neurologic exam: Confirm true seizure (pseudo status usually atypical); look for localizing signs.
TESTS
Lab
• Glucose (rapid determination)
• Electrolytes, CBC, osmolarity
• Creatine phosphokinase
• Calcium, magnesium, phosphate
• Arterial blood gases, carboxyhemoglobin
• Toxicology screen, anticonvulsant levels
• Liver/renal function
• Coagulation profile
Imaging
• Noncontrast CT scan in new-onset seizure
• MRI or PET if more detail needed
• CXR for endotracheal tube position or suspicion of aspiration pneumonitis
Diagnostic Procedures/Surgery
• Lumbar puncture (if meningitis is suspected) NOTE: Intracranial pressure may be increased.
• EEG: Use to differentiate pseudoseizures, reveal nonconvulsive status, and confirm successful treatment. Check EEG on any patient not awake 30 minutes after seizure.
Pathological Findings
Variable
DIFFERENTIAL DIAGNOSIS
• Pseudostatus may occur with pseudoseizures. Check EEG; avoid dangerous therapy.
• Comatose or paralyzed patients and other forms of status require neurologic exam and EEG.
TREATMENT
PRE-HOSPITAL
• Support ABCs and protect patient from injury.
• Out of hospital treatment by paramedics or caretakers using buccal midazolam or rectal diazepam has been recommended (doses below).
STABILIZATION
Begin treatment if seizure lasts >5 minutes.
Simultaneous goals are
• Stop seizure.
• Find cause.
• Treat secondary complications.
GENERAL MEASURES
• Manage airway, breathing, and circulation.
• Monitor pulse oximetry, end-tidal CO2, BP, ECG, and temperature.
• Observe and confirm fit is status epilepticus.
• Give oxygen (intubate and hyperventilate if hypoventilation, hypoxia, and/or hypercarbia occur or if aspiration is a concern. If intubation is needed, use rocuronium bromide 0.6 mg/kga short-acting nondepolarizer)
• Establish 2 IV lines.
• Draw blood for initial lab studies.
• Protect patient from injury: Place on side, clear/suction airway, prevent tongue laceration.
• Place nasograstic tube in comatose patient.
• Treat any fever.
• Stop the seizure (see "Medication" below).
Diet
NPO
Activity
Bed rest
SPECIAL THERAPY
IV Fluids
• Give maintenance fluids.
• Hemodynamic instability may require fluid boluses or vasopressors (e.g., dopamine).
MEDICATION (DRUGS)
Drug(s) of choice depend on the type of seizure. Approach tonic/clonic status epilepticus as follows
• Thiamine: 100 mg IV or IM (adults only)
• 50% dextrose: If blood sugar low or cannot be measured, give 50 mL IV (for child use D25W; give 2 mL/kg slowly).
• Naloxone (Narcan): If pupils are myotic or drug overdose is suspected, give 2 mg IV (for child0.1 mg/kg IV, up to 2 mg slowly).
• Pyridoxine: If isoniazid poisoning is suspected
• Antibiotics: If meningitis is strongly suspected
• For nerve agent poisoning, give atropine, benzodiazepines, and pralidoxime (2-PAM).
First Line
• To stop seizures if IV access available
- Start with lorazepam (Ativan) (1)[A]
Give 0.05-0.15 mg/kg IV at 1-2 mg per minute to maximum of 8 mg (for child, 0.05-0.1 mg/kg IV at 2 mg/min to maximum of 4 mg)
May repeat every 10 minutes 2
- After 5 minutes, if seizure persists, add 2nd agent, fosphenytoin (Cerebyx) (2)[B], prodrug of phenytoin
15-20 mg phenytoin equivalents (PE)/kg IV at 150 mg PE per minute
May add 5-10 mg PE/kg IV
Maintenance 4-6 mg PE/kg/d IV or IM (child dose same as adult)
- If these fail, treat as refractory status epilepticus (see below).
• To stop seizures if IV access not available
- In small children, use intraosseous infusion of IV doses of benzodiazepine and fosphenytoin.
- Or use rectal diazepam (Valium)
0.2-0.5 mg/kg (child 20 mg maximum)
Use the gel form (Diastat) or IV solution.
- Or, Lorazepam (sublingual): Use IV dose.
- Or, Midazolam (Versed): 0.2 mg/kg IM or 0.5 mg/kg intranasal or buccal (onset 5-10 minutes)
- And Fosphenytoin IM: Use IV dose (slowly).
• If seizures persist (refractory status)
- Admit to ICU and induce anesthesia/drug coma (2)[B], give infusion of short-acting agent to stop seizures (see choices below).
Requires intubation, ventilation, and monitoring of EEG, ECG, pulse oximetry, and (often) BP support.
Monitor temperature and treat/cool if febrile.
Adjust to keep EEG at burst suppression.
Maintain infusion for 12-24 hours, then withdraw anesthetic infusion gradually while continuing anticonvulsant therapy.
- Use midazolam (Versed): 0.2-0.5 mg/kg slow IV bolus injection, followed by 0.5-10 ug/kg/min IV drip, titrated to burst suppression
Tachyphylaxis may develop.
- Or propofol (Diprivan): 3-5 mg/kg IV (in elderly, halve initial dose), follow with 30-150 ug/kg/min IV titrated to burst suppression
- Or thiopental (Pentothal): To 6 mg/kg in divided doses, then add 50 mg IV every 2-5 minutes to produce burst suppression, maintain with IV drip of 0.2% solution; start at 2-5 mg/kg/h and adjust based on EEG
- Contraindications: See package inserts.
Benzodiazepines (diazepam, lorazepam, midazolam) in narrow-angle glaucoma
Barbiturates in acute intermittent porphyria
Propofol in allergy to soybean oil, egg, lecithin, or glycerol
Valproic acid in hepatic disease and pregnancy (risk of neural tube defects)
- Precautions
Reduce dosage of depressants in patients with shock, coma, or alcohol intoxication.
Most drugs listed may exacerbate porphyria; exceptions: Lorazepam, midazolam, propofol.
Benzodiazepines: Apnea may occur with rapid IV injection. Reduce dose in the chronic pulmonary patient, renal failure, the elderly, and hepatic insufficiency.
Diazepam: Venous thrombosis/phlebitis
Propofol: Strict aseptic technique required. May cause stinging discomfort on injection. Prolonged use may cause lactic acidosis, lipemia, heart failure, systemic collapse, and death in both children and adults. Safety not established for child 3 years old
Fosphenytoin (Cerebyx)/Phenytoin: Safety is not established for children. Monitor for arrhythmias, prolonged QT interval, and hypotension. If these occur, decrease rate of administration. Use with caution in liver disease, hyperglycemia, the elderly, and pregnancy (increased risk of malformations, may lead to vitamin K deficiency bleeding problems in both mother and newborn). Abrupt withdrawal may precipitate status. Overdose may cause paradoxical inefficacy.
Valproic acid: May decrease platelet function; may cause hyperammonemic encephalopathy.
- Significant possible interactions
Fosphenytoin/phenytoin: Increased serum levels and toxicity of warfarin, disulfiram, phenylbutazone, and isoniazid. Decrease dose with renal insufficiency.
Valproic acid: Increased toxicity of phenytoin/fosphenytoin
Second Line
• Diazepam (Valium): (2)[B] Use for lorazepam
- 0.2-0.5 mg/kg IV at 5 mg/min up to a dose of 30 mg (for child 0.3 mg/kg at 2 mg/min IV up to 10 mg total)
- Repeat q5min 3, wears off quickly
• Phenytoin: (2)[B]Use for fosphenytoin. Doses are the same (mg for mg Phenytoin equivalents), but must be given more slowly (1 mg/kg/min) to lessen toxicity and cardiovascular depression
• Other 2nd-line drugs
- Pentobarbital: 10-15 mg/kg IV loading dose over 1 hour, followed by continuous infusion of 0.5-1 mg/kg/h; adjust based on EEG
- Lidocaine (Xylocaine): 1-3 mg/kg IV bolus. If effective, drip at 3-10 mg/kg/h IV.
- Valproic acid: Clinical pilot studies have used 15-40 mg/kg IV loading dose over 5-10 minutes, followed by 1-5 mg/kg/h.
• Investigational drugs: Isoflurane or desflurane (by inhalation), ketamine, etomidate, nimodipine, chlormethiazole, topiramate (PO), levetiracetam, lamotrigine
SURGERY
Experimentalexcision of epileptic focus or propagation pathways
FOLLOW-UP
DISPOSITION
Admission Criteria
Admit to stop seizures and stabilize medical condition. Refractory status needs ICU care.
Discharge Criteria
Control of seizures and therapeutic levels of maintenance anticonvulsants
Issues for Referral
Refractory or nonconvulsive status is best referred to a neurologist.
PROGNOSIS
• Prolonged seizures (>30 minutes) may cause neurologic injury or death. For seizure >4 hours, mortality is 50%; >12 hours, mortality is 80%.
• Mortality is 16-25% in adults, 3-19% in children, extremely high in neonates, and up to 76% in the elderly. Morbidity/mortality may be related to acute CNS insult, stress from repeated seizures, cardiopulmonary arrest, renal failure, hyperthermia, aspiration pneumonia, the underlying pathology, or the treatment instituted.
PATIENT MONITORING
Therapeutic blood levels of anticonvulsants
REFERENCES
1. Prasad K, et al. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev. 2005, Issue 4: CD003723. DOI:10.1002/14651858.CD003723.pub2.
2. Walker M, Status epilepticus: An evidence based guide. BMJ. 2005;331:673-677.
3. Marik P, Varon J. The management of status epilepticus. Chest. 2004;126(2):582-591.
MISCELLANEOUS
See also: Seizure disorders; Seizures, Febrile
BASICS
DESCRIPTION
Epileptic seizure >30 minutes or absence of full recovery of consciousness between seizures. Tonic/clonic (grand mal or generalized convulsive) status epilepticus is the most common and most serious form. For description and treatment of additional types of status (focal, nonconvulsive, and neonatal) see "References".
• System(s) Affected: Nervous
• Synonym(s): Status convulsivus
ALERT
Status epilepticus is a life-threatening emergency; begin treatment if seizure lasts >5 minutes. Rapid control of seizure is critical to success.
GENERAL PREVENTION
Establish maintenance regimen of anticonvulsant.
EPIDEMIOLOGY
• Predominant age: >50% of new cases of status epilepticus occur in young children.
• Predominant sex: Male > Female
Incidence
• 18-50 cases per 100,000 per year; 1/3 as unprovoked 1st seizure, 1/6 in patients with known epilepsy, 1/2 secondary to acute CNS insult.
• Incidence is 2 times higher in elderly.
RISK FACTORS
• Seizure disorder plus any precipitating insult
• Prior history of status epilepticus (recurrence rate is 17% in children; 50% in those with neurologic abnormality)
• Porphyria
Genetics
Unknown
PATHOPHYSIOLOGY
• Direct neuronal injury: Probably an excitotoxic mechanism related to prolonged depolarization-induced apoptosis or necrotic cell death
• Associated autonomic phenomena: Excess catecholamine secretion resulting in glandular hypersecretion, piloerection, hyperthermia, cyclic pupillary dilation, and prolonged apnea/cyanosis
• Metabolic changes: Lactic acidosis, carbon dioxide narcosis, hyperkalemia, hyperglycemia followed by hypoglycemia
• Cardiac changes: Hypertension (followed by hypotension), arrhythmias, high output failure
• Respiratory changes: Increased secretions, lax tongue, possible airway obstruction, pulmonary edema, aspiration
• Renal complications: Acute tubular necrosis from myoglobinuria after rhabdomyolysis. Cerebrovascular changes: Loss of autoregulation, focal ischemia, cerebral edema; Todd paralysis may occur.
• Postitictal findings: Fever, tachycardia, mydriasis, conjugate deviation of eyes, decreased corneal reflex, positive Babinski sign; fecal and urinary incontinence; tongue, cheek, or lip injury
ETIOLOGY
Etiology varies by age group
• In adults: Usually related to a known condition, for example, established epilepsy, alcohol withdrawal, anticonvulsant withdrawal/noncompliance, or acquired CNS lesion (especially frontal)
• In children: May present in status epilepticus as their 1st seizure owing to febrile seizure, new-onset epilepsy, CNS infection, metabolic derangement
• Neonatal status: Most often related to meningitis or metabolic disorders (deficiencies of calcium, magnesium, or pyridoxine); needs careful workup for cause
• Acute or chronic CNS injury-trauma, infection, stroke, mass/vascular lesion, metabolic disorder, encephalopathy (hypoxic or degenerative type)
• Intoxication: Cocaine, tricyclic antidepressants, isoniazid, chloroquine, cephalosporins, penicillins, ciprofloxacin, cyclosporin, theophylline, tacrolimus, tiagabine, and nerve agent poisoning
• Idiopathic
DIAGNOSIS
SIGNS AND SYMPTOMS
Depends on the duration and type of seizure
• Recurrent generalized (tonic/clonic) convulsions are most common.
- May be preceded by aura
- Tonic phase (stiffening) for 30-45 seconds
- Clonic phase (rhythmic jerking) for 2-5 minutes
- No intervening consciousness; seizure recurs
History
• Pursue available drug history.
• Must search for the primary pathology
Physical Exam
Neurologic exam: Confirm true seizure (pseudo status usually atypical); look for localizing signs.
TESTS
Lab
• Glucose (rapid determination)
• Electrolytes, CBC, osmolarity
• Creatine phosphokinase
• Calcium, magnesium, phosphate
• Arterial blood gases, carboxyhemoglobin
• Toxicology screen, anticonvulsant levels
• Liver/renal function
• Coagulation profile
Imaging
• Noncontrast CT scan in new-onset seizure
• MRI or PET if more detail needed
• CXR for endotracheal tube position or suspicion of aspiration pneumonitis
Diagnostic Procedures/Surgery
• Lumbar puncture (if meningitis is suspected) NOTE: Intracranial pressure may be increased.
• EEG: Use to differentiate pseudoseizures, reveal nonconvulsive status, and confirm successful treatment. Check EEG on any patient not awake 30 minutes after seizure.
Pathological Findings
Variable
DIFFERENTIAL DIAGNOSIS
• Pseudostatus may occur with pseudoseizures. Check EEG; avoid dangerous therapy.
• Comatose or paralyzed patients and other forms of status require neurologic exam and EEG.
TREATMENT
PRE-HOSPITAL
• Support ABCs and protect patient from injury.
• Out of hospital treatment by paramedics or caretakers using buccal midazolam or rectal diazepam has been recommended (doses below).
STABILIZATION
Begin treatment if seizure lasts >5 minutes.
Simultaneous goals are
• Stop seizure.
• Find cause.
• Treat secondary complications.
GENERAL MEASURES
• Manage airway, breathing, and circulation.
• Monitor pulse oximetry, end-tidal CO2, BP, ECG, and temperature.
• Observe and confirm fit is status epilepticus.
• Give oxygen (intubate and hyperventilate if hypoventilation, hypoxia, and/or hypercarbia occur or if aspiration is a concern. If intubation is needed, use rocuronium bromide 0.6 mg/kga short-acting nondepolarizer)
• Establish 2 IV lines.
• Draw blood for initial lab studies.
• Protect patient from injury: Place on side, clear/suction airway, prevent tongue laceration.
• Place nasograstic tube in comatose patient.
• Treat any fever.
• Stop the seizure (see "Medication" below).
Diet
NPO
Activity
Bed rest
SPECIAL THERAPY
IV Fluids
• Give maintenance fluids.
• Hemodynamic instability may require fluid boluses or vasopressors (e.g., dopamine).
MEDICATION (DRUGS)
Drug(s) of choice depend on the type of seizure. Approach tonic/clonic status epilepticus as follows
• Thiamine: 100 mg IV or IM (adults only)
• 50% dextrose: If blood sugar low or cannot be measured, give 50 mL IV (for child use D25W; give 2 mL/kg slowly).
• Naloxone (Narcan): If pupils are myotic or drug overdose is suspected, give 2 mg IV (for child0.1 mg/kg IV, up to 2 mg slowly).
• Pyridoxine: If isoniazid poisoning is suspected
• Antibiotics: If meningitis is strongly suspected
• For nerve agent poisoning, give atropine, benzodiazepines, and pralidoxime (2-PAM).
First Line
• To stop seizures if IV access available
- Start with lorazepam (Ativan) (1)[A]
Give 0.05-0.15 mg/kg IV at 1-2 mg per minute to maximum of 8 mg (for child, 0.05-0.1 mg/kg IV at 2 mg/min to maximum of 4 mg)
May repeat every 10 minutes 2
- After 5 minutes, if seizure persists, add 2nd agent, fosphenytoin (Cerebyx) (2)[B], prodrug of phenytoin
15-20 mg phenytoin equivalents (PE)/kg IV at 150 mg PE per minute
May add 5-10 mg PE/kg IV
Maintenance 4-6 mg PE/kg/d IV or IM (child dose same as adult)
- If these fail, treat as refractory status epilepticus (see below).
• To stop seizures if IV access not available
- In small children, use intraosseous infusion of IV doses of benzodiazepine and fosphenytoin.
- Or use rectal diazepam (Valium)
0.2-0.5 mg/kg (child 20 mg maximum)
Use the gel form (Diastat) or IV solution.
- Or, Lorazepam (sublingual): Use IV dose.
- Or, Midazolam (Versed): 0.2 mg/kg IM or 0.5 mg/kg intranasal or buccal (onset 5-10 minutes)
- And Fosphenytoin IM: Use IV dose (slowly).
• If seizures persist (refractory status)
- Admit to ICU and induce anesthesia/drug coma (2)[B], give infusion of short-acting agent to stop seizures (see choices below).
Requires intubation, ventilation, and monitoring of EEG, ECG, pulse oximetry, and (often) BP support.
Monitor temperature and treat/cool if febrile.
Adjust to keep EEG at burst suppression.
Maintain infusion for 12-24 hours, then withdraw anesthetic infusion gradually while continuing anticonvulsant therapy.
- Use midazolam (Versed): 0.2-0.5 mg/kg slow IV bolus injection, followed by 0.5-10 ug/kg/min IV drip, titrated to burst suppression
Tachyphylaxis may develop.
- Or propofol (Diprivan): 3-5 mg/kg IV (in elderly, halve initial dose), follow with 30-150 ug/kg/min IV titrated to burst suppression
- Or thiopental (Pentothal): To 6 mg/kg in divided doses, then add 50 mg IV every 2-5 minutes to produce burst suppression, maintain with IV drip of 0.2% solution; start at 2-5 mg/kg/h and adjust based on EEG
- Contraindications: See package inserts.
Benzodiazepines (diazepam, lorazepam, midazolam) in narrow-angle glaucoma
Barbiturates in acute intermittent porphyria
Propofol in allergy to soybean oil, egg, lecithin, or glycerol
Valproic acid in hepatic disease and pregnancy (risk of neural tube defects)
- Precautions
Reduce dosage of depressants in patients with shock, coma, or alcohol intoxication.
Most drugs listed may exacerbate porphyria; exceptions: Lorazepam, midazolam, propofol.
Benzodiazepines: Apnea may occur with rapid IV injection. Reduce dose in the chronic pulmonary patient, renal failure, the elderly, and hepatic insufficiency.
Diazepam: Venous thrombosis/phlebitis
Propofol: Strict aseptic technique required. May cause stinging discomfort on injection. Prolonged use may cause lactic acidosis, lipemia, heart failure, systemic collapse, and death in both children and adults. Safety not established for child 3 years old
Fosphenytoin (Cerebyx)/Phenytoin: Safety is not established for children. Monitor for arrhythmias, prolonged QT interval, and hypotension. If these occur, decrease rate of administration. Use with caution in liver disease, hyperglycemia, the elderly, and pregnancy (increased risk of malformations, may lead to vitamin K deficiency bleeding problems in both mother and newborn). Abrupt withdrawal may precipitate status. Overdose may cause paradoxical inefficacy.
Valproic acid: May decrease platelet function; may cause hyperammonemic encephalopathy.
- Significant possible interactions
Fosphenytoin/phenytoin: Increased serum levels and toxicity of warfarin, disulfiram, phenylbutazone, and isoniazid. Decrease dose with renal insufficiency.
Valproic acid: Increased toxicity of phenytoin/fosphenytoin
Second Line
• Diazepam (Valium): (2)[B] Use for lorazepam
- 0.2-0.5 mg/kg IV at 5 mg/min up to a dose of 30 mg (for child 0.3 mg/kg at 2 mg/min IV up to 10 mg total)
- Repeat q5min 3, wears off quickly
• Phenytoin: (2)[B]Use for fosphenytoin. Doses are the same (mg for mg Phenytoin equivalents), but must be given more slowly (1 mg/kg/min) to lessen toxicity and cardiovascular depression
• Other 2nd-line drugs
- Pentobarbital: 10-15 mg/kg IV loading dose over 1 hour, followed by continuous infusion of 0.5-1 mg/kg/h; adjust based on EEG
- Lidocaine (Xylocaine): 1-3 mg/kg IV bolus. If effective, drip at 3-10 mg/kg/h IV.
- Valproic acid: Clinical pilot studies have used 15-40 mg/kg IV loading dose over 5-10 minutes, followed by 1-5 mg/kg/h.
• Investigational drugs: Isoflurane or desflurane (by inhalation), ketamine, etomidate, nimodipine, chlormethiazole, topiramate (PO), levetiracetam, lamotrigine
SURGERY
Experimentalexcision of epileptic focus or propagation pathways
FOLLOW-UP
DISPOSITION
Admission Criteria
Admit to stop seizures and stabilize medical condition. Refractory status needs ICU care.
Discharge Criteria
Control of seizures and therapeutic levels of maintenance anticonvulsants
Issues for Referral
Refractory or nonconvulsive status is best referred to a neurologist.
PROGNOSIS
• Prolonged seizures (>30 minutes) may cause neurologic injury or death. For seizure >4 hours, mortality is 50%; >12 hours, mortality is 80%.
• Mortality is 16-25% in adults, 3-19% in children, extremely high in neonates, and up to 76% in the elderly. Morbidity/mortality may be related to acute CNS insult, stress from repeated seizures, cardiopulmonary arrest, renal failure, hyperthermia, aspiration pneumonia, the underlying pathology, or the treatment instituted.
PATIENT MONITORING
Therapeutic blood levels of anticonvulsants
REFERENCES
1. Prasad K, et al. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev. 2005, Issue 4: CD003723. DOI:10.1002/14651858.CD003723.pub2.
2. Walker M, Status epilepticus: An evidence based guide. BMJ. 2005;331:673-677.
3. Marik P, Varon J. The management of status epilepticus. Chest. 2004;126(2):582-591.
MISCELLANEOUS
See also: Seizure disorders; Seizures, Febrile
SPRAINS AND STRAINS
SPRAINS AND STRAINS - John Herbert Stevenson, MD; Christopher Lutryzkowski, MD; Peter L. Hoth, MD
BASICS
DESCRIPTION
• Sprains are complete or partial ligamentous injuries either within the body of the ligament or at the site of attachment to bone.
- May be classified as Grade I, II, or III (AMA Ligament Injury Classification) (4)
- Grade I: Stretch injury without ligamentous laxity
- Grade II: Partial tear with increased ligamentous laxity but firm end-point on exam
- Grade III: Complete tear with increased ligamentous laxity and no firm end-point on exam
- Physical exam is the key to the diagnosis.
- Usually secondary to trauma (falls, twisting injuries or motor vehicle accidents)
• Strains are partial or complete disruptions of the muscle, muscle/tendon junction, or tendon; they can be associated with overuse injuries. May be classified as
- 1st degree: Minimal damage to muscle, tendon or musculotendinous unit.
- 2nd degree: Partial tear to the muscle, tendon, or musculotendinous unit
- 3rd degree: Complete disruption of the muscle, etc. (4)
• System(s) Affected: Musculoskeletal
ALERT
Geriatric Considerations
More likely to see associated bony injuries due to decreased joint flexibility and prevalence of osteoporosis and osteopenia
Pediatric Considerations
• Sprains and strains have been found to account for 24% of injuries in pediatric patients.
• 3 million pediatric sports injuries occur annually.
• Must be concerned about physeal/apophyseal injuries in the skeletally immature.
GENERAL PREVENTION
• Maintain a reasonable level of physical conditioning.
• Avoid excessive physical stresses, and wear proper exercise gear (particularly shoes).
• Use proper equipment for the activity.
• Know the risks associated with the intended activity.
• Use appropriate conditioning, warm-up, and cool-down exercises.
• Single leg balancing may help prevent ankle sprains. (1)
• Taping/bracing postinjury may be of short-term benefit for future injury prevention of ankle sprains. (5)[B]
EPIDEMIOLOGY
Incidence
~80% of all US athletes at sometime in their career will experience a sprain or strain that involves the upper or lower extremities, or spine.
Prevalence
• Ankle sprains are one of the most common injuries seen in the primary care setting, making up to 30% of sports medicine clinic visits. (7)
• Predominant age
- Sprains: Any age when patient is physically active
- Strains: Usually 15-40 years
• Predominant sex: Male > Female
RISK FACTORS
• Change in or improper shoe gear, protective gear, or environment (e.g., surface)
• Inappropriate sudden increase in training schedule
• Prior history of sprain or strain
ETIOLOGY
• Falls
• Motor vehicle accident
• Trauma
• Excessive exercise
• Inadequate warm-up and stretching prior to activity
• Poor conditioning
ASSOCIATED CONDITIONS
• Hemarthrosis
• Stress, avulsion, or other fractures
• Syndesmotic injuries
• Contusions
• Wounds
• Dislocations
• Subluxations
DIAGNOSIS
SIGNS AND SYMPTOMS
• Swelling
• Pain
• Ecchymosis (usually late)
• Tenderness
• Gait disturbances if severe
• Decreased ROM of joint and joint instability
History
• May describe feeling or hearing pop or snap
• May remember mechanism (key in diagnosis)
Physical Exam
Sprains
• Grade I: Tenderness without laxity
• Grade II: Tenderness, with increased laxity on exam but firm endpoint
• Grade III: Tenderness, with increased laxity on exam and no firm endpoint
TESTS
Special tests
• Examination under anesthesia and/or arthroscopy may be required in some cases.
• For ankle, use the anterior drawer test, which tests the integrity of the anterior talofibular ligament.
• Apprehension test may indicate glenohumeral ligament sprain of the shoulder.
• Lachman test assesses integrity of ACL.
Imaging
• Radiographs may be needed to rule out bony injury; stress views may be helpful.
• Ankle films (Ottawa ankle rules) [A]
- Bone tenderness in posterior aspect distal 6 cm of tibia/fibula
- Inability to bear weight, both immediately or in emergency department/office
- Age >18 and 55 (8)
• Foot films: Only required if midfoot zone pain is present and
- Bone tenderness at base of 5th metatarsal; or
- Bone tenderness at navicular: or
- Inability to bear weight, immediately or in emergency department
• CT scan of the affected area may be required if occult fracture is suspected, with negative films.
• MRI is gold standard for imaging soft-tissue structures including muscle, ligamentous, and intra-articular structures.
• Exam under anesthesia in difficult cases.
Diagnostic Procedures/Surgery
Surgery may be required for some partial and complete sprains. Need for surgery depends on the ability of ligaments or muscle to heal on their own or ability to attain full ROM and stability of the affected joint.
DIFFERENTIAL DIAGNOSIS
• Tendonitis
• Bursitis
• Contusion
• Hematoma
• Fracture
• Rheumatologic process
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• History and physical exam along with treatment of the worst possible suspected injury
• Acutely: PRICEMM therapy: Protection, relative rest, ice, compression, elevation, medications, modalities. For cryotherapy, see (9)[B].
- Elastic bandage wrap (Ace) if comfortable
- Jones dressing for more severe injuries
• Orthosis (splint) for pain relief and stability; air cast-type devices provide effective stability and pain relief for ankle sprains.
• Crutches and crutch gait training
• Stirrup-type ankle brace (3)[A]
Diet
Weight loss if obesity is etiologic.
Activity
If affected joint has full strength and ROM, patient can advance activity as tolerated.
SPECIAL THERAPY
Physical Therapy
• Useful adjunct after injury (6)[B]
• Proprioception retraining (2)[C]
• Core strengthening (2)[C]
• Eccentric exercises (2)[C]
MEDICATION (DRUGS)
First Line
• NSAIDs (9)[C]
- Ibuprofen: 200-800 mg t.i.d.
- Naproxen: 375-500 mg b.i.d.
- Indomethacin: 25-50 mg t.i.d.
- Acetaminophen (11)[B]
- Narcotics for severe pain (e.g., acetaminophen-hydrocodone)
• Contraindications: Refer to the manufacturer's profile of each drug.
• Precautions: Refer to the manufacturer's profile of each drug.
• Significant possible interactions: Refer to the manufacturer's profile of each drug.
SURGERY
Casting and surgery are reserved for select grade III injuries.
FOLLOW-UP
DISPOSITION
Issues for Referral
• ACL sprain in athletes/physically active
• Salter-Harris physeal fractures
• Lack of improvement with conservative measures
• Joint instability
• Tendon disruption (i.e., Achilles, biceps).
PROGNOSIS
With appropriate treatment and rest, 1-8 weeks or longer for recovery, depending on severity of injury
COMPLICATIONS
• Chronic joint instability
• Arthritis
• Muscle contracture
PATIENT MONITORING
After initial treatment, consider rehabilitation. Direct emphasis toward limiting swelling and providing a painfree full ROM.
REFERENCES
1. McGuine TA, Keene JS. The effect of a balance training program on the risk of ankle sprains in high school athletes. Am J Sports Med. 2006;34(7):1103-1111.
2. Brukner PD, Crossley KM, Morris H, et al. Recent advances in sports medicine. Med J Aust. 2006;184(4):188-193.
3. Boyce SH, Quigley MA, Campbell S. Management of ankle sprains: A randomized controlled trial of the treatment of inversion ankle sprains using an elastic support bandage or an Aircast ankle brace. Br J Sports Med. 2005;39(2):91-96.
4. O'Connor F, et al. Sports medicine: Just the facts. New York: McGraw-Hill, 2005;34.
5. Handoll HHG, Rowe BH, Quinn KM, et al. Interventions for preventing ankle injuries. Cochrane Database of Systematic Rev. 5/26/2005 review.
6. Kerkhoffs, et al. Immobilisation and functional treatment for acute lateral ankle ligament injuries in adults. Cochrane Database of Systematic Rev.12/16/2004 review.
7. Mahaffey D, Hilts M, Fields KB. Ankle and foot injuries in sports. Clin Fam Pract. 1999;1:233-250.
8. Stiell IG, McKnight RD, Greenberg GH, et al. Implementation of the Ottawa ankle rules. JAMA. 1994;271:827-832.
9. Nyland J. Therapeutic modality: Rehabilitation of the injured athlete. Clin Sports Med. 2004;23(2): 299-313, vii.
10. Mehallo CJ. Practical management: Nonsteroidal anti-inflammatory drug use in athletic injuries. Clin J Sport Med. 2006;16(2):170-174.
11. Dalton JD Jr., Schweinle JE. Randomized controlled noninferiority trial to compare extended release acetaminophen and ibuprofen for the treatment of ankle sprains. Ann Emerg Med.2006;48(5):615-623.
MISCELLANEOUS
See also: Tendonitis
BASICS
DESCRIPTION
• Sprains are complete or partial ligamentous injuries either within the body of the ligament or at the site of attachment to bone.
- May be classified as Grade I, II, or III (AMA Ligament Injury Classification) (4)
- Grade I: Stretch injury without ligamentous laxity
- Grade II: Partial tear with increased ligamentous laxity but firm end-point on exam
- Grade III: Complete tear with increased ligamentous laxity and no firm end-point on exam
- Physical exam is the key to the diagnosis.
- Usually secondary to trauma (falls, twisting injuries or motor vehicle accidents)
• Strains are partial or complete disruptions of the muscle, muscle/tendon junction, or tendon; they can be associated with overuse injuries. May be classified as
- 1st degree: Minimal damage to muscle, tendon or musculotendinous unit.
- 2nd degree: Partial tear to the muscle, tendon, or musculotendinous unit
- 3rd degree: Complete disruption of the muscle, etc. (4)
• System(s) Affected: Musculoskeletal
ALERT
Geriatric Considerations
More likely to see associated bony injuries due to decreased joint flexibility and prevalence of osteoporosis and osteopenia
Pediatric Considerations
• Sprains and strains have been found to account for 24% of injuries in pediatric patients.
• 3 million pediatric sports injuries occur annually.
• Must be concerned about physeal/apophyseal injuries in the skeletally immature.
GENERAL PREVENTION
• Maintain a reasonable level of physical conditioning.
• Avoid excessive physical stresses, and wear proper exercise gear (particularly shoes).
• Use proper equipment for the activity.
• Know the risks associated with the intended activity.
• Use appropriate conditioning, warm-up, and cool-down exercises.
• Single leg balancing may help prevent ankle sprains. (1)
• Taping/bracing postinjury may be of short-term benefit for future injury prevention of ankle sprains. (5)[B]
EPIDEMIOLOGY
Incidence
~80% of all US athletes at sometime in their career will experience a sprain or strain that involves the upper or lower extremities, or spine.
Prevalence
• Ankle sprains are one of the most common injuries seen in the primary care setting, making up to 30% of sports medicine clinic visits. (7)
• Predominant age
- Sprains: Any age when patient is physically active
- Strains: Usually 15-40 years
• Predominant sex: Male > Female
RISK FACTORS
• Change in or improper shoe gear, protective gear, or environment (e.g., surface)
• Inappropriate sudden increase in training schedule
• Prior history of sprain or strain
ETIOLOGY
• Falls
• Motor vehicle accident
• Trauma
• Excessive exercise
• Inadequate warm-up and stretching prior to activity
• Poor conditioning
ASSOCIATED CONDITIONS
• Hemarthrosis
• Stress, avulsion, or other fractures
• Syndesmotic injuries
• Contusions
• Wounds
• Dislocations
• Subluxations
DIAGNOSIS
SIGNS AND SYMPTOMS
• Swelling
• Pain
• Ecchymosis (usually late)
• Tenderness
• Gait disturbances if severe
• Decreased ROM of joint and joint instability
History
• May describe feeling or hearing pop or snap
• May remember mechanism (key in diagnosis)
Physical Exam
Sprains
• Grade I: Tenderness without laxity
• Grade II: Tenderness, with increased laxity on exam but firm endpoint
• Grade III: Tenderness, with increased laxity on exam and no firm endpoint
TESTS
Special tests
• Examination under anesthesia and/or arthroscopy may be required in some cases.
• For ankle, use the anterior drawer test, which tests the integrity of the anterior talofibular ligament.
• Apprehension test may indicate glenohumeral ligament sprain of the shoulder.
• Lachman test assesses integrity of ACL.
Imaging
• Radiographs may be needed to rule out bony injury; stress views may be helpful.
• Ankle films (Ottawa ankle rules) [A]
- Bone tenderness in posterior aspect distal 6 cm of tibia/fibula
- Inability to bear weight, both immediately or in emergency department/office
- Age >18 and 55 (8)
• Foot films: Only required if midfoot zone pain is present and
- Bone tenderness at base of 5th metatarsal; or
- Bone tenderness at navicular: or
- Inability to bear weight, immediately or in emergency department
• CT scan of the affected area may be required if occult fracture is suspected, with negative films.
• MRI is gold standard for imaging soft-tissue structures including muscle, ligamentous, and intra-articular structures.
• Exam under anesthesia in difficult cases.
Diagnostic Procedures/Surgery
Surgery may be required for some partial and complete sprains. Need for surgery depends on the ability of ligaments or muscle to heal on their own or ability to attain full ROM and stability of the affected joint.
DIFFERENTIAL DIAGNOSIS
• Tendonitis
• Bursitis
• Contusion
• Hematoma
• Fracture
• Rheumatologic process
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• History and physical exam along with treatment of the worst possible suspected injury
• Acutely: PRICEMM therapy: Protection, relative rest, ice, compression, elevation, medications, modalities. For cryotherapy, see (9)[B].
- Elastic bandage wrap (Ace) if comfortable
- Jones dressing for more severe injuries
• Orthosis (splint) for pain relief and stability; air cast-type devices provide effective stability and pain relief for ankle sprains.
• Crutches and crutch gait training
• Stirrup-type ankle brace (3)[A]
Diet
Weight loss if obesity is etiologic.
Activity
If affected joint has full strength and ROM, patient can advance activity as tolerated.
SPECIAL THERAPY
Physical Therapy
• Useful adjunct after injury (6)[B]
• Proprioception retraining (2)[C]
• Core strengthening (2)[C]
• Eccentric exercises (2)[C]
MEDICATION (DRUGS)
First Line
• NSAIDs (9)[C]
- Ibuprofen: 200-800 mg t.i.d.
- Naproxen: 375-500 mg b.i.d.
- Indomethacin: 25-50 mg t.i.d.
- Acetaminophen (11)[B]
- Narcotics for severe pain (e.g., acetaminophen-hydrocodone)
• Contraindications: Refer to the manufacturer's profile of each drug.
• Precautions: Refer to the manufacturer's profile of each drug.
• Significant possible interactions: Refer to the manufacturer's profile of each drug.
SURGERY
Casting and surgery are reserved for select grade III injuries.
FOLLOW-UP
DISPOSITION
Issues for Referral
• ACL sprain in athletes/physically active
• Salter-Harris physeal fractures
• Lack of improvement with conservative measures
• Joint instability
• Tendon disruption (i.e., Achilles, biceps).
PROGNOSIS
With appropriate treatment and rest, 1-8 weeks or longer for recovery, depending on severity of injury
COMPLICATIONS
• Chronic joint instability
• Arthritis
• Muscle contracture
PATIENT MONITORING
After initial treatment, consider rehabilitation. Direct emphasis toward limiting swelling and providing a painfree full ROM.
REFERENCES
1. McGuine TA, Keene JS. The effect of a balance training program on the risk of ankle sprains in high school athletes. Am J Sports Med. 2006;34(7):1103-1111.
2. Brukner PD, Crossley KM, Morris H, et al. Recent advances in sports medicine. Med J Aust. 2006;184(4):188-193.
3. Boyce SH, Quigley MA, Campbell S. Management of ankle sprains: A randomized controlled trial of the treatment of inversion ankle sprains using an elastic support bandage or an Aircast ankle brace. Br J Sports Med. 2005;39(2):91-96.
4. O'Connor F, et al. Sports medicine: Just the facts. New York: McGraw-Hill, 2005;34.
5. Handoll HHG, Rowe BH, Quinn KM, et al. Interventions for preventing ankle injuries. Cochrane Database of Systematic Rev. 5/26/2005 review.
6. Kerkhoffs, et al. Immobilisation and functional treatment for acute lateral ankle ligament injuries in adults. Cochrane Database of Systematic Rev.12/16/2004 review.
7. Mahaffey D, Hilts M, Fields KB. Ankle and foot injuries in sports. Clin Fam Pract. 1999;1:233-250.
8. Stiell IG, McKnight RD, Greenberg GH, et al. Implementation of the Ottawa ankle rules. JAMA. 1994;271:827-832.
9. Nyland J. Therapeutic modality: Rehabilitation of the injured athlete. Clin Sports Med. 2004;23(2): 299-313, vii.
10. Mehallo CJ. Practical management: Nonsteroidal anti-inflammatory drug use in athletic injuries. Clin J Sport Med. 2006;16(2):170-174.
11. Dalton JD Jr., Schweinle JE. Randomized controlled noninferiority trial to compare extended release acetaminophen and ibuprofen for the treatment of ankle sprains. Ann Emerg Med.2006;48(5):615-623.
MISCELLANEOUS
See also: Tendonitis
SPOROTRICHOSIS
SPOROTRICHOSIS - Linda J. Machado, MD; Ronald A. Greenfield, MD
BASICS
DESCRIPTION
• Subacute or chronic fungal infection
• Occurs in the following forms
- Cutaneous or lymphocutaneous
- Pulmonary
- Osteoarticular
- Disseminated
• Most likely to occur in farmers, horticulturists, and gardeners
• System(s) Affected: Hemic/Lymphatic/Immunologic; Musculoskeletal; Skin/Exocrine
• Synonym(s): Schenck disease; Rose gardener disease
GENERAL PREVENTION
• Avoid areas where sporotrichosis is endemic.
• Wear gloves when working in soil.
EPIDEMIOLOGY
• Predominant age: Adults
• Predominant sex: Male > Female (mostly as a result of occupational exposure)
ALERT
Pediatric Considerations
Rare
Incidence
1:100,000 person/year
RISK FACTORS
• Gardening: Contact with mulch, sphagnum moss, hay, timber, or thorny bushes
• Occupations involving the handling of gardening materials: Nursery workers, landscapers, florists, carpenters
• Animal handlers (transmission from animals, especially cats, to humans has been documented)
• Immunocompromised patient (e.g., because of drugs or HIV infection)
• Alcoholism (factor for pulmonary and disseminated forms)
• HIV/AIDS patients are at increased risk for disseminated disease involving the CNS.
Genetics
No known genetic pattern
PATHOPHYSIOLOGY
• Lymphocutaneous
• Primary lesion forms 1-10+ weeks following direct inoculation and spreads along lymphatic channels.
• Osteoarticular
• Results from direct extension of a cutaneous lesion or dissemination
• Pulmonary
• Pathogenesis unclear, likely inhalation or dissemination
• Disseminated disease results from hematogenous spread
ETIOLOGY
Infection with Sporothrix schenckii, a fungus found in soil, sphagnum peat moss, and decaying vegetation
ASSOCIATED CONDITIONS
See "Risk Factors".
DIAGNOSIS
SIGNS AND SYMPTOMS
• Cutaneous or lymphocutaneous
- Characteristic skin lesions beginning as an inoculation chancre, or erythematous plaque with satellite, small papule, painless, movable, subcutaneous nodules in a linear distribution. Lesions progress to larger nodules, which may ulcerate and drain. Affects primarily upper extremities.
- Additional lesions spread proximally along lymphatics.
• Pulmonary
- Cough, occasionally productive
- Rare hemoptysis
- Cavitary lung disease
- Hilar adenopathy
- Signs and symptoms indistinguishable from other chronic pneumonias
• Osteoarticular
- Subacute or chronic inflammatory arthritis, often monoarticular; may persist for many years
- Signs and symptoms of osteomyelitis
- Generally afebrile
• Disseminated
- Multifocal skin lesions
- Polyarticular arthritis
- Weight loss
- Chronic lymphocytic meningitis
History
Skin trauma-associated involving contact with plants or plant products. Animal-to-human transmission documented (dogs, cats, horses, squirrels, pigs, and insects) (2)
Physical Exam
See "Signs and Symptoms".
TESTS
Immunohistochemical staining of biopsy specimens
Lab
• Culture of S. schenckii in sputum, pus, synovial fluid, or bone drainage
• Organism found with difficulty with periodic acid-Schiff and Gomori stains of skin or other biopsied lesions
• Drugs that may alter lab results: Antifungal drugs
Imaging
Chest and skeletal x-rays
Diagnostic Procedures/Surgery
• Careful history and physical examination
• Culture of draining lesions
• Culture of inflammatory joint effusions or sputum
• Biopsy if diagnosis not confirmed
Pathological Findings
Granulomas with central necrosis
DIFFERENTIAL DIAGNOSIS
• Cutaneous or lymphocutaneous (2)
- Sporotrichoid nocardiosis
- Leishmaniasis
- Chromomycosis
- Atypical mycobacterial infection (Mycobacterium marinum, M. chelonae, M. kansasii)
- Tularemia
- Plague
• Pulmonary
- Tuberculosis
- Sarcoidosis
- Chronic fungal pneumonia
- Neoplasm
- Atypical mycobacterial infection (M. avium complex, M. kansasii)
- Rhodococcus equi infection
- Nocardia spp. infections
• Osteoarticular
- Rheumatoid arthritis
- Bacterial arthritis/osteomyelitis
TREATMENT
STABILIZATION
• Many patients can be managed on an outpatient basis.
• Hospitalization for adjunctive surgical procedures or initiation of amphotericin B therapy
GENERAL MEASURES
• Local heat application is useful for cutaneous and lymphocutaneous disease.
• Keep cutaneous lesions clean.
• Repeated drainage of infected joints may be indicated.
Diet
No special diet
Activity
No restrictions
MEDICATION (DRUGS)
First Line
• Cutaneous or lymphocutaneous disease
- Itraconazole 100-200 mg/d for 3-6 months (3)[A]
- Fluconazole 400 mg/d for 6 months (3)[B]
- Potassium iodide saturated solution (SSKI) is an alternative treatment. Initially, 5 drops orally t.i.d., increased by 1 drop each dose to 40-50 drops t.i.d. as tolerated for 3-6 months. (3)[B] Dilute in a beverage to disguise taste.
• Pulmonary
- Amphotericin B for extensive or life-threatening disease (0.5 mg/kg/d up to 1-2 g total dose) (3)[B]
- Itraconazole 200 mg b.i.d. for non-life-threatening disease (3)[B]
- Surgical resection combined with antifungals when feasible (3)[B]
• Osteoarticular: Itraconazole 200 mg b.i.d. for 12 months (3)[A]
• Fluconazole 800 mg/d for 12 months (3)[B]
• Meningeal and disseminated: Amphotericin B, total dose, 1-2 g (3)[A]
• AIDS: Amphotericin B until clinical improvement, (3)[B] then itraconazole 200 mg b.i.d (3)[C]
• Pregnancy: Local hyperthermia for lymphocu-taneous infection (3)[B]; amphotericin B for serious infection (3)[A]
• SSKI is contraindicated in tuberculosis.
• Precautions
- Amphotericin B may cause fever, chills, nausea, and vomiting. Refer to manufacturer's literature for precautions, adverse effects, and interactions.
- SSKI requires extra care if patient also has tuberculosis, kidney disease, renal dysfunction, or hyperthyroidism. May cause folliculitis and tender, swollen salivary glands
- Itraconazole capsule absorption may be decreased with concomitant administration of antacids or gastric acid secretion suppressors.
• Significant possible interactions
- SSKI taken concurrently with amiloride, spironolactone, or triamterene may result in hyperkalemia.
- Itraconazole taken with terfenadine or astemizole may result in life-threatening cardiac dysrhythmias.
Second Line
Terbinafine, though not approved for treatment of sporotrichosis, may be a reasonable alternative to itraconazole for lymphocutaneous disease. (3)[C],(4)
SURGERY
• Synovectomy of infected joints may be indicated.
• Surgical debridement of osteomyelitis is usually indicated.
FOLLOW-UP
DISPOSITION
Issues for Referral
Infectious diseases consultation suggested for optimal management
PROGNOSIS
• Excellent for complete recovery from cutaneous or lymphocutaneous infections
• Other disease forms demonstrate a chronic indolent course and are variably responsive to therapy.
• AIDS patients often have a poor outcome.
COMPLICATIONS
• Secondary bacterial infection
• Bone and joint deformities from osteoarticular disease
• Rare ocular disease due to direct inoculation
PATIENT MONITORING
• Check for compliance with long-term drug therapy (SSKI should be continued for 1-2 months after lesions heal).
• Hepatic enzyme tests should be monitored periodically in patients receiving itraconazole treatment for >1 month.
REFERENCES
1. Pappas PG. Sporotrichosis. In: Dismukes WE, Pappas PG, Sobel JD, eds. Clinical Mycology. New York, NY: Oxford University Press; 2003: 346-354.
2. Rex JH, Okhuysen PC. Sporothrix schenckii. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 6th ed. New York, NY: Elsevier Churchill Livingstone; 2005: 2984-2988.
3. Kauffman CA, Haijeh R, Chapman SW, for the Mycoses Study Group. Practice guidelines for the management of patients with sporotrichosis. Clin Infect Dis. 2000;30:684-687.
4. Greenfield RA. Sporothrix schenckii. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious Diseases. 3rd ed. Philadelphia, PA: Lippincott Williams; Wilkins; 2004: 2246-2249.
BASICS
DESCRIPTION
• Subacute or chronic fungal infection
• Occurs in the following forms
- Cutaneous or lymphocutaneous
- Pulmonary
- Osteoarticular
- Disseminated
• Most likely to occur in farmers, horticulturists, and gardeners
• System(s) Affected: Hemic/Lymphatic/Immunologic; Musculoskeletal; Skin/Exocrine
• Synonym(s): Schenck disease; Rose gardener disease
GENERAL PREVENTION
• Avoid areas where sporotrichosis is endemic.
• Wear gloves when working in soil.
EPIDEMIOLOGY
• Predominant age: Adults
• Predominant sex: Male > Female (mostly as a result of occupational exposure)
ALERT
Pediatric Considerations
Rare
Incidence
1:100,000 person/year
RISK FACTORS
• Gardening: Contact with mulch, sphagnum moss, hay, timber, or thorny bushes
• Occupations involving the handling of gardening materials: Nursery workers, landscapers, florists, carpenters
• Animal handlers (transmission from animals, especially cats, to humans has been documented)
• Immunocompromised patient (e.g., because of drugs or HIV infection)
• Alcoholism (factor for pulmonary and disseminated forms)
• HIV/AIDS patients are at increased risk for disseminated disease involving the CNS.
Genetics
No known genetic pattern
PATHOPHYSIOLOGY
• Lymphocutaneous
• Primary lesion forms 1-10+ weeks following direct inoculation and spreads along lymphatic channels.
• Osteoarticular
• Results from direct extension of a cutaneous lesion or dissemination
• Pulmonary
• Pathogenesis unclear, likely inhalation or dissemination
• Disseminated disease results from hematogenous spread
ETIOLOGY
Infection with Sporothrix schenckii, a fungus found in soil, sphagnum peat moss, and decaying vegetation
ASSOCIATED CONDITIONS
See "Risk Factors".
DIAGNOSIS
SIGNS AND SYMPTOMS
• Cutaneous or lymphocutaneous
- Characteristic skin lesions beginning as an inoculation chancre, or erythematous plaque with satellite, small papule, painless, movable, subcutaneous nodules in a linear distribution. Lesions progress to larger nodules, which may ulcerate and drain. Affects primarily upper extremities.
- Additional lesions spread proximally along lymphatics.
• Pulmonary
- Cough, occasionally productive
- Rare hemoptysis
- Cavitary lung disease
- Hilar adenopathy
- Signs and symptoms indistinguishable from other chronic pneumonias
• Osteoarticular
- Subacute or chronic inflammatory arthritis, often monoarticular; may persist for many years
- Signs and symptoms of osteomyelitis
- Generally afebrile
• Disseminated
- Multifocal skin lesions
- Polyarticular arthritis
- Weight loss
- Chronic lymphocytic meningitis
History
Skin trauma-associated involving contact with plants or plant products. Animal-to-human transmission documented (dogs, cats, horses, squirrels, pigs, and insects) (2)
Physical Exam
See "Signs and Symptoms".
TESTS
Immunohistochemical staining of biopsy specimens
Lab
• Culture of S. schenckii in sputum, pus, synovial fluid, or bone drainage
• Organism found with difficulty with periodic acid-Schiff and Gomori stains of skin or other biopsied lesions
• Drugs that may alter lab results: Antifungal drugs
Imaging
Chest and skeletal x-rays
Diagnostic Procedures/Surgery
• Careful history and physical examination
• Culture of draining lesions
• Culture of inflammatory joint effusions or sputum
• Biopsy if diagnosis not confirmed
Pathological Findings
Granulomas with central necrosis
DIFFERENTIAL DIAGNOSIS
• Cutaneous or lymphocutaneous (2)
- Sporotrichoid nocardiosis
- Leishmaniasis
- Chromomycosis
- Atypical mycobacterial infection (Mycobacterium marinum, M. chelonae, M. kansasii)
- Tularemia
- Plague
• Pulmonary
- Tuberculosis
- Sarcoidosis
- Chronic fungal pneumonia
- Neoplasm
- Atypical mycobacterial infection (M. avium complex, M. kansasii)
- Rhodococcus equi infection
- Nocardia spp. infections
• Osteoarticular
- Rheumatoid arthritis
- Bacterial arthritis/osteomyelitis
TREATMENT
STABILIZATION
• Many patients can be managed on an outpatient basis.
• Hospitalization for adjunctive surgical procedures or initiation of amphotericin B therapy
GENERAL MEASURES
• Local heat application is useful for cutaneous and lymphocutaneous disease.
• Keep cutaneous lesions clean.
• Repeated drainage of infected joints may be indicated.
Diet
No special diet
Activity
No restrictions
MEDICATION (DRUGS)
First Line
• Cutaneous or lymphocutaneous disease
- Itraconazole 100-200 mg/d for 3-6 months (3)[A]
- Fluconazole 400 mg/d for 6 months (3)[B]
- Potassium iodide saturated solution (SSKI) is an alternative treatment. Initially, 5 drops orally t.i.d., increased by 1 drop each dose to 40-50 drops t.i.d. as tolerated for 3-6 months. (3)[B] Dilute in a beverage to disguise taste.
• Pulmonary
- Amphotericin B for extensive or life-threatening disease (0.5 mg/kg/d up to 1-2 g total dose) (3)[B]
- Itraconazole 200 mg b.i.d. for non-life-threatening disease (3)[B]
- Surgical resection combined with antifungals when feasible (3)[B]
• Osteoarticular: Itraconazole 200 mg b.i.d. for 12 months (3)[A]
• Fluconazole 800 mg/d for 12 months (3)[B]
• Meningeal and disseminated: Amphotericin B, total dose, 1-2 g (3)[A]
• AIDS: Amphotericin B until clinical improvement, (3)[B] then itraconazole 200 mg b.i.d (3)[C]
• Pregnancy: Local hyperthermia for lymphocu-taneous infection (3)[B]; amphotericin B for serious infection (3)[A]
• SSKI is contraindicated in tuberculosis.
• Precautions
- Amphotericin B may cause fever, chills, nausea, and vomiting. Refer to manufacturer's literature for precautions, adverse effects, and interactions.
- SSKI requires extra care if patient also has tuberculosis, kidney disease, renal dysfunction, or hyperthyroidism. May cause folliculitis and tender, swollen salivary glands
- Itraconazole capsule absorption may be decreased with concomitant administration of antacids or gastric acid secretion suppressors.
• Significant possible interactions
- SSKI taken concurrently with amiloride, spironolactone, or triamterene may result in hyperkalemia.
- Itraconazole taken with terfenadine or astemizole may result in life-threatening cardiac dysrhythmias.
Second Line
Terbinafine, though not approved for treatment of sporotrichosis, may be a reasonable alternative to itraconazole for lymphocutaneous disease. (3)[C],(4)
SURGERY
• Synovectomy of infected joints may be indicated.
• Surgical debridement of osteomyelitis is usually indicated.
FOLLOW-UP
DISPOSITION
Issues for Referral
Infectious diseases consultation suggested for optimal management
PROGNOSIS
• Excellent for complete recovery from cutaneous or lymphocutaneous infections
• Other disease forms demonstrate a chronic indolent course and are variably responsive to therapy.
• AIDS patients often have a poor outcome.
COMPLICATIONS
• Secondary bacterial infection
• Bone and joint deformities from osteoarticular disease
• Rare ocular disease due to direct inoculation
PATIENT MONITORING
• Check for compliance with long-term drug therapy (SSKI should be continued for 1-2 months after lesions heal).
• Hepatic enzyme tests should be monitored periodically in patients receiving itraconazole treatment for >1 month.
REFERENCES
1. Pappas PG. Sporotrichosis. In: Dismukes WE, Pappas PG, Sobel JD, eds. Clinical Mycology. New York, NY: Oxford University Press; 2003: 346-354.
2. Rex JH, Okhuysen PC. Sporothrix schenckii. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 6th ed. New York, NY: Elsevier Churchill Livingstone; 2005: 2984-2988.
3. Kauffman CA, Haijeh R, Chapman SW, for the Mycoses Study Group. Practice guidelines for the management of patients with sporotrichosis. Clin Infect Dis. 2000;30:684-687.
4. Greenfield RA. Sporothrix schenckii. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious Diseases. 3rd ed. Philadelphia, PA: Lippincott Williams; Wilkins; 2004: 2246-2249.
SPINAL STENOSIS
SPINAL STENOSIS - Dhruv B. Pateder, MD; Donald S. Corenman, MD, DC
BASICS
DESCRIPTION
Spinal stenosis is a condition in which a narrowing of the spinal canal and foramen occurs. Although myriad of etiologies exist, in the most generic sense, it refers to compression of the lumbar spinal elements secondary to arthritic changes (bone spurs, hypertrophied ligamentum flavum, disc space narrowing). This condition generally causes back/buttock pain with possible radiation in the lower extremities if foraminal stenosis also is present.
GENERAL PREVENTION
There is no known way to prevent spinal stenosis but symptoms can be alleviated by any means that "open up" the spinal canal and foramen, such as leaning forward when walking.
EPIDEMIOLOGY
The prevalence of spinal stenosis increases with age, because it is essentially an arthritic condition from "wear and tear" on the normal spine.
• Symptoms develop in 5th and 6th decades
• No sex predominance
• Degenerative spondylolisthesis with spinal stenosis is 4 times more common in women.
Incidence
The incidence of symptomatic spinal stenosis is as high as 8% of the population.
Prevalence
The prevalence increases with age and can be as high as 100% on assessment by radiographic studies on elderly patients; however, it is important to remember that not all patients with radiographic spinal stenosis are symptomatic.
RISK FACTORS
Increasing age and spinal arthritis
Genetics
No definitive genetic links
PATHOPHYSIOLOGY
Disc dehydration leads to loss of height with bulging of annulus and ligamentum flavum into the spinal canal, thus increasing joint loading of facets. This leads to reactive sclerosis and osteophytic bone growth, leading to further compression of neural elements in the spinal canal and the foramen.
ETIOLOGY
• Congenital
• Chondrodystrophy
• Idiopathic
• Acquired
• Degenerative
• Spondylolytic
• Iatrogenic
• Posttraumatic
• Tumorous (primary or metastatic)
ASSOCIATED CONDITIONS
Spinal stenosis can be associated with a congenitally narrowed spinal canal and osteoarthritic changes of the lumbar spine.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Longstanding back pain that progresses to buttock and lower extremity pain
• Neurogenic claudication (pain, tightness, numbness, and subjective weakness of lower extremities)
• Symptoms worsen with standing, walking, back extension
• Symptoms improve with sitting or leaning forward
History
• Insidious onset
• Progresses slowly
• Symptoms worse when walking "uphill" and improve with leaning forward ("while pushing cart in grocery store")
Physical Exam
There maybe few physical findings even in effected patients
• Gait alteration (rule out cervical myelopathy or intracranial pathology)
• Loss of lumbar lordosis
• Decreased ROM of lumbar spine
• Pain with extension of the lumbar spine
• Straight-leg-raise test maybe positive if nerve root entrapment is present.
• Muscle weakness most commonly present in L5 distribution
TESTS
Spinal stenosis is generally diagnosed with a combination of history, physical examination, and imaging studies (MRI is best).
Lab
CBC, ESR, CRP if infection or cancer are in differential
Imaging
• AP and lateral radiographs of spine show degenerative changes or spondylolisthesis and rule out fractures, infection, or tumor; flexion/extension views help evaluate instability
• MRI will demonstrate compression of neural elements
• CT myelography is comparable to MRI in demonstrating neural compression but is an invasive procedure (dye injection associated with post spinal headache)
Diagnostic Procedures/Surgery
Selective injections can be used to localize source of pain in patients with multiple sites of neural compression and unclear findings. Surgical decompression is the only definitive treatment in patients who continue to be symptomatic after nonoperative treatment
Pathological Findings
• Decreased disc height
• Facet hypertrophy
• Spinal canal and/or foraminal narrowing
• Possible intervertebral instability
DIFFERENTIAL DIAGNOSIS
• Vascular claudication can also cause calf pain after ambulation; however, no back/buttock pain is present in vascular claudication. Also, the symptoms of vascular claudication do not improve with leaning forward.
• Disc herniation
• Cervical myelopathy
• Spinal stenosis in thoracic spine
TREATMENT
No good, randomized, controlled studies have examined operative versus nonoperative treatment for spinal stenosis. The general protocol among spinal surgeons is to treat spinal stenosis nonoperatively unless the symptoms impede patient's life. Decompressive surgery is quite successful in alleviating symptoms of spinal stenosis; there is controversy whether a fusion should be performed along with the decompression, because of risk of future spondylolisthesis.
PRE-HOSPITAL
Spinal stenosis generally does not lead to neurologic damage. Surgery is essentially for pain relief, allowing patients to become more mobile, thus improving overall health.
STABILIZATION
• Brace or corset may help for short time but not recommended long-term, because it leads to paraspinal muscle weakness.
• Patient should be encouraged to continue to be active despite pain to prevent deconditioning.
• Weight loss
Diet
If undergoing surgery, optimize nutritional status.
Activity
As tolerated, as long as no other pathology is present (e.g., fractures, gross instability, etc.)
SPECIAL THERAPY
Aquatic therapy is generally helpful for muscle and general conditioning.
Physical Therapy
• General conditioning (these patients are able to ride an exercise bicycle without many problems, because they can lean forward and relieve symptoms).
• Aquatic therapy
• Back extensor muscle strengthening
• Abdominal muscle strengthening
• Gait training
MEDICATION (DRUGS)
No role for maintenance opiates
First Line
• Anti-inflammatory medications (unless GI side-effects)
• Enteric coated aspirin (less GI side-effects)
• Acetaminophen
Second Line
• COX-2 inhibitors (be aware of changing side-effect profile)
• Lumbar epidural steroids
SURGERY
• Indicated when patient fails nonoperative treatment and cannot attain a tolerable quality of life. Preoperative clearance by an internist, cardiologist and/or anesthesiologist is necessary.
• Decompression of neural elements is mainstay of treatment. This generally entails a laminectomy, but foraminotomies and discectomy should also be performed if they are involved in neural compression.
• X STOP is a new device that is lodged between spinous process and indirectly decompresses the spinal canal with minimal surgery; significantly better outcomes compared to nonoperative treatment.
• Fusion is necessary when instability is present or an extensive decompression (with disruption of the pars interarticularis and/or >50% or articular facets) results in instability.
• Instrumentation with pedicle screws is commonly used to achieve fusion.
FOLLOW-UP
Routine follow-up is at 6 weeks, 3 months, 6 months, 1 year, 2 years, then every 2 years.
DISPOSITION
Admission Criteria
Unremitting pain that prevents the ability to perform activities of daily living or acute or progressive neurologic deficit.
Discharge Criteria
Improved pain or after neurologic deficit has been addressed (usually via surgical decompression)
Issues for Referral
Refer to a spine surgeon when patients are unwilling to live with the pain, have a worsening spinal deformity, or have a neurologic deficit (rare in arthritic spinal stenosis).
PROGNOSIS
• Spinal stenosis generally worsens with time.
• Surgery is successful in improving pain and symptoms in patients who fail nonoperative treatment.
COMPLICATIONS
• Severe spinal stenosis can lead to bowel and/or bladder dysfunction.
• Surgical complications include infection, neurologic injury, pseudarthrosis, chronic pain, and disability.
PATIENT MONITORING
Patients are monitored for improvement of symptoms, fusion (if one was performed), and development of any complications after nonoperative or operative care.
REFERENCES
1. Noponen-Hietala N, Kyllonen E, Mannikko M, et al. Sequence variations in the collagen IX and XI genes are associated with degenerative lumbar spinal stenosis. Ann Rheum Dis. 2003;62(12):208-214.
2. Hilibrand AS, Rand N. Degenerative lumbar stenosis: Diagnosis and management. J Am Acad Orthop Surg. 1999;7(4):239-249.
3. Amundsen T, Wever H, Lilleas F, et al. Lumbar spinal stenosis: Clinical and radiologic stenosis. Spine. 1995;20:1178-1186.
4. Zucherman JF, Hsu KY, Hartjen CA, et al. A multicenter, prospective, randomized trial evaluating the X STOP interspinous process decompression system for the treatment of neurogenic intermittent claudication: Two-year follow-up results. Spine. 2005;30(12):1351-1358.
5. Yuan HA, Garfin SR, Dickman CA, et al. A historical cohort study of pedicle screw fixation in thoracic, lumbar and sacral spinal fusions. Spine. 1994;19(Suppl 20):2279S-2296S.
BASICS
DESCRIPTION
Spinal stenosis is a condition in which a narrowing of the spinal canal and foramen occurs. Although myriad of etiologies exist, in the most generic sense, it refers to compression of the lumbar spinal elements secondary to arthritic changes (bone spurs, hypertrophied ligamentum flavum, disc space narrowing). This condition generally causes back/buttock pain with possible radiation in the lower extremities if foraminal stenosis also is present.
GENERAL PREVENTION
There is no known way to prevent spinal stenosis but symptoms can be alleviated by any means that "open up" the spinal canal and foramen, such as leaning forward when walking.
EPIDEMIOLOGY
The prevalence of spinal stenosis increases with age, because it is essentially an arthritic condition from "wear and tear" on the normal spine.
• Symptoms develop in 5th and 6th decades
• No sex predominance
• Degenerative spondylolisthesis with spinal stenosis is 4 times more common in women.
Incidence
The incidence of symptomatic spinal stenosis is as high as 8% of the population.
Prevalence
The prevalence increases with age and can be as high as 100% on assessment by radiographic studies on elderly patients; however, it is important to remember that not all patients with radiographic spinal stenosis are symptomatic.
RISK FACTORS
Increasing age and spinal arthritis
Genetics
No definitive genetic links
PATHOPHYSIOLOGY
Disc dehydration leads to loss of height with bulging of annulus and ligamentum flavum into the spinal canal, thus increasing joint loading of facets. This leads to reactive sclerosis and osteophytic bone growth, leading to further compression of neural elements in the spinal canal and the foramen.
ETIOLOGY
• Congenital
• Chondrodystrophy
• Idiopathic
• Acquired
• Degenerative
• Spondylolytic
• Iatrogenic
• Posttraumatic
• Tumorous (primary or metastatic)
ASSOCIATED CONDITIONS
Spinal stenosis can be associated with a congenitally narrowed spinal canal and osteoarthritic changes of the lumbar spine.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Longstanding back pain that progresses to buttock and lower extremity pain
• Neurogenic claudication (pain, tightness, numbness, and subjective weakness of lower extremities)
• Symptoms worsen with standing, walking, back extension
• Symptoms improve with sitting or leaning forward
History
• Insidious onset
• Progresses slowly
• Symptoms worse when walking "uphill" and improve with leaning forward ("while pushing cart in grocery store")
Physical Exam
There maybe few physical findings even in effected patients
• Gait alteration (rule out cervical myelopathy or intracranial pathology)
• Loss of lumbar lordosis
• Decreased ROM of lumbar spine
• Pain with extension of the lumbar spine
• Straight-leg-raise test maybe positive if nerve root entrapment is present.
• Muscle weakness most commonly present in L5 distribution
TESTS
Spinal stenosis is generally diagnosed with a combination of history, physical examination, and imaging studies (MRI is best).
Lab
CBC, ESR, CRP if infection or cancer are in differential
Imaging
• AP and lateral radiographs of spine show degenerative changes or spondylolisthesis and rule out fractures, infection, or tumor; flexion/extension views help evaluate instability
• MRI will demonstrate compression of neural elements
• CT myelography is comparable to MRI in demonstrating neural compression but is an invasive procedure (dye injection associated with post spinal headache)
Diagnostic Procedures/Surgery
Selective injections can be used to localize source of pain in patients with multiple sites of neural compression and unclear findings. Surgical decompression is the only definitive treatment in patients who continue to be symptomatic after nonoperative treatment
Pathological Findings
• Decreased disc height
• Facet hypertrophy
• Spinal canal and/or foraminal narrowing
• Possible intervertebral instability
DIFFERENTIAL DIAGNOSIS
• Vascular claudication can also cause calf pain after ambulation; however, no back/buttock pain is present in vascular claudication. Also, the symptoms of vascular claudication do not improve with leaning forward.
• Disc herniation
• Cervical myelopathy
• Spinal stenosis in thoracic spine
TREATMENT
No good, randomized, controlled studies have examined operative versus nonoperative treatment for spinal stenosis. The general protocol among spinal surgeons is to treat spinal stenosis nonoperatively unless the symptoms impede patient's life. Decompressive surgery is quite successful in alleviating symptoms of spinal stenosis; there is controversy whether a fusion should be performed along with the decompression, because of risk of future spondylolisthesis.
PRE-HOSPITAL
Spinal stenosis generally does not lead to neurologic damage. Surgery is essentially for pain relief, allowing patients to become more mobile, thus improving overall health.
STABILIZATION
• Brace or corset may help for short time but not recommended long-term, because it leads to paraspinal muscle weakness.
• Patient should be encouraged to continue to be active despite pain to prevent deconditioning.
• Weight loss
Diet
If undergoing surgery, optimize nutritional status.
Activity
As tolerated, as long as no other pathology is present (e.g., fractures, gross instability, etc.)
SPECIAL THERAPY
Aquatic therapy is generally helpful for muscle and general conditioning.
Physical Therapy
• General conditioning (these patients are able to ride an exercise bicycle without many problems, because they can lean forward and relieve symptoms).
• Aquatic therapy
• Back extensor muscle strengthening
• Abdominal muscle strengthening
• Gait training
MEDICATION (DRUGS)
No role for maintenance opiates
First Line
• Anti-inflammatory medications (unless GI side-effects)
• Enteric coated aspirin (less GI side-effects)
• Acetaminophen
Second Line
• COX-2 inhibitors (be aware of changing side-effect profile)
• Lumbar epidural steroids
SURGERY
• Indicated when patient fails nonoperative treatment and cannot attain a tolerable quality of life. Preoperative clearance by an internist, cardiologist and/or anesthesiologist is necessary.
• Decompression of neural elements is mainstay of treatment. This generally entails a laminectomy, but foraminotomies and discectomy should also be performed if they are involved in neural compression.
• X STOP is a new device that is lodged between spinous process and indirectly decompresses the spinal canal with minimal surgery; significantly better outcomes compared to nonoperative treatment.
• Fusion is necessary when instability is present or an extensive decompression (with disruption of the pars interarticularis and/or >50% or articular facets) results in instability.
• Instrumentation with pedicle screws is commonly used to achieve fusion.
FOLLOW-UP
Routine follow-up is at 6 weeks, 3 months, 6 months, 1 year, 2 years, then every 2 years.
DISPOSITION
Admission Criteria
Unremitting pain that prevents the ability to perform activities of daily living or acute or progressive neurologic deficit.
Discharge Criteria
Improved pain or after neurologic deficit has been addressed (usually via surgical decompression)
Issues for Referral
Refer to a spine surgeon when patients are unwilling to live with the pain, have a worsening spinal deformity, or have a neurologic deficit (rare in arthritic spinal stenosis).
PROGNOSIS
• Spinal stenosis generally worsens with time.
• Surgery is successful in improving pain and symptoms in patients who fail nonoperative treatment.
COMPLICATIONS
• Severe spinal stenosis can lead to bowel and/or bladder dysfunction.
• Surgical complications include infection, neurologic injury, pseudarthrosis, chronic pain, and disability.
PATIENT MONITORING
Patients are monitored for improvement of symptoms, fusion (if one was performed), and development of any complications after nonoperative or operative care.
REFERENCES
1. Noponen-Hietala N, Kyllonen E, Mannikko M, et al. Sequence variations in the collagen IX and XI genes are associated with degenerative lumbar spinal stenosis. Ann Rheum Dis. 2003;62(12):208-214.
2. Hilibrand AS, Rand N. Degenerative lumbar stenosis: Diagnosis and management. J Am Acad Orthop Surg. 1999;7(4):239-249.
3. Amundsen T, Wever H, Lilleas F, et al. Lumbar spinal stenosis: Clinical and radiologic stenosis. Spine. 1995;20:1178-1186.
4. Zucherman JF, Hsu KY, Hartjen CA, et al. A multicenter, prospective, randomized trial evaluating the X STOP interspinous process decompression system for the treatment of neurogenic intermittent claudication: Two-year follow-up results. Spine. 2005;30(12):1351-1358.
5. Yuan HA, Garfin SR, Dickman CA, et al. A historical cohort study of pedicle screw fixation in thoracic, lumbar and sacral spinal fusions. Spine. 1994;19(Suppl 20):2279S-2296S.
SUBSTANCE USE DISORDERS
SUBSTANCE USE DISORDERS - S. Lindsey Clarke, MD
BASICS
DESCRIPTION
• Any pattern of substance use causing significant physical, mental, or social dysfunction
• Substances of abuse include
- Alcohol
- Amphetamines (black beauties, truck drivers, hearts, uppers, speed)
- Anabolic steroids (nandrolone [Durabolin], oxandrolone); testosterone (Depo-Testosterone)
- Barbiturates (barbs, red birds, yellow jackets)
- Benzodiazepines (downers, candy, tranks)
- Cannabinoids: Hashish, marijuana (dope, grass, joint, pot, reefer, sinsemilla, weed)
- Cocaine (coke, crack, blow, rocks, snow)
- Codeine (Cody, school boy)
- Fentanyl (Apache, China girl, dance fever)
- Flunitrazepam (Mexican Valium, roofies)
- -Hydroxybutyrate (GHB, liquid ecstasy, woman's Viagra)
- Heroin (diacetylmorphine; horse, junk, smack, white horse, brown sugar)
- Inhalants (gasoline, glue, paint thinners, nitrous oxide)
- Ketamine (cat Valium, Special K, vitamin K)
- Lysergic acid diethylamide (LSD; acid, microdot, cubes, yellow sunshine)
- Mescaline, psilocybin (mushrooms, peyote)
- Methadone (Methadose)
- Methamphetamines (crank, crystal, ice, fire, speed; and "designer drugs": Adam, clarity, ecstasy, Eve, MDMA, XTC, lover's speed)
- Methaqualone (Quaalude, mandrex)
- Methylphenidate (Ritalin, JIF, Skippy, MPH)
- Morphine (M, Miss Emma, monkey)
- Nicotine (tobacco)
- Opium (Paregoric, big O, block)
- Oxycodone, hydrocodone, hydromorphone, meperidine, propoxyphene
- Phencyclidine (PCP; angel dust, hog, love boat, peace pill, supergrass, ozone, wack)
• System(s) Affected: Cardiovascular; Endocrine/Metabolic; Nervous
• Synonym(s): Drug abuse; Drug dependence; Substance abuse
ALERT
Geriatric Considerations
• Alcohol is the most commonly abused substance and often goes unrecognized.
• Higher potential for drug interactions
Pregnancy Considerations
Pregnant women: Substance abuse may cause major problems that can lead to fetal abnormality, morbidity, and death of infant and mother.
GENERAL PREVENTION
Early identification and aggressive early intervention (mild substance use disorders respond better to treatment intervention)
EPIDEMIOLOGY
• Predominant age: Age 16-25
• Predominant sex: Male > Female
Prevalence
• 19.1 million or 7.9% of Americans reported use of an illicit substance in past month in 2004; rates: 10.6% for 12-17; 21.7% for 18-20 years
• 1 in 6 males 18-25 years uses marijuana.
• 36% in the US used a drug at least once.
RISK FACTORS
• Male gender, young adult
• Depression, anxiety
• Other substance use disorders
• Family history
• Peer or family use or approval
• Low socioeconomic status
• Unemployment
• Accessibility of substances of abuse
• Family dysfunction or trauma
• Antisocial personality disorder
• Academic problems, school dropout
• Criminal involvement
Genetics
Substances of abuse affect dopamine, acetylcholine, -aminobutyric acid, norepinephrine, opioid, and serotonin receptors. Variant alleles may account for differences in susceptibility to substance use disorders.
ETIOLOGY
Multifactorial, including genetic, environmental
ASSOCIATED CONDITIONS
• Depression
• Personality disorders
• Bipolar affective disorder
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• History of infections, e.g., endocarditis, hepatitis B or C, tuberculosis, sexually transmitted diseases, or recurrent pneumonia
• Social or behavioral problems, including chaotic relationships and/or employment
• Frequent visits to emergency department
• Criminal incarceration
• History of blackouts, insomnia, mood swings, chronic pain, repetitive trauma
• Anxiety, fatigue, depression, psychosis
• Sexual assault with GHB, Rohypnol
Physical Exam
• Dilated or constricted pupils, response to light
• Needle marks on skin
• Nasal septum perforation (with cocaine use)
• Cardiac dysrhythmias, pathologic murmurs
TESTS
• TICS (2-Item Conjoint Screen): At least 1 positive response is 79% sensitive, 78% specific for current substance use disorder (5)[B]
- In the last year, have you ever drunk or used drugs more than you meant to?
- Have you felt you wanted or needed to cut down on your drinking or drug use in the past year?
• CAGE-AID (CAGE Adapted to Include Drugs): (5)[B] More than 2 "yes" answers on original CAGE is ~85% sensitive, 90% specific for alcohol use disorder
- Have you ever tried to Cut down on your alcohol or drug use?
- Do you get Annoyed when people comment on your drinking or drug use?
- Do you feel Guilty about things you have done while drinking or using drugs?
- Do you need an Eye-opener to get started in the morning?
Lab
• Blood alcohol concentration
• Urine drug screen, confirmatory tests
• Approximate detection limits
- Alcohol: 6-10 hours
- Amphetamines and variants: 2-3 days
- Barbiturates: 2-10 days
- Benzodiazepines: 1-6 weeks
- Cocaine: 2-3 days
- Heroin: 1-1.5 days
- LSD, psilocybin: 8 hours
- Marijuana: 1 day to 4 weeks
- Methadone: 1 day to 1 week
- Opioids: 1-3 days
- PCP: 7-14 days
- Anabolic steroids: Oral, 3 weeks; injectable, 3 months; nandrolone, 9 months
• For altered mental status consider: CBC, glucose, chemistry panel, TSH, RPR, urinalysis, head CT scan, chest x-ray, ECG, lumbar puncture, arterial blood gas, blood cultures
• HIV, hepatitis B and C screens
Imaging
ECG for endocarditis
DSM-IV TR Criteria
• Substance abuse: A maladaptive pattern of substance use manifested by one (or more) of the following
- Failure to fulfill major obligations at work, school, or home
- Recurrent use in hazardous situations
- Recurrent substance-related legal problems
- Continued substance use despite substance-related social or interpersonal problems
• Substance dependence: A maladaptive pattern of substance use manifested by 3 (or more) of the following
- Tolerance
- Withdrawal
- Using the substance more than intended
- Persistent desire or attempts to cut down/stop
- Much time spent obtaining, using, or recovering from the substance
- Social, occupational, or recreational activities sacrificed for substance use
- Continued use despite substance-related physical or psychological problems
DIFFERENTIAL DIAGNOSIS
• Depression, anxiety, or other mental states
• Metabolic causes of altered mental status (hypoxia, hypoglycemia, infection, thiamine deficiency, hypothyroidism, thyrotoxicosis)
• Delirium, agitation
• Attention defecit hyperactivity disorder
• Medication toxicity
TREATMENT
PRE-HOSPITAL
Determine substances abused early (may influence disposition).
STABILIZATION
Look for signs of severe infection (e.g., bacterial endocarditis).
GENERAL MEASURES
• Behavioral and cognitive therapy
• Community reinforcement
• Interventional counseling
• Nonjudgmental, medically oriented attitude
• Self-help groups to aid recovery (Alcoholics Anonymous, other 12-step programs)
• Support groups for family (Al-Anon and Alateen)
• Monitoring for infectious diseases and other complications
Diet
Patients often are malnourished.
Activity
Restricted if dangerous, psychotic, or disoriented
Nursing
• Frequent vital signs during withdrawal
• Monitor for signs of drug use in hospital.
IV Fluids
Maintenance until taking fluids well PO
MEDICATION (DRUGS)
First Line
• Alcohol withdrawal: See "Alcohol Use Disorders" chapter.
• Benzodiazepine or barbiturate withdrawal:
- Substitution of longer-acting benzodiazepine or phenobarbital (3)[C]
- Tapering doses of the agent of dependence
- Buspirone 5-15 PO b.i.d.
• Cocaine or stimulant withdrawal: No agent with clear benefit (3)[A]
• Nicotine withdrawal
- Bupropion 150 mg PO b.i.d. (3)[B]
- Nicotine replacement systems (patches, gum)
• Opioid withdrawal
- Methadone 20-35 mg/d PO, use restricted to inpatient settings and specially licensed clinics (2,3)[A]
- Buprenorphine 2-16 mg SL daily, use restricted to licensed clinics and qualified physicians (see www.buprenorphine.samhsa.gov/howto.html) (1,2,3)[A]
- Naltrexone 50 mg/d PO or 100 mg PO thrice weekly (2,3)[A]
- Clonidine 0.1-0.2 mg PO q4h for 5-10 days, often used in combination with other agents (2,3)[A]
• Adjuncts to therapy
- Antiemetics, nonaddictive analgesics for opioid withdrawal
- Fluoxetine, desipramine for comorbid depressive states or symptoms that persist 1 week after acute stimulant withdrawal (3)[B]
- Lithium for comorbid bipolar affective states
- Nonaddictive anxiolytics (buspirone, hydroxyzine) or clonazepam (4)[C]
- Trazodone or nonaddictive hypnotics (eszopiclone, zolpidem) for insomnia (4)[C]
- Use all medications in conjunction with psychosocial, behavioral interventions (2-4)[C]
• Contraindications
- Buprenorphine in lactation
- Naltrexone in pregnancy, liver disease
• Precautions
- Clonidine may cause hypotension.
• Significant possible interactions
- Buprenorphine and ketoconazole, erythromycin, or HIV protease inhibitors
- Naltrexone and opioid medications (may precipitate or exacerbate withdrawal)
FOLLOW-UP
DISPOSITION
Admission Criteria
• Indications for inpatient detoxification
- History of withdrawal symptoms, e.g., seizures
- Disorientation
- Threat of harm to self or others
- Obstacles to close monitoring (follow-up)
- Comorbid medical illness
- Pregnancy
• For inpatient narcotic or polysubstance detoxification, strongly consider admission to a qualified substance abuse treatment facility.
Discharge Criteria
Detoxification complete
Issues for Referral
• Consider addiction specialist, especially for opioid and polysubstance abuse.
• Maintenance therapy for opioid dependence (e.g., methadone) only in specially licensed clinics
• Psychiatry for comorbid psychiatric disorders
• Social services
PROGNOSIS
• Patients in treatment for longer periods of time (at least a year) have higher success rates.
• Counseling combined with drug therapy is more successful than either 1 alone.
COMPLICATIONS
• Hepatitis, HIV, tuberculosis, syphilis
• Subacute bacterial endocarditis
• Malnutrition
• Social problems, including arrest
• Poor marital adjustment and violence
• Depression, schizophrenia
• Serious harm to self and others
• Sexual assault with GHB, Rohypnol
• Overdoses resulting in seizures, arrhythmias, cardiac and respiratory arrest, coma, death
PATIENT MONITORING
• Verify patient's compliance with the substance abuse treatment program.
• Following treatment, follow-up on medical issues and provide support for continued abstinence.
REFERENCES
1. Abramowicz M, ed. Buprenorphine. Med Lett. 2003;45(1150):13-15.
2. Fiellin DA. Office-based treatment of opioid- dependent patients. N Engl J Med. 2002;347(11)
3. Kosten TR. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348(18):1786.
4. Jones EM. Common problems in patients recovering from chemical dependency. Am Fam Physician. 2003;68(10):1971-1978.
5. Brown RL. A two-item conjoint screen for alcohol and other drug problems. J Am Board Fam Pract. 2001;14(2):95-106.
MISCELLANEOUS
See also: Alcohol use disorders
BASICS
DESCRIPTION
• Any pattern of substance use causing significant physical, mental, or social dysfunction
• Substances of abuse include
- Alcohol
- Amphetamines (black beauties, truck drivers, hearts, uppers, speed)
- Anabolic steroids (nandrolone [Durabolin], oxandrolone); testosterone (Depo-Testosterone)
- Barbiturates (barbs, red birds, yellow jackets)
- Benzodiazepines (downers, candy, tranks)
- Cannabinoids: Hashish, marijuana (dope, grass, joint, pot, reefer, sinsemilla, weed)
- Cocaine (coke, crack, blow, rocks, snow)
- Codeine (Cody, school boy)
- Fentanyl (Apache, China girl, dance fever)
- Flunitrazepam (Mexican Valium, roofies)
- -Hydroxybutyrate (GHB, liquid ecstasy, woman's Viagra)
- Heroin (diacetylmorphine; horse, junk, smack, white horse, brown sugar)
- Inhalants (gasoline, glue, paint thinners, nitrous oxide)
- Ketamine (cat Valium, Special K, vitamin K)
- Lysergic acid diethylamide (LSD; acid, microdot, cubes, yellow sunshine)
- Mescaline, psilocybin (mushrooms, peyote)
- Methadone (Methadose)
- Methamphetamines (crank, crystal, ice, fire, speed; and "designer drugs": Adam, clarity, ecstasy, Eve, MDMA, XTC, lover's speed)
- Methaqualone (Quaalude, mandrex)
- Methylphenidate (Ritalin, JIF, Skippy, MPH)
- Morphine (M, Miss Emma, monkey)
- Nicotine (tobacco)
- Opium (Paregoric, big O, block)
- Oxycodone, hydrocodone, hydromorphone, meperidine, propoxyphene
- Phencyclidine (PCP; angel dust, hog, love boat, peace pill, supergrass, ozone, wack)
• System(s) Affected: Cardiovascular; Endocrine/Metabolic; Nervous
• Synonym(s): Drug abuse; Drug dependence; Substance abuse
ALERT
Geriatric Considerations
• Alcohol is the most commonly abused substance and often goes unrecognized.
• Higher potential for drug interactions
Pregnancy Considerations
Pregnant women: Substance abuse may cause major problems that can lead to fetal abnormality, morbidity, and death of infant and mother.
GENERAL PREVENTION
Early identification and aggressive early intervention (mild substance use disorders respond better to treatment intervention)
EPIDEMIOLOGY
• Predominant age: Age 16-25
• Predominant sex: Male > Female
Prevalence
• 19.1 million or 7.9% of Americans reported use of an illicit substance in past month in 2004; rates: 10.6% for 12-17; 21.7% for 18-20 years
• 1 in 6 males 18-25 years uses marijuana.
• 36% in the US used a drug at least once.
RISK FACTORS
• Male gender, young adult
• Depression, anxiety
• Other substance use disorders
• Family history
• Peer or family use or approval
• Low socioeconomic status
• Unemployment
• Accessibility of substances of abuse
• Family dysfunction or trauma
• Antisocial personality disorder
• Academic problems, school dropout
• Criminal involvement
Genetics
Substances of abuse affect dopamine, acetylcholine, -aminobutyric acid, norepinephrine, opioid, and serotonin receptors. Variant alleles may account for differences in susceptibility to substance use disorders.
ETIOLOGY
Multifactorial, including genetic, environmental
ASSOCIATED CONDITIONS
• Depression
• Personality disorders
• Bipolar affective disorder
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• History of infections, e.g., endocarditis, hepatitis B or C, tuberculosis, sexually transmitted diseases, or recurrent pneumonia
• Social or behavioral problems, including chaotic relationships and/or employment
• Frequent visits to emergency department
• Criminal incarceration
• History of blackouts, insomnia, mood swings, chronic pain, repetitive trauma
• Anxiety, fatigue, depression, psychosis
• Sexual assault with GHB, Rohypnol
Physical Exam
• Dilated or constricted pupils, response to light
• Needle marks on skin
• Nasal septum perforation (with cocaine use)
• Cardiac dysrhythmias, pathologic murmurs
TESTS
• TICS (2-Item Conjoint Screen): At least 1 positive response is 79% sensitive, 78% specific for current substance use disorder (5)[B]
- In the last year, have you ever drunk or used drugs more than you meant to?
- Have you felt you wanted or needed to cut down on your drinking or drug use in the past year?
• CAGE-AID (CAGE Adapted to Include Drugs): (5)[B] More than 2 "yes" answers on original CAGE is ~85% sensitive, 90% specific for alcohol use disorder
- Have you ever tried to Cut down on your alcohol or drug use?
- Do you get Annoyed when people comment on your drinking or drug use?
- Do you feel Guilty about things you have done while drinking or using drugs?
- Do you need an Eye-opener to get started in the morning?
Lab
• Blood alcohol concentration
• Urine drug screen, confirmatory tests
• Approximate detection limits
- Alcohol: 6-10 hours
- Amphetamines and variants: 2-3 days
- Barbiturates: 2-10 days
- Benzodiazepines: 1-6 weeks
- Cocaine: 2-3 days
- Heroin: 1-1.5 days
- LSD, psilocybin: 8 hours
- Marijuana: 1 day to 4 weeks
- Methadone: 1 day to 1 week
- Opioids: 1-3 days
- PCP: 7-14 days
- Anabolic steroids: Oral, 3 weeks; injectable, 3 months; nandrolone, 9 months
• For altered mental status consider: CBC, glucose, chemistry panel, TSH, RPR, urinalysis, head CT scan, chest x-ray, ECG, lumbar puncture, arterial blood gas, blood cultures
• HIV, hepatitis B and C screens
Imaging
ECG for endocarditis
DSM-IV TR Criteria
• Substance abuse: A maladaptive pattern of substance use manifested by one (or more) of the following
- Failure to fulfill major obligations at work, school, or home
- Recurrent use in hazardous situations
- Recurrent substance-related legal problems
- Continued substance use despite substance-related social or interpersonal problems
• Substance dependence: A maladaptive pattern of substance use manifested by 3 (or more) of the following
- Tolerance
- Withdrawal
- Using the substance more than intended
- Persistent desire or attempts to cut down/stop
- Much time spent obtaining, using, or recovering from the substance
- Social, occupational, or recreational activities sacrificed for substance use
- Continued use despite substance-related physical or psychological problems
DIFFERENTIAL DIAGNOSIS
• Depression, anxiety, or other mental states
• Metabolic causes of altered mental status (hypoxia, hypoglycemia, infection, thiamine deficiency, hypothyroidism, thyrotoxicosis)
• Delirium, agitation
• Attention defecit hyperactivity disorder
• Medication toxicity
TREATMENT
PRE-HOSPITAL
Determine substances abused early (may influence disposition).
STABILIZATION
Look for signs of severe infection (e.g., bacterial endocarditis).
GENERAL MEASURES
• Behavioral and cognitive therapy
• Community reinforcement
• Interventional counseling
• Nonjudgmental, medically oriented attitude
• Self-help groups to aid recovery (Alcoholics Anonymous, other 12-step programs)
• Support groups for family (Al-Anon and Alateen)
• Monitoring for infectious diseases and other complications
Diet
Patients often are malnourished.
Activity
Restricted if dangerous, psychotic, or disoriented
Nursing
• Frequent vital signs during withdrawal
• Monitor for signs of drug use in hospital.
IV Fluids
Maintenance until taking fluids well PO
MEDICATION (DRUGS)
First Line
• Alcohol withdrawal: See "Alcohol Use Disorders" chapter.
• Benzodiazepine or barbiturate withdrawal:
- Substitution of longer-acting benzodiazepine or phenobarbital (3)[C]
- Tapering doses of the agent of dependence
- Buspirone 5-15 PO b.i.d.
• Cocaine or stimulant withdrawal: No agent with clear benefit (3)[A]
• Nicotine withdrawal
- Bupropion 150 mg PO b.i.d. (3)[B]
- Nicotine replacement systems (patches, gum)
• Opioid withdrawal
- Methadone 20-35 mg/d PO, use restricted to inpatient settings and specially licensed clinics (2,3)[A]
- Buprenorphine 2-16 mg SL daily, use restricted to licensed clinics and qualified physicians (see www.buprenorphine.samhsa.gov/howto.html) (1,2,3)[A]
- Naltrexone 50 mg/d PO or 100 mg PO thrice weekly (2,3)[A]
- Clonidine 0.1-0.2 mg PO q4h for 5-10 days, often used in combination with other agents (2,3)[A]
• Adjuncts to therapy
- Antiemetics, nonaddictive analgesics for opioid withdrawal
- Fluoxetine, desipramine for comorbid depressive states or symptoms that persist 1 week after acute stimulant withdrawal (3)[B]
- Lithium for comorbid bipolar affective states
- Nonaddictive anxiolytics (buspirone, hydroxyzine) or clonazepam (4)[C]
- Trazodone or nonaddictive hypnotics (eszopiclone, zolpidem) for insomnia (4)[C]
- Use all medications in conjunction with psychosocial, behavioral interventions (2-4)[C]
• Contraindications
- Buprenorphine in lactation
- Naltrexone in pregnancy, liver disease
• Precautions
- Clonidine may cause hypotension.
• Significant possible interactions
- Buprenorphine and ketoconazole, erythromycin, or HIV protease inhibitors
- Naltrexone and opioid medications (may precipitate or exacerbate withdrawal)
FOLLOW-UP
DISPOSITION
Admission Criteria
• Indications for inpatient detoxification
- History of withdrawal symptoms, e.g., seizures
- Disorientation
- Threat of harm to self or others
- Obstacles to close monitoring (follow-up)
- Comorbid medical illness
- Pregnancy
• For inpatient narcotic or polysubstance detoxification, strongly consider admission to a qualified substance abuse treatment facility.
Discharge Criteria
Detoxification complete
Issues for Referral
• Consider addiction specialist, especially for opioid and polysubstance abuse.
• Maintenance therapy for opioid dependence (e.g., methadone) only in specially licensed clinics
• Psychiatry for comorbid psychiatric disorders
• Social services
PROGNOSIS
• Patients in treatment for longer periods of time (at least a year) have higher success rates.
• Counseling combined with drug therapy is more successful than either 1 alone.
COMPLICATIONS
• Hepatitis, HIV, tuberculosis, syphilis
• Subacute bacterial endocarditis
• Malnutrition
• Social problems, including arrest
• Poor marital adjustment and violence
• Depression, schizophrenia
• Serious harm to self and others
• Sexual assault with GHB, Rohypnol
• Overdoses resulting in seizures, arrhythmias, cardiac and respiratory arrest, coma, death
PATIENT MONITORING
• Verify patient's compliance with the substance abuse treatment program.
• Following treatment, follow-up on medical issues and provide support for continued abstinence.
REFERENCES
1. Abramowicz M, ed. Buprenorphine. Med Lett. 2003;45(1150):13-15.
2. Fiellin DA. Office-based treatment of opioid- dependent patients. N Engl J Med. 2002;347(11)
3. Kosten TR. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348(18):1786.
4. Jones EM. Common problems in patients recovering from chemical dependency. Am Fam Physician. 2003;68(10):1971-1978.
5. Brown RL. A two-item conjoint screen for alcohol and other drug problems. J Am Board Fam Pract. 2001;14(2):95-106.
MISCELLANEOUS
See also: Alcohol use disorders
SOMATIZATION DISORDER
SOMATIZATION DISORDER - Laurie A. Carrier, MD
BASICS
DESCRIPTION
• A pattern of recurring, multiple, clinically significant somatic complaints beginning 30 years of age that occur over a period of several years and result in treatment being sought or significant impairment in social, occupational, or other important areas of functioning.
• Each of the following criteria must be met, with individual symptoms occurring at any time during the course of the disturbance
- 4 pain symptoms: Different sites or functions
- 2 gastrointestinal symptoms: Other than pain
- 1 sexual symptom
- 1 pseudoneurological symptom
• The above symptoms are not intentionally produced or feigned.
• Chronic course, fluctuating in severity
• Affected individual rarely goes 1 year without seeking medical attention prompted by unexplained somatic complaints
• System(s) Affected: Multiple
• Synonym(s): Briquet syndrome
EPIDEMIOLOGY
• Predominant age: Usually, the 1st symptoms appear in adolescence and the full criteria are met by 30 years of age
• Predominant sex: Female > Male (10:1)
- 10 more common in women than in men
• The type and frequency of somatic complaints may differ among cultures, so symptom reviews should be adjusted by culture.
Prevalence
• Ranges from 0.2-2% among women and 0.2% in men
• 1 in 500 adults in the US
• 544,000 people affected in the US
RISK FACTORS
• Child abuse, particularly sexual abuse, has been shown to be a risk factor.
• Symptoms begin or worsen after losses (for example, job, close relative, or friend).
• Greater intensity of symptoms often occurs with stress.
Genetics
• Observed in 10-20% of female 1st-degree biological relatives of women with Somatization Disorder (SD)
• Male relatives of woman with this disorder show an increased risk of Antisocial Personality Disorder and substance-related disorders.
ETIOLOGY
• The exact cause of this disorder is unknown.
• Adoption studies indicate that both genetic and environmental factors contribute to the risk of SD.
ASSOCIATED CONDITIONS
• Comorbid with other psychiatric conditions, including major depression (55% of patients), anxiety disorders (34%), personality disorders (61%), and panic disorders (26%)
DIAGNOSIS
SIGNS AND SYMPTOMS
• Pain symptoms (4 or more) related to different sites, such as head, abdomen, back, joints, extremities, chest, or rectum, or related to body functions such as menstruation, sexual intercourse, or urination
• Gastrointestinal symptoms (2 or more, excluding pain) such as nausea, bloating, vomiting (not during pregnancy), diarrhea, intolerance of several foods
• Sexual symptoms (at least 1, excluding pain) including indifference to sex, difficulties with erection or ejaculation, irregular menses, excessive menstrual bleeding, or vomiting throughout all 9 months of pregnancy
• Pseudoneurological symptoms (at least 1) including impaired balance or coordination, weak or paralyzed muscles, lump in throat or trouble swallowing, loss of voice, retention of urine, hallucinations, numbness (to touch or pain), double vision, blindness, deafness, seizures, amnesia or other dissociative symptoms, loss of consciousness (other than with fainting). None of these are limited to pain.
History
• Multiple somatic complaints including pain symptoms, gastrointestinal symptoms, a sexual symptom, and neurological symptoms
• Patients usually have a grossly positive review of symptoms.
Physical Exam
Remarkable for absence of objective findings to fully explain the many subjective complaints
TESTS
Several screening tools are available which help to identify symptoms as somatic.
• PHQ-15 (screens and monitors symptoms) (1)[C]
• MMPI (identifies somatization) (2)[C]
• Perley-Guze Checklist (helps the physician identify SD)
Lab
Laboratory test results do not support the subjective complaints.
Imaging
Imaging studies do not support the subjective complaints.
Pathological Findings
None are identified.
DIFFERENTIAL DIAGNOSIS
• Other psychiatric illnesses must be ruled out
- Depressive disorders
- Anxiety disorders
- Schizophrenia
- Other somatoform disorders: Conversion disorder, Factitious disorders, Hypochondriasis, Pain disorder
• General medical conditions, with vague, multiple, confusing symptoms, must be ruled out
- Systemic Lupus Erythematosus
- Hyperpartathyroidism
- Hyper- or Hypothyroidism
- Lyme disease
- Porphyria
TREATMENT
GENERAL MEASURES
• The goal of treatment is to help the person learn to control the symptoms.
• A supportive relationship with a sympathetic health care provider is the most important aspect of treatment. (3)[C]
- Regularly scheduled appointments should be maintained to review symptoms and the person's coping mechanisms (at least 15 minutes once a month). (3)[C]
- Acknowledgment and explanation of test results should occur.
• The involvement of a single physician is important, as a history of seeking medical attention and "doctor shopping" is common.
• Antidepressant or antianxiety medication and referral to a support group or psychiatrist can help patients who are willing to participate in their treatment.
• Patients usually receive the most benefit from primary care physicians who accept the limitations of treatment, listen to their patient's concerns, and provide reassurance.
• It is not helpful to tell patients that their symptoms are imaginary.
SPECIAL THERAPY
Treatment typically includes long-term therapy which has been shown to decrease the severity of symptoms.
• Cognitive behavioral therapy has been shown to be the most efficacious treatment in SD. (4-6)[C]
• Psychotherapy
• Supportive therapy
MEDICATION (DRUGS)
Antidepressants (e.g., SSRIs) help in some cases.
FOLLOW-UP
Patients should have regularly scheduled follow-up with a primary care doctor, psychiatrist, or therapist.
DISPOSITION
Issues for Referral
• Referrals to specialist for further investigation of somatic complaints should be discouraged.
• Referrals to support groups or to a psychiatrist may be helpful.
PROGNOSIS
• Chronic course, fluctuating in severity
• Full remission is rare.
• Individuals with this disorder do not experience any significant difference in mortality rate or significant illness.
COMPLICATIONS
• May result from invasive testing and from multiple evaluations that are performed while looking for the cause of the symptoms
• A dependency on pain relievers or sedatives may develop.
REFERENCES
1. Kroenke K, Spitzer R, Williams J. The PHQ-15: Validity of a new measure for evaluating the severity of somatic symptoms. Psychosom Med. 2002;64:258-266.
2. Wetzel RD, et al. MMPI screening scales for Somatization Disorder. Psychol Rep. 1999;85(1):341-348.
3. Servan-Schreiber NR, Tabas G, Kolb D. Somatizing patients: Part II. Practical management. Am Fam Physician. 2000;61(5):1423-1430.
4. Kroenke K, Swindle R. Cognitive-Behavioral therapy for somatization and symptom syndromes: A critical review of controlled clinical trials. Psychother Psychosom. 2000;69:205.
5. Mai F. Somatization disorder: A practical review. Can J Psychiatry. 2004;49:652-662.
6. Speckens AE, van Hemert AM, Spinhoven P, Hawton KE, Bolk JH, Rooijmans HG. Cognitive behavioural therapy for medically unexplained physical symptoms: A randomised controlled trial. BMJ. 1995;311:1328-1332.
7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text revision. Washington, DC: American Psychiatric Association, 2000.
MISCELLANEOUS
See also: Somatoform disorders
BASICS
DESCRIPTION
• A pattern of recurring, multiple, clinically significant somatic complaints beginning 30 years of age that occur over a period of several years and result in treatment being sought or significant impairment in social, occupational, or other important areas of functioning.
• Each of the following criteria must be met, with individual symptoms occurring at any time during the course of the disturbance
- 4 pain symptoms: Different sites or functions
- 2 gastrointestinal symptoms: Other than pain
- 1 sexual symptom
- 1 pseudoneurological symptom
• The above symptoms are not intentionally produced or feigned.
• Chronic course, fluctuating in severity
• Affected individual rarely goes 1 year without seeking medical attention prompted by unexplained somatic complaints
• System(s) Affected: Multiple
• Synonym(s): Briquet syndrome
EPIDEMIOLOGY
• Predominant age: Usually, the 1st symptoms appear in adolescence and the full criteria are met by 30 years of age
• Predominant sex: Female > Male (10:1)
- 10 more common in women than in men
• The type and frequency of somatic complaints may differ among cultures, so symptom reviews should be adjusted by culture.
Prevalence
• Ranges from 0.2-2% among women and 0.2% in men
• 1 in 500 adults in the US
• 544,000 people affected in the US
RISK FACTORS
• Child abuse, particularly sexual abuse, has been shown to be a risk factor.
• Symptoms begin or worsen after losses (for example, job, close relative, or friend).
• Greater intensity of symptoms often occurs with stress.
Genetics
• Observed in 10-20% of female 1st-degree biological relatives of women with Somatization Disorder (SD)
• Male relatives of woman with this disorder show an increased risk of Antisocial Personality Disorder and substance-related disorders.
ETIOLOGY
• The exact cause of this disorder is unknown.
• Adoption studies indicate that both genetic and environmental factors contribute to the risk of SD.
ASSOCIATED CONDITIONS
• Comorbid with other psychiatric conditions, including major depression (55% of patients), anxiety disorders (34%), personality disorders (61%), and panic disorders (26%)
DIAGNOSIS
SIGNS AND SYMPTOMS
• Pain symptoms (4 or more) related to different sites, such as head, abdomen, back, joints, extremities, chest, or rectum, or related to body functions such as menstruation, sexual intercourse, or urination
• Gastrointestinal symptoms (2 or more, excluding pain) such as nausea, bloating, vomiting (not during pregnancy), diarrhea, intolerance of several foods
• Sexual symptoms (at least 1, excluding pain) including indifference to sex, difficulties with erection or ejaculation, irregular menses, excessive menstrual bleeding, or vomiting throughout all 9 months of pregnancy
• Pseudoneurological symptoms (at least 1) including impaired balance or coordination, weak or paralyzed muscles, lump in throat or trouble swallowing, loss of voice, retention of urine, hallucinations, numbness (to touch or pain), double vision, blindness, deafness, seizures, amnesia or other dissociative symptoms, loss of consciousness (other than with fainting). None of these are limited to pain.
History
• Multiple somatic complaints including pain symptoms, gastrointestinal symptoms, a sexual symptom, and neurological symptoms
• Patients usually have a grossly positive review of symptoms.
Physical Exam
Remarkable for absence of objective findings to fully explain the many subjective complaints
TESTS
Several screening tools are available which help to identify symptoms as somatic.
• PHQ-15 (screens and monitors symptoms) (1)[C]
• MMPI (identifies somatization) (2)[C]
• Perley-Guze Checklist (helps the physician identify SD)
Lab
Laboratory test results do not support the subjective complaints.
Imaging
Imaging studies do not support the subjective complaints.
Pathological Findings
None are identified.
DIFFERENTIAL DIAGNOSIS
• Other psychiatric illnesses must be ruled out
- Depressive disorders
- Anxiety disorders
- Schizophrenia
- Other somatoform disorders: Conversion disorder, Factitious disorders, Hypochondriasis, Pain disorder
• General medical conditions, with vague, multiple, confusing symptoms, must be ruled out
- Systemic Lupus Erythematosus
- Hyperpartathyroidism
- Hyper- or Hypothyroidism
- Lyme disease
- Porphyria
TREATMENT
GENERAL MEASURES
• The goal of treatment is to help the person learn to control the symptoms.
• A supportive relationship with a sympathetic health care provider is the most important aspect of treatment. (3)[C]
- Regularly scheduled appointments should be maintained to review symptoms and the person's coping mechanisms (at least 15 minutes once a month). (3)[C]
- Acknowledgment and explanation of test results should occur.
• The involvement of a single physician is important, as a history of seeking medical attention and "doctor shopping" is common.
• Antidepressant or antianxiety medication and referral to a support group or psychiatrist can help patients who are willing to participate in their treatment.
• Patients usually receive the most benefit from primary care physicians who accept the limitations of treatment, listen to their patient's concerns, and provide reassurance.
• It is not helpful to tell patients that their symptoms are imaginary.
SPECIAL THERAPY
Treatment typically includes long-term therapy which has been shown to decrease the severity of symptoms.
• Cognitive behavioral therapy has been shown to be the most efficacious treatment in SD. (4-6)[C]
• Psychotherapy
• Supportive therapy
MEDICATION (DRUGS)
Antidepressants (e.g., SSRIs) help in some cases.
FOLLOW-UP
Patients should have regularly scheduled follow-up with a primary care doctor, psychiatrist, or therapist.
DISPOSITION
Issues for Referral
• Referrals to specialist for further investigation of somatic complaints should be discouraged.
• Referrals to support groups or to a psychiatrist may be helpful.
PROGNOSIS
• Chronic course, fluctuating in severity
• Full remission is rare.
• Individuals with this disorder do not experience any significant difference in mortality rate or significant illness.
COMPLICATIONS
• May result from invasive testing and from multiple evaluations that are performed while looking for the cause of the symptoms
• A dependency on pain relievers or sedatives may develop.
REFERENCES
1. Kroenke K, Spitzer R, Williams J. The PHQ-15: Validity of a new measure for evaluating the severity of somatic symptoms. Psychosom Med. 2002;64:258-266.
2. Wetzel RD, et al. MMPI screening scales for Somatization Disorder. Psychol Rep. 1999;85(1):341-348.
3. Servan-Schreiber NR, Tabas G, Kolb D. Somatizing patients: Part II. Practical management. Am Fam Physician. 2000;61(5):1423-1430.
4. Kroenke K, Swindle R. Cognitive-Behavioral therapy for somatization and symptom syndromes: A critical review of controlled clinical trials. Psychother Psychosom. 2000;69:205.
5. Mai F. Somatization disorder: A practical review. Can J Psychiatry. 2004;49:652-662.
6. Speckens AE, van Hemert AM, Spinhoven P, Hawton KE, Bolk JH, Rooijmans HG. Cognitive behavioural therapy for medically unexplained physical symptoms: A randomised controlled trial. BMJ. 1995;311:1328-1332.
7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text revision. Washington, DC: American Psychiatric Association, 2000.
MISCELLANEOUS
See also: Somatoform disorders
SNAKE ENVENOMATIONS: ELAPIDAE (CORAL SNAKE)
SNAKE ENVENOMATIONS: ELAPIDAE (CORAL SNAKE) - Alan L. Williams, MD; Pamela M. Williams, MD
BASICS
DESCRIPTION
• Symptom complex following envenomation by a snake of the family Elapidae
- Local signs and symptoms are mild in envenomation of Elapidae, even those that prove to be severe envenomations.
- Neurologic symptoms may be delayed; they have been reported to develop up to 12 or more hours after the envenomation.
• In the US, these snakes include the genera Micrurus and Micruroides, commonly called "coral snakes."
- The Sonoran or Arizona coral snake is found mainly in Arizona (Micruroides euryxanthus)
- Texas coral snake (Micrurus fulvius tenere) in Texas, Arkansas, and Louisiana
- Eastern coral snake (Micrurus fulvius fulvius) throughout the southeast.
• Coral snakes have a characteristic rounded head with round pupils.
ALERT
• Coloration is important: North American coral snakes have broad rings of red and black separated by narrow rings of yellow.
- In contrast, milk snakes are nonpoisonous snakes with similar coloration. The areas of orange/red and yellow/white are separated by bands of black.
• "Red on yellow, kill a fellow; red on black, friend of Jack."
• System(s) Affected: Nervous; Skin/Exocrine
• Synonym(s): Neurotoxic snakebite; Snakebite
GENERAL PREVENTION
• Use preventive measures if handling snakes.
• In snake-infested areas
- Wear protective shoes and clothing when walking.
- Do not insert hands or feet into cracks, crevices, or hollow logs.
- Carry a flashlight if walking at night.
EPIDEMIOLOGY
• Predominant age: 19-30 years
• Predominant sex: Male > Female
Incidence
• Coral snake bites comprise ~4% of identified snakebites reported to American Association of Poision Control Centers (AAPCC).
• 100 reported each year in the US
RISK FACTORS
Coral snakes are nocturnal and timid; therefore, they rarely bite humans. They must be deliberately provoked to bite.
ETIOLOGY
Venom is primarily a neurotoxin; little or no cytotoxin to cause local tissue reaction
DIAGNOSIS
SIGNS AND SYMPTOMS
• Fang marks; may be shallow or appear as scratch (>75%)
• Onset of symptoms following envenomation may be delayed 10-12 hours.
- Local swelling (50%)
- Numbness/change in sensation (50%)
- Nausea/vomiting (50%)
- Weakness (25%)
- Dizziness (15%)
- Diplopia (15%)
- Muscle fasciculations (15%)
- Dysarthia
- Dysphagia with increased salivation
History
• Snake identification is helpful, but should not place others at risk for being bitten.
• A digital photo may be a safe means to identify the snake.
• Determine previous snakebite history, any allergy to horse serum.
TESTS
• Baseline and serial pulmonary function with special attention to peak flow and vital capacity as well as oxygen saturation may help in early recognition of decreasing ventilatory function.
• Skin test for horse serum sensitivity
Lab
• Creatine phosphokinase often elevated
• Consider blood ethanol level.
DIFFERENTIAL DIAGNOSIS
• Bite of other venomous snake (Crotalidae) without envenomation ("dry bite")
• Bite of a nonvenomous snake
TREATMENT
PRE-HOSPITAL
• Pressure/immobilization of the affected limb is under study, but currently there are insufficient data to determine its efficacy.
• Transportation of a calm and still patient to a treatment facility is the primary goal.
• Administer O2.
• Obtain IV access.
STABILIZATION
ABCs, O2, monitored bed
GENERAL MEASURES
• All patients with any of the following should be admitted to hospital for intensive care monitoring
- Confirmed bite by a snake identified as a coral snake
- History of the snake having chewed on the person
• Perform a skin test for horse serum sensitivity.
- If negative, give antivenin to Micrurus fulvius fulvius early, even when there are no neurologic signs or symptoms.
- If skin test is positive, contact the AAPCC to help coordinate care with experienced consultants.
• Give tetanus toxoid if needed.
• Support vital signs; intubation may be necessary if respiratory compromise ensues.
• Good supportive care with cardiac, respiratory, neurologic monitoring
• Reassurance
• Immobilize extremity and keep at level of heart.
• Contact the AAPCC Regional Center for your area.
Diet
NPO initially
Activity
Bed rest initially. May need physical therapy in severe cases of envenomation
MEDICATION (DRUGS)
First Line
• No antivenin is available for Micruroides euryxanthus.
• Antivenin to the North American coral snake (Micrurus fulvius fulvius antivenin) (1)[C]
- Horse serum product effective only for the envenomation of the Texas and eastern coral snakes (Micrurus fulvius tenere and Micrurus fulvius fulvius)
- Perform skin testing 1st.
- Initial dose: 4-6 reconstituted vials added to 250 mL of normal saline
Begin infusion at 3-5 mL/h; if no systemic reaction occurs, increase until a rate of 1 diluted vial is being given every 30 minutes.
Because of the low numbers of patients treated with antivenin, an exact dosing schedule has not been determined.
- If a patient has been treated with antivenin and starts to develop neurologic symptoms, an additional 10-15 vials may be necessary. (2)[C]
- If skin test is positive, the literature is not clear regarding specific recommendations; however, pretreatment with diphenhydramine (Benadryl; 1 mg/kg per dose q6h IV; adults 25-50 mg IV), steroids (e.g., methylprednisolone [Solu-Medrol] 1-2 mg/kg per dose q8h IV), and other antihistamines (e.g., cimetidine 10 mg/kg per dose IV; adults 300 mg IV) may allow for infusion of antivenin. In this instance, obtain toxicology consultation from the AAPCC-certified Poison Information Center for your area.
• Contraindication: History of allergy to horse serum
• Precautions: Have equipment and medications readily at hand to treat anaphylaxis.
• Adverse reactions: Anaphylaxis, serum sickness
ALERT
Avoid sedatives and opioids, which may compound any respiratory compromise. (2)[C]
FOLLOW-UP
DISPOSITION
Admission Criteria
All suspect coral snake bites warrant admission for observation and treatment.
Discharge Criteria
• Discharge should not occur until the patient has made neurologic recovery to the point at which there is no concern of respiratory failure.
• Asymptomatic patients admitted for observation may be discharged after 24-48 hours.
PROGNOSIS
• Neurologic deterioration may progress despite antivenin administration. Complete paralysis may occur.
• Early, elective intubation during progression of paralysis may help to prevent aspiration pneumonia.
• Neurologic symptoms can last 3-6 days despite treatment with antivenin.
• Muscle strength may not return to normal for 4-6 weeks.
• Long-term morbidity is rare.
• Mortality does occur even with antivenin therapy.
ALERT
Pregnancy Considerations
• Limited data, but there have been reports of miscarriage following snakebite
• Treatment that optimizes maternal health is presumed to be the best available treatment for the fetus.
COMPLICATIONS
• Local wound infection
• Aspiration pneumonia
PATIENT MONITORING
First return visit within 48 hours, then as clinically indicated
REFERENCES
1. Kitchens CS, Van Mierop LHS. Envenomation by the eastern coral snake (Micrurus fulvius fulvius). JAMA. 1987;258:1615-1618.
2. Gold BS, Barish RA, Dart RC. North American snake envenomation: Diagnosis, treatment, and management. Emerg Med Clin North Am. 2004;22:423-443.
MISCELLANEOUS
See also: Snake envenomations: crotalidae
BASICS
DESCRIPTION
• Symptom complex following envenomation by a snake of the family Elapidae
- Local signs and symptoms are mild in envenomation of Elapidae, even those that prove to be severe envenomations.
- Neurologic symptoms may be delayed; they have been reported to develop up to 12 or more hours after the envenomation.
• In the US, these snakes include the genera Micrurus and Micruroides, commonly called "coral snakes."
- The Sonoran or Arizona coral snake is found mainly in Arizona (Micruroides euryxanthus)
- Texas coral snake (Micrurus fulvius tenere) in Texas, Arkansas, and Louisiana
- Eastern coral snake (Micrurus fulvius fulvius) throughout the southeast.
• Coral snakes have a characteristic rounded head with round pupils.
ALERT
• Coloration is important: North American coral snakes have broad rings of red and black separated by narrow rings of yellow.
- In contrast, milk snakes are nonpoisonous snakes with similar coloration. The areas of orange/red and yellow/white are separated by bands of black.
• "Red on yellow, kill a fellow; red on black, friend of Jack."
• System(s) Affected: Nervous; Skin/Exocrine
• Synonym(s): Neurotoxic snakebite; Snakebite
GENERAL PREVENTION
• Use preventive measures if handling snakes.
• In snake-infested areas
- Wear protective shoes and clothing when walking.
- Do not insert hands or feet into cracks, crevices, or hollow logs.
- Carry a flashlight if walking at night.
EPIDEMIOLOGY
• Predominant age: 19-30 years
• Predominant sex: Male > Female
Incidence
• Coral snake bites comprise ~4% of identified snakebites reported to American Association of Poision Control Centers (AAPCC).
• 100 reported each year in the US
RISK FACTORS
Coral snakes are nocturnal and timid; therefore, they rarely bite humans. They must be deliberately provoked to bite.
ETIOLOGY
Venom is primarily a neurotoxin; little or no cytotoxin to cause local tissue reaction
DIAGNOSIS
SIGNS AND SYMPTOMS
• Fang marks; may be shallow or appear as scratch (>75%)
• Onset of symptoms following envenomation may be delayed 10-12 hours.
- Local swelling (50%)
- Numbness/change in sensation (50%)
- Nausea/vomiting (50%)
- Weakness (25%)
- Dizziness (15%)
- Diplopia (15%)
- Muscle fasciculations (15%)
- Dysarthia
- Dysphagia with increased salivation
History
• Snake identification is helpful, but should not place others at risk for being bitten.
• A digital photo may be a safe means to identify the snake.
• Determine previous snakebite history, any allergy to horse serum.
TESTS
• Baseline and serial pulmonary function with special attention to peak flow and vital capacity as well as oxygen saturation may help in early recognition of decreasing ventilatory function.
• Skin test for horse serum sensitivity
Lab
• Creatine phosphokinase often elevated
• Consider blood ethanol level.
DIFFERENTIAL DIAGNOSIS
• Bite of other venomous snake (Crotalidae) without envenomation ("dry bite")
• Bite of a nonvenomous snake
TREATMENT
PRE-HOSPITAL
• Pressure/immobilization of the affected limb is under study, but currently there are insufficient data to determine its efficacy.
• Transportation of a calm and still patient to a treatment facility is the primary goal.
• Administer O2.
• Obtain IV access.
STABILIZATION
ABCs, O2, monitored bed
GENERAL MEASURES
• All patients with any of the following should be admitted to hospital for intensive care monitoring
- Confirmed bite by a snake identified as a coral snake
- History of the snake having chewed on the person
• Perform a skin test for horse serum sensitivity.
- If negative, give antivenin to Micrurus fulvius fulvius early, even when there are no neurologic signs or symptoms.
- If skin test is positive, contact the AAPCC to help coordinate care with experienced consultants.
• Give tetanus toxoid if needed.
• Support vital signs; intubation may be necessary if respiratory compromise ensues.
• Good supportive care with cardiac, respiratory, neurologic monitoring
• Reassurance
• Immobilize extremity and keep at level of heart.
• Contact the AAPCC Regional Center for your area.
Diet
NPO initially
Activity
Bed rest initially. May need physical therapy in severe cases of envenomation
MEDICATION (DRUGS)
First Line
• No antivenin is available for Micruroides euryxanthus.
• Antivenin to the North American coral snake (Micrurus fulvius fulvius antivenin) (1)[C]
- Horse serum product effective only for the envenomation of the Texas and eastern coral snakes (Micrurus fulvius tenere and Micrurus fulvius fulvius)
- Perform skin testing 1st.
- Initial dose: 4-6 reconstituted vials added to 250 mL of normal saline
Begin infusion at 3-5 mL/h; if no systemic reaction occurs, increase until a rate of 1 diluted vial is being given every 30 minutes.
Because of the low numbers of patients treated with antivenin, an exact dosing schedule has not been determined.
- If a patient has been treated with antivenin and starts to develop neurologic symptoms, an additional 10-15 vials may be necessary. (2)[C]
- If skin test is positive, the literature is not clear regarding specific recommendations; however, pretreatment with diphenhydramine (Benadryl; 1 mg/kg per dose q6h IV; adults 25-50 mg IV), steroids (e.g., methylprednisolone [Solu-Medrol] 1-2 mg/kg per dose q8h IV), and other antihistamines (e.g., cimetidine 10 mg/kg per dose IV; adults 300 mg IV) may allow for infusion of antivenin. In this instance, obtain toxicology consultation from the AAPCC-certified Poison Information Center for your area.
• Contraindication: History of allergy to horse serum
• Precautions: Have equipment and medications readily at hand to treat anaphylaxis.
• Adverse reactions: Anaphylaxis, serum sickness
ALERT
Avoid sedatives and opioids, which may compound any respiratory compromise. (2)[C]
FOLLOW-UP
DISPOSITION
Admission Criteria
All suspect coral snake bites warrant admission for observation and treatment.
Discharge Criteria
• Discharge should not occur until the patient has made neurologic recovery to the point at which there is no concern of respiratory failure.
• Asymptomatic patients admitted for observation may be discharged after 24-48 hours.
PROGNOSIS
• Neurologic deterioration may progress despite antivenin administration. Complete paralysis may occur.
• Early, elective intubation during progression of paralysis may help to prevent aspiration pneumonia.
• Neurologic symptoms can last 3-6 days despite treatment with antivenin.
• Muscle strength may not return to normal for 4-6 weeks.
• Long-term morbidity is rare.
• Mortality does occur even with antivenin therapy.
ALERT
Pregnancy Considerations
• Limited data, but there have been reports of miscarriage following snakebite
• Treatment that optimizes maternal health is presumed to be the best available treatment for the fetus.
COMPLICATIONS
• Local wound infection
• Aspiration pneumonia
PATIENT MONITORING
First return visit within 48 hours, then as clinically indicated
REFERENCES
1. Kitchens CS, Van Mierop LHS. Envenomation by the eastern coral snake (Micrurus fulvius fulvius). JAMA. 1987;258:1615-1618.
2. Gold BS, Barish RA, Dart RC. North American snake envenomation: Diagnosis, treatment, and management. Emerg Med Clin North Am. 2004;22:423-443.
MISCELLANEOUS
See also: Snake envenomations: crotalidae
SNAKE ENVENOMATIONS
SNAKE ENVENOMATIONS: CROTALIDAE - Alan L. Williams, MD; Pamela M. Williams, MD
BASICS
DESCRIPTION
• Symptom complex following envenomation by a snake of the family Crotalidae (pit vipers)
• Includes snakes of the genera Crotalus (rattlesnakes), Agkistrodon (moccasins), and Sistrurus (pygmy rattlesnakes)
• Occur most commonly in the southeastern and southwestern US
• North American crotalid characteristics: Triangular-shaped heads, eyes with elliptical pupils, and small heat-sensing facial pits located between the nostril and the eye
- In contrast, nonpoisonous snakes in the US generally have small round heads and round pupils, except coral snakes, which are brightly colored.
• System(s) Affected: Cardiovascular; Hemic/Lymphatic/Immunologic; Nervous; Skin/Exocrine
• Synonym(s): Snakebite; Venomous snakebite; Pit viper snakebite
GENERAL PREVENTION
• Use preventive measures if handling snakes.
• In snake-infested areas
- Wear protective shoes and clothing when walking.
- Do not insert hands or feet into cracks, crevices, or hollow logs.
- Carry a flashlight if walking at night.
EPIDEMIOLOGY
• Predominant age: 19-30 years
• Predominant sex: Male > Female
Incidence
• ~2,400 reported crotalid snakebites in the US annually accounting for 92% of reported identified snakebites US
- 2,000 additional reported bites from unknown snakes.
• The actual incidence of envenomation may be higher due to underreporting or lower due to dry bites.
RISK FACTORS
• Risk-taking behaviors
• Acute ethanol intoxication or intoxication with other drugs that impair judgment
PATHOPHYSIOLOGY
Clinical problems related to envenomation include tissue damage, coagulopathy, thrombocytopenia, hypovolemia, and neruotoxicity.
ETIOLOGY
• Pit viper venom is a complex mixture that contains cytotoxins, hemotoxins, neurotoxins, and cardiotoxins.
• Toxin composition varies from bite to bite even with the same snake.
• Envenomation can affect all major organ systems.
• Mojave Rattlesnake venom is more neurotoxic than that of other crotalids, and can cause respiratory depression.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Vary from minor local injury to severe systemic illness
• Fang marks may be 2 or only 1 (>90%)
• Pain out of proportion to puncture wound (usually within minutes of the bite) (>50%)
• Edema of site, progressing proximally up extremity (>50%)
• Weakness, dizziness (>50%)
• Numbness/tingling in extremity, mouth, tongue (>50%)
• Ecchymosis of skin, vesicles around bite (may take hours to develop) (>50%)
• Tachycardia (>50%)
• Nausea/vomiting (50%)
• Hypo- or hypertension (50%)
• Muscle fasciculations (50%)
• Mental status changes, including coma (25%)
• Change in sensation of taste
History
• Snake identification is helpful, but should not place others at risk for being bitten.
• A digital photo may be a safe means to identify the snake.
TESTS
Lab
• Complete blood count (hemoglobin/hematocrit decreased in 50%) (decrease in platelets 50%)
• Prothrombin time/international normalized ratio, A-PTT (prolonged in >50%)
• Fibrinogen (decreased in 50%), fibrin degradation products (increased in 50%)
• Urinalysis: glycosuria (50%), proteinuria (25%), hematuria (25%)
• Type and cross-match "to hold" in severe envenomations
• Electrolytes, BUN, creatinine
• Liver function tests
• Creatine kinase in severe envenomations
• Serum ethanol level if suspicious
• Disorders that may alter lab results
- Preexisting anemia or polycythemia
- Advanced liver disease
- Kidney disease
- Platelet disorders
• Drugs that may alter lab results
- Anticoagulants
DIFFERENTIAL DIAGNOSIS
• Bite of nonvenomous snake
• Bite of venomous species other than those of Crotalidae family
TREATMENT
PRE-HOSPITAL
• Patients with true envenomations need emergency department evaluation.
• Rapid transportation should take priority over all but the most basic first aid.
- Most field snakebite treatments (cutting the bite, attempting to remove poison with suction, and constriction bandages) have been shown to be ineffective and potentially harmful.
• Reassure patient, minimize patient movement during transport
• Splint area of bite allowing room for swelling.
- Position affected extremity at or below level of heart.
STABILIZATION
• Support vital signs, place on monitor, O2 as needed, obtain IV access
• Reassurance
• Remove rings and constrictive items.
GENERAL MEASURES
• Evaluate all prehospital care. Use of tourniquet and pressure dressings are controversial. If tourniquet has been placed in prehospital setting, sudden removal could bolus patient with venom. The tourniquet or constriction band should be removed only after beginning treatment with antivenom.
• Obtain toxicology consultation by contacting American Association of Poison Control Centers (AAPCC) Regional Poison Information Center.
• Level 1
- If local signs of edema are confined to area of bite, without any other symptom of envenomation, place IV line of crystalloid at maintenance rates and draw baseline laboratory studies.
- Place reference marks for measuring circumference of extremity at 10 cm and 20 cm proximal to site of envenomation.
Measure every 15 minutes and trace leading edge of swelling.
- Give tetanus toxoid if needed.
- Provide pain relief.
- Repeat laboratory studies in 6 hours. If all remain normal and swelling does not progress, observe 8-12 hours then follow up as outpatient.
- If swelling progresses or systemic signs and symptoms appear, patient needs admission and further therapy (progresses to Level 2).
• Level 2
- If edema, vesicles, erythema progress beyond the immediate bite area or there are associated systemic signs/symptoms or laboratory abnormalities, give IV antivenom plus all Level 1 management.
- Intensive care monitoring may be necessary.
- Repeat laboratory evaluations q6h initially until stable, then less frequently.
- Blood products are necessary only for coagulopathies with clinical bleeding, not for treatment of laboratory abnormalities.
Antivenom treatment may reverse hematologic abnormalities and should be given 1st.
- Have equipment and medications readily at hand to treat allergic reactions to antivenom.
Diet
Nothing by mouth initially
Activity
Bed rest, with extremity elevated
MEDICATION (DRUGS)
First Line
• Crotalidae polyvalent immune Fab (Ovine) (1)[B]
- No skin test necessary
- Initial dose: 5 reconstituted vials added to normal saline to make total volume of 250 mL
10 mL of sterile water added to each vial. Swirl only (do not shake), so as to not denature proteins.
Infuse IV slowly for the 1st 10 minutes, then increase rate to 250 mL/h to run remainder over 60 minutes.
After 1st infusion is complete, if all signs/symptoms of envenomation have not ceased, give up to two more doses of 4-6 vials until initial control is achieved.
- Maintenance: After initial control of symptoms, administer 3 maintenance doses of 2 vials at 6, 12, and 18 hours following time of initial control.
• Precautions: Papain is used in the manufacturing process of Crotalidae polyvalent immune Fab; patients with papaya allergies may be at risk for allergic reaction.
• Adverse reactions: Anaphylaxis, serum sickness
Second Line
Pain relief with opiate (e.g., morphine sulfate 0.1-0.2 mg/kg per dose q2-6h as needed) or acetaminophen (10-15 mg/kg per dose q4-6h as needed; maximum 4 g/d in adults)
ALERT
Avoid aspirin and other anticoagulants.
SURGERY
• Fasciotomy is rarely needed in snake envenomations.
• Envenomation may mimic compartment syndrome, making clinical distinction difficult.
• Decision to perform a fasciotomy should be based on measured compartmental pressures.
FOLLOW-UP
DISPOSITION
Admission Criteria
• Dry bites may be observed for 8-12 hours and the patient discharged if there is no evidence of envenomation.
• Anyone receiving antivenom should be admitted, likely to the ICU.
PROGNOSIS
Mortality: 0.1% in reported bites
ALERT
Geriatric Considerations
• Course may be more severe.
• Consider EKG, CXR, ABG if underlying conditions may be exacerbated by stress of envenomation.
Pediatric Considerations
• Course may be more severe.
• CroFab dosing is the same as for adults. (2)[C]
Pregnancy Considerations
• Limited data, but there have been reports of miscarriage following snakebite
• Treatment that optimizes maternal health is presumed to be the best available treatment for the fetus.
• There are no studies of CroFab in pregnant women.
COMPLICATIONS
• Local wound infection (rare)
• Bleeding after discharge from hospital
- Patients should be told to report nosebleeds, excessive bleeding after brushing teeth, blood in stools or vomitus, or excessive menstrual bleeding.
PATIENT MONITORING
• Phone follow up in 12-24 hours for discharged dry bites.
• 1st return visit within 48 hours after hospital discharge, then as clinically indicated
• Physical therapy referral should be made early for optimal outpatient intervention.
REFERENCES
1. Dart RC, et al. A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States. Ann Emerg Med. 2001;161:2030-2036.
2. Schmidt JM. Antivenom therapy for snakebites in children: Is there evidence? Curr Opin Pediatr. 2005;17:234-238.
3. Gold BS, Barish RA, Dart RC. North American snake envenomation: Diagnosis, treatment, and management. Emerg Med Clin North Am. 2004;22:423-443.
MISCELLANEOUS
See also: Snake envenomations: elapidae
BASICS
DESCRIPTION
• Symptom complex following envenomation by a snake of the family Crotalidae (pit vipers)
• Includes snakes of the genera Crotalus (rattlesnakes), Agkistrodon (moccasins), and Sistrurus (pygmy rattlesnakes)
• Occur most commonly in the southeastern and southwestern US
• North American crotalid characteristics: Triangular-shaped heads, eyes with elliptical pupils, and small heat-sensing facial pits located between the nostril and the eye
- In contrast, nonpoisonous snakes in the US generally have small round heads and round pupils, except coral snakes, which are brightly colored.
• System(s) Affected: Cardiovascular; Hemic/Lymphatic/Immunologic; Nervous; Skin/Exocrine
• Synonym(s): Snakebite; Venomous snakebite; Pit viper snakebite
GENERAL PREVENTION
• Use preventive measures if handling snakes.
• In snake-infested areas
- Wear protective shoes and clothing when walking.
- Do not insert hands or feet into cracks, crevices, or hollow logs.
- Carry a flashlight if walking at night.
EPIDEMIOLOGY
• Predominant age: 19-30 years
• Predominant sex: Male > Female
Incidence
• ~2,400 reported crotalid snakebites in the US annually accounting for 92% of reported identified snakebites US
- 2,000 additional reported bites from unknown snakes.
• The actual incidence of envenomation may be higher due to underreporting or lower due to dry bites.
RISK FACTORS
• Risk-taking behaviors
• Acute ethanol intoxication or intoxication with other drugs that impair judgment
PATHOPHYSIOLOGY
Clinical problems related to envenomation include tissue damage, coagulopathy, thrombocytopenia, hypovolemia, and neruotoxicity.
ETIOLOGY
• Pit viper venom is a complex mixture that contains cytotoxins, hemotoxins, neurotoxins, and cardiotoxins.
• Toxin composition varies from bite to bite even with the same snake.
• Envenomation can affect all major organ systems.
• Mojave Rattlesnake venom is more neurotoxic than that of other crotalids, and can cause respiratory depression.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Vary from minor local injury to severe systemic illness
• Fang marks may be 2 or only 1 (>90%)
• Pain out of proportion to puncture wound (usually within minutes of the bite) (>50%)
• Edema of site, progressing proximally up extremity (>50%)
• Weakness, dizziness (>50%)
• Numbness/tingling in extremity, mouth, tongue (>50%)
• Ecchymosis of skin, vesicles around bite (may take hours to develop) (>50%)
• Tachycardia (>50%)
• Nausea/vomiting (50%)
• Hypo- or hypertension (50%)
• Muscle fasciculations (50%)
• Mental status changes, including coma (25%)
• Change in sensation of taste
History
• Snake identification is helpful, but should not place others at risk for being bitten.
• A digital photo may be a safe means to identify the snake.
TESTS
Lab
• Complete blood count (hemoglobin/hematocrit decreased in 50%) (decrease in platelets 50%)
• Prothrombin time/international normalized ratio, A-PTT (prolonged in >50%)
• Fibrinogen (decreased in 50%), fibrin degradation products (increased in 50%)
• Urinalysis: glycosuria (50%), proteinuria (25%), hematuria (25%)
• Type and cross-match "to hold" in severe envenomations
• Electrolytes, BUN, creatinine
• Liver function tests
• Creatine kinase in severe envenomations
• Serum ethanol level if suspicious
• Disorders that may alter lab results
- Preexisting anemia or polycythemia
- Advanced liver disease
- Kidney disease
- Platelet disorders
• Drugs that may alter lab results
- Anticoagulants
DIFFERENTIAL DIAGNOSIS
• Bite of nonvenomous snake
• Bite of venomous species other than those of Crotalidae family
TREATMENT
PRE-HOSPITAL
• Patients with true envenomations need emergency department evaluation.
• Rapid transportation should take priority over all but the most basic first aid.
- Most field snakebite treatments (cutting the bite, attempting to remove poison with suction, and constriction bandages) have been shown to be ineffective and potentially harmful.
• Reassure patient, minimize patient movement during transport
• Splint area of bite allowing room for swelling.
- Position affected extremity at or below level of heart.
STABILIZATION
• Support vital signs, place on monitor, O2 as needed, obtain IV access
• Reassurance
• Remove rings and constrictive items.
GENERAL MEASURES
• Evaluate all prehospital care. Use of tourniquet and pressure dressings are controversial. If tourniquet has been placed in prehospital setting, sudden removal could bolus patient with venom. The tourniquet or constriction band should be removed only after beginning treatment with antivenom.
• Obtain toxicology consultation by contacting American Association of Poison Control Centers (AAPCC) Regional Poison Information Center.
• Level 1
- If local signs of edema are confined to area of bite, without any other symptom of envenomation, place IV line of crystalloid at maintenance rates and draw baseline laboratory studies.
- Place reference marks for measuring circumference of extremity at 10 cm and 20 cm proximal to site of envenomation.
Measure every 15 minutes and trace leading edge of swelling.
- Give tetanus toxoid if needed.
- Provide pain relief.
- Repeat laboratory studies in 6 hours. If all remain normal and swelling does not progress, observe 8-12 hours then follow up as outpatient.
- If swelling progresses or systemic signs and symptoms appear, patient needs admission and further therapy (progresses to Level 2).
• Level 2
- If edema, vesicles, erythema progress beyond the immediate bite area or there are associated systemic signs/symptoms or laboratory abnormalities, give IV antivenom plus all Level 1 management.
- Intensive care monitoring may be necessary.
- Repeat laboratory evaluations q6h initially until stable, then less frequently.
- Blood products are necessary only for coagulopathies with clinical bleeding, not for treatment of laboratory abnormalities.
Antivenom treatment may reverse hematologic abnormalities and should be given 1st.
- Have equipment and medications readily at hand to treat allergic reactions to antivenom.
Diet
Nothing by mouth initially
Activity
Bed rest, with extremity elevated
MEDICATION (DRUGS)
First Line
• Crotalidae polyvalent immune Fab (Ovine) (1)[B]
- No skin test necessary
- Initial dose: 5 reconstituted vials added to normal saline to make total volume of 250 mL
10 mL of sterile water added to each vial. Swirl only (do not shake), so as to not denature proteins.
Infuse IV slowly for the 1st 10 minutes, then increase rate to 250 mL/h to run remainder over 60 minutes.
After 1st infusion is complete, if all signs/symptoms of envenomation have not ceased, give up to two more doses of 4-6 vials until initial control is achieved.
- Maintenance: After initial control of symptoms, administer 3 maintenance doses of 2 vials at 6, 12, and 18 hours following time of initial control.
• Precautions: Papain is used in the manufacturing process of Crotalidae polyvalent immune Fab; patients with papaya allergies may be at risk for allergic reaction.
• Adverse reactions: Anaphylaxis, serum sickness
Second Line
Pain relief with opiate (e.g., morphine sulfate 0.1-0.2 mg/kg per dose q2-6h as needed) or acetaminophen (10-15 mg/kg per dose q4-6h as needed; maximum 4 g/d in adults)
ALERT
Avoid aspirin and other anticoagulants.
SURGERY
• Fasciotomy is rarely needed in snake envenomations.
• Envenomation may mimic compartment syndrome, making clinical distinction difficult.
• Decision to perform a fasciotomy should be based on measured compartmental pressures.
FOLLOW-UP
DISPOSITION
Admission Criteria
• Dry bites may be observed for 8-12 hours and the patient discharged if there is no evidence of envenomation.
• Anyone receiving antivenom should be admitted, likely to the ICU.
PROGNOSIS
Mortality: 0.1% in reported bites
ALERT
Geriatric Considerations
• Course may be more severe.
• Consider EKG, CXR, ABG if underlying conditions may be exacerbated by stress of envenomation.
Pediatric Considerations
• Course may be more severe.
• CroFab dosing is the same as for adults. (2)[C]
Pregnancy Considerations
• Limited data, but there have been reports of miscarriage following snakebite
• Treatment that optimizes maternal health is presumed to be the best available treatment for the fetus.
• There are no studies of CroFab in pregnant women.
COMPLICATIONS
• Local wound infection (rare)
• Bleeding after discharge from hospital
- Patients should be told to report nosebleeds, excessive bleeding after brushing teeth, blood in stools or vomitus, or excessive menstrual bleeding.
PATIENT MONITORING
• Phone follow up in 12-24 hours for discharged dry bites.
• 1st return visit within 48 hours after hospital discharge, then as clinically indicated
• Physical therapy referral should be made early for optimal outpatient intervention.
REFERENCES
1. Dart RC, et al. A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States. Ann Emerg Med. 2001;161:2030-2036.
2. Schmidt JM. Antivenom therapy for snakebites in children: Is there evidence? Curr Opin Pediatr. 2005;17:234-238.
3. Gold BS, Barish RA, Dart RC. North American snake envenomation: Diagnosis, treatment, and management. Emerg Med Clin North Am. 2004;22:423-443.
MISCELLANEOUS
See also: Snake envenomations: elapidae
SLEEP APNEA, OBSTRUCTIVE
SLEEP APNEA, OBSTRUCTIVE - Anjali Koka, MD; Frank J. Domino, MD
BASICS
DESCRIPTION
• Obstructive sleep apnea (OSA) is defined as repetitive episodes of cessation of airflow at nose and mouth during sleep due to obstruction at level of the pharynx.
- Associated with oxygen desaturation and nocturnal asphyxia
- 60% of people with OSA snore
- Apneas often terminate with a snort or gasp.
- Repetitive apneas produce sleep disruption, leading to excessive daytime sleepiness.
- Usual course is chronic
• System(s) Affected: Cardiovascular; Nervous; Pulmonary
• Synonym(s): Pickwickian syndrome; Sleep apnea syndrome; Nocturnal upper airway occlusion
GENERAL PREVENTION
See "Patient Education."
EPIDEMIOLOGY
• Predominant age: Middle age
• Predominant sex: Male > Female (2-3:1)
Incidence
Undetermined
Prevalence
• 4% for males and 2% for females (estimated)
• Prevalence increases with age.
RISK FACTORS
• Obesity
• Male sex
• Postmenopausal female
• Age >40 years old
• Nasal obstruction (due to polyps, rhinitis, or deviated septum)
• Anatomic narrowing (tonsillar hypertrophy, macroglossia, micrognathia, retrognathia, craniofacial abnormalities)
• Acromegaly
• Hypothyroidism
• Neurologic syndromes (muscular dystrophy, cerebral palsy)
• Alcohol/Sedative intake before bedtime
• Smoking
Genetics
Hereditary factors unknown; familial patterns seen
PATHOPHYSIOLOGY
OSA occurs when the naso- or oropharynx collapses passively during inspiration. A balance of anatomic and neuromuscular factors contribute to pharyngeal collapse.
• Anatomic abnormalities predispose the airway to collapse by decreasing the area of the upper airway or increasing the pressure surrounding the airway.
• Abnormal pharyngeal muscle control during sleep can decrease tonic input to upper airway muscles and can reduce reflexes to keep the upper airway open.
ETIOLOGY
Upper airway narrowing may be due to
• Obesity
• Enlarged tonsils or uvula
• Low soft palate
• Redundant tissue in soft palate or tonsillar pillars
• Large or posteriorly located tongue
• Craniofacial abnormalities
• Alcohol or sedative use before bedtime
ASSOCIATED CONDITIONS
• Hypertension
• Stroke
• Cardiovascular disease
• Cardiac arrythmias
• CHF
• Nasal obstructive problems
• Insulin resistance
DIAGNOSIS
SIGNS AND SYMPTOMS
• Daytime symptoms
- Excessive daytime sleepiness (cardinal symptom)
- Tired or unrefreshed upon morning awakening
- Sore or dry throat
- Complaints of poor concentration, memory problems, irritability, mood changes
- Morning headaches
- Decreased libido
- Depression
- Daytime fatigue or tiredness
- Systemic and pulmonary hypertension
• Nighttime symptoms
- Loud snoring
- Snort or gasp that arouses patient from sleep
- Disrupted sleep, nocturia
- Witnessed apneic episodes at night
History
Be sure to elicit a complete history of daytime and nighttime symptoms. Symptoms can be insidious and present for years.
• Evaluation of EDS
- Mild symptoms begin during quiet activities (reading, watching television).
- Severe symptoms begin during dynamic activities (work, driving).
Physical Exam
Most patients have a normal physical exam or may have hypertension, obesity, or appear sleepy.
• Focus of head and neck exam
- Oropharynx
Narrowing of the lateral airway wall
Tonsillar hypertrophy
Micrognathia or retrognathia
Long or thick uvula
High, arched hard palate
Soft palate edema
Macroglossia
- Nasopharynx
Deviated nasal septum
Poor nasal airflow
- Short neck with large circumference
TESTS
Lab
When clinically indicated
• TSH to rule out hypothyroidism
• Hct to evaluate polycythemia which can indicate nocturnal hypoxemia
• ABG to evaluate daytime hypercapnia
Imaging
Cephalometric measurements from lateral head and neck radiographs can aid in surgery treatments.
Diagnostic Procedures/Surgery
• Gold standard remains polysomnography (PSG), a nighttime sleep study
- Demonstrates severity of hypoxemia, sleep disruption, and cardiac arrhythmias associated with obstructive sleep apnea and elevated end tidal CO2
- Shows repetitive episodes of cessation or marked reduction in airflow despite continued respiratory efforts
- These apneic episodes must last at least 10 seconds and occur 10-15 times per hour to be considered clinically significant.
- Complete PSG is expensive, and health insurance may not cover the cost. In the future, portable monitoring will diagnose OSA once standards are established.
• Multiple sleep latency testing provides an objective measurement of daytime sleepiness.
• The apnea/hypoapnea index is defined as the total number of apneas and hypopneas divided by the total sleep time.
- Mild OSA: AHI = 5-15
- Moderate OSA: AHI = 15-30
- Severe OSA: AHI >30
• Drugs that may alter lab results: Benzodiazepines and other sedatives can amplify the severity of apnea seen on sleep study.
DIFFERENTIAL DIAGNOSIS
• Other causes of excessive daytime sleepiness such as
- Narcolepsy
- Idiopathic daytime hypersomnolence
- Inadequate sleep time
- Depressive episodes with excessive daytime sleepiness
- Periodic limb movements disorder
• Respiratory disorders with nocturnal awakenings such as asthma, chronic obstructive pulmonary disease, CHF
• Central sleep apnea may mimic obstructive sleep apnea.
• Sudden nocturnal awakenings due to panic attacks
• Sleep-related choking or laryngospasm
• Gastroesophageal reflux may also present with similar symptoms.
• Sleep-associated seizures (temporal lobe epilepsy)
TREATMENT
Outpatient for treatment or sleep study; inpatient for surgery
GENERAL MEASURES
• Continuous positive airway pressure (CPAP) treatment that restores regular nighttime breathing not only reduces snoring and ESD, but also decreases the risk for stroke (1)[B] and CHF and lowers blood pressure over the short-term. (2)[A]
• The most effective treatment for OSA is nasal CPAP. CPAP prevents the soft tissue in pharynx from collapsing, thus eliminating apneas and restoring oxygen saturation.
- Mild to moderate obstructive sleep apnea: CPAP, surgery, dental appliances
- Moderate to severe obstructive sleep apnea: CPAPA or BiPAP is the standard therapy.
• If OSA is present only when supine, keep the patient off his back (e.g., tennis ball in pocket sewn on back of nightshirt; fanny-pack with tennis balls worn at back).
• Avoid driving, if excessive daytime sleepiness is significant.
• No alcohol within 6 hours of bedtime
• Avoid sedatives and sleeping pills.
Diet
Overweight patients must lose weight, and all patients must avoid weight gain. Weight loss alone can relieve symptoms of OSA. (3)[A]
Activity
• Significantly sleepy patients should not drive a motor vehicle or operate dangerous equipment.
• Avoid alcohol, smoking, and sedatives.
MEDICATION (DRUGS)
First Line
Medications are generally not effective in treating OSA except in patients with rapid eye movement (REM) sleep-related apnea in whom protriptyline or fluoxetine may be helpful.
SURGERY
Surgical correction of the upper airway is not first line treatment and should only be considered in OSA that is not controllable with CPAP or weight loss. Surgeries: Uvulopalatopharyngoplasty (effective in 40% patients), tracheostomy, craniofacial surgery
FOLLOW-UP
PROGNOSIS
• With appropriate control of apneas, excessive daytime sleepiness dramatically improves quickly.
• Lifelong compliance with weight loss or nasal CPAP is necessary for therapy of obstructive sleep apnea.
• Untreated, obstructive sleep apnea appears to progress in severity.
• Significant morbidity and mortality due to OSA is usually secondary to arrhythmias, cardiac ischemia or hypertensive complications, or motor vehicle accidents.
COMPLICATIONS
Untreated OSA increases the risk for development of hypertension, stroke, myocardial infarction, diabetes, cardiovascular disease, and work-related and driving accidents
PATIENT MONITORING
• Physician follow-up improves compliance with CPAP therapy.
• Observe for return of snoring, EDS, or sleep disruption, which may indicate inadequate control of apneas.
ALERT
Pediatric Considerations
• The prevalence of pediatric OSA is 1-2% in children 4-5 years of age, and the peak incidence is between 3 and 6 years of age. Gender ratio: M = F
• Etiology: The most common cause is tonsillar hypertrophy. Additional causes are obesity and craniofacial abnormalities. OSA is also seen in children with neuromuscular diseases, such as cerebral palsy, spinal muscular atrophy due to abnormal pharyngeal muscle control.
• Sign and symptoms: Nighttime: Loud snoring, restlessness, and sweating. Daytime: Hyperactivity and decreased school performance. EDS is not a significant symptom.
• Diagnosis: Gold standard is PSG. Abnormal apnea/hypopnea index is different in children; >1-2 per hour is abnormal.
• Treatment: Surgery is the 1st-line treatment in cases due to tonsillar enlargement (improves symptoms in 70%). For cases due to obesity or craniofacial abnormalities, patients can use CPAP.
Pregnancy Considerations
Rare
REFERENCES
1. Yaggi HK, et al. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353:2034-2041.
2. Giles T, et al. Continuous positive airways pressure for obstructive sleep apnoea in adults. Cochrane Database Syst Rev. 2006;(1):CD001106.
3. Ryan CF. Sleep x 9: an approach to treatment of obstructive sleep apnoea/hypopnoea syndrome including upper airway surgery. Thorax. 2005;60(7):595-604.
ADDITIONAL READING
• Kryger MH. Principles and Practice of Sleep Medicine. 3rd ed. Philadelphia, PA: WB Saunders; 2000.
• Thorpy MJ. Handbook of Sleep Disorders. New York, NY: Marcel Dekker; 1990.
BASICS
DESCRIPTION
• Obstructive sleep apnea (OSA) is defined as repetitive episodes of cessation of airflow at nose and mouth during sleep due to obstruction at level of the pharynx.
- Associated with oxygen desaturation and nocturnal asphyxia
- 60% of people with OSA snore
- Apneas often terminate with a snort or gasp.
- Repetitive apneas produce sleep disruption, leading to excessive daytime sleepiness.
- Usual course is chronic
• System(s) Affected: Cardiovascular; Nervous; Pulmonary
• Synonym(s): Pickwickian syndrome; Sleep apnea syndrome; Nocturnal upper airway occlusion
GENERAL PREVENTION
See "Patient Education."
EPIDEMIOLOGY
• Predominant age: Middle age
• Predominant sex: Male > Female (2-3:1)
Incidence
Undetermined
Prevalence
• 4% for males and 2% for females (estimated)
• Prevalence increases with age.
RISK FACTORS
• Obesity
• Male sex
• Postmenopausal female
• Age >40 years old
• Nasal obstruction (due to polyps, rhinitis, or deviated septum)
• Anatomic narrowing (tonsillar hypertrophy, macroglossia, micrognathia, retrognathia, craniofacial abnormalities)
• Acromegaly
• Hypothyroidism
• Neurologic syndromes (muscular dystrophy, cerebral palsy)
• Alcohol/Sedative intake before bedtime
• Smoking
Genetics
Hereditary factors unknown; familial patterns seen
PATHOPHYSIOLOGY
OSA occurs when the naso- or oropharynx collapses passively during inspiration. A balance of anatomic and neuromuscular factors contribute to pharyngeal collapse.
• Anatomic abnormalities predispose the airway to collapse by decreasing the area of the upper airway or increasing the pressure surrounding the airway.
• Abnormal pharyngeal muscle control during sleep can decrease tonic input to upper airway muscles and can reduce reflexes to keep the upper airway open.
ETIOLOGY
Upper airway narrowing may be due to
• Obesity
• Enlarged tonsils or uvula
• Low soft palate
• Redundant tissue in soft palate or tonsillar pillars
• Large or posteriorly located tongue
• Craniofacial abnormalities
• Alcohol or sedative use before bedtime
ASSOCIATED CONDITIONS
• Hypertension
• Stroke
• Cardiovascular disease
• Cardiac arrythmias
• CHF
• Nasal obstructive problems
• Insulin resistance
DIAGNOSIS
SIGNS AND SYMPTOMS
• Daytime symptoms
- Excessive daytime sleepiness (cardinal symptom)
- Tired or unrefreshed upon morning awakening
- Sore or dry throat
- Complaints of poor concentration, memory problems, irritability, mood changes
- Morning headaches
- Decreased libido
- Depression
- Daytime fatigue or tiredness
- Systemic and pulmonary hypertension
• Nighttime symptoms
- Loud snoring
- Snort or gasp that arouses patient from sleep
- Disrupted sleep, nocturia
- Witnessed apneic episodes at night
History
Be sure to elicit a complete history of daytime and nighttime symptoms. Symptoms can be insidious and present for years.
• Evaluation of EDS
- Mild symptoms begin during quiet activities (reading, watching television).
- Severe symptoms begin during dynamic activities (work, driving).
Physical Exam
Most patients have a normal physical exam or may have hypertension, obesity, or appear sleepy.
• Focus of head and neck exam
- Oropharynx
Narrowing of the lateral airway wall
Tonsillar hypertrophy
Micrognathia or retrognathia
Long or thick uvula
High, arched hard palate
Soft palate edema
Macroglossia
- Nasopharynx
Deviated nasal septum
Poor nasal airflow
- Short neck with large circumference
TESTS
Lab
When clinically indicated
• TSH to rule out hypothyroidism
• Hct to evaluate polycythemia which can indicate nocturnal hypoxemia
• ABG to evaluate daytime hypercapnia
Imaging
Cephalometric measurements from lateral head and neck radiographs can aid in surgery treatments.
Diagnostic Procedures/Surgery
• Gold standard remains polysomnography (PSG), a nighttime sleep study
- Demonstrates severity of hypoxemia, sleep disruption, and cardiac arrhythmias associated with obstructive sleep apnea and elevated end tidal CO2
- Shows repetitive episodes of cessation or marked reduction in airflow despite continued respiratory efforts
- These apneic episodes must last at least 10 seconds and occur 10-15 times per hour to be considered clinically significant.
- Complete PSG is expensive, and health insurance may not cover the cost. In the future, portable monitoring will diagnose OSA once standards are established.
• Multiple sleep latency testing provides an objective measurement of daytime sleepiness.
• The apnea/hypoapnea index is defined as the total number of apneas and hypopneas divided by the total sleep time.
- Mild OSA: AHI = 5-15
- Moderate OSA: AHI = 15-30
- Severe OSA: AHI >30
• Drugs that may alter lab results: Benzodiazepines and other sedatives can amplify the severity of apnea seen on sleep study.
DIFFERENTIAL DIAGNOSIS
• Other causes of excessive daytime sleepiness such as
- Narcolepsy
- Idiopathic daytime hypersomnolence
- Inadequate sleep time
- Depressive episodes with excessive daytime sleepiness
- Periodic limb movements disorder
• Respiratory disorders with nocturnal awakenings such as asthma, chronic obstructive pulmonary disease, CHF
• Central sleep apnea may mimic obstructive sleep apnea.
• Sudden nocturnal awakenings due to panic attacks
• Sleep-related choking or laryngospasm
• Gastroesophageal reflux may also present with similar symptoms.
• Sleep-associated seizures (temporal lobe epilepsy)
TREATMENT
Outpatient for treatment or sleep study; inpatient for surgery
GENERAL MEASURES
• Continuous positive airway pressure (CPAP) treatment that restores regular nighttime breathing not only reduces snoring and ESD, but also decreases the risk for stroke (1)[B] and CHF and lowers blood pressure over the short-term. (2)[A]
• The most effective treatment for OSA is nasal CPAP. CPAP prevents the soft tissue in pharynx from collapsing, thus eliminating apneas and restoring oxygen saturation.
- Mild to moderate obstructive sleep apnea: CPAP, surgery, dental appliances
- Moderate to severe obstructive sleep apnea: CPAPA or BiPAP is the standard therapy.
• If OSA is present only when supine, keep the patient off his back (e.g., tennis ball in pocket sewn on back of nightshirt; fanny-pack with tennis balls worn at back).
• Avoid driving, if excessive daytime sleepiness is significant.
• No alcohol within 6 hours of bedtime
• Avoid sedatives and sleeping pills.
Diet
Overweight patients must lose weight, and all patients must avoid weight gain. Weight loss alone can relieve symptoms of OSA. (3)[A]
Activity
• Significantly sleepy patients should not drive a motor vehicle or operate dangerous equipment.
• Avoid alcohol, smoking, and sedatives.
MEDICATION (DRUGS)
First Line
Medications are generally not effective in treating OSA except in patients with rapid eye movement (REM) sleep-related apnea in whom protriptyline or fluoxetine may be helpful.
SURGERY
Surgical correction of the upper airway is not first line treatment and should only be considered in OSA that is not controllable with CPAP or weight loss. Surgeries: Uvulopalatopharyngoplasty (effective in 40% patients), tracheostomy, craniofacial surgery
FOLLOW-UP
PROGNOSIS
• With appropriate control of apneas, excessive daytime sleepiness dramatically improves quickly.
• Lifelong compliance with weight loss or nasal CPAP is necessary for therapy of obstructive sleep apnea.
• Untreated, obstructive sleep apnea appears to progress in severity.
• Significant morbidity and mortality due to OSA is usually secondary to arrhythmias, cardiac ischemia or hypertensive complications, or motor vehicle accidents.
COMPLICATIONS
Untreated OSA increases the risk for development of hypertension, stroke, myocardial infarction, diabetes, cardiovascular disease, and work-related and driving accidents
PATIENT MONITORING
• Physician follow-up improves compliance with CPAP therapy.
• Observe for return of snoring, EDS, or sleep disruption, which may indicate inadequate control of apneas.
ALERT
Pediatric Considerations
• The prevalence of pediatric OSA is 1-2% in children 4-5 years of age, and the peak incidence is between 3 and 6 years of age. Gender ratio: M = F
• Etiology: The most common cause is tonsillar hypertrophy. Additional causes are obesity and craniofacial abnormalities. OSA is also seen in children with neuromuscular diseases, such as cerebral palsy, spinal muscular atrophy due to abnormal pharyngeal muscle control.
• Sign and symptoms: Nighttime: Loud snoring, restlessness, and sweating. Daytime: Hyperactivity and decreased school performance. EDS is not a significant symptom.
• Diagnosis: Gold standard is PSG. Abnormal apnea/hypopnea index is different in children; >1-2 per hour is abnormal.
• Treatment: Surgery is the 1st-line treatment in cases due to tonsillar enlargement (improves symptoms in 70%). For cases due to obesity or craniofacial abnormalities, patients can use CPAP.
Pregnancy Considerations
Rare
REFERENCES
1. Yaggi HK, et al. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353:2034-2041.
2. Giles T, et al. Continuous positive airways pressure for obstructive sleep apnoea in adults. Cochrane Database Syst Rev. 2006;(1):CD001106.
3. Ryan CF. Sleep x 9: an approach to treatment of obstructive sleep apnoea/hypopnoea syndrome including upper airway surgery. Thorax. 2005;60(7):595-604.
ADDITIONAL READING
• Kryger MH. Principles and Practice of Sleep Medicine. 3rd ed. Philadelphia, PA: WB Saunders; 2000.
• Thorpy MJ. Handbook of Sleep Disorders. New York, NY: Marcel Dekker; 1990.
SMELL AND TASTE DISORDERS
SMELL AND TASTE DISORDERS - Steven M. Bromley, MD
BASICS
DESCRIPTION
• The senses of smell and taste allow full appreciation of the flavor and palatability of foods and also serve as an early-warning system against toxins, polluted air, smoke, and spoiled food products. Physiologically, the chemical senses aid in normal digestion by triggering gastrointestinal secretions. Smell or taste dysfunction may have a significant impact on quality of life.
• Loss of smell occurs more frequently than loss of taste, and patients frequently confuse the concepts of flavor loss (as a result of smell impairment) with taste loss (impaired ability to sense sweet, sour, salty, or bitter).
• Smell depends on the functioning of cranial nerve I (olfactory nerve) and cranial nerve V (trigeminal nerve).
• Taste depends on the functioning of cranial nerves VII, IX, and X. Because of these multiple pathways, total loss of taste (ageusia) is rare.
• System(s) Affected: Nervous
• Synonym(s): Burning mouth syndrome
GENERAL PREVENTION
• Avoid exposure to chemicals, smoke, and radiation.
• Maintain good oral and nasal health, with routine visits to the dentist.
• Eat a well-balanced diet for optimal nutrition.
EPIDEMIOLOGY
• Predominant age: Chemosensory loss is age dependent.
• Predominant sex: Male > Female (Men also begin to lose ability to smell earlier in life than do women.)
Incidence
Estimated >2 million; 200,000 visit a physician each year.
Prevalence
• Age >80 years: 80% have major olfactory impairment; nearly 50% are anosmic.
• Ages 65-80 years: 60% have major olfactory impairment; nearly 25% are anosmic.
• Age 65 years: 1-2% have smell impairment.
RISK FACTORS
Genetics
Smell and taste disturbances may be related to genetically associated underlying diseases (e.g., Kallmann syndrome, Alzheimer disease, migraine, and rheumatologic and endocrine disorders).
ETIOLOGY
• Smell and/or taste disturbances
- Nutritional factors (malnutrition, vitamin deficiencies, liver disease, anemia)
- Endocrine disorders (thyroid disease, diabetes mellitus, renal disease)
- Head trauma
- Migraine headache (gustatory aura, olfactory aura)
- Sjogren syndrome
- Toxic chemical exposure
- Industrial agent exposure
- Aging
- Medications (see below)
- Neurodegenerative diseases (multiple sclerosis, Alzheimer disease, cerebrovascular accident, Parkinson disease)
- Infections (upper respiratory infection, oral and perioral infections, candidiasis, coxsackievirus, AIDS, viral hepatitis, herpes simplex virus)
• Possible causes of smell disturbance
- Nasal and sinus disease (allergies, rhinitis, rhinorrhea)
- Cigarette smoking
- Cocaine abuse (intranasal)
- Radiation treatment of head and neck
- Congenital conditions
- Neoplasm (brain tumor, nasal polyps, intranasal tumor)
- Systemic lupus erythematosus
- Bell palsy
- Oral or perioral skin lesion
- Damage to cranial nerve I or V
• Possible causes of taste loss
- Oral appliances
- Dental procedures
- Intraoral abscess
- Gingivitis
- Damage to cranial nerve VI, IX, or X
• Selected medications that reportedly alter smell and taste
- Antibiotics: Ampicillin, azithromycin (Zithromax), ciprofloxacin (Cipro), clarithromycin (Biaxin), griseofulvin (Grisactin), metronidazole (Flagyl), ofloxacin (Floxin), tetracycline, terbinafine (Lamisil)
- Anticonvulsants: Carbamazepine (Tegretol), phenytoin (Dilantin)
- Antidepressants: Amitriptyline (Elavil), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Pamelor)
- Antihistamines and decongestants: Chlorpheniramine, loratadine (Claritin), pseudoephedrine
- Antihypertensives and cardiac medications: Acetazolamide (Diamox), amiloride (Midamor), betaxolol (Betoptic), captopril (Capoten), diltiazem (Cardizem), enalapril (Vasotec), hydrochlorothiazide (Esidrix) and combinations, nifedipine (Procardia), nitroglycerin, propranolol (Inderal), spironolactone (Aldactone)
- Anti-inflammatory agents: Auranofin (Ridaura), colchicine, dexamethasone (Decadron), gold (Myochrysine), hydrocortisone, penicillamine (Cuprimine)
- Antimanic drugs: Lithium
- Antineoplastics: Cisplatin (Platinol), doxorubicin (Adriamycin), methotrexate (Rheumatrex), vincristine (Oncovin)
- Antiparkinsonian agents: Levodopa (Larodopa; with carbidopa: Sinemet)
- Antipsychotics: Clozapine (Clozaril), trifluoperazine (Stelazine)
- Antithyroid agents: Methimazole (Tapazole), propylthiouracil
- Lipid-lowering agents: Fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol)
- Muscle relaxants: Baclofen (Lioresal), dantrolene (Dantrium)
ALERT
Pregnancy Considerations
Uncommon cause of smell and taste disturbances. Many women report increased sensitivity to odors during pregnancy as well as an increased dislike for bitter and a preference for salty substances.
ASSOCIATED CONDITIONS
Smell and taste disturbances are primarily symptoms; it is essential to look for possible underlying cause.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Problems with smell and taste
• Weight loss
• Malnutrition
• Impaired immunity
• Worsening of medical illness
• Increased use of sugar and salt to compensate for diminished senses of smell and taste
TESTS
• Olfactory tests
- Smell identification test: Evaluates the ability to identify 40 microencapsulated "scratch and sniff" odorants
- 3-item forced-choice microencapsulated Pocket Smell Test
- Brief smell identification test
- Squeeze-bottle odor threshold test kit
• Taste tests (more difficult because no convenient standardized tests are presently available)
- Solutions containing sucrose (sweet), sodium chloride (salty), quinine (bitter), and citric acid (sour) are helpful.
- Electrogustometry: A portable battery-powered device delivers small currents to different parts of the tongue to obtain threshold and suprathreshold measures.
Lab
• Hematocrit
• Hemoglobin
• WBC count
• BUN
• Blood glucose
• Creatinine
• Bilirubin
• Alkaline phosphatase
• Prothrombin time
• ESR
• Altered thyroid function tests
• Eosinophil count
• IgE
Imaging
• Plain radiographs have substantial limitations (rarely useful).
• CT scanning is the most useful and cost-effective technique for assessing sinonasal disorders and is superior to MRI in evaluating bony structures. Coronal CT scans are particularly valuable in assessing paranasal anatomy.
• MRI is useful in defining soft tissue disease; therefore, it is the technique of choice to image the olfactory bulbs, tracts, and cortical parenchyma.
Diagnostic Procedures/Surgery
• Medical history
• Physical examination
DIFFERENTIAL DIAGNOSIS
• Epilepsy (gustatory aura)
• Epilepsy (olfactory aura)
• Memory impairment
• Psychiatric conditions
ALERT
Geriatric Considerations
Aging is a cause of smell/taste deficits; consider a diagnosis of exclusion.
Pediatric Considerations
Delayed puberty in association with anosmia (with or without midline craniofacial abnormalities, deafness, or renal abnormalities) suggests the possibility of Kallmann syndrome.
TREATMENT
STABILIZATION
Outpatient care usually
GENERAL MEASURES
• Appropriate treatment for underlying cause
• Quit smoking.
• Some drug-related dysgeusias can be reversed with cessation of the offending agent.
• Eliminate exposures (e.g., volatile gases, toxins, repeated use of oxygen-liberating mouthwashes).
• Stop repeated oral trauma (e.g., appliances, tongue-biting behaviors).
• Proper nutritional and dietary assessment
• Formal dental evaluation
Diet
• Caution patients not to overindulge as compensation for the bland taste of food. For example, patients with diabetes may need help in avoiding excessive sugar intake as an inappropriate way of improving food taste.
• Patients with chemosensory impairment should use measuring devices when cooking and should not "cook by taste."
• Optimizing food texture, aroma, temperature, and color may improve the overall food experience when taste is limited.
MEDICATION (DRUGS)
• Corticosteroids topically (e.g., aqueous nasal spray) or systemically (e.g., oral prednisone) may be helpful. Prednisone 60 mg/d for 4 days, with the dosage tapered by 10 mg/d thereafter
• Artificial saliva (e.g., Xero-Lube) may be helpful in patients with xerostomia.
• Pilocarpine (Salagen) 5-10 mg PO t.i.d. may help with dry mouth/xerostomia. Response may take 6-12 weeks.
• Chlorhexidine (Peridex) 0.12% oral rinse may help with gingivitis or dysgeusia.
• Zinc and vitamins (A, B complex) when deficiency is suspected
SURGERY
If needed for treatment of underlying cause
FOLLOW-UP
PROGNOSIS
• In general, the olfactory system regenerates poorly after a head injury. Most patients who recover smell function subsequent to head trauma do so within 12 weeks of injury.
• Patients who quit smoking typically have improved olfactory function and flavor sensation over time.
• Many taste disorders (dysgeusias) resolve spontaneously within a few years of onset.
• Conditions such as radiation-induced xerostomia and Bell palsy generally improve over time.
COMPLICATIONS
Permanent loss of ability to smell or taste
PATIENT MONITORING
Patients with persistent smell and taste complaints may need to be referred to otolaryngologist, neurologist, or subspecialist at a smell and taste center.
REFERENCES
1. Bromley SM. Smell and taste disorders: A primary care approach. Am Fam Phys. 2000;61:427-436.
2. Deems DA, et al. Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center. Arch Otolaryngol Head Neck Surg. 1991;117:519-528.
PATIENT TEACHING
• Patients with permanent smell dysfunction must develop adaptive strategies for dealing with hygiene, appetite, safety, and health.
• Check smoke detectors frequently.
• Use electric instead of gas appliances (if anosmic).
• Check food expiration dates frequently; discard old food.
BASICS
DESCRIPTION
• The senses of smell and taste allow full appreciation of the flavor and palatability of foods and also serve as an early-warning system against toxins, polluted air, smoke, and spoiled food products. Physiologically, the chemical senses aid in normal digestion by triggering gastrointestinal secretions. Smell or taste dysfunction may have a significant impact on quality of life.
• Loss of smell occurs more frequently than loss of taste, and patients frequently confuse the concepts of flavor loss (as a result of smell impairment) with taste loss (impaired ability to sense sweet, sour, salty, or bitter).
• Smell depends on the functioning of cranial nerve I (olfactory nerve) and cranial nerve V (trigeminal nerve).
• Taste depends on the functioning of cranial nerves VII, IX, and X. Because of these multiple pathways, total loss of taste (ageusia) is rare.
• System(s) Affected: Nervous
• Synonym(s): Burning mouth syndrome
GENERAL PREVENTION
• Avoid exposure to chemicals, smoke, and radiation.
• Maintain good oral and nasal health, with routine visits to the dentist.
• Eat a well-balanced diet for optimal nutrition.
EPIDEMIOLOGY
• Predominant age: Chemosensory loss is age dependent.
• Predominant sex: Male > Female (Men also begin to lose ability to smell earlier in life than do women.)
Incidence
Estimated >2 million; 200,000 visit a physician each year.
Prevalence
• Age >80 years: 80% have major olfactory impairment; nearly 50% are anosmic.
• Ages 65-80 years: 60% have major olfactory impairment; nearly 25% are anosmic.
• Age 65 years: 1-2% have smell impairment.
RISK FACTORS
Genetics
Smell and taste disturbances may be related to genetically associated underlying diseases (e.g., Kallmann syndrome, Alzheimer disease, migraine, and rheumatologic and endocrine disorders).
ETIOLOGY
• Smell and/or taste disturbances
- Nutritional factors (malnutrition, vitamin deficiencies, liver disease, anemia)
- Endocrine disorders (thyroid disease, diabetes mellitus, renal disease)
- Head trauma
- Migraine headache (gustatory aura, olfactory aura)
- Sjogren syndrome
- Toxic chemical exposure
- Industrial agent exposure
- Aging
- Medications (see below)
- Neurodegenerative diseases (multiple sclerosis, Alzheimer disease, cerebrovascular accident, Parkinson disease)
- Infections (upper respiratory infection, oral and perioral infections, candidiasis, coxsackievirus, AIDS, viral hepatitis, herpes simplex virus)
• Possible causes of smell disturbance
- Nasal and sinus disease (allergies, rhinitis, rhinorrhea)
- Cigarette smoking
- Cocaine abuse (intranasal)
- Radiation treatment of head and neck
- Congenital conditions
- Neoplasm (brain tumor, nasal polyps, intranasal tumor)
- Systemic lupus erythematosus
- Bell palsy
- Oral or perioral skin lesion
- Damage to cranial nerve I or V
• Possible causes of taste loss
- Oral appliances
- Dental procedures
- Intraoral abscess
- Gingivitis
- Damage to cranial nerve VI, IX, or X
• Selected medications that reportedly alter smell and taste
- Antibiotics: Ampicillin, azithromycin (Zithromax), ciprofloxacin (Cipro), clarithromycin (Biaxin), griseofulvin (Grisactin), metronidazole (Flagyl), ofloxacin (Floxin), tetracycline, terbinafine (Lamisil)
- Anticonvulsants: Carbamazepine (Tegretol), phenytoin (Dilantin)
- Antidepressants: Amitriptyline (Elavil), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Pamelor)
- Antihistamines and decongestants: Chlorpheniramine, loratadine (Claritin), pseudoephedrine
- Antihypertensives and cardiac medications: Acetazolamide (Diamox), amiloride (Midamor), betaxolol (Betoptic), captopril (Capoten), diltiazem (Cardizem), enalapril (Vasotec), hydrochlorothiazide (Esidrix) and combinations, nifedipine (Procardia), nitroglycerin, propranolol (Inderal), spironolactone (Aldactone)
- Anti-inflammatory agents: Auranofin (Ridaura), colchicine, dexamethasone (Decadron), gold (Myochrysine), hydrocortisone, penicillamine (Cuprimine)
- Antimanic drugs: Lithium
- Antineoplastics: Cisplatin (Platinol), doxorubicin (Adriamycin), methotrexate (Rheumatrex), vincristine (Oncovin)
- Antiparkinsonian agents: Levodopa (Larodopa; with carbidopa: Sinemet)
- Antipsychotics: Clozapine (Clozaril), trifluoperazine (Stelazine)
- Antithyroid agents: Methimazole (Tapazole), propylthiouracil
- Lipid-lowering agents: Fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol)
- Muscle relaxants: Baclofen (Lioresal), dantrolene (Dantrium)
ALERT
Pregnancy Considerations
Uncommon cause of smell and taste disturbances. Many women report increased sensitivity to odors during pregnancy as well as an increased dislike for bitter and a preference for salty substances.
ASSOCIATED CONDITIONS
Smell and taste disturbances are primarily symptoms; it is essential to look for possible underlying cause.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Problems with smell and taste
• Weight loss
• Malnutrition
• Impaired immunity
• Worsening of medical illness
• Increased use of sugar and salt to compensate for diminished senses of smell and taste
TESTS
• Olfactory tests
- Smell identification test: Evaluates the ability to identify 40 microencapsulated "scratch and sniff" odorants
- 3-item forced-choice microencapsulated Pocket Smell Test
- Brief smell identification test
- Squeeze-bottle odor threshold test kit
• Taste tests (more difficult because no convenient standardized tests are presently available)
- Solutions containing sucrose (sweet), sodium chloride (salty), quinine (bitter), and citric acid (sour) are helpful.
- Electrogustometry: A portable battery-powered device delivers small currents to different parts of the tongue to obtain threshold and suprathreshold measures.
Lab
• Hematocrit
• Hemoglobin
• WBC count
• BUN
• Blood glucose
• Creatinine
• Bilirubin
• Alkaline phosphatase
• Prothrombin time
• ESR
• Altered thyroid function tests
• Eosinophil count
• IgE
Imaging
• Plain radiographs have substantial limitations (rarely useful).
• CT scanning is the most useful and cost-effective technique for assessing sinonasal disorders and is superior to MRI in evaluating bony structures. Coronal CT scans are particularly valuable in assessing paranasal anatomy.
• MRI is useful in defining soft tissue disease; therefore, it is the technique of choice to image the olfactory bulbs, tracts, and cortical parenchyma.
Diagnostic Procedures/Surgery
• Medical history
• Physical examination
DIFFERENTIAL DIAGNOSIS
• Epilepsy (gustatory aura)
• Epilepsy (olfactory aura)
• Memory impairment
• Psychiatric conditions
ALERT
Geriatric Considerations
Aging is a cause of smell/taste deficits; consider a diagnosis of exclusion.
Pediatric Considerations
Delayed puberty in association with anosmia (with or without midline craniofacial abnormalities, deafness, or renal abnormalities) suggests the possibility of Kallmann syndrome.
TREATMENT
STABILIZATION
Outpatient care usually
GENERAL MEASURES
• Appropriate treatment for underlying cause
• Quit smoking.
• Some drug-related dysgeusias can be reversed with cessation of the offending agent.
• Eliminate exposures (e.g., volatile gases, toxins, repeated use of oxygen-liberating mouthwashes).
• Stop repeated oral trauma (e.g., appliances, tongue-biting behaviors).
• Proper nutritional and dietary assessment
• Formal dental evaluation
Diet
• Caution patients not to overindulge as compensation for the bland taste of food. For example, patients with diabetes may need help in avoiding excessive sugar intake as an inappropriate way of improving food taste.
• Patients with chemosensory impairment should use measuring devices when cooking and should not "cook by taste."
• Optimizing food texture, aroma, temperature, and color may improve the overall food experience when taste is limited.
MEDICATION (DRUGS)
• Corticosteroids topically (e.g., aqueous nasal spray) or systemically (e.g., oral prednisone) may be helpful. Prednisone 60 mg/d for 4 days, with the dosage tapered by 10 mg/d thereafter
• Artificial saliva (e.g., Xero-Lube) may be helpful in patients with xerostomia.
• Pilocarpine (Salagen) 5-10 mg PO t.i.d. may help with dry mouth/xerostomia. Response may take 6-12 weeks.
• Chlorhexidine (Peridex) 0.12% oral rinse may help with gingivitis or dysgeusia.
• Zinc and vitamins (A, B complex) when deficiency is suspected
SURGERY
If needed for treatment of underlying cause
FOLLOW-UP
PROGNOSIS
• In general, the olfactory system regenerates poorly after a head injury. Most patients who recover smell function subsequent to head trauma do so within 12 weeks of injury.
• Patients who quit smoking typically have improved olfactory function and flavor sensation over time.
• Many taste disorders (dysgeusias) resolve spontaneously within a few years of onset.
• Conditions such as radiation-induced xerostomia and Bell palsy generally improve over time.
COMPLICATIONS
Permanent loss of ability to smell or taste
PATIENT MONITORING
Patients with persistent smell and taste complaints may need to be referred to otolaryngologist, neurologist, or subspecialist at a smell and taste center.
REFERENCES
1. Bromley SM. Smell and taste disorders: A primary care approach. Am Fam Phys. 2000;61:427-436.
2. Deems DA, et al. Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center. Arch Otolaryngol Head Neck Surg. 1991;117:519-528.
PATIENT TEACHING
• Patients with permanent smell dysfunction must develop adaptive strategies for dealing with hygiene, appetite, safety, and health.
• Check smoke detectors frequently.
• Use electric instead of gas appliances (if anosmic).
• Check food expiration dates frequently; discard old food.
SINUSITIS
SINUSITIS - Rebecca Musher Gross, MD
BASICS
DESCRIPTION
• Acute rhinosinusitis (generally called sinusitis) is a symptomatic inflammation of the paranasal sinuses of 4 weeks duration resulting from impaired drainage and retained secretions. Disease is subacute when symptomatic for 4-12 weeks; chronic when symptomatic for >12 weeks
• System(s) Affected: HEENT; Pulmonary
GENERAL PREVENTION
No documented preventive measures
EPIDEMIOLOGY
• Of ~1 billion viral respiratory illnesses in the US each year, perhaps 200 million (10%) are associated with inflammation, impaired drainage and retained secretions in sinuses; ~20 million cases are secondarily infected by bacteria.
• Diagnosis of acute bacterial rhinosinusitis is 5th leading reason for prescribing antibiotics, accounting for 9% of all pediatric and 21% of all adult antibiotic prescriptions in 2002.
• Many of these diagnoses are erroneous.
• Incidence highest in early fall through early spring (related to incidence of viral URI)
RISK FACTORS
• Viral upper respiratory infection
• Allergic rhinitis
• Asthma
• Cigarette smoking
• Trauma
• Dental infections and procedures
• Anatomical variations
- Tonsillar and adenoid hypertrophy
- Turbinate hypertrophy, nasal polyps
- Deviated septum
- Cleft palate
• Immunodeficiency (e.g., HIV)
• Cystic fibrosis
Genetics
No known genetic pattern
PATHOPHYSIOLOGY
• Important features
- Inflammation and edema of the sinus mucosa
- Obstruction of the sinus ostia
- Impaired mucociliary clearance
• Secretions that are not cleared become hospitable to bacterial growth.
• Inflammatory response (neutrophil influx and release of cytokines) damages mucosal surfaces.
ETIOLOGY
• Viral: Vast majority of cases (rhinovirus, influenza A and B, parainfluenza virus, respiratory syncytial, adeno-, corona-, and entero-viruses
• Bacterial (complicates 0.2-2% of viral cases)
- More likely if symptoms worsen >5-7 days or do not improve >10 days
- Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the most common bacterial etiologies.
- Often overdiagnosed, which leads to overuse of, and increasing resistance to, antibiotics
• Fungal infection seen In immunocompromised hosts (uncontrolled diabetes, neutropenia, glucocorticosteroids) or as nosocomial infection
DIAGNOSIS
History and physical exam suggest the diagnosis in the majority of cases.
SIGNS AND SYMPTOMS
• Major challenge is to distinguish between viral and bacterial disease; use constellation of symptoms rather than a particular sign or symptom.
• Symptoms predictive of bacterial sinusitis
- Persistent symptoms for 10 days
- Worsening of symptoms >5-7 days after initial improvement
- Persistent purulent nasal discharge
- Unilateral maxillary tooth or facial pain
- Unilateral maxillary sinus tenderness
- Appearance of fever (usually low-grade)
• Associated symptoms
- Headache
- Nasal congestion
- Retro-orbital pain
- Otalgia
- Hyposomia
- Halitosis
- Chronic cough
• Symptoms requiring urgent attention
- Visual disturbances, especially diplopia
- Periorbital swelling or erythema
- Altered mental status
Physical Exam
• Fever
• Edema and erythema of nasal mucosa
• Purulent discharge
• Tenderness to palpation over sinus(es)
TESTS
• None indicated in routine evaluation
• Transillumination of the sinuses
- May confirm fluid in sinuses
- Value is limited as it does not distinguish between viral and bacterial etiology.
Lab
None indicated in routine evaluation
Imaging
• Routine use of sinus radiography discouraged because: (i) 3 clinical findings may have similar diagnostic accuracy as imaging and (ii) imaging does not distinguish viral from bacterial etiology.
• Limited coronal CT can be useful in recurrent infection or failure to respond to medical therapy.
Diagnostic Procedures/Surgery
• Gold standard = transnasal endoscopic or sublabial maxillary antrum aspiration culture; generally performed only in recurrent and/or complicated cases (1,2)[A]
Pathological Findings
• Inflammation
• Edema
• Thickened mucosa
• Impaired ciliary function
• Metaplasia of ciliated columnar cells
• Relative acidosis and hypoxia within sinuses
• Polyps
DIFFERENTIAL DIAGNOSIS
• Dental disease
• Cystic fibrosis
• Wegener granulomatosis
• HIV infection
• Kartagener syndrome
• Immotile cilia syndrome
• Neoplasm
TREATMENT
• Majority of cases treated in outpatient setting
• Hospitalization for complications (meningitis, orbital cellulitis or abscess, brain abscess)
GENERAL MEASURES
• Adequate hydration
• Steam inhalation 20-30 minutes t.i.d.
• Saline irrigation or saline nose drops
• Sleep with head of bed elevated.
• Avoid exposure to cigarette smoke, fumes.
• Avoid dehydrants (caffeine and alcohol).
• Antibiotics indicated only when findings suggest bacterial infection
• Analgesics, NSAIDs (see below)
• Acute viral sinusitis is self-limiting, and antibiotics should not be used.
Diet
No special diet
Activity
Adequate rest, otherwise no restrictions
MEDICATION (DRUGS)
First Line
• Decongestants
- Pseudoephedrine HCl
- Phenylephrine (limited use)
- Oxymetazoline (i.e., Afrin) (limited use)
• Analgesics
- Acetaminophen
- Aspirin
- NSAIDs
- Acetaminophen-codeine
• Antibiotics
- Antibiotics appear to have a slight advantage over placebo, yet most patients improve without therapy.
- Major issue: Distinguish bacterial from viral
- Reserve antibiotic use for patients with moderate to severe disease.
- Treat 10-14 days unless otherwise specified.
- Choice should be based on understanding of antibiotic resistance in the community.
- Multiple meta-analyses have demonstrated NO benefit of newer antibiotics over Amoxicillin, Trimethoprim-sulfamethoxazole, or Doxycyclin.
- Initial therapy (2)[A]
- Amoxicillin: 500 mg-1 g t.i.d. (adults); 80-90 mg/kg/d divided q8h (children)
- Trimethoprim-sulfamethoxazole: 160 mg/800 mg q12h in adults and 8-12 mg/kg/d of trimethoprim component divided q12h for children
- Doxycyline 100 mg PO b.i.d.
Second Line
• Amoxicillin-clavulanate (Augmentin) 875 mg/ 125 mg q12h (adults); 30 mg/kg/d of amoxicillin component divided b.i.d. in children
• Cefpodoxime (Vantin): 200 mg q12h in adults and 10 mg/kg/d divided b.i.d. in children
• Cefuroxime axetil (Ceftin): 250 mg q12hrs in adults and 30 mg/kg/d divided q12h in children
• Telithromycin: 800 mg/d 5 days in adults, no pediatric indication
• Azithromycin (Zithromax): 500 mg on day 1 and 250 mg on days 2-5 in adults; 10 mg/kg on day 1 and 5 mg/kg on days 2-5 in children
• Clarithromycin: 500 mg b.i.d. (regular) or 1000 mg/d (extended release) in adults; 15 mg/kd/d divided b.i.d. in children
• Levofloxacin (Levaquin): 500 mg/d in adults; if patients have had antibiotics within past 4-6 weeks or if no response to above therapy within 72 hours, change to
- High dose amoxicillin/clavulanate
- Cephalosporins as above
- Fluoroquinolones as above
• NOTE: Bacteriologic failure rates up to 20-25% are possible with use of azithromycin and clarithromycin (2)[C]
• If lack of response to 3 weeks of antibiotics, consider
- CT scan of sinuses
- Ear, nose, and throat referral
• Precautions
- Decongestants can exacerbate hypertension.
- Prolonged use of topical decongestants (>4 days) may precipitate rhinitis medicamentosa.
- Sulfonamides may induce Stevens-Johnson syndrome (risk ~1 in 2,000): Inform patients to report any mucous membrane ulcerations.
• Significant possible interactions
- Warfarin (Coumadin): Increased effect of warfarin with macrolides or TMP/SMX, resulting in marked increase in INR and PT
- Statins should be stopped when macrolides or telithromycin are prescribed due to increased risk of myopathy, rhabdomyolysis.
Other Medications
• As allergies may be a predisposing factor, some patients may benefit from use of oral antihistamines or nasal steroids.
• Oral antihistamines
- Loratadine (Claritin)
- Fexofenadine (Allegra)
- Cetirizine (Zyrtec)
- Chlorpheniramine (Chlor-Trimeton)
- Diphenhydramine (Benadryl)
• Leukotriene inhibitors (Singulair, Accolate) may be indicated in patients with concomitant asthma.
• Nasal steroids (i.e., fluticasone [Flonase])
ALERT
Pediatric Considerations
• Sinuses are not fully developed until age 20, but the maxillary and ethmoid sinuses, although small, are present from birth.
• As children have an average of 6-8 colds per year, they are at risk for development of sinusitis.
• Diagnosis can be more difficult than in adults, as symptoms are often more subtle.
Pregnancy Considerations
• Rhinitis of pregnancy predisposes to sinusitis.
• Nasal irrigation with saline as well as pseudophedrine are safe during pregnancy and lactation.
• Antibiotics considered to be safe in pregnancy and lactation
- Amoxicillin and amoxicillin-clavulanate (B)
- Cephalosporins (B)
- Azithromycin (B)
• Contraindicated in pregnancy and lactation
- Clarithromycin
- Telithromycin
• Safe in lactation but not during pregnancy
- Levofloxacin
SURGERY
• If medical therapy fails, consider sinus irrigation.
• Functional endoscopic sinus surgery is the preferred treatment for medically recalcitrant cases (2)[C]
• Absolute surgical indications
- Massive nasal polyposis
- Acute complications: Subperiosteal or orbital abscess, frontal soft tissue spread of infection
- Mucocele or mucopyocele
- Invasive or allergic fungal sinusitis
- Suspected obstructing tumor
- CSF rhinorrhea
FOLLOW-UP
DISPOSITION
Admission Criteria
Complications as below
Issues for Referral
• Complications as below
• Failure of treatment
PROGNOSIS
Alleviation of symptoms within 72 hours with complete resolution within 10-14 days
COMPLICATIONS
• Meningitis
• Orbital cellulitis
• Brain abscess
• Cavernous sinus thrombosis
• Osteomyelitis
• Subdural empyema
PATIENT MONITORING
• Instruct for proper use of all medications.
• Return if no improvement after 72 hours or no resolution of symptoms after 10 days of antibiotics.
• If symptoms resolve, no routine follow-up, is needed.
REFERENCES
1. Sande MA, Gwaltney JM. Acute community-acquired bacterial sinusitis: Continuing challenges and current management. Clin Infect Dis. 2004;39:S151-S158.
2. Varonen H, et al. Comparison of ultrasound, radiography, and clinical examination in the diagnosis of acute maxillary sinusitis: A systematic review. J Clin Epidemiol. 2000;53:940-948.
3. Sinus and Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg. 2004;130:1-45.
4. Williams JW Jr, et al. Antibiotics for acute maxillary sinusitis. Cochrane Database Syst Rev. 2003;2:CD000243.
BASICS
DESCRIPTION
• Acute rhinosinusitis (generally called sinusitis) is a symptomatic inflammation of the paranasal sinuses of 4 weeks duration resulting from impaired drainage and retained secretions. Disease is subacute when symptomatic for 4-12 weeks; chronic when symptomatic for >12 weeks
• System(s) Affected: HEENT; Pulmonary
GENERAL PREVENTION
No documented preventive measures
EPIDEMIOLOGY
• Of ~1 billion viral respiratory illnesses in the US each year, perhaps 200 million (10%) are associated with inflammation, impaired drainage and retained secretions in sinuses; ~20 million cases are secondarily infected by bacteria.
• Diagnosis of acute bacterial rhinosinusitis is 5th leading reason for prescribing antibiotics, accounting for 9% of all pediatric and 21% of all adult antibiotic prescriptions in 2002.
• Many of these diagnoses are erroneous.
• Incidence highest in early fall through early spring (related to incidence of viral URI)
RISK FACTORS
• Viral upper respiratory infection
• Allergic rhinitis
• Asthma
• Cigarette smoking
• Trauma
• Dental infections and procedures
• Anatomical variations
- Tonsillar and adenoid hypertrophy
- Turbinate hypertrophy, nasal polyps
- Deviated septum
- Cleft palate
• Immunodeficiency (e.g., HIV)
• Cystic fibrosis
Genetics
No known genetic pattern
PATHOPHYSIOLOGY
• Important features
- Inflammation and edema of the sinus mucosa
- Obstruction of the sinus ostia
- Impaired mucociliary clearance
• Secretions that are not cleared become hospitable to bacterial growth.
• Inflammatory response (neutrophil influx and release of cytokines) damages mucosal surfaces.
ETIOLOGY
• Viral: Vast majority of cases (rhinovirus, influenza A and B, parainfluenza virus, respiratory syncytial, adeno-, corona-, and entero-viruses
• Bacterial (complicates 0.2-2% of viral cases)
- More likely if symptoms worsen >5-7 days or do not improve >10 days
- Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the most common bacterial etiologies.
- Often overdiagnosed, which leads to overuse of, and increasing resistance to, antibiotics
• Fungal infection seen In immunocompromised hosts (uncontrolled diabetes, neutropenia, glucocorticosteroids) or as nosocomial infection
DIAGNOSIS
History and physical exam suggest the diagnosis in the majority of cases.
SIGNS AND SYMPTOMS
• Major challenge is to distinguish between viral and bacterial disease; use constellation of symptoms rather than a particular sign or symptom.
• Symptoms predictive of bacterial sinusitis
- Persistent symptoms for 10 days
- Worsening of symptoms >5-7 days after initial improvement
- Persistent purulent nasal discharge
- Unilateral maxillary tooth or facial pain
- Unilateral maxillary sinus tenderness
- Appearance of fever (usually low-grade)
• Associated symptoms
- Headache
- Nasal congestion
- Retro-orbital pain
- Otalgia
- Hyposomia
- Halitosis
- Chronic cough
• Symptoms requiring urgent attention
- Visual disturbances, especially diplopia
- Periorbital swelling or erythema
- Altered mental status
Physical Exam
• Fever
• Edema and erythema of nasal mucosa
• Purulent discharge
• Tenderness to palpation over sinus(es)
TESTS
• None indicated in routine evaluation
• Transillumination of the sinuses
- May confirm fluid in sinuses
- Value is limited as it does not distinguish between viral and bacterial etiology.
Lab
None indicated in routine evaluation
Imaging
• Routine use of sinus radiography discouraged because: (i) 3 clinical findings may have similar diagnostic accuracy as imaging and (ii) imaging does not distinguish viral from bacterial etiology.
• Limited coronal CT can be useful in recurrent infection or failure to respond to medical therapy.
Diagnostic Procedures/Surgery
• Gold standard = transnasal endoscopic or sublabial maxillary antrum aspiration culture; generally performed only in recurrent and/or complicated cases (1,2)[A]
Pathological Findings
• Inflammation
• Edema
• Thickened mucosa
• Impaired ciliary function
• Metaplasia of ciliated columnar cells
• Relative acidosis and hypoxia within sinuses
• Polyps
DIFFERENTIAL DIAGNOSIS
• Dental disease
• Cystic fibrosis
• Wegener granulomatosis
• HIV infection
• Kartagener syndrome
• Immotile cilia syndrome
• Neoplasm
TREATMENT
• Majority of cases treated in outpatient setting
• Hospitalization for complications (meningitis, orbital cellulitis or abscess, brain abscess)
GENERAL MEASURES
• Adequate hydration
• Steam inhalation 20-30 minutes t.i.d.
• Saline irrigation or saline nose drops
• Sleep with head of bed elevated.
• Avoid exposure to cigarette smoke, fumes.
• Avoid dehydrants (caffeine and alcohol).
• Antibiotics indicated only when findings suggest bacterial infection
• Analgesics, NSAIDs (see below)
• Acute viral sinusitis is self-limiting, and antibiotics should not be used.
Diet
No special diet
Activity
Adequate rest, otherwise no restrictions
MEDICATION (DRUGS)
First Line
• Decongestants
- Pseudoephedrine HCl
- Phenylephrine (limited use)
- Oxymetazoline (i.e., Afrin) (limited use)
• Analgesics
- Acetaminophen
- Aspirin
- NSAIDs
- Acetaminophen-codeine
• Antibiotics
- Antibiotics appear to have a slight advantage over placebo, yet most patients improve without therapy.
- Major issue: Distinguish bacterial from viral
- Reserve antibiotic use for patients with moderate to severe disease.
- Treat 10-14 days unless otherwise specified.
- Choice should be based on understanding of antibiotic resistance in the community.
- Multiple meta-analyses have demonstrated NO benefit of newer antibiotics over Amoxicillin, Trimethoprim-sulfamethoxazole, or Doxycyclin.
- Initial therapy (2)[A]
- Amoxicillin: 500 mg-1 g t.i.d. (adults); 80-90 mg/kg/d divided q8h (children)
- Trimethoprim-sulfamethoxazole: 160 mg/800 mg q12h in adults and 8-12 mg/kg/d of trimethoprim component divided q12h for children
- Doxycyline 100 mg PO b.i.d.
Second Line
• Amoxicillin-clavulanate (Augmentin) 875 mg/ 125 mg q12h (adults); 30 mg/kg/d of amoxicillin component divided b.i.d. in children
• Cefpodoxime (Vantin): 200 mg q12h in adults and 10 mg/kg/d divided b.i.d. in children
• Cefuroxime axetil (Ceftin): 250 mg q12hrs in adults and 30 mg/kg/d divided q12h in children
• Telithromycin: 800 mg/d 5 days in adults, no pediatric indication
• Azithromycin (Zithromax): 500 mg on day 1 and 250 mg on days 2-5 in adults; 10 mg/kg on day 1 and 5 mg/kg on days 2-5 in children
• Clarithromycin: 500 mg b.i.d. (regular) or 1000 mg/d (extended release) in adults; 15 mg/kd/d divided b.i.d. in children
• Levofloxacin (Levaquin): 500 mg/d in adults; if patients have had antibiotics within past 4-6 weeks or if no response to above therapy within 72 hours, change to
- High dose amoxicillin/clavulanate
- Cephalosporins as above
- Fluoroquinolones as above
• NOTE: Bacteriologic failure rates up to 20-25% are possible with use of azithromycin and clarithromycin (2)[C]
• If lack of response to 3 weeks of antibiotics, consider
- CT scan of sinuses
- Ear, nose, and throat referral
• Precautions
- Decongestants can exacerbate hypertension.
- Prolonged use of topical decongestants (>4 days) may precipitate rhinitis medicamentosa.
- Sulfonamides may induce Stevens-Johnson syndrome (risk ~1 in 2,000): Inform patients to report any mucous membrane ulcerations.
• Significant possible interactions
- Warfarin (Coumadin): Increased effect of warfarin with macrolides or TMP/SMX, resulting in marked increase in INR and PT
- Statins should be stopped when macrolides or telithromycin are prescribed due to increased risk of myopathy, rhabdomyolysis.
Other Medications
• As allergies may be a predisposing factor, some patients may benefit from use of oral antihistamines or nasal steroids.
• Oral antihistamines
- Loratadine (Claritin)
- Fexofenadine (Allegra)
- Cetirizine (Zyrtec)
- Chlorpheniramine (Chlor-Trimeton)
- Diphenhydramine (Benadryl)
• Leukotriene inhibitors (Singulair, Accolate) may be indicated in patients with concomitant asthma.
• Nasal steroids (i.e., fluticasone [Flonase])
ALERT
Pediatric Considerations
• Sinuses are not fully developed until age 20, but the maxillary and ethmoid sinuses, although small, are present from birth.
• As children have an average of 6-8 colds per year, they are at risk for development of sinusitis.
• Diagnosis can be more difficult than in adults, as symptoms are often more subtle.
Pregnancy Considerations
• Rhinitis of pregnancy predisposes to sinusitis.
• Nasal irrigation with saline as well as pseudophedrine are safe during pregnancy and lactation.
• Antibiotics considered to be safe in pregnancy and lactation
- Amoxicillin and amoxicillin-clavulanate (B)
- Cephalosporins (B)
- Azithromycin (B)
• Contraindicated in pregnancy and lactation
- Clarithromycin
- Telithromycin
• Safe in lactation but not during pregnancy
- Levofloxacin
SURGERY
• If medical therapy fails, consider sinus irrigation.
• Functional endoscopic sinus surgery is the preferred treatment for medically recalcitrant cases (2)[C]
• Absolute surgical indications
- Massive nasal polyposis
- Acute complications: Subperiosteal or orbital abscess, frontal soft tissue spread of infection
- Mucocele or mucopyocele
- Invasive or allergic fungal sinusitis
- Suspected obstructing tumor
- CSF rhinorrhea
FOLLOW-UP
DISPOSITION
Admission Criteria
Complications as below
Issues for Referral
• Complications as below
• Failure of treatment
PROGNOSIS
Alleviation of symptoms within 72 hours with complete resolution within 10-14 days
COMPLICATIONS
• Meningitis
• Orbital cellulitis
• Brain abscess
• Cavernous sinus thrombosis
• Osteomyelitis
• Subdural empyema
PATIENT MONITORING
• Instruct for proper use of all medications.
• Return if no improvement after 72 hours or no resolution of symptoms after 10 days of antibiotics.
• If symptoms resolve, no routine follow-up, is needed.
REFERENCES
1. Sande MA, Gwaltney JM. Acute community-acquired bacterial sinusitis: Continuing challenges and current management. Clin Infect Dis. 2004;39:S151-S158.
2. Varonen H, et al. Comparison of ultrasound, radiography, and clinical examination in the diagnosis of acute maxillary sinusitis: A systematic review. J Clin Epidemiol. 2000;53:940-948.
3. Sinus and Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg. 2004;130:1-45.
4. Williams JW Jr, et al. Antibiotics for acute maxillary sinusitis. Cochrane Database Syst Rev. 2003;2:CD000243.
SILICOSIS
SILICOSIS - Robert P. Baughman, MD
BASICS
DESCRIPTION
Pneumoconiosis (fibrogenic) caused by inhaling silica dust (in the form of quartz, cristobalite, or tridymite)
• Chronic (classical) silicosis can be simple or complicated.
• Chronic simple silicosis is asymptomatic, nonprogressive after the exposure ends, and consists solely of small round radiographic pulmonary opacities.
• Chronic complicated silicosis has progressively worsening symptoms and enlarging pulmonary opacities, even after exposure ends.
• Subacute silicosis develops after 3-6 years of high exposure, and resembles chronic complicated silicosis.
• Acute silicosis develops within a couple years of massive exposure and is clinically distinct from the other forms.
• System(s) Affected: Pulmonary
ALERT
Geriatric Considerations
Symptoms and complications more severe
Geriatric Considerations
Unusual
GENERAL PREVENTION
• Avoid dust exposure.
• Substitute other materials for silica.
• Respiratory protective devices for unavoidable short-term exposure
EPIDEMIOLOGY
• Predominant age: 40-75
• Predominant sex: Male > Female
Incidence
Unknown
Prevalence
Unknown
RISK FACTORS
Industrial activities that involve cutting, polishing, or shearing rock, or involve the use of sand, including
• Metal mining (copper, silver, gold, lead, hard coal)
• Foundries
• Pottery making
• Sandstone cutting
• Granite cutting
Genetics
No known genetic pattern
ETIOLOGY
• Chronic simple silicosis: 10-12 years of exposure to silica dust
• Chronic complicated silicosis: >20 years of exposure
• Subacute silicosis: 3-6 years of heavy exposure
• Acute silicosis: 2 years of massive exposure
ASSOCIATED CONDITIONS
• Tuberculosis
• Caplan syndrome (coexistence of rheumatoid arthritis with a pneumoconiosis)
DIAGNOSIS
SIGNS AND SYMPTOMS
• Chronic simple silicosis
- Asymptomatic
- Cough and mild dyspnea typically accompany, and are due to smoking or occupational bronchitis.
• Chronic complicated silicosis; subacute silicosis
- Chest tightness
- Cough
- Dyspnea
- Expectoration
- Signs and symptoms of right heart failure as cor pulmonale develops
• Acute silicosis
- Dry cough
- Fever
- Severe dyspnea
TESTS
Special tests
• Pulmonary function testing is normal in simple silicosis. Other forms show decreased pulmonary compliance, decreased lung volumes, and decreased diffusing capacity.
• International Labor Office (ILO) classification system for quantification of chest radiograph abnormalities
• Yearly purified protein derivative (PPD) test
Lab
• Hypoxemia
• Hypercarbia
Imaging
Chest radiograph
• Chronic simple silicosis
- Eggshell calcification in hilar and mediastinal lymph nodes
- Small round opacities, initially in upper lobes
• Chronic complicated silicosis, subacute silicosis
- Pulmonary opacities >1 cm
- Opacities form bilateral conglomerate shadows (progressive massive fibrosis)
- Opacities initially peripheral, later migrate toward hilum
- Opacities may cavitate. (Rule out tuberculosis!)
- High-resolution CT scan provides more definition of infiltrates and is helpful in identifying nodules.
Diagnostic Procedures/Surgery
• Bronchoscopy
• Detailed occupational history
• Open lung biopsy
Pathological Findings
Lung
• Pleural adhesions
• Pleural thickening
• Gray-black subpleural nodules
• Blackened lung
• Leathery lung
• Concentric layers of dense connective tissue
• Cellular infiltrate
• Ischemic degeneration of central nodule
• Metachromatic silica particles
DIFFERENTIAL DIAGNOSIS
• Chronic simple silicosis
- Sarcoidosis
- Radiographic eggshell calcifications also seen in sarcoidosis and Hodgkin's disease
• Chronic complicated silicosis, subacute silicosis
- Coal worker pneumoconiosis
- Consider especially when consolidations are rapidly progressive, unilateral, or cavitatingtuberculosis, neoplasia, fungal pneumonia
• Acute silicosis: Alveolar proteinosis
TREATMENT
GENERAL MEASURES
• No known effective treatment
• Postural drainage
• Mist inhalation
• Chest physical therapy
• Breathing exercises
Diet
• No special diet
• Increase fluid intake
Activity
Maintain regular exercise program.
MEDICATION (DRUGS)
First Line
• None specific for silicosis
• Isoniazid: 300 mg/d for 1 year, if tuberculin skin test is positive
• Silicotuberculosis requires at least 3 antituberculous drugs initially, including rifampin.
• Contraindications: Avoid sedatives and hypnotics.
• Precautions: Refer to the manufacturer's literature.
• Significant possible interactions: Refer to the manufacturer's literature.
Second Line
Antifibrinogenic agents remain investigational.
SURGERY
• Lung transplantation
• Whole lung lavage remains investigational.
FOLLOW-UP
PROGNOSIS
• Chronic simple silicosis: Remains asymptomatic and does not progress if exposure ends.
• Chronic complicated silicosis; subacute silicosis: Progressive pulmonary fibrosis with cor pulmonale and right heart failure, even after exposure ends
COMPLICATIONS
• Progressive massive fibrosis
• Respiratory infection
• Pneumothorax
• Emphysema
• Cor pulmonale
• Right heart failure
• Mycobacterial infections
• Fungal infections
PATIENT MONITORING
• Monitor for heart failure and hypoxemia.
• Treat intercurrent infections aggressively.
REFERENCES
1. Banks DE, et al. Strategies for the treatment of pneumoconiosis. Occup Med. 1993;8:205-232.
2. Silicosis and Silicate Disease Committee. Diseases associated with exposure to silica and non-fibrous silicate materials. Arch Pathol Lab Med. 1988;112:673.
MISCELLANEOUS
Other notes
• Silica: Formula for calculating the threshold limit value for respirable dust: Threshold limit value = (10 mg per m2/% SiO2) + 2
• See also: Chronic obstructive pulmonary disease and emphysema; Cor pulmonale; Pneumothorax; Tuberculosis
BASICS
DESCRIPTION
Pneumoconiosis (fibrogenic) caused by inhaling silica dust (in the form of quartz, cristobalite, or tridymite)
• Chronic (classical) silicosis can be simple or complicated.
• Chronic simple silicosis is asymptomatic, nonprogressive after the exposure ends, and consists solely of small round radiographic pulmonary opacities.
• Chronic complicated silicosis has progressively worsening symptoms and enlarging pulmonary opacities, even after exposure ends.
• Subacute silicosis develops after 3-6 years of high exposure, and resembles chronic complicated silicosis.
• Acute silicosis develops within a couple years of massive exposure and is clinically distinct from the other forms.
• System(s) Affected: Pulmonary
ALERT
Geriatric Considerations
Symptoms and complications more severe
Geriatric Considerations
Unusual
GENERAL PREVENTION
• Avoid dust exposure.
• Substitute other materials for silica.
• Respiratory protective devices for unavoidable short-term exposure
EPIDEMIOLOGY
• Predominant age: 40-75
• Predominant sex: Male > Female
Incidence
Unknown
Prevalence
Unknown
RISK FACTORS
Industrial activities that involve cutting, polishing, or shearing rock, or involve the use of sand, including
• Metal mining (copper, silver, gold, lead, hard coal)
• Foundries
• Pottery making
• Sandstone cutting
• Granite cutting
Genetics
No known genetic pattern
ETIOLOGY
• Chronic simple silicosis: 10-12 years of exposure to silica dust
• Chronic complicated silicosis: >20 years of exposure
• Subacute silicosis: 3-6 years of heavy exposure
• Acute silicosis: 2 years of massive exposure
ASSOCIATED CONDITIONS
• Tuberculosis
• Caplan syndrome (coexistence of rheumatoid arthritis with a pneumoconiosis)
DIAGNOSIS
SIGNS AND SYMPTOMS
• Chronic simple silicosis
- Asymptomatic
- Cough and mild dyspnea typically accompany, and are due to smoking or occupational bronchitis.
• Chronic complicated silicosis; subacute silicosis
- Chest tightness
- Cough
- Dyspnea
- Expectoration
- Signs and symptoms of right heart failure as cor pulmonale develops
• Acute silicosis
- Dry cough
- Fever
- Severe dyspnea
TESTS
Special tests
• Pulmonary function testing is normal in simple silicosis. Other forms show decreased pulmonary compliance, decreased lung volumes, and decreased diffusing capacity.
• International Labor Office (ILO) classification system for quantification of chest radiograph abnormalities
• Yearly purified protein derivative (PPD) test
Lab
• Hypoxemia
• Hypercarbia
Imaging
Chest radiograph
• Chronic simple silicosis
- Eggshell calcification in hilar and mediastinal lymph nodes
- Small round opacities, initially in upper lobes
• Chronic complicated silicosis, subacute silicosis
- Pulmonary opacities >1 cm
- Opacities form bilateral conglomerate shadows (progressive massive fibrosis)
- Opacities initially peripheral, later migrate toward hilum
- Opacities may cavitate. (Rule out tuberculosis!)
- High-resolution CT scan provides more definition of infiltrates and is helpful in identifying nodules.
Diagnostic Procedures/Surgery
• Bronchoscopy
• Detailed occupational history
• Open lung biopsy
Pathological Findings
Lung
• Pleural adhesions
• Pleural thickening
• Gray-black subpleural nodules
• Blackened lung
• Leathery lung
• Concentric layers of dense connective tissue
• Cellular infiltrate
• Ischemic degeneration of central nodule
• Metachromatic silica particles
DIFFERENTIAL DIAGNOSIS
• Chronic simple silicosis
- Sarcoidosis
- Radiographic eggshell calcifications also seen in sarcoidosis and Hodgkin's disease
• Chronic complicated silicosis, subacute silicosis
- Coal worker pneumoconiosis
- Consider especially when consolidations are rapidly progressive, unilateral, or cavitatingtuberculosis, neoplasia, fungal pneumonia
• Acute silicosis: Alveolar proteinosis
TREATMENT
GENERAL MEASURES
• No known effective treatment
• Postural drainage
• Mist inhalation
• Chest physical therapy
• Breathing exercises
Diet
• No special diet
• Increase fluid intake
Activity
Maintain regular exercise program.
MEDICATION (DRUGS)
First Line
• None specific for silicosis
• Isoniazid: 300 mg/d for 1 year, if tuberculin skin test is positive
• Silicotuberculosis requires at least 3 antituberculous drugs initially, including rifampin.
• Contraindications: Avoid sedatives and hypnotics.
• Precautions: Refer to the manufacturer's literature.
• Significant possible interactions: Refer to the manufacturer's literature.
Second Line
Antifibrinogenic agents remain investigational.
SURGERY
• Lung transplantation
• Whole lung lavage remains investigational.
FOLLOW-UP
PROGNOSIS
• Chronic simple silicosis: Remains asymptomatic and does not progress if exposure ends.
• Chronic complicated silicosis; subacute silicosis: Progressive pulmonary fibrosis with cor pulmonale and right heart failure, even after exposure ends
COMPLICATIONS
• Progressive massive fibrosis
• Respiratory infection
• Pneumothorax
• Emphysema
• Cor pulmonale
• Right heart failure
• Mycobacterial infections
• Fungal infections
PATIENT MONITORING
• Monitor for heart failure and hypoxemia.
• Treat intercurrent infections aggressively.
REFERENCES
1. Banks DE, et al. Strategies for the treatment of pneumoconiosis. Occup Med. 1993;8:205-232.
2. Silicosis and Silicate Disease Committee. Diseases associated with exposure to silica and non-fibrous silicate materials. Arch Pathol Lab Med. 1988;112:673.
MISCELLANEOUS
Other notes
• Silica: Formula for calculating the threshold limit value for respirable dust: Threshold limit value = (10 mg per m2/% SiO2) + 2
• See also: Chronic obstructive pulmonary disease and emphysema; Cor pulmonale; Pneumothorax; Tuberculosis
SIALADENITIS
SIALADENITIS - Felix B. Chang, MD; Thomas Jaquith-Houston, MD
BASICS
DESCRIPTION
• Sialadenitis is an inflammation of the salivary glands, most commonly from bacteria or virus infection. Inflammation often arises in the excretory duct.
• The parotid or submandibular glands are most frequently affected.
• Inflammation is likely caused by salivary stasis allowing retrograde passage of organisms.
• Inflammation may also follow trauma, spread of infection from adjoining tissues, and via hematogenous routes during bacteremia.
• Inflammation may lead to stone formation (sialolithiasis), or an obstructed duct may lead to inflammation of the gland. Stones are more commonly associated with the submaxillary glands.
• Recurrent infections or other chronic inflammatory processes may lead to decreased gland function, resulting in xerostomia.
• System(s) Affected: Gastrointestinal; Skin/Exocrine
• Synonym(s): Sialadenosis
EPIDEMIOLOGY
• Most commonly seen in debilitated patients
• 50-60 years of age
• Male = Female
• Immune-compromised patients
• Postoperative patients
• Of the medically ill patient with sialoadenitis
- 25% have a malignant lesion
- 50% have a pre-existing infection elsewhere than head and neck
ALERT
Pediatric Considerations
• Rare in children
• Cases have been reported in premature neonates: Neonatal suppurative parotitis
- Staphylococcus aureus
- Escherichia coli
- Pseudomonas aeruginosa
- B Streptococci
• Recurrent parotitis of childhood
- Age of onset 8 months-16 years
- Male > Female
- S. aureus
- S. viridans
Incidence
• ~0.02% of hospital admission
• Occurs between 1/1,000 and 1/2,000 operative procedures
RISK FACTORS
• Dehydration
• Fever
• Hypercalcemia
• Severely debilitated patient
• Diabetes mellitus
• Hypothyroidism
• Lack of salivary stimulation (postoperative patients)
• Treatment with radiation or chemotherapy for underlying malignant disease
• Patients undergoing major abdominal and hip repair surgery have been identified as being at increased risk for acute suppurative sialadenitis.
• Bulimia and anorexia nervosa
• Sjogren syndrome
• Chronic illness
• Immune compromise
• Cachexia
Genetics
A familial form of recurrent parotitis of childhood has been described with autosomal inheritance.
PATHOPHYSIOLOGY
• Acute infection of the salivary glands is caused by retrograde bacterial contamination of the salivary ducts from the oral cavity.
• Mechanical impairment of salivary flow also predisposes to acute infection (trauma, foreign body).
• Ductal obstruction is generally secondary to mucous plug caused by stasis of saliva with increased viscosity with subsequent stasis and infection.
ETIOLOGY
• Bacteria from the oral cavity are the most common infectious cause of sialadenitis
- Staphylococcus aureus
- Streptococcus
- Haemophilus Influenzae
- Pseudomonas
- Enterobacter
- Klebsiella
- Enterococcus
- Proteus
- Candida spp.
- Anaerobic bacteria
Peptostreptococcus
Bacteroides spp.
Fusobacterium
• The causative agents of the following diseases may also infect a salivary gland, resulting in sialadenitis
- Mumps
- Actinomycosis
- Tuberculosis
- Syphilis
- Cytomegalovirus
- Cat scratch disease
• Drug: Terbinafine
ASSOCIATED CONDITIONS
• Rheumatoid arthritis (Sjogren syndrome)
• Sarcoidosis (Heerfordt syndrome)
• Sicca syndrome
• HIV
• Kuttner tumor
• Malnutrition
DIAGNOSIS
SIGNS AND SYMPTOMS
• Enlarged, painful salivary gland
• Increase pain with meals
• Purulent discharge from duct orifice
• Red, painful duct orifice
• Fever
• Malaise
• Xerostomia
• Decreased salivary secretion (aptyalism)
History
Check for recent dehydration.
Physical Exam
• Erythema, tenderness at the duct opening
• Induration and pitting of the skin with involvement of the masseteric and submandibular spatial planes in severe cases
• Bimanual palpation of the gland results in suppurative discharge from the duct orifice in 3/4 of cases of acute suppurative sialadenitis.
• Bilateral involvement in up to 25% of cases
TESTS
Lab
• Not often warranted. WBC; leukocytosis with predominant of neutrophils if bacterial or lymphocytosis if viral
• Serum amylase normal
• Culture of the purulent discharge from the duct (suppurative sialadenitis)
Imaging
• Consider ultrasound or CT scan in patients not responding to treatment in 48-72 hours.
• Radiographs may reveal a stone in sialolithiasis.
• Ultrasound may show ductal dilatation and a stone.
• CT may show abscess in advanced infection.
• Sialography is contraindicated in acute infection.
• MRI may be used to evaluate the salivary duct architecture noninvasively.
Diagnostic Procedures/Surgery
• Digital manipulation of the duct may express pus from the ductal orifice.
• Percutaneous needle aspiration of the involve duct in cases of suppurative sialadenitis, limit the amount of contamination by means of an intraoral route.
Pathological Findings
With chronic infection of the gland
• Enlarged gland
• Ductal dilatation with retention of saliva
• Acinar atrophy, or acinus dilated and filled with mucus
• Purulent/seropurulent exudate within the duct
• Glandular replacement by fibrotic tissue
• Infiltration with leukocytes
DIFFERENTIAL DIAGNOSIS
• Decreased salivary secretion is associated with
- Drugs
Tricyclic antidepressants (e.g., amitriptyline), phenothiazines (e.g., chlorpromazine, fluphenazine, thioridazine, prochlorperazine)
Anticholinergics
Antihistaminics: Diphenhydramine
- Myxedema
- Plummer-Vinson disease
- Pernicious anemia
- Febrile diseases
- Neuropsychiatric disorders
- Mikulicz disease (benign lymphoepithelial lesion)
• Enlarged glands may be the result of a variety of neoplasms, including
- Pleomorphic adenoma
- Mucoepidermoid carcinoma
- Other tumor types may occur very rarely (e.g., lipoma, neurofibroma, fibrosarcoma, melanoma, lymphocytoma, Hodgkin)
- Lymphangitis external otitis
- Bezold abscess
- Cervical adenitis
- Dental abscesses
- Infected brachial cleft or sebaceous cyst.
• Also, obesity results in what appears to be enlarged parotids, but the bilateral nature and nonprogressive course should help differentiate this from malignant neoplasms.
TREATMENT
STABILIZATION
Outpatient care
GENERAL MEASURES
• A heating pad and/or cool compresses may be comforting.
• Massaging the gland may express pus and relieve some of the pressure.
• Rehydration
• Oral cavity irrigations
Diet
Avoid pain-producing sialagogues (e.g., lemon) during an acute episode.
Activity
Unrestricted
SPECIAL THERAPY
IV Fluids
Fluid and electrolyte replacement
MEDICATION (DRUGS)
• Antibiotics
- Penicillin V (Pen-Vee K) 250-500 mg q.i.d.
- Erythromycin 250 mg q.i.d.
- Amoxicillin-clavulanate (Augmentin) 500 mg t.i.d.
- Cefuroxime (Ceftin) 750-1500 mg/IM/IV q8h Children: 20-30 mg/kg/d suspension PO divided b.i.d.
- Clindamycin in patients allergic to penicillin
- IV antibiotics in severe cases
- Methicillin-resistant S. aureus may require vancomycin or linezolid
• Analgesics, e.g., codeine, hydrocodone, NSAIDs
SURGERY
Superficial parotidectomy in patients with chronic nonspecific sialadenitis. Complications include temporary (or permanent) facial nerve weakness and neuromas, but a reduction in symptoms may be expected.
FOLLOW-UP
DISPOSITION
Complete recovery unless the patient has underlying obstruction (ductal stricture, tumor or stone)
Admission Criteria
• Severely ill
• Dehydration
• IV antibiotics
• Intractable pain
• Complications
Discharge Criteria
Response to antimicrobial therapy is seen within 48-72 hours of initiating treatment; treatment should continue for 1 week after resolution of symptoms.
Issues for Referral
Refer cases that do not resolve despite appropriate antibiotic therapy to ENT.
PROGNOSIS
Good; complete recovery
COMPLICATIONS
• Suppurative sialadenitis
- Abscess
- Bacteremia
- Osteomyelitis
- Thrombophlebitis of the jugular vein
- Septicemia
- Respiratory obstruction
- Facial nerve paralysis
- Death
• Occasional loss of salivary function
REFERENCES
1. Bhatty MA, et al. Chronic non-specific parotid sialadenitis. Br J Plast Surg. 1998;517-521.
2. Chitre VV, Premchandra DJ. Review: Recurrent parotiditis. Arch Dis Child. 1997;77:559-363.
3. Salivary gland infections: MedlinePlus, US National Institutes of Health web site. http:// www.nim.nih.gov/medlineplus/ency/article/ 001041.htm.
MISCELLANEOUS
See also: Sjogren syndrome
BASICS
DESCRIPTION
• Sialadenitis is an inflammation of the salivary glands, most commonly from bacteria or virus infection. Inflammation often arises in the excretory duct.
• The parotid or submandibular glands are most frequently affected.
• Inflammation is likely caused by salivary stasis allowing retrograde passage of organisms.
• Inflammation may also follow trauma, spread of infection from adjoining tissues, and via hematogenous routes during bacteremia.
• Inflammation may lead to stone formation (sialolithiasis), or an obstructed duct may lead to inflammation of the gland. Stones are more commonly associated with the submaxillary glands.
• Recurrent infections or other chronic inflammatory processes may lead to decreased gland function, resulting in xerostomia.
• System(s) Affected: Gastrointestinal; Skin/Exocrine
• Synonym(s): Sialadenosis
EPIDEMIOLOGY
• Most commonly seen in debilitated patients
• 50-60 years of age
• Male = Female
• Immune-compromised patients
• Postoperative patients
• Of the medically ill patient with sialoadenitis
- 25% have a malignant lesion
- 50% have a pre-existing infection elsewhere than head and neck
ALERT
Pediatric Considerations
• Rare in children
• Cases have been reported in premature neonates: Neonatal suppurative parotitis
- Staphylococcus aureus
- Escherichia coli
- Pseudomonas aeruginosa
- B Streptococci
• Recurrent parotitis of childhood
- Age of onset 8 months-16 years
- Male > Female
- S. aureus
- S. viridans
Incidence
• ~0.02% of hospital admission
• Occurs between 1/1,000 and 1/2,000 operative procedures
RISK FACTORS
• Dehydration
• Fever
• Hypercalcemia
• Severely debilitated patient
• Diabetes mellitus
• Hypothyroidism
• Lack of salivary stimulation (postoperative patients)
• Treatment with radiation or chemotherapy for underlying malignant disease
• Patients undergoing major abdominal and hip repair surgery have been identified as being at increased risk for acute suppurative sialadenitis.
• Bulimia and anorexia nervosa
• Sjogren syndrome
• Chronic illness
• Immune compromise
• Cachexia
Genetics
A familial form of recurrent parotitis of childhood has been described with autosomal inheritance.
PATHOPHYSIOLOGY
• Acute infection of the salivary glands is caused by retrograde bacterial contamination of the salivary ducts from the oral cavity.
• Mechanical impairment of salivary flow also predisposes to acute infection (trauma, foreign body).
• Ductal obstruction is generally secondary to mucous plug caused by stasis of saliva with increased viscosity with subsequent stasis and infection.
ETIOLOGY
• Bacteria from the oral cavity are the most common infectious cause of sialadenitis
- Staphylococcus aureus
- Streptococcus
- Haemophilus Influenzae
- Pseudomonas
- Enterobacter
- Klebsiella
- Enterococcus
- Proteus
- Candida spp.
- Anaerobic bacteria
Peptostreptococcus
Bacteroides spp.
Fusobacterium
• The causative agents of the following diseases may also infect a salivary gland, resulting in sialadenitis
- Mumps
- Actinomycosis
- Tuberculosis
- Syphilis
- Cytomegalovirus
- Cat scratch disease
• Drug: Terbinafine
ASSOCIATED CONDITIONS
• Rheumatoid arthritis (Sjogren syndrome)
• Sarcoidosis (Heerfordt syndrome)
• Sicca syndrome
• HIV
• Kuttner tumor
• Malnutrition
DIAGNOSIS
SIGNS AND SYMPTOMS
• Enlarged, painful salivary gland
• Increase pain with meals
• Purulent discharge from duct orifice
• Red, painful duct orifice
• Fever
• Malaise
• Xerostomia
• Decreased salivary secretion (aptyalism)
History
Check for recent dehydration.
Physical Exam
• Erythema, tenderness at the duct opening
• Induration and pitting of the skin with involvement of the masseteric and submandibular spatial planes in severe cases
• Bimanual palpation of the gland results in suppurative discharge from the duct orifice in 3/4 of cases of acute suppurative sialadenitis.
• Bilateral involvement in up to 25% of cases
TESTS
Lab
• Not often warranted. WBC; leukocytosis with predominant of neutrophils if bacterial or lymphocytosis if viral
• Serum amylase normal
• Culture of the purulent discharge from the duct (suppurative sialadenitis)
Imaging
• Consider ultrasound or CT scan in patients not responding to treatment in 48-72 hours.
• Radiographs may reveal a stone in sialolithiasis.
• Ultrasound may show ductal dilatation and a stone.
• CT may show abscess in advanced infection.
• Sialography is contraindicated in acute infection.
• MRI may be used to evaluate the salivary duct architecture noninvasively.
Diagnostic Procedures/Surgery
• Digital manipulation of the duct may express pus from the ductal orifice.
• Percutaneous needle aspiration of the involve duct in cases of suppurative sialadenitis, limit the amount of contamination by means of an intraoral route.
Pathological Findings
With chronic infection of the gland
• Enlarged gland
• Ductal dilatation with retention of saliva
• Acinar atrophy, or acinus dilated and filled with mucus
• Purulent/seropurulent exudate within the duct
• Glandular replacement by fibrotic tissue
• Infiltration with leukocytes
DIFFERENTIAL DIAGNOSIS
• Decreased salivary secretion is associated with
- Drugs
Tricyclic antidepressants (e.g., amitriptyline), phenothiazines (e.g., chlorpromazine, fluphenazine, thioridazine, prochlorperazine)
Anticholinergics
Antihistaminics: Diphenhydramine
- Myxedema
- Plummer-Vinson disease
- Pernicious anemia
- Febrile diseases
- Neuropsychiatric disorders
- Mikulicz disease (benign lymphoepithelial lesion)
• Enlarged glands may be the result of a variety of neoplasms, including
- Pleomorphic adenoma
- Mucoepidermoid carcinoma
- Other tumor types may occur very rarely (e.g., lipoma, neurofibroma, fibrosarcoma, melanoma, lymphocytoma, Hodgkin)
- Lymphangitis external otitis
- Bezold abscess
- Cervical adenitis
- Dental abscesses
- Infected brachial cleft or sebaceous cyst.
• Also, obesity results in what appears to be enlarged parotids, but the bilateral nature and nonprogressive course should help differentiate this from malignant neoplasms.
TREATMENT
STABILIZATION
Outpatient care
GENERAL MEASURES
• A heating pad and/or cool compresses may be comforting.
• Massaging the gland may express pus and relieve some of the pressure.
• Rehydration
• Oral cavity irrigations
Diet
Avoid pain-producing sialagogues (e.g., lemon) during an acute episode.
Activity
Unrestricted
SPECIAL THERAPY
IV Fluids
Fluid and electrolyte replacement
MEDICATION (DRUGS)
• Antibiotics
- Penicillin V (Pen-Vee K) 250-500 mg q.i.d.
- Erythromycin 250 mg q.i.d.
- Amoxicillin-clavulanate (Augmentin) 500 mg t.i.d.
- Cefuroxime (Ceftin) 750-1500 mg/IM/IV q8h Children: 20-30 mg/kg/d suspension PO divided b.i.d.
- Clindamycin in patients allergic to penicillin
- IV antibiotics in severe cases
- Methicillin-resistant S. aureus may require vancomycin or linezolid
• Analgesics, e.g., codeine, hydrocodone, NSAIDs
SURGERY
Superficial parotidectomy in patients with chronic nonspecific sialadenitis. Complications include temporary (or permanent) facial nerve weakness and neuromas, but a reduction in symptoms may be expected.
FOLLOW-UP
DISPOSITION
Complete recovery unless the patient has underlying obstruction (ductal stricture, tumor or stone)
Admission Criteria
• Severely ill
• Dehydration
• IV antibiotics
• Intractable pain
• Complications
Discharge Criteria
Response to antimicrobial therapy is seen within 48-72 hours of initiating treatment; treatment should continue for 1 week after resolution of symptoms.
Issues for Referral
Refer cases that do not resolve despite appropriate antibiotic therapy to ENT.
PROGNOSIS
Good; complete recovery
COMPLICATIONS
• Suppurative sialadenitis
- Abscess
- Bacteremia
- Osteomyelitis
- Thrombophlebitis of the jugular vein
- Septicemia
- Respiratory obstruction
- Facial nerve paralysis
- Death
• Occasional loss of salivary function
REFERENCES
1. Bhatty MA, et al. Chronic non-specific parotid sialadenitis. Br J Plast Surg. 1998;517-521.
2. Chitre VV, Premchandra DJ. Review: Recurrent parotiditis. Arch Dis Child. 1997;77:559-363.
3. Salivary gland infections: MedlinePlus, US National Institutes of Health web site. http:// www.nim.nih.gov/medlineplus/ency/article/ 001041.htm.
MISCELLANEOUS
See also: Sjogren syndrome
SHOCK, CIRCULATORY
SHOCK, CIRCULATORY - Felix Chang, MD
BASICS
DESCRIPTION
Inadequate tissue perfusion resulting in organ dysfunction. Classified as
• Hypovolemic shock
- Cardiac output is severely reduced due to loss of intravascular volume.
- Blood loss is most common cause.
• Cardiogenic shock
- Cardiac output is severely compromised by loss of myocardial muscle function, valvular dysfunction, or arrhythmia.
- Myocardial infarction is most common cause.
• Obstructive shock
- Cardiac output reduced due to obstruction of venous return to the heart (vena cava syndrome), compression of the heart, (pericardial tamponade, tension pneumothorax), or disrupted cardiac outflow (aortic dissection, pulmonary embolism).
• Distributive shock
- Reduced systemic vascular resistance and effective circulating volume. Dilated peripheral vessels shunt blood flow away from perfusion of critical organs.
- Most commonly due to sepsis and inflammation, which cause vasodilation and increased capillary permeability.
• Neurogenic
- Venous pooling in periphery (most often owing to spinal shock or drug overdose); behaves much like hypovolemic shock.
GENERAL PREVENTION
Prompt treatment of underlying condition.
EPIDEMIOLOGY
• Predominant age: Increased in elderly, somewhat dependent on underlying cause
• Predominant sex: Male = Female
ETIOLOGY
• Hypovolemic shock
- Hemorrhagic: Blood loss owing to trauma or gastrointestinal bleeding
- Nonhemorrhagic: 3rd-space loss of plasma volume (pancreatitis, bowel obstruction, infarction, anaphylaxis, diarrhea, burns)
• Cardiogenic shock
- Acute myocardial infarction (>40% of left ventricular myocardium)
- Arrhythmia (heart block, ventricular tachycardia, atrial fibrillation with rapid ventricular response, etc.)
- Acute valvular dysfunction: Mitral valve due to papillary muscle rupture following inferior myocardial infarctions or after rupture of chordae; aortic or mitral valve dysfunction, for example in bacterial endocarditis
- Ventricular septal rupture following anterior/septal myocardial infarction
• Obstructive shock
- Pericardial tamponade
- Inferior/superior vena caval obstruction usually owing to neoplasms
- Aortic dissection
- Massive pulmonary embolism
• Distributive shock: High-output shock is a result of sepsis, toxic shock, burns, or anaphylaxis. Severe noninfectious systemic inflammatory response can be due to sepsis, but also can independently cause distributive shock.
• Neurogenic: Venous pooling when loss of sympathetic innervation causes loss of venous tone (e.g., acute spinal injury, general or spinal anesthesia, or overdose of sedative drugs)
ASSOCIATED CONDITIONS
See "Etiology."
DIAGNOSIS
SIGNS AND SYMPTOMS
• Signs/symptoms of underlying disease
- Upper gastrointestinal (UGI) tract bleeding (hematemesis, melena)
- Sepsis (fever, chills, symptoms of underlying infection such as dysuria, costovertebral angle tenderness in urosepsis)
- Myocardial infarction (chest pain, diaphoresis, nausea, vomiting, S4 or S3 gallop, new heart murmur, rales)
- Jugular-venous distention (JVD), pulsus paradoxus in pericardial tamponade
• Signs/symptoms of underperfusion of organ systems
- Brain: Confusion, anxiety, agitation, coma
- Kidney: Oliguria
- Skin: Peripheral cyanosis, sluggish capillary refill, mottling, and/or coolness; may be overly perfused (flushed and warm) in high-output (septic) shock
- Gastrointestinal tract: Absence of bowel sounds
- Circulation: Thready pulses, tachycardia, hypotension, secondary cardiac ischemia (ST depression), or heart failure.
TESTS
• Pulmonary artery (Swan-Ganz) catheterization
- Serial measurement of cardiac output; central venous, pulmonary arterial, and pulmonary arterial occlusion pressures (left atrial pressure); and vascular resistance
- Mixed venous blood gases can be drawn from the catheter.
- Was standard of care, but recent studies suggest increased mortality with use, thus this practice is currently controversial. (1)[B]
• ECG
- Valvular failure
- Pericardial effusions
- Echo-guided pericardiocentesis
• Endoscopy if suspect GI bleed
Lab
• Specific to shock
- Elevated lactate (>2 mmol/L) suggests anaerobic metabolism from underperfusion.
- Reduced mixed venous Po2 obtained from the pulmonary artery indicates vigorous extraction of oxygen from tissues owing to underperfusion.
• For underlying diseases responsible for shock
- ECG, creatine kinase levels (serial), troponin levels (serial)
- Arterial blood gases
- Gram stain and culture of infected sites
- Blood cultures
- CBC (serial determination of hemoglobin and hematocrit in bleeding patients)
- Type and cross bleeding patients
Imaging
Depends on suspected underlying etiology
TREATMENT
STABILIZATION
• Support airway, breathing, circulation
• Continuous ECG monitoring with frequent assessment of BP, respiratory status, and urine output
GENERAL MEASURES
• Therapy involves aggressive volume resuscitation with control of the underlying etiology and monitoring of end-organ perfusion.
• Maintain Sao2 >92% with supplemental oxygen. Intubate and mechanically ventilate if patient cannot oxygenate adequately or has markedly increased breathing effort.
• Correct plasma volume deficits rapidly with crystalloids and/or packed RBCs.
• Correction of coagulation derangement by administration of coagulation factors (fresh frozen plasma, cryoprecipitate) and platelets if coagulopathy (prolonged prothrombin time, partial thromboplastin time, or platelet count 50 X 109/L) is present in a patient who is bleeding.
• Tachyarrhythmias (other than sinus tachycardia) should be promptly corrected by electrocardioversion. Insert transvenous pacemaker to correct bradyrhythmias.
• Vasopressors to correct hypotension or low cardiac output owing to myocardial failure or hypotension caused by low vascular resistance
• Treat underlying conditions, for example
- Hemorrhagic
Trauma
GI blood loss may require endoscopic or surgical intervention
- Sepsis
Empiric antibiotic therapy.
Hydrocortisone and vasopressin improve BP. Consider when patients do not improve in response to fluids, antibiotics, and low doses of vasopressors.
- Cardiogenic shock
Therapy should help reduce cardiac ischemia (oxygen, nitrates) and accomplish rapid reperfusion of injured, but potentially viable, myocardium. A balloon pump may temporize by providing improved coronary blood flow during and after diagnostic testing and revascularization therapy.
If shock is a result of acute failure of the mitral or aortic valve, surgical valve replacement may be lifesaving.
Diet
NPO
Activity
Bed rest
SPECIAL THERAPY
IV Fluids
Infusion of crystalloids to support BP
MEDICATION (DRUGS)
• In addition to specific treatment of underlying condition, use medications to support perfusion. (2)[B]
• Dopamine IV effects depend on dosing
- Augments contractility, cardiac output and heart rate at moderate doses via -1 effects. Increases BP by a combination of increased cardiac output and, at higher doses, vasoconstriction (via -effects).
• Norepinephrine IV: Augments BP by increasing vascular resistance (). Cardiac output in septic shock maintained/ increased (-1).
• Phenylephrine IV: Pure -agonist that increases BP via vasoconstriction
• Dobutamine IV: Inotropic agent with -1 effects
- Augments contractility and cardiac output (-1); does not raise BP because of vasodilation (-2).
• Vasopressin: Used in patients refractory to inotropic agents. Increases vascular smooth muscle tone, may increase mean arterial pressure (3)[B]
• Activated protein C: In the PROWESS study, APC was shown to reduce mortality from severe sepsis at 28 days from 31-25%. (4)[B] Treatment of DIC is critical to prevent sepsis-related organ failure. Activated protein C may help by effects on microcirculation. (5,6)[B]
• Corticosteroids: Low doses of hydrocortisone and fludrocortisone may reduce mortality in shock from sepsis. (7,8)[B]
• Precautions
- Myocardial oxygen consumption is increased by increased heart rate, afterload, and contractility.
- Pressors can increase myocardial ischemia if present and may precipitate or worsen tachyarrhythmias. Use in lowest possible dose for as limited period as possible.
SURGERY
In hemorrhagic and septic shock, surgery may be indicated to correct the underlying pathology.
FOLLOW-UP
DISPOSITION
ICU care
PROGNOSIS
Mortality is determined by a complex interaction of primary disease causing shock, age, coexisting chronic disease, and shock severity as marked by the number of acute organ system failures that follow shock.
ALERT
Geriatric Considerations
Prognosis guarded
COMPLICATIONS
• Multiple organs may be damaged by underperfusion during shock.
• Acute tubular necrosis
• Ischemic hepatitis
• Ischemic bowel
• Abdominal compartment syndrome
• Adult respiratory distress syndrome
• Encephalopathy and/or cerebrovascular accident
PATIENT MONITORING
Careful monitoring in intensive care
REFERENCES
1. Shah MR, Hasselad V, Binany C. Impact of the pulmonary artery catheter in critically ill patients. JAMA 2005;294:1664-1670.
2. Holmes CL. Vasoactive drugs in the intensive care unit. Curr Opin Crit Care 2005;11:413-417.
3. Holmes CL, Patel BM, Russell JA, et al. Physiology of vasopressin relevant to management of septic shock. Chest 2001;120:989-1002.
4. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-709.
5. Ince C: The microcirculation is the motor of sepsis. Crit Care 2005;S13-19.
6. Zeerleder S, Hack CE, Wuillemin WA. Disseminated intravascular coagulation in sepsis. Chest 2005;128:2864-2875.
7. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med 2003;348:727-734.
8. Annane D, Sebill V, Charpentier C et al. Effect of treatment with low does of hydrocortisone and fludrocortisones on mortality of patients with septic shock. JAMA 2002;862-871.
BASICS
DESCRIPTION
Inadequate tissue perfusion resulting in organ dysfunction. Classified as
• Hypovolemic shock
- Cardiac output is severely reduced due to loss of intravascular volume.
- Blood loss is most common cause.
• Cardiogenic shock
- Cardiac output is severely compromised by loss of myocardial muscle function, valvular dysfunction, or arrhythmia.
- Myocardial infarction is most common cause.
• Obstructive shock
- Cardiac output reduced due to obstruction of venous return to the heart (vena cava syndrome), compression of the heart, (pericardial tamponade, tension pneumothorax), or disrupted cardiac outflow (aortic dissection, pulmonary embolism).
• Distributive shock
- Reduced systemic vascular resistance and effective circulating volume. Dilated peripheral vessels shunt blood flow away from perfusion of critical organs.
- Most commonly due to sepsis and inflammation, which cause vasodilation and increased capillary permeability.
• Neurogenic
- Venous pooling in periphery (most often owing to spinal shock or drug overdose); behaves much like hypovolemic shock.
GENERAL PREVENTION
Prompt treatment of underlying condition.
EPIDEMIOLOGY
• Predominant age: Increased in elderly, somewhat dependent on underlying cause
• Predominant sex: Male = Female
ETIOLOGY
• Hypovolemic shock
- Hemorrhagic: Blood loss owing to trauma or gastrointestinal bleeding
- Nonhemorrhagic: 3rd-space loss of plasma volume (pancreatitis, bowel obstruction, infarction, anaphylaxis, diarrhea, burns)
• Cardiogenic shock
- Acute myocardial infarction (>40% of left ventricular myocardium)
- Arrhythmia (heart block, ventricular tachycardia, atrial fibrillation with rapid ventricular response, etc.)
- Acute valvular dysfunction: Mitral valve due to papillary muscle rupture following inferior myocardial infarctions or after rupture of chordae; aortic or mitral valve dysfunction, for example in bacterial endocarditis
- Ventricular septal rupture following anterior/septal myocardial infarction
• Obstructive shock
- Pericardial tamponade
- Inferior/superior vena caval obstruction usually owing to neoplasms
- Aortic dissection
- Massive pulmonary embolism
• Distributive shock: High-output shock is a result of sepsis, toxic shock, burns, or anaphylaxis. Severe noninfectious systemic inflammatory response can be due to sepsis, but also can independently cause distributive shock.
• Neurogenic: Venous pooling when loss of sympathetic innervation causes loss of venous tone (e.g., acute spinal injury, general or spinal anesthesia, or overdose of sedative drugs)
ASSOCIATED CONDITIONS
See "Etiology."
DIAGNOSIS
SIGNS AND SYMPTOMS
• Signs/symptoms of underlying disease
- Upper gastrointestinal (UGI) tract bleeding (hematemesis, melena)
- Sepsis (fever, chills, symptoms of underlying infection such as dysuria, costovertebral angle tenderness in urosepsis)
- Myocardial infarction (chest pain, diaphoresis, nausea, vomiting, S4 or S3 gallop, new heart murmur, rales)
- Jugular-venous distention (JVD), pulsus paradoxus in pericardial tamponade
• Signs/symptoms of underperfusion of organ systems
- Brain: Confusion, anxiety, agitation, coma
- Kidney: Oliguria
- Skin: Peripheral cyanosis, sluggish capillary refill, mottling, and/or coolness; may be overly perfused (flushed and warm) in high-output (septic) shock
- Gastrointestinal tract: Absence of bowel sounds
- Circulation: Thready pulses, tachycardia, hypotension, secondary cardiac ischemia (ST depression), or heart failure.
TESTS
• Pulmonary artery (Swan-Ganz) catheterization
- Serial measurement of cardiac output; central venous, pulmonary arterial, and pulmonary arterial occlusion pressures (left atrial pressure); and vascular resistance
- Mixed venous blood gases can be drawn from the catheter.
- Was standard of care, but recent studies suggest increased mortality with use, thus this practice is currently controversial. (1)[B]
• ECG
- Valvular failure
- Pericardial effusions
- Echo-guided pericardiocentesis
• Endoscopy if suspect GI bleed
Lab
• Specific to shock
- Elevated lactate (>2 mmol/L) suggests anaerobic metabolism from underperfusion.
- Reduced mixed venous Po2 obtained from the pulmonary artery indicates vigorous extraction of oxygen from tissues owing to underperfusion.
• For underlying diseases responsible for shock
- ECG, creatine kinase levels (serial), troponin levels (serial)
- Arterial blood gases
- Gram stain and culture of infected sites
- Blood cultures
- CBC (serial determination of hemoglobin and hematocrit in bleeding patients)
- Type and cross bleeding patients
Imaging
Depends on suspected underlying etiology
TREATMENT
STABILIZATION
• Support airway, breathing, circulation
• Continuous ECG monitoring with frequent assessment of BP, respiratory status, and urine output
GENERAL MEASURES
• Therapy involves aggressive volume resuscitation with control of the underlying etiology and monitoring of end-organ perfusion.
• Maintain Sao2 >92% with supplemental oxygen. Intubate and mechanically ventilate if patient cannot oxygenate adequately or has markedly increased breathing effort.
• Correct plasma volume deficits rapidly with crystalloids and/or packed RBCs.
• Correction of coagulation derangement by administration of coagulation factors (fresh frozen plasma, cryoprecipitate) and platelets if coagulopathy (prolonged prothrombin time, partial thromboplastin time, or platelet count 50 X 109/L) is present in a patient who is bleeding.
• Tachyarrhythmias (other than sinus tachycardia) should be promptly corrected by electrocardioversion. Insert transvenous pacemaker to correct bradyrhythmias.
• Vasopressors to correct hypotension or low cardiac output owing to myocardial failure or hypotension caused by low vascular resistance
• Treat underlying conditions, for example
- Hemorrhagic
Trauma
GI blood loss may require endoscopic or surgical intervention
- Sepsis
Empiric antibiotic therapy.
Hydrocortisone and vasopressin improve BP. Consider when patients do not improve in response to fluids, antibiotics, and low doses of vasopressors.
- Cardiogenic shock
Therapy should help reduce cardiac ischemia (oxygen, nitrates) and accomplish rapid reperfusion of injured, but potentially viable, myocardium. A balloon pump may temporize by providing improved coronary blood flow during and after diagnostic testing and revascularization therapy.
If shock is a result of acute failure of the mitral or aortic valve, surgical valve replacement may be lifesaving.
Diet
NPO
Activity
Bed rest
SPECIAL THERAPY
IV Fluids
Infusion of crystalloids to support BP
MEDICATION (DRUGS)
• In addition to specific treatment of underlying condition, use medications to support perfusion. (2)[B]
• Dopamine IV effects depend on dosing
- Augments contractility, cardiac output and heart rate at moderate doses via -1 effects. Increases BP by a combination of increased cardiac output and, at higher doses, vasoconstriction (via -effects).
• Norepinephrine IV: Augments BP by increasing vascular resistance (). Cardiac output in septic shock maintained/ increased (-1).
• Phenylephrine IV: Pure -agonist that increases BP via vasoconstriction
• Dobutamine IV: Inotropic agent with -1 effects
- Augments contractility and cardiac output (-1); does not raise BP because of vasodilation (-2).
• Vasopressin: Used in patients refractory to inotropic agents. Increases vascular smooth muscle tone, may increase mean arterial pressure (3)[B]
• Activated protein C: In the PROWESS study, APC was shown to reduce mortality from severe sepsis at 28 days from 31-25%. (4)[B] Treatment of DIC is critical to prevent sepsis-related organ failure. Activated protein C may help by effects on microcirculation. (5,6)[B]
• Corticosteroids: Low doses of hydrocortisone and fludrocortisone may reduce mortality in shock from sepsis. (7,8)[B]
• Precautions
- Myocardial oxygen consumption is increased by increased heart rate, afterload, and contractility.
- Pressors can increase myocardial ischemia if present and may precipitate or worsen tachyarrhythmias. Use in lowest possible dose for as limited period as possible.
SURGERY
In hemorrhagic and septic shock, surgery may be indicated to correct the underlying pathology.
FOLLOW-UP
DISPOSITION
ICU care
PROGNOSIS
Mortality is determined by a complex interaction of primary disease causing shock, age, coexisting chronic disease, and shock severity as marked by the number of acute organ system failures that follow shock.
ALERT
Geriatric Considerations
Prognosis guarded
COMPLICATIONS
• Multiple organs may be damaged by underperfusion during shock.
• Acute tubular necrosis
• Ischemic hepatitis
• Ischemic bowel
• Abdominal compartment syndrome
• Adult respiratory distress syndrome
• Encephalopathy and/or cerebrovascular accident
PATIENT MONITORING
Careful monitoring in intensive care
REFERENCES
1. Shah MR, Hasselad V, Binany C. Impact of the pulmonary artery catheter in critically ill patients. JAMA 2005;294:1664-1670.
2. Holmes CL. Vasoactive drugs in the intensive care unit. Curr Opin Crit Care 2005;11:413-417.
3. Holmes CL, Patel BM, Russell JA, et al. Physiology of vasopressin relevant to management of septic shock. Chest 2001;120:989-1002.
4. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-709.
5. Ince C: The microcirculation is the motor of sepsis. Crit Care 2005;S13-19.
6. Zeerleder S, Hack CE, Wuillemin WA. Disseminated intravascular coagulation in sepsis. Chest 2005;128:2864-2875.
7. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med 2003;348:727-734.
8. Annane D, Sebill V, Charpentier C et al. Effect of treatment with low does of hydrocortisone and fludrocortisones on mortality of patients with septic shock. JAMA 2002;862-871.
SEXUAL DYSFUNCTION IN WOMEN
SEXUAL DYSFUNCTION IN WOMEN - Lisa M. Schroeder, MD
BASICS
DESCRIPTION
Difficulty getting or staying sexually aroused, reaching orgasm too quickly, difficulty or inability to reach orgasm, inability to relax, lack of interest in sex, distaste or revulsion with sex, too little foreplay, too little tenderness after intercourse
• Most women who have orgasms do not do so during intercourse, and mistakenly think this is dysfunction.
• 4 major types
- Disorder of desire: Both hypo- and hyper- (initiation and response), global desire disorder, couple desire discrepancy, situational desire disorderthese must be evaluated in the context of the relationship overall
- Disorder of arousal
- Dyspareunia, vaginismus
- Disorders of orgasm: Primary and secondary, during masturbation or coitus, situational or partner specific
• System(s) Affected: Nervous; Reproductive; Genitourinary; Psychiatric
• Synonym(s): Hypoactive sexual desire disorder; Sexual aversion disorder; Female sexual arousal disorder; Inhibited female orgasm
ALERT
Geriatric Considerations
• Societal expectations about geriatric sexuality (especially the myth older women are not sexually active) can cause distress if the patient has sexual desires or sexual experience.
• Normal physiologic changes in aging are misinterpreted as dysfunction.
Pregnancy Considerations
Often affects sexual function in women, but the effect varies depending on the patient and couple's beliefs about pregnancy and the problem.
EPIDEMIOLOGY
• Predominant age
- Postpubertal age group
- Women's ability to experience orgasm increases gradually from puberty.
- In later, teens, nearly 1/2 have not had orgasm; by mid-30s, about 10% have not.
- Sex role stereotypes can be a factor.
• Predominant sex: Female (heterosexual, homosexual, and bisexual women)
Prevalence
• 1:5 women are sexually dissatisfied, and 2/3 of women report some degree of sexual dysfunction. Only 1/3 of anorgasmic women in general think it is a problem.
• Overall prevalence for dysfunction is 15-30% of all women. Desire disorders are complaint of 30-55% of individual patients presenting to clinics, and 31% of couples; arousal disorders present in 14-48% in community studies. Orgasmic disorders probably the most common; 10% primary, and up to 65-80% secondary in community studies.
• There are many barriers to seeking help, so data for prevalence incomplete; barriers include stigma of exposing sexual inadequacy, fear of unknown therapy, e.g., of having to perform before a therapist.
RISK FACTORS
• Couple discrepancies in expectations, cultural backgrounds
• Attitudes toward sexuality in family of origin
• Previous sexual trauma
• Chronic medical problems
- Cardiovascular disease
- Endocrine disorders
- HTN
- Neurologic disorders
• Smoking
ETIOLOGY
• Interrelational difficulties and conflict regarding intimacy
• Anxiety
• Survivor of sexual abuse, including incest
• Alcohol
• Drug use, including prescription medications (e.g., monoamine oxidase inhibitors, tricyclic antidepressants, especially selective serotonin reuptake inhibitor antidepressants, beta blockers)
• Proximity of other people in household
• Anorgasmia can be due to diabetes.
• Spinal cord damage
• Hormonal imbalance
• Thyroid disease
• Sexual frequency myths
• Control issues in the relationships
• Dyspareunia, including vaginal dryness causing interference with lubrication, secondary to infection or endocrine
• There are few endocrine data on women with sexual dysfunction.
ASSOCIATED CONDITIONS
Marital stress
DIAGNOSIS
SIGNS AND SYMPTOMS
• Complaint to health care provider (if the clinician inquires, over twice as many are revealed than if clinician waits for patient to mention)
• Infertility
• Marital conflict
• Family dysfunction
Physical Exam
Most commonly a normal exam
• Assess for vaginal atrophy, adequate estrogenization
• Assess for infection
• Recognize signs of anxiety, apprehension, and pain during speculum and pelvic exam.
TESTS
Special tests: May need life experiences or some other psychological inventory to evaluate couple. (Alcohol, marijuana, or other illicit drug use may make these evaluations unreliable.)
Lab
As needed to identify infections and other medical causes
Pathological Findings
Varied if any
DIFFERENTIAL DIAGNOSIS
• Medication side effects
- Psychotropics
- Monoamine oxidase inhibitors
- Tricyclic and other antidepressants
• Marital dysfunction including domestic violence
• Decreased sensation secondary to back or nerve disease
• Multiple sclerosis
• Abdominal surgery (can interfere with pelvic innervation)
• Depression
• Vaginitis
• Decreased vaginal lubrication secondary to hormonal imbalance
• Pregnancy
• Anatomic or congenital abnormalities
• Pseudodyspareunia (use of complaint of pain to distance from partner)
TREATMENT
GENERAL MEASURES
• For childhood trauma: Scripting, psychotherapy, cognitive restructuring
• For anorgasmia: Directed masturbation and "homework" with partners
• For prescription drug causes: Reduced dosages or change to different medication
• Other: Family therapy, sensate conditioning; referral to specialized sex therapy
Diet
Weight reduction if needed for either partner
Activity
Varies with couple
SPECIAL THERAPY
Complementary and Alternative Medicine
• Yohimbe-not recommended, potentially dangerous
• DHEA-androgenic effects, will decrease HDL cholesterol
MEDICATION (DRUGS)
These are usually multifactorial psychosocial conditions. Using medications doesn't address the cause of the problem and can make it worse. Sildenafil: Some evidence on the effectiveness for arousal and orgasm disorders (1,2)[B]
ALERT
Do not use with nitrates
- Bupropion: May be useful in treating sexual dysfunction, or as an adjunct for SSRI induced sexual dysfunction (3-5)[B]
- Postmenopausal women
Adding testosterone to hormone replacement therapy may increase sexual desire. (6)[A]
Several RCT show an improvement in sexual desire.
Estrogen replacement may help to improve vaginal atrophy and clitoral sensitivity.
- Premenopausal women
Some data suggest that testosterone may be low with decreased libido.
No clear studies indicate testosterone replacement as beneficial.
FOLLOW-UP
DISPOSITION
Issues for Referral
• Sexual abuse, partner violence
• Marital counseling
PROGNOSIS
• Lack of desire is the most difficult to treat (50% successful by patient report), and success is sometimes less optimal than patient's initial wish.
• Best predictors are desire to change and overall healthy relationship.
COMPLICATIONS
Marital or family stress, breakup, and divorce.
PATIENT MONITORING
Varies with patient
REFERENCES
1. Basson R, Brotto L. Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: A randomized controlled trial. Br J Obstect Gynaecol. 2003;11:1014-1024.
2. Caruso S, et al. Premenopausal women affected by sexual arousal disorder treated with sildenafil: A double blind, crossover, placebo-controlled study. Br J Obstect Gynaecol. 2001;108(6):623-628.
3. Segraves RT, Clayton A, Croft H, et al. Bupropion sustained release for the treatment of hypoactive sexual desire disorder in premenopausal women. J Clin Psychopharmacol. 2004;24(3):339-342.
4. Rudkin L, Taylor MJ, Hawton K. Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database Syst Rev. 2004;(4):CD003382.
5. Ginzburg R, Wong Y, Fader JS. Effect of bupropion on sexual dysfunction. Ann Pharmacother. 2005;39(12):2096-2099.
6. Mayo Clin Proc. 2004;79(Suppl):S19-S24.
ADDITIONAL READING
• Bancroft J. Human Sexuality and Its Problems. 2nd ed. New York, NY: Churchill Livingstone; 1989.
• Leiblum SR, Rosen RC. Principles and Practice of Sex Therapy: Update for the 1990s. New York, NY: The Guilford Press; 1989.
• Wincze JP, Carey MP. Sexual Dysfunction: A Guide for Assessment and Treatment. New York, NY: The Guilford Press; 1991.
• Basaria S, Dobs A. Safety and advere effects of androgens: How to counsel patients. Mayo Clin Proc. 2004;79(Suppl):S25-S32.
MISCELLANEOUS
• See also: Vaginismus
• Other notes
- Women must feel safe in order to let go and lose some control to experience orgasm.
- Performance anxiety makes males ejaculate prematurely, whereas it inhibits orgasm in women.
- Simple lack of knowledge about anatomy and physiology of sex can lead to problems.
BASICS
DESCRIPTION
Difficulty getting or staying sexually aroused, reaching orgasm too quickly, difficulty or inability to reach orgasm, inability to relax, lack of interest in sex, distaste or revulsion with sex, too little foreplay, too little tenderness after intercourse
• Most women who have orgasms do not do so during intercourse, and mistakenly think this is dysfunction.
• 4 major types
- Disorder of desire: Both hypo- and hyper- (initiation and response), global desire disorder, couple desire discrepancy, situational desire disorderthese must be evaluated in the context of the relationship overall
- Disorder of arousal
- Dyspareunia, vaginismus
- Disorders of orgasm: Primary and secondary, during masturbation or coitus, situational or partner specific
• System(s) Affected: Nervous; Reproductive; Genitourinary; Psychiatric
• Synonym(s): Hypoactive sexual desire disorder; Sexual aversion disorder; Female sexual arousal disorder; Inhibited female orgasm
ALERT
Geriatric Considerations
• Societal expectations about geriatric sexuality (especially the myth older women are not sexually active) can cause distress if the patient has sexual desires or sexual experience.
• Normal physiologic changes in aging are misinterpreted as dysfunction.
Pregnancy Considerations
Often affects sexual function in women, but the effect varies depending on the patient and couple's beliefs about pregnancy and the problem.
EPIDEMIOLOGY
• Predominant age
- Postpubertal age group
- Women's ability to experience orgasm increases gradually from puberty.
- In later, teens, nearly 1/2 have not had orgasm; by mid-30s, about 10% have not.
- Sex role stereotypes can be a factor.
• Predominant sex: Female (heterosexual, homosexual, and bisexual women)
Prevalence
• 1:5 women are sexually dissatisfied, and 2/3 of women report some degree of sexual dysfunction. Only 1/3 of anorgasmic women in general think it is a problem.
• Overall prevalence for dysfunction is 15-30% of all women. Desire disorders are complaint of 30-55% of individual patients presenting to clinics, and 31% of couples; arousal disorders present in 14-48% in community studies. Orgasmic disorders probably the most common; 10% primary, and up to 65-80% secondary in community studies.
• There are many barriers to seeking help, so data for prevalence incomplete; barriers include stigma of exposing sexual inadequacy, fear of unknown therapy, e.g., of having to perform before a therapist.
RISK FACTORS
• Couple discrepancies in expectations, cultural backgrounds
• Attitudes toward sexuality in family of origin
• Previous sexual trauma
• Chronic medical problems
- Cardiovascular disease
- Endocrine disorders
- HTN
- Neurologic disorders
• Smoking
ETIOLOGY
• Interrelational difficulties and conflict regarding intimacy
• Anxiety
• Survivor of sexual abuse, including incest
• Alcohol
• Drug use, including prescription medications (e.g., monoamine oxidase inhibitors, tricyclic antidepressants, especially selective serotonin reuptake inhibitor antidepressants, beta blockers)
• Proximity of other people in household
• Anorgasmia can be due to diabetes.
• Spinal cord damage
• Hormonal imbalance
• Thyroid disease
• Sexual frequency myths
• Control issues in the relationships
• Dyspareunia, including vaginal dryness causing interference with lubrication, secondary to infection or endocrine
• There are few endocrine data on women with sexual dysfunction.
ASSOCIATED CONDITIONS
Marital stress
DIAGNOSIS
SIGNS AND SYMPTOMS
• Complaint to health care provider (if the clinician inquires, over twice as many are revealed than if clinician waits for patient to mention)
• Infertility
• Marital conflict
• Family dysfunction
Physical Exam
Most commonly a normal exam
• Assess for vaginal atrophy, adequate estrogenization
• Assess for infection
• Recognize signs of anxiety, apprehension, and pain during speculum and pelvic exam.
TESTS
Special tests: May need life experiences or some other psychological inventory to evaluate couple. (Alcohol, marijuana, or other illicit drug use may make these evaluations unreliable.)
Lab
As needed to identify infections and other medical causes
Pathological Findings
Varied if any
DIFFERENTIAL DIAGNOSIS
• Medication side effects
- Psychotropics
- Monoamine oxidase inhibitors
- Tricyclic and other antidepressants
• Marital dysfunction including domestic violence
• Decreased sensation secondary to back or nerve disease
• Multiple sclerosis
• Abdominal surgery (can interfere with pelvic innervation)
• Depression
• Vaginitis
• Decreased vaginal lubrication secondary to hormonal imbalance
• Pregnancy
• Anatomic or congenital abnormalities
• Pseudodyspareunia (use of complaint of pain to distance from partner)
TREATMENT
GENERAL MEASURES
• For childhood trauma: Scripting, psychotherapy, cognitive restructuring
• For anorgasmia: Directed masturbation and "homework" with partners
• For prescription drug causes: Reduced dosages or change to different medication
• Other: Family therapy, sensate conditioning; referral to specialized sex therapy
Diet
Weight reduction if needed for either partner
Activity
Varies with couple
SPECIAL THERAPY
Complementary and Alternative Medicine
• Yohimbe-not recommended, potentially dangerous
• DHEA-androgenic effects, will decrease HDL cholesterol
MEDICATION (DRUGS)
These are usually multifactorial psychosocial conditions. Using medications doesn't address the cause of the problem and can make it worse. Sildenafil: Some evidence on the effectiveness for arousal and orgasm disorders (1,2)[B]
ALERT
Do not use with nitrates
- Bupropion: May be useful in treating sexual dysfunction, or as an adjunct for SSRI induced sexual dysfunction (3-5)[B]
- Postmenopausal women
Adding testosterone to hormone replacement therapy may increase sexual desire. (6)[A]
Several RCT show an improvement in sexual desire.
Estrogen replacement may help to improve vaginal atrophy and clitoral sensitivity.
- Premenopausal women
Some data suggest that testosterone may be low with decreased libido.
No clear studies indicate testosterone replacement as beneficial.
FOLLOW-UP
DISPOSITION
Issues for Referral
• Sexual abuse, partner violence
• Marital counseling
PROGNOSIS
• Lack of desire is the most difficult to treat (50% successful by patient report), and success is sometimes less optimal than patient's initial wish.
• Best predictors are desire to change and overall healthy relationship.
COMPLICATIONS
Marital or family stress, breakup, and divorce.
PATIENT MONITORING
Varies with patient
REFERENCES
1. Basson R, Brotto L. Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: A randomized controlled trial. Br J Obstect Gynaecol. 2003;11:1014-1024.
2. Caruso S, et al. Premenopausal women affected by sexual arousal disorder treated with sildenafil: A double blind, crossover, placebo-controlled study. Br J Obstect Gynaecol. 2001;108(6):623-628.
3. Segraves RT, Clayton A, Croft H, et al. Bupropion sustained release for the treatment of hypoactive sexual desire disorder in premenopausal women. J Clin Psychopharmacol. 2004;24(3):339-342.
4. Rudkin L, Taylor MJ, Hawton K. Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database Syst Rev. 2004;(4):CD003382.
5. Ginzburg R, Wong Y, Fader JS. Effect of bupropion on sexual dysfunction. Ann Pharmacother. 2005;39(12):2096-2099.
6. Mayo Clin Proc. 2004;79(Suppl):S19-S24.
ADDITIONAL READING
• Bancroft J. Human Sexuality and Its Problems. 2nd ed. New York, NY: Churchill Livingstone; 1989.
• Leiblum SR, Rosen RC. Principles and Practice of Sex Therapy: Update for the 1990s. New York, NY: The Guilford Press; 1989.
• Wincze JP, Carey MP. Sexual Dysfunction: A Guide for Assessment and Treatment. New York, NY: The Guilford Press; 1991.
• Basaria S, Dobs A. Safety and advere effects of androgens: How to counsel patients. Mayo Clin Proc. 2004;79(Suppl):S25-S32.
MISCELLANEOUS
• See also: Vaginismus
• Other notes
- Women must feel safe in order to let go and lose some control to experience orgasm.
- Performance anxiety makes males ejaculate prematurely, whereas it inhibits orgasm in women.
- Simple lack of knowledge about anatomy and physiology of sex can lead to problems.
SERUM SICKNESS
SERUM SICKNESS - Brian P. Vickery, MD
BASICS
DESCRIPTION
An acute Type III hypersensitivity reaction, classically described 1-3 weeks following administration of nonhuman serum or with exposure to certain medications. Reactions tend to peak around day 10 postexposure. Serum sicknesslike reactions (SSLR) occur after administration of certain drugs, especially antibiotics.
• System(s) Affected: Heme/Lymphatic/Immunologic; Musculoskeletal; Skin/Exocrine; Cardiovascular; Gastrointestinal; Genitourinary
EPIDEMIOLOGY
No gender or age predominance
RISK FACTORS
Preceding exposure to drugs or serum
PATHOPHYSIOLOGY
• Immunoglobulin G (IgG) antibodies form immune complexes with the antigen in circulation.
• When an excess of antibody or antigen occurs, small complexes are formed which are cleared rapidly and do not generally cause reactions.
• When concentrations of antibody and antigen are approximately equal, intermediate size immune complexes are formed which are deposited in tissues and efficiently activate complement.
• Complement activation causes release of inflammatory mediators, recruitment of leukocytes, and vascular leak.
ETIOLOGY
• Anti-thymocyte globulin (ATG)
• Antimicrobials
- Cephalosporins, esp. Cefaclor
- Minocycline
- TMP/SMX
- Rifampin
- Penicillins
- Streptokinase
• Monoclonal antibodies
• SSRIs
• Propranolol
• Vaccines
• Equine diptheria antiserum
• Rabies antiserum
• Rabbit antiserum
• Crotalidae antivenin
DIAGNOSIS
SIGNS AND SYMPTOMS
Characterized by an ill-appearing patient with fever, arthralgias, morbilliform or urticarial skin rash, and lymphadenopathy
• Fever
• Arthralgia/myalgia
• Morbilliform or urticarial rash, especially at injection site
• Malaise
• Pruritus
• Nausea
• Vomiting
• Abdominal pain
• Hepatomegaly or splenomegaly
• Lymphadenopathy, especially in location draining injection site
• Headache (usually due to TMJ arthralgia)
• Arthritis
History
• History of exposure to medication or serum in preceding 1-3 weeks
• Absence of chronic constitutional symptoms
TESTS
Lab
Detection of immune complexes in serum is not widely available and of limited clinical value.
• C3/C4: Helpful if low but can be normal
• ESR/CRP: Usually elevated
• CBC with differential: Leukocytosis
• Liver enzymes: Transaminitis
• Serum electrolytes: Renal insufficiency (rare)
• Urinalysis: Nephritis (rare)
ALERT
Special Considerations
If rash is atypical or does not improve after withdrawing suspected drug, consider
- Antinuclear antibodies (ANA)
- Antineutrophil cytoplasmic antibodies (ANCA)
- Rheumatoid factor (RF)
- Cryoglobulins
- Skin biopsy with immunofluorescence
DIFFERENTIAL DIAGNOSIS
• Systemic vasculitis
- Periarteritis nodosa
- Wegener granulomatosis
- Cryoglobulinemia
- Juvenile idiopathic arthritis
- Kawasaki syndrome
- Henoch-Schonlein purpura
- Hypersensitivity vasculitis
• Sepsis
• Rheumatic fever
• Viral syndrome
• Anaphylaxis
• Drug hypersensitivity
• Stevens-Johnson/TEN
TREATMENT
GENERAL MEASURES
• Mainstay of treatment is to remove the offending antigen.
• Reticuloendothelial system removes immune complexes, leading to improvement and resolution within 48-72 hours (depending upon half-life of antigen).
Activity
Bed rest during acute illness if arthralgia/myalgia severe
MEDICATION (DRUGS)
First Line
• Diphenhydramine or hydroxyzine 25-50 mg IV/PO q4-6h for urticaria and generalized pruritus
• NSAIDs may offer relief of arthralgia/myalgia.
Second Line
Prednisone
• 40 mg/d PO 5-7 days if inflammation is severe or 1st-line drugs fail
FOLLOW-UP
DISPOSITION
Admission Criteria
Most patients with acute serum sickness or SSLR will require admission for observation and exclusion of other diagnoses.
Discharge Criteria
• When significant improvement in inflammation occurs after stopping suspected drug
• When ambulatory and tolerating PO
PROGNOSIS
Favorable
• Self-limiting with improvement in 48-72 hours once offending antigen removed
COMPLICATIONS
• Vasculitis
• Neuropathy
• Hepatitis
• Glomerulonephritis
• Anaphylaxis
• Shock
• Death
REFERENCES
1. Friedmann PS, et al. Mechanisms in cutaneous drug hypersensitivity reactions. Clin Exp Allergy. 2003;33(7):861-872.
2. Jancar S, et al. Immune complex-mediated tissue injury: A multistep paradigm. Trends Immunol. 2005: 26(1):48-55.
3. Roujeau JC, et al. Severe adverse cutaneous reactions to drugs. N Engl J Med. 1994;331:1272-1285.
ADDITIONAL READING
• Pichler WJ. Immune mechanism of drug hypersensitivity. Immunol Allergy Clin N Am. 2004;24:373-397.
• Frank MM, Hester CG. Immune complexes and allergic disease. In: Adkinson NF, et al. Middleton's Allergy: Principles and Practice. 6th ed. Philadephia, PA: Elsevier; 2003:997-1014.
BASICS
DESCRIPTION
An acute Type III hypersensitivity reaction, classically described 1-3 weeks following administration of nonhuman serum or with exposure to certain medications. Reactions tend to peak around day 10 postexposure. Serum sicknesslike reactions (SSLR) occur after administration of certain drugs, especially antibiotics.
• System(s) Affected: Heme/Lymphatic/Immunologic; Musculoskeletal; Skin/Exocrine; Cardiovascular; Gastrointestinal; Genitourinary
EPIDEMIOLOGY
No gender or age predominance
RISK FACTORS
Preceding exposure to drugs or serum
PATHOPHYSIOLOGY
• Immunoglobulin G (IgG) antibodies form immune complexes with the antigen in circulation.
• When an excess of antibody or antigen occurs, small complexes are formed which are cleared rapidly and do not generally cause reactions.
• When concentrations of antibody and antigen are approximately equal, intermediate size immune complexes are formed which are deposited in tissues and efficiently activate complement.
• Complement activation causes release of inflammatory mediators, recruitment of leukocytes, and vascular leak.
ETIOLOGY
• Anti-thymocyte globulin (ATG)
• Antimicrobials
- Cephalosporins, esp. Cefaclor
- Minocycline
- TMP/SMX
- Rifampin
- Penicillins
- Streptokinase
• Monoclonal antibodies
• SSRIs
• Propranolol
• Vaccines
• Equine diptheria antiserum
• Rabies antiserum
• Rabbit antiserum
• Crotalidae antivenin
DIAGNOSIS
SIGNS AND SYMPTOMS
Characterized by an ill-appearing patient with fever, arthralgias, morbilliform or urticarial skin rash, and lymphadenopathy
• Fever
• Arthralgia/myalgia
• Morbilliform or urticarial rash, especially at injection site
• Malaise
• Pruritus
• Nausea
• Vomiting
• Abdominal pain
• Hepatomegaly or splenomegaly
• Lymphadenopathy, especially in location draining injection site
• Headache (usually due to TMJ arthralgia)
• Arthritis
History
• History of exposure to medication or serum in preceding 1-3 weeks
• Absence of chronic constitutional symptoms
TESTS
Lab
Detection of immune complexes in serum is not widely available and of limited clinical value.
• C3/C4: Helpful if low but can be normal
• ESR/CRP: Usually elevated
• CBC with differential: Leukocytosis
• Liver enzymes: Transaminitis
• Serum electrolytes: Renal insufficiency (rare)
• Urinalysis: Nephritis (rare)
ALERT
Special Considerations
If rash is atypical or does not improve after withdrawing suspected drug, consider
- Antinuclear antibodies (ANA)
- Antineutrophil cytoplasmic antibodies (ANCA)
- Rheumatoid factor (RF)
- Cryoglobulins
- Skin biopsy with immunofluorescence
DIFFERENTIAL DIAGNOSIS
• Systemic vasculitis
- Periarteritis nodosa
- Wegener granulomatosis
- Cryoglobulinemia
- Juvenile idiopathic arthritis
- Kawasaki syndrome
- Henoch-Schonlein purpura
- Hypersensitivity vasculitis
• Sepsis
• Rheumatic fever
• Viral syndrome
• Anaphylaxis
• Drug hypersensitivity
• Stevens-Johnson/TEN
TREATMENT
GENERAL MEASURES
• Mainstay of treatment is to remove the offending antigen.
• Reticuloendothelial system removes immune complexes, leading to improvement and resolution within 48-72 hours (depending upon half-life of antigen).
Activity
Bed rest during acute illness if arthralgia/myalgia severe
MEDICATION (DRUGS)
First Line
• Diphenhydramine or hydroxyzine 25-50 mg IV/PO q4-6h for urticaria and generalized pruritus
• NSAIDs may offer relief of arthralgia/myalgia.
Second Line
Prednisone
• 40 mg/d PO 5-7 days if inflammation is severe or 1st-line drugs fail
FOLLOW-UP
DISPOSITION
Admission Criteria
Most patients with acute serum sickness or SSLR will require admission for observation and exclusion of other diagnoses.
Discharge Criteria
• When significant improvement in inflammation occurs after stopping suspected drug
• When ambulatory and tolerating PO
PROGNOSIS
Favorable
• Self-limiting with improvement in 48-72 hours once offending antigen removed
COMPLICATIONS
• Vasculitis
• Neuropathy
• Hepatitis
• Glomerulonephritis
• Anaphylaxis
• Shock
• Death
REFERENCES
1. Friedmann PS, et al. Mechanisms in cutaneous drug hypersensitivity reactions. Clin Exp Allergy. 2003;33(7):861-872.
2. Jancar S, et al. Immune complex-mediated tissue injury: A multistep paradigm. Trends Immunol. 2005: 26(1):48-55.
3. Roujeau JC, et al. Severe adverse cutaneous reactions to drugs. N Engl J Med. 1994;331:1272-1285.
ADDITIONAL READING
• Pichler WJ. Immune mechanism of drug hypersensitivity. Immunol Allergy Clin N Am. 2004;24:373-397.
• Frank MM, Hester CG. Immune complexes and allergic disease. In: Adkinson NF, et al. Middleton's Allergy: Principles and Practice. 6th ed. Philadephia, PA: Elsevier; 2003:997-1014.
SEPSIS
SEPSIS - Suzanne Klainer, MD
BASICS
DESCRIPTION
• Sepsis is the systemic response to infection; it is defined as systemic inflammatory response syndrome (SIRS) with documented infection.
• SIRS is an inflammatory reaction to various clinical insults (e.g., severe trauma or burn) manifested by 2 of the following
- Temperature >38C or 36C
- Heart rate >90/min
- Respiratory rate >20/min or PaCO2 32 mm Hg
- WBC count >12,000/mm3, 4,000/mm3, or >10% immature forms (bands)
• Severe sepsis: When associated with organ dysfunction or hypotension
• Septic shock: Sepsis induced hypotension (systolic BP 90 mm Hg or 40 mm Hg drop from baseline) despite adequate fluid resuscitation plus hypoperfusion abnormalities (oliguria, lactic acidosis, acute change in mental status)
• MODS: Multiple organ dysfunction syndrome
• Bacteremia: Bacteria in the blood; may have no accompanying symptoms
• Synonym(s): Septicemia; Sepsis neonatorum
ALERT
Geriatric Considerations
• Often more difficult to diagnose clinically in the elderly
• Change in mental status/behavior may be only early manifestation
Pediatric Considerations
Screen newborns for infection due to prolonged rupture of membranes (>24 hours), maternal fever, and prematurity.
Pregnancy Considerations
-Lactam antibiotics, aminoglycosides, and erythromycin are considered safe.
GENERAL PREVENTION
• Vaccination: Pneumococcal (geriatric patients, patients with certain chronic diseases), Haemophilus influenzae type B (infants, young children)
• -Globulin (for hypo- or agammaglobulinemic patients)
• Hand washing by hospital personnel, appropriate catheter care, and so forth, for hospitalized patients
EPIDEMIOLOGY
Predominant age: All ages
Incidence
• 3 cases per 1,000 population
• 2 cases per 100 patients admitted to hospital (1)
RISK FACTORS
• Positive blood cultures
• Age extremes (very old and very young)
• Impaired host (see "Associated Conditions")
• Critically ill patients
• Indwelling catheters: Intravascular, urinary, biliary
• Complicated labor and delivery: Premature and/or prolonged rupture of membranes, other complications
• Certain surgical procedures
Genetics
Single-nucleotide polymorphisms (i.e., cytokine and cytokine receptor genes) influence the risk for the development of sepsis and the risk of mortality from sepsis.
PATHOPHYSIOLOGY
In sepsis, the dysregulation of the inflammatory process is precipitated by an imbalance between pro- and anti-inflammatory mediators, resulting in widespread systemic tissue destruction and organ dysfunction.
ETIOLOGY
• Specific etiologic agents include
- Gram-positive organisms: Most commonly Staphylococcus spp., Streptococcus spp., Enterococcus spp.
- Gram-negative organisms: Most commonly Escherichia coli, Klebsiella spp., Proteus spp., Pseudomonas spp.
- Fungi: Most commonly Candida spp.
- Other agents: Anaerobes. See also "Differential Diagnosis."
• Common sources of septicemia include
- Lungs
- Urinary tract
- Intra-abdominal focus: Biliary tree, abscess, peritonitis
- Intravascular catheters
- Skin: Cellulitis, decubitus ulcer, gangrene
- Heart valves
ASSOCIATED CONDITIONS
• Immunologic disorders
- Neutropenia, HIV, hypo-/agammaglobulinemia, complement deficiency, splenectomy
• Diabetes mellitus
• Alcoholism
• Malignancy
• Cirrhosis
• Burns
• Multiple trauma
• IV drug abuse
• Malnutrition
DIAGNOSIS
SIGNS AND SYMPTOMS
• Fever
• Chills, rigors
• Myalgias
• Changes in mental status: Restlessness, agitation, confusion, delirium, lethargy, stupor, coma
• Tachycardia
• Tachypnea
• Hypotension
• Skin lesions: Erythema, petechiae, ecthyma gangrenosum, embolic lesions, purpura
• Signs and symptoms related to site of primary infection
- Respiratory tract: Cough, sputum production, dyspnea, chest pain
- Urinary tract: Dysuria, flank pain, frequency, urgency
- Intra-abdominal source: Nausea, vomiting, diarrhea, constipation, abdominal pain
- CNS: Stiff neck, headache, photophobia, focal neurologic signs
• Signs and symptoms related to end-organ failure
- Pulmonary: Cyanosis
- Renal: Oliguria, anuria
- Hepatic: Jaundice
- Cardiac: CHF
TESTS
• Antigen detection systems Counterimmunoelectrophoresis and latex agglutination tests (pneumococcus, H. influenzae type B, group B streptococcus, meningococcus)
• Gram stain of buffy coat smears occasionally useful
Lab
• Positive blood cultures (not required for diagnosis)
• Positive cultures from other sites (sputum, urine, CSF, wound)
• Gram stain of clinical specimens (sputum, urine, CSF, wound)
• Common
- Leukocytosis
- Proteinuria
- Hypoxemia
- Hyperglycemia
- Hypocalcemia
- Mild hyperbilirubinemia
• Less common (more severe cases)
- Lactic acidosis
- Leukopenia
- Azotemia
- Thrombocytopenia
- Prolonged prothrombin time
- Anemia
- Hypoglycemia
• Drugs that may alter lab results: Prior antibiotic use
Imaging
• Radiographs (e.g., chest)
• Ultrasound, CT scan, or MRI may be useful in delineating sites of infection.
Diagnostic Procedures/Surgery
• Aspiration of potentially infected body fluids (pleural, peritoneal, CSF) when appropriate
• Biopsy, drainage of potentially infected tissues (abscess, biliary tree, others) when appropriate
Pathological Findings
• Inflammation at primary site of infection
• Disseminated intravascular coagulation
• Noncardiogenic pulmonary edema
DIFFERENTIAL DIAGNOSIS
• Shock of other etiology
• Bacteremia without sepsis
• Localized infection
• SIRS
• Viral diseases (influenza, dengue and other hemorrhagic viruses, West Nile)
• Rickettsial diseases (Rocky Mountain spotted fever, endemic typhus)
• Spirochetal diseases (leptospirosis, relapsing fever [Borrelia sp.], Jarisch-Herxheimer reaction in syphilis)
• Protozoal diseases (Toxoplasma gondii, Trypanosoma cruzi, Pneumocystis carinii, Plasmodium falciparum)
• Collagen vascular diseases, vasculitides, myocardial infarction, pulmonary embolus, thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome, thyrotoxicosis, adrenal insufficiency (Addison disease)
TREATMENT
STABILIZATION
• Hospitalization
• Intensive care treatment of patients with shock, respiratory failure
GENERAL MEASURES
• ABCs
- Oxygen supplementation, monitoring
Intubation and invasive monitors if necessary for respiratory failure/hemodynamic instability
• Initial resuscitation targeted at
- CVP: 8-12 mm Hg
- MAP 65 mm Hg
- Urine output 0.5 mL/kg/h
- Central venous/mixed venous oxygen saturation 70% (2)[A]
• Identification of etiology
- Removal or drainage of septic foci
• Transfusion of RBCs, platelets, and/or fresh frozen plasma for coagulopathy
• Stress ulcer and deep venous thrombosis prophylactic measures
• Tight glucose control (3)[B]
Diet
• NPO initially
• Enteral feeds beneficial when possible however, IV alimentation is appropriate in severely malnourished patients and in patients who will be unable to receive enteral alimentation within the week.
SPECIAL THERAPY
Ventilatory support: See "Acute Respiratory Distress Syndrome (ARDS)"
IV Fluids
No evidence to support 1 type of fluid over another (colloid/crystalloid) (2)[B]
MEDICATION (DRUGS)
First Line
• Pressors
- Norepinephrine/dopamine 1st line (2)[C]
- Renal dose dopamine not recommended (2)[B]
• Antibiotic coverage immediately after cultures are obtained (1)[C]
- Should be broad-spectrum initially, with emphasis on most likely pathogen.
- After culture results are available, treatment should be organism-specific.
- Knowledge of antibiotic susceptibility patterns of local pathogens is extremely important.
• Neonatal (7 days old) sepsis: Ampicillin 300 mg/kg/d in 3 divided doses and gentamicin (Garamycin) 5 mg/kg/d in 2 divided doses
• Nonimmunocompromised child: Cefotaxime (Claforan): 200 mg/kg/d in 4 divided doses
• Adult (pseudomonas not suspected): Vancomycin plus gram-negative coverage (cefepime 1-2 g q12h or gentamicin 3-5 mg/kg/d divided over 2-3 doses)
• Adult in whom pseudomonas is suspected (neutropenic/burn, e.g.): Vancomycin plus double pseudomonal coverage (ceftazidime 1-2 g IV/IM q8-12h; gentamicin, piperacillin-tazobactam 3.375 g IV q6h, ciprofloxacin 400 mg IV q8-12h, e.g.)
• Antifungal: When fungal infection is suspected
• Contraindications: History of anaphylaxis or other allergic reaction to the antibiotic
ALERT
Dose adjustments are required for renal function.
- Significant possible interactions
Aminoglycosides: Increased nephrotoxicity with enflurane, cisplatin, and possibly vancomycin; increased ototoxicity with loop diuretics; increased paralysis with neuromuscular blocking agents
Ampicillin: Increased frequency of rash with allopurinol
Second Line
• IV hydrocortisone (2)[A]
- May benefit patients who require vasopressor therapy to maintain BP
- Long-term mortality benefit not proven
• Drotrecogin alfa (Xigris) (2)[B]
- 24 ug/kg/h for 96 hours in patients with severe sepsis (APACHE score >24)
• Increases risk of bleeding
• Not recommended in children
• Polyclonal IVIG as adjuvant therapy in bacterial sepsis or septic shock (4)[B]
SURGERY
• Drainage of infected sites
• Debridement of necrotic tissues
FOLLOW-UP
PROGNOSIS
Even with optimal care, mortality is 10-50% overall; this is increased in patients with
• Neutropenia
• Diabetes
• Alcoholism
• Renal failure
• Respiratory failure
• Hypogammaglobulinemia
• Certain etiologic agents (e.g., Pseudomonas aeruginosa)
• Delay in appropriate antimicrobial therapy
• Patients at the age extremes
COMPLICATIONS
• Death
• Adult respiratory distress syndrome
• Multiorgan failure (cardiac, pulmonary, renal, hepatic)
• Disseminated intravascular coagulation
• Gastrointestinal hemorrhage
PATIENT MONITORING
• Depends on source of infection, underlying disease(s)
• Drug levels if necessary
• BUN, creatinine, electrolytes and CBCs at least twice weekly; more frequently if unstable
• In unstable patients: Invasive hemodynamic monitoring, arterial blood gas, venous gas, frequent electrolytes.
REFERENCES
1. Angus DC, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated cost of care. Crit Care Med. 2001;29:1303.
2. Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign Management Guidelines Committee. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858-873.
3. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:1644-1655.
4. Alejandria et al. Intravenous immunoglobin for treating sepsis and septic shock. Cochrane Database of Systematic Rev. 1, 2006.
5. Bochud et al. Antibiotics in sepsis. Intensive Care Med. 2001;27:14.
MISCELLANEOUS
• High-dose steroids are of no benefit.
• See also: Candidiasis; Endocarditis, infective; Listeriosis, Meningitis, bacterial; Pneumonia, bacterial; Pyelonephritis, Rocky Mountain spotted fever; Toxic shock syndrome; Tularemia
BASICS
DESCRIPTION
• Sepsis is the systemic response to infection; it is defined as systemic inflammatory response syndrome (SIRS) with documented infection.
• SIRS is an inflammatory reaction to various clinical insults (e.g., severe trauma or burn) manifested by 2 of the following
- Temperature >38C or 36C
- Heart rate >90/min
- Respiratory rate >20/min or PaCO2 32 mm Hg
- WBC count >12,000/mm3, 4,000/mm3, or >10% immature forms (bands)
• Severe sepsis: When associated with organ dysfunction or hypotension
• Septic shock: Sepsis induced hypotension (systolic BP 90 mm Hg or 40 mm Hg drop from baseline) despite adequate fluid resuscitation plus hypoperfusion abnormalities (oliguria, lactic acidosis, acute change in mental status)
• MODS: Multiple organ dysfunction syndrome
• Bacteremia: Bacteria in the blood; may have no accompanying symptoms
• Synonym(s): Septicemia; Sepsis neonatorum
ALERT
Geriatric Considerations
• Often more difficult to diagnose clinically in the elderly
• Change in mental status/behavior may be only early manifestation
Pediatric Considerations
Screen newborns for infection due to prolonged rupture of membranes (>24 hours), maternal fever, and prematurity.
Pregnancy Considerations
-Lactam antibiotics, aminoglycosides, and erythromycin are considered safe.
GENERAL PREVENTION
• Vaccination: Pneumococcal (geriatric patients, patients with certain chronic diseases), Haemophilus influenzae type B (infants, young children)
• -Globulin (for hypo- or agammaglobulinemic patients)
• Hand washing by hospital personnel, appropriate catheter care, and so forth, for hospitalized patients
EPIDEMIOLOGY
Predominant age: All ages
Incidence
• 3 cases per 1,000 population
• 2 cases per 100 patients admitted to hospital (1)
RISK FACTORS
• Positive blood cultures
• Age extremes (very old and very young)
• Impaired host (see "Associated Conditions")
• Critically ill patients
• Indwelling catheters: Intravascular, urinary, biliary
• Complicated labor and delivery: Premature and/or prolonged rupture of membranes, other complications
• Certain surgical procedures
Genetics
Single-nucleotide polymorphisms (i.e., cytokine and cytokine receptor genes) influence the risk for the development of sepsis and the risk of mortality from sepsis.
PATHOPHYSIOLOGY
In sepsis, the dysregulation of the inflammatory process is precipitated by an imbalance between pro- and anti-inflammatory mediators, resulting in widespread systemic tissue destruction and organ dysfunction.
ETIOLOGY
• Specific etiologic agents include
- Gram-positive organisms: Most commonly Staphylococcus spp., Streptococcus spp., Enterococcus spp.
- Gram-negative organisms: Most commonly Escherichia coli, Klebsiella spp., Proteus spp., Pseudomonas spp.
- Fungi: Most commonly Candida spp.
- Other agents: Anaerobes. See also "Differential Diagnosis."
• Common sources of septicemia include
- Lungs
- Urinary tract
- Intra-abdominal focus: Biliary tree, abscess, peritonitis
- Intravascular catheters
- Skin: Cellulitis, decubitus ulcer, gangrene
- Heart valves
ASSOCIATED CONDITIONS
• Immunologic disorders
- Neutropenia, HIV, hypo-/agammaglobulinemia, complement deficiency, splenectomy
• Diabetes mellitus
• Alcoholism
• Malignancy
• Cirrhosis
• Burns
• Multiple trauma
• IV drug abuse
• Malnutrition
DIAGNOSIS
SIGNS AND SYMPTOMS
• Fever
• Chills, rigors
• Myalgias
• Changes in mental status: Restlessness, agitation, confusion, delirium, lethargy, stupor, coma
• Tachycardia
• Tachypnea
• Hypotension
• Skin lesions: Erythema, petechiae, ecthyma gangrenosum, embolic lesions, purpura
• Signs and symptoms related to site of primary infection
- Respiratory tract: Cough, sputum production, dyspnea, chest pain
- Urinary tract: Dysuria, flank pain, frequency, urgency
- Intra-abdominal source: Nausea, vomiting, diarrhea, constipation, abdominal pain
- CNS: Stiff neck, headache, photophobia, focal neurologic signs
• Signs and symptoms related to end-organ failure
- Pulmonary: Cyanosis
- Renal: Oliguria, anuria
- Hepatic: Jaundice
- Cardiac: CHF
TESTS
• Antigen detection systems Counterimmunoelectrophoresis and latex agglutination tests (pneumococcus, H. influenzae type B, group B streptococcus, meningococcus)
• Gram stain of buffy coat smears occasionally useful
Lab
• Positive blood cultures (not required for diagnosis)
• Positive cultures from other sites (sputum, urine, CSF, wound)
• Gram stain of clinical specimens (sputum, urine, CSF, wound)
• Common
- Leukocytosis
- Proteinuria
- Hypoxemia
- Hyperglycemia
- Hypocalcemia
- Mild hyperbilirubinemia
• Less common (more severe cases)
- Lactic acidosis
- Leukopenia
- Azotemia
- Thrombocytopenia
- Prolonged prothrombin time
- Anemia
- Hypoglycemia
• Drugs that may alter lab results: Prior antibiotic use
Imaging
• Radiographs (e.g., chest)
• Ultrasound, CT scan, or MRI may be useful in delineating sites of infection.
Diagnostic Procedures/Surgery
• Aspiration of potentially infected body fluids (pleural, peritoneal, CSF) when appropriate
• Biopsy, drainage of potentially infected tissues (abscess, biliary tree, others) when appropriate
Pathological Findings
• Inflammation at primary site of infection
• Disseminated intravascular coagulation
• Noncardiogenic pulmonary edema
DIFFERENTIAL DIAGNOSIS
• Shock of other etiology
• Bacteremia without sepsis
• Localized infection
• SIRS
• Viral diseases (influenza, dengue and other hemorrhagic viruses, West Nile)
• Rickettsial diseases (Rocky Mountain spotted fever, endemic typhus)
• Spirochetal diseases (leptospirosis, relapsing fever [Borrelia sp.], Jarisch-Herxheimer reaction in syphilis)
• Protozoal diseases (Toxoplasma gondii, Trypanosoma cruzi, Pneumocystis carinii, Plasmodium falciparum)
• Collagen vascular diseases, vasculitides, myocardial infarction, pulmonary embolus, thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome, thyrotoxicosis, adrenal insufficiency (Addison disease)
TREATMENT
STABILIZATION
• Hospitalization
• Intensive care treatment of patients with shock, respiratory failure
GENERAL MEASURES
• ABCs
- Oxygen supplementation, monitoring
Intubation and invasive monitors if necessary for respiratory failure/hemodynamic instability
• Initial resuscitation targeted at
- CVP: 8-12 mm Hg
- MAP 65 mm Hg
- Urine output 0.5 mL/kg/h
- Central venous/mixed venous oxygen saturation 70% (2)[A]
• Identification of etiology
- Removal or drainage of septic foci
• Transfusion of RBCs, platelets, and/or fresh frozen plasma for coagulopathy
• Stress ulcer and deep venous thrombosis prophylactic measures
• Tight glucose control (3)[B]
Diet
• NPO initially
• Enteral feeds beneficial when possible however, IV alimentation is appropriate in severely malnourished patients and in patients who will be unable to receive enteral alimentation within the week.
SPECIAL THERAPY
Ventilatory support: See "Acute Respiratory Distress Syndrome (ARDS)"
IV Fluids
No evidence to support 1 type of fluid over another (colloid/crystalloid) (2)[B]
MEDICATION (DRUGS)
First Line
• Pressors
- Norepinephrine/dopamine 1st line (2)[C]
- Renal dose dopamine not recommended (2)[B]
• Antibiotic coverage immediately after cultures are obtained (1)[C]
- Should be broad-spectrum initially, with emphasis on most likely pathogen.
- After culture results are available, treatment should be organism-specific.
- Knowledge of antibiotic susceptibility patterns of local pathogens is extremely important.
• Neonatal (7 days old) sepsis: Ampicillin 300 mg/kg/d in 3 divided doses and gentamicin (Garamycin) 5 mg/kg/d in 2 divided doses
• Nonimmunocompromised child: Cefotaxime (Claforan): 200 mg/kg/d in 4 divided doses
• Adult (pseudomonas not suspected): Vancomycin plus gram-negative coverage (cefepime 1-2 g q12h or gentamicin 3-5 mg/kg/d divided over 2-3 doses)
• Adult in whom pseudomonas is suspected (neutropenic/burn, e.g.): Vancomycin plus double pseudomonal coverage (ceftazidime 1-2 g IV/IM q8-12h; gentamicin, piperacillin-tazobactam 3.375 g IV q6h, ciprofloxacin 400 mg IV q8-12h, e.g.)
• Antifungal: When fungal infection is suspected
• Contraindications: History of anaphylaxis or other allergic reaction to the antibiotic
ALERT
Dose adjustments are required for renal function.
- Significant possible interactions
Aminoglycosides: Increased nephrotoxicity with enflurane, cisplatin, and possibly vancomycin; increased ototoxicity with loop diuretics; increased paralysis with neuromuscular blocking agents
Ampicillin: Increased frequency of rash with allopurinol
Second Line
• IV hydrocortisone (2)[A]
- May benefit patients who require vasopressor therapy to maintain BP
- Long-term mortality benefit not proven
• Drotrecogin alfa (Xigris) (2)[B]
- 24 ug/kg/h for 96 hours in patients with severe sepsis (APACHE score >24)
• Increases risk of bleeding
• Not recommended in children
• Polyclonal IVIG as adjuvant therapy in bacterial sepsis or septic shock (4)[B]
SURGERY
• Drainage of infected sites
• Debridement of necrotic tissues
FOLLOW-UP
PROGNOSIS
Even with optimal care, mortality is 10-50% overall; this is increased in patients with
• Neutropenia
• Diabetes
• Alcoholism
• Renal failure
• Respiratory failure
• Hypogammaglobulinemia
• Certain etiologic agents (e.g., Pseudomonas aeruginosa)
• Delay in appropriate antimicrobial therapy
• Patients at the age extremes
COMPLICATIONS
• Death
• Adult respiratory distress syndrome
• Multiorgan failure (cardiac, pulmonary, renal, hepatic)
• Disseminated intravascular coagulation
• Gastrointestinal hemorrhage
PATIENT MONITORING
• Depends on source of infection, underlying disease(s)
• Drug levels if necessary
• BUN, creatinine, electrolytes and CBCs at least twice weekly; more frequently if unstable
• In unstable patients: Invasive hemodynamic monitoring, arterial blood gas, venous gas, frequent electrolytes.
REFERENCES
1. Angus DC, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated cost of care. Crit Care Med. 2001;29:1303.
2. Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign Management Guidelines Committee. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858-873.
3. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:1644-1655.
4. Alejandria et al. Intravenous immunoglobin for treating sepsis and septic shock. Cochrane Database of Systematic Rev. 1, 2006.
5. Bochud et al. Antibiotics in sepsis. Intensive Care Med. 2001;27:14.
MISCELLANEOUS
• High-dose steroids are of no benefit.
• See also: Candidiasis; Endocarditis, infective; Listeriosis, Meningitis, bacterial; Pneumonia, bacterial; Pyelonephritis, Rocky Mountain spotted fever; Toxic shock syndrome; Tularemia
SEIZURES, FEBRILE
SEIZURES, FEBRILE - Malgorzata E. Klonowska, MD; Wyley Hall, MD
BASICS
DESCRIPTION
• A seizure that occurs in children between 6 months and 5 years of age, in association with fever and in the absence of CNS infection or previous diagnosis of epilepsy
• Simple febrile seizure (FS) (~80%)
- Duration 15 minutes
- Generalized seizure with no focal features
- No recurrence in 24 hours
• Complex FS (~20%)
- Duration >15 minutes
- Focal features
- >1 seizure in 24 hours
EPIDEMIOLOGY
• FS are the most common seizures in children.
• ~3% of children affected (1,2)[B]
• Average age of onset is 18-22 months, usually before the age of 3 years.
• Males have a slightly higher incidence.
RISK FACTORS
• For 1st FS
- Family history of FS
- Neurodevelopmental abnormality
- >50% of children will have no identifiable risk factors
• For recurrent FS
- Onset at age 18 months
- Family history of FS
- Temperature 40C (104F) with prior FS
• For subsequent epilepsy after FS
- Family history of epilepsy
- Complex FS
- Neurodevelopmental abnormality
Genetics
• Complex polygenic basis
• A history of FS in immediate family members is present in 10-40% of cases.
• Monozygotic twins have a much higher concordance rate than dizygotic twins, supporting a genetic contribution.
• Susceptibility of FS has been linked to several genetic loci in different families.
• The syndrome of generalized epilepsy with FS plus (GEFS+) is characterized by heterogeneous epilepsy phenotypes with complex inheritance. (3)
• The most common phenotype is a continuation of FS >6 years of age associated with afebrile tonic-clonic seizures as well as other seizure types.
• Sodium channel and GABAA receptor genes have been associated with FS and GEFS+. (3)
PATHOPHYSIOLOGY
The underlying pathophysiology is unknown.
ASSOCIATED CONDITIONS
• Any viral or bacterial infections can provoke FS.
• Human herpesvirus-6 and herpes simplex virus have been associated with increased risk.
• The risk of FS is increased on the day of administration of diphtheria, tetanus toxoid, and whole-cell pertussis vaccine and 8-14 days after measles, mumps, rubella vaccine, but these are not associated with any long-term adverse effects.
DIAGNOSIS
PRE HOSPITAL
FS may be the 1st sign of illness.
SIGNS AND SYMPTOMS
• Temperature >38C (100.5F), usually 39C (102.2F), average 40C (104F)
• Pyrexia may follow an a FS, although this will rarely exceed 38C (100.5F)
History
• Description of seizure, presence of fever, character of illness
• Lethargy, irritability, decreased feeding, vomiting
• Recent treatment with antibiotics (meningitis can be masked if partially treated)
• Recent immunization
• Patient and family history of seizures
• Evaluate for other causes of seizures, such as trauma or toxin exposure
Physical Exam
• Usually normal neurologic exam
• Further workup indicated if evidence of meningitis (nuchal rigidity, drowsiness, bulging fontanelle, papilledema, petechiae)
• Focal neurologic signs
• Postictal (Todd) paralysis may be observed after a focal seizure.
• Stigmata of a neurocutaneous or metabolic disorder
TESTS
• The most urgent diagnostic decision is whether to perform a lumbar puncture (LP)
- The incidence of meningitis in children with FS is no higher than in febrile children without seizure.
- The earliest sign of meningitis (in 13-16% of children) can be a seizure and fever.
• LP in 12-month-olds with FS should be strongly considered, in 12-18-month-olds with FS should be considered, and in >18-month-olds is not routinely warranted but recommended in the presence of meningismus or other clinical suspicion of meningitis. (4)
• Cerebrospinal fluid is more likely to be abnormal in children with FS if
- Complex FS
- Prolonged postictal state
- Initial seizure >3 years of age
• A recognized source of fever (e.g., otitis media) does not exclude the presence of meningitis. (4)
• In practice, the decision to perform LP should be tailored to each individual child's presentation.
ALERT
Pediatric Considerations
In infants 2 years, clinical signs and symptoms of meningitis may be minimal or absent.
Lab
• Routine measurement of serum electrolytes, calcium, phosphorous, magnesium, CBC, and serum glucose are low-yield and should not be routinely performed unless clinically indicated. (2,4)
• Serum glucose should be obtained if there is a prolonged postictal state or recurrent seizures.
• Laboratory testing should be directed at identifying source of fever.
Imaging
• Routine neuroimaging is not indicated in the evaluation of simple or complex FS. (4,5)
• Neuroimaging should be performed if the physical examination points to a possible structural lesion (e.g., micro/macrocephaly, focal neurologic signs, symptoms of increased intracranial pressure).
Diagnostic Procedures/Surgery
• Electroencephalography (EEG) is not recommended as part of evaluation of a neurologically healthy child with a 1st simple FS. (4)
• EEG is recommended in children with complex FS who have developmental delay or abnormal neurologic signs and symptoms.
• EEG does not predict the recurrence of FS or the development of epilepsy. (4)
DIFFERENTIAL DIAGNOSIS
• Rigors
• Syncope
• Febrile delirium (acute and transient confusional state associated with high fever)
• Breath-holding spell
TREATMENT
PRE-HOSPITAL
• During seizure, protect child from injury. Place child in lateral position to maintain airway and allow drainage of secretions/vomitus if present.
• Observe seizure closely.
STABILIZATION
• Assessment of airway, breathing, and circulatory status
• Seizures >5 minutes duration should be treated, usually with a benzodiazepine as 1st-line therapy (e.g., lorazepam [0.05-0.1 mg/kg]), which may be repeated if seizure persists; then proceed to fosphenytoin 15-20 mg/kg IV if needed.
GENERAL MEASURES
• Identify whether an underlying illness exists.
• Evaluate source of fever (e.g., meningitis, otitis media, upper or lower respiratory tract infection, urinary tract infection, gastroenteritis, post-immunization). (5)
• Supportive care
Activity
No activity restrictions are necessary
MEDICATION (DRUGS)
• Although anticonvulsants may be effective in reducing FS, the potential side effects outweigh the benefits. (1)
• Therefore, anticonvulsant therapy is not generally recommended for children with FS. (1)
• In situations of parental anxiety or frequent or prolonged FS, diazepam may be effective in preventing recurrence, but appropriate education and emotional support is more beneficial. (1)
• Diazepam may be administered as
- Oral diazepam intermittently during febrile illness (e.g., 0.3 mg/kg q8h)
- Diazepam rectal gel (Diastat) 0.5 mg/kg acutely for seizures of >5 minutes in duration
• Note: Diazepam can lead to significant lethargy and possibly mask signs of a serious illness such as meningitis.
• Antipyretics may be given for comfort, but have not been shown to reduce the risk of FS. (1)
FOLLOW-UP
PROGNOSIS
• Excellent prognosis
• Extremely low morbidity and mortality rate
• There is no known risk of neurologic sequelae including neurologic deficits and intellectual impairment. (1)
• Children with FS are at risk for developing recurrent FS.
• The major factor increasing recurrence rate is younger age at time of 1st seizure.
• Risk of developing further FS after 1st FS at
- 1 year of age is ~50%(1)
- >1 year of age is ~30%(1)
- Risk of at least 1 additional recurrence after 2nd FS is 50%
• ~50-75% of recurrence is within 1 year of initial seizure, ~90% within 2 years
• Risk of epilepsy after a simple FS is slightly greater than the 1% risk of FS in the general population (1)
- Risk of epilepsy after multiple FS with 1st seizure at 1 year of age is 2.4% (1)
- Risk of epilepsy after a complex FS has been reported to be 4.1-6%. (2)[B]
- Factors that increase risk of epilepsy include neurodevelopmental abnormality, increased number of characteristics of complex partial seizures, and family history of epilepsy.
COMPLICATIONS
• It remains controversial whether FS cause the later development of mesial temporal sclerosis.
• Retrospective studies show an association between temporal lobe epilepsy and FS, but prospective, controlled, population-based studies failed to confirm this association.
• The association may represent an inherent susceptibility in some children to both FS and epilepsy resulting from complex interactions between several genetic and environmental factors.
PATIENT MONITORING
Depends on clinical status of patient
REFERENCES
1. American Academy of Pediatrics, Provisional Committee on Quality Improvement and Subcommittee on Febrile Seizures. Practice parameter: Long-term treatment of the child with simple febrile seizures. Pediatrics. 1999;103(6):1307-1309.
2. Baumer JH. Evidence based guideline for post-seizure management in children presenting acutely to secondary care. Arch Dis Child. 2004;89:278-280.
3. Scheffer IE, et al. Neonatal epilepsy syndromes and generalized epilepsy with febrile seizure plus (GEFS+). Epilepsia. 2005;46(10):41-47.
4. American Academy of Pediatrics, Provisional Committee on Quality Improvement and Subcommittee on Febrile Seizure. Practice parameter: the neurodiagnostic evaluation of the child with a first simple febrile seizure. Pediatrics. 1996;97(5):769-772.
5. DiMario FJ, Jr. Children presenting with complex febrile seizures do not routinely need computer tomography scanning in the emergency department. Pediatrics. 2006;117:528-530.
BASICS
DESCRIPTION
• A seizure that occurs in children between 6 months and 5 years of age, in association with fever and in the absence of CNS infection or previous diagnosis of epilepsy
• Simple febrile seizure (FS) (~80%)
- Duration 15 minutes
- Generalized seizure with no focal features
- No recurrence in 24 hours
• Complex FS (~20%)
- Duration >15 minutes
- Focal features
- >1 seizure in 24 hours
EPIDEMIOLOGY
• FS are the most common seizures in children.
• ~3% of children affected (1,2)[B]
• Average age of onset is 18-22 months, usually before the age of 3 years.
• Males have a slightly higher incidence.
RISK FACTORS
• For 1st FS
- Family history of FS
- Neurodevelopmental abnormality
- >50% of children will have no identifiable risk factors
• For recurrent FS
- Onset at age 18 months
- Family history of FS
- Temperature 40C (104F) with prior FS
• For subsequent epilepsy after FS
- Family history of epilepsy
- Complex FS
- Neurodevelopmental abnormality
Genetics
• Complex polygenic basis
• A history of FS in immediate family members is present in 10-40% of cases.
• Monozygotic twins have a much higher concordance rate than dizygotic twins, supporting a genetic contribution.
• Susceptibility of FS has been linked to several genetic loci in different families.
• The syndrome of generalized epilepsy with FS plus (GEFS+) is characterized by heterogeneous epilepsy phenotypes with complex inheritance. (3)
• The most common phenotype is a continuation of FS >6 years of age associated with afebrile tonic-clonic seizures as well as other seizure types.
• Sodium channel and GABAA receptor genes have been associated with FS and GEFS+. (3)
PATHOPHYSIOLOGY
The underlying pathophysiology is unknown.
ASSOCIATED CONDITIONS
• Any viral or bacterial infections can provoke FS.
• Human herpesvirus-6 and herpes simplex virus have been associated with increased risk.
• The risk of FS is increased on the day of administration of diphtheria, tetanus toxoid, and whole-cell pertussis vaccine and 8-14 days after measles, mumps, rubella vaccine, but these are not associated with any long-term adverse effects.
DIAGNOSIS
PRE HOSPITAL
FS may be the 1st sign of illness.
SIGNS AND SYMPTOMS
• Temperature >38C (100.5F), usually 39C (102.2F), average 40C (104F)
• Pyrexia may follow an a FS, although this will rarely exceed 38C (100.5F)
History
• Description of seizure, presence of fever, character of illness
• Lethargy, irritability, decreased feeding, vomiting
• Recent treatment with antibiotics (meningitis can be masked if partially treated)
• Recent immunization
• Patient and family history of seizures
• Evaluate for other causes of seizures, such as trauma or toxin exposure
Physical Exam
• Usually normal neurologic exam
• Further workup indicated if evidence of meningitis (nuchal rigidity, drowsiness, bulging fontanelle, papilledema, petechiae)
• Focal neurologic signs
• Postictal (Todd) paralysis may be observed after a focal seizure.
• Stigmata of a neurocutaneous or metabolic disorder
TESTS
• The most urgent diagnostic decision is whether to perform a lumbar puncture (LP)
- The incidence of meningitis in children with FS is no higher than in febrile children without seizure.
- The earliest sign of meningitis (in 13-16% of children) can be a seizure and fever.
• LP in 12-month-olds with FS should be strongly considered, in 12-18-month-olds with FS should be considered, and in >18-month-olds is not routinely warranted but recommended in the presence of meningismus or other clinical suspicion of meningitis. (4)
• Cerebrospinal fluid is more likely to be abnormal in children with FS if
- Complex FS
- Prolonged postictal state
- Initial seizure >3 years of age
• A recognized source of fever (e.g., otitis media) does not exclude the presence of meningitis. (4)
• In practice, the decision to perform LP should be tailored to each individual child's presentation.
ALERT
Pediatric Considerations
In infants 2 years, clinical signs and symptoms of meningitis may be minimal or absent.
Lab
• Routine measurement of serum electrolytes, calcium, phosphorous, magnesium, CBC, and serum glucose are low-yield and should not be routinely performed unless clinically indicated. (2,4)
• Serum glucose should be obtained if there is a prolonged postictal state or recurrent seizures.
• Laboratory testing should be directed at identifying source of fever.
Imaging
• Routine neuroimaging is not indicated in the evaluation of simple or complex FS. (4,5)
• Neuroimaging should be performed if the physical examination points to a possible structural lesion (e.g., micro/macrocephaly, focal neurologic signs, symptoms of increased intracranial pressure).
Diagnostic Procedures/Surgery
• Electroencephalography (EEG) is not recommended as part of evaluation of a neurologically healthy child with a 1st simple FS. (4)
• EEG is recommended in children with complex FS who have developmental delay or abnormal neurologic signs and symptoms.
• EEG does not predict the recurrence of FS or the development of epilepsy. (4)
DIFFERENTIAL DIAGNOSIS
• Rigors
• Syncope
• Febrile delirium (acute and transient confusional state associated with high fever)
• Breath-holding spell
TREATMENT
PRE-HOSPITAL
• During seizure, protect child from injury. Place child in lateral position to maintain airway and allow drainage of secretions/vomitus if present.
• Observe seizure closely.
STABILIZATION
• Assessment of airway, breathing, and circulatory status
• Seizures >5 minutes duration should be treated, usually with a benzodiazepine as 1st-line therapy (e.g., lorazepam [0.05-0.1 mg/kg]), which may be repeated if seizure persists; then proceed to fosphenytoin 15-20 mg/kg IV if needed.
GENERAL MEASURES
• Identify whether an underlying illness exists.
• Evaluate source of fever (e.g., meningitis, otitis media, upper or lower respiratory tract infection, urinary tract infection, gastroenteritis, post-immunization). (5)
• Supportive care
Activity
No activity restrictions are necessary
MEDICATION (DRUGS)
• Although anticonvulsants may be effective in reducing FS, the potential side effects outweigh the benefits. (1)
• Therefore, anticonvulsant therapy is not generally recommended for children with FS. (1)
• In situations of parental anxiety or frequent or prolonged FS, diazepam may be effective in preventing recurrence, but appropriate education and emotional support is more beneficial. (1)
• Diazepam may be administered as
- Oral diazepam intermittently during febrile illness (e.g., 0.3 mg/kg q8h)
- Diazepam rectal gel (Diastat) 0.5 mg/kg acutely for seizures of >5 minutes in duration
• Note: Diazepam can lead to significant lethargy and possibly mask signs of a serious illness such as meningitis.
• Antipyretics may be given for comfort, but have not been shown to reduce the risk of FS. (1)
FOLLOW-UP
PROGNOSIS
• Excellent prognosis
• Extremely low morbidity and mortality rate
• There is no known risk of neurologic sequelae including neurologic deficits and intellectual impairment. (1)
• Children with FS are at risk for developing recurrent FS.
• The major factor increasing recurrence rate is younger age at time of 1st seizure.
• Risk of developing further FS after 1st FS at
- 1 year of age is ~50%(1)
- >1 year of age is ~30%(1)
- Risk of at least 1 additional recurrence after 2nd FS is 50%
• ~50-75% of recurrence is within 1 year of initial seizure, ~90% within 2 years
• Risk of epilepsy after a simple FS is slightly greater than the 1% risk of FS in the general population (1)
- Risk of epilepsy after multiple FS with 1st seizure at 1 year of age is 2.4% (1)
- Risk of epilepsy after a complex FS has been reported to be 4.1-6%. (2)[B]
- Factors that increase risk of epilepsy include neurodevelopmental abnormality, increased number of characteristics of complex partial seizures, and family history of epilepsy.
COMPLICATIONS
• It remains controversial whether FS cause the later development of mesial temporal sclerosis.
• Retrospective studies show an association between temporal lobe epilepsy and FS, but prospective, controlled, population-based studies failed to confirm this association.
• The association may represent an inherent susceptibility in some children to both FS and epilepsy resulting from complex interactions between several genetic and environmental factors.
PATIENT MONITORING
Depends on clinical status of patient
REFERENCES
1. American Academy of Pediatrics, Provisional Committee on Quality Improvement and Subcommittee on Febrile Seizures. Practice parameter: Long-term treatment of the child with simple febrile seizures. Pediatrics. 1999;103(6):1307-1309.
2. Baumer JH. Evidence based guideline for post-seizure management in children presenting acutely to secondary care. Arch Dis Child. 2004;89:278-280.
3. Scheffer IE, et al. Neonatal epilepsy syndromes and generalized epilepsy with febrile seizure plus (GEFS+). Epilepsia. 2005;46(10):41-47.
4. American Academy of Pediatrics, Provisional Committee on Quality Improvement and Subcommittee on Febrile Seizure. Practice parameter: the neurodiagnostic evaluation of the child with a first simple febrile seizure. Pediatrics. 1996;97(5):769-772.
5. DiMario FJ, Jr. Children presenting with complex febrile seizures do not routinely need computer tomography scanning in the emergency department. Pediatrics. 2006;117:528-530.
SEIZURE DISORDERS
SEIZURE DISORDERS - Shawn H. Blanchard, MD; William L. Toffler, MD
BASICS
DESCRIPTION
A seizure is a sudden change in cortical electrical activity, manifested through motor, sensory, or behavioral changes, with or without an alteration in consciousness.
• System(s) Affected: Nervous
• Synonym(s): Convulsions; Epilepsy; Fits; Spells; Attacks
ALERT
Geriatric Considerations
Fractures from falls are more common in the osteopenic age range.
Pediatric Considerations
• Breast-feeding is not contraindicated in mothers taking anticonvulsant medication; however, drug levels can be measured if sedation occurs in the infant.
• Pharmaceutical labeling is 1C or 1D, and consideration toward consultation should be entertained.
Pregnancy Considerations
• Serum levels of anticonvulsants may decline; frequent monitoring recommended
• 2-fold increased risk of congenital malformation in mothers taking anticonvulsant medications
• All anticonvulsants recommend against use both during pregnancy and while nursing
GENERAL PREVENTION
Maintain adequate epileptic drug therapy; continue efforts at insuring compliance and/or access to medication.
EPIDEMIOLOGY
• Predominant age: Pediatric and geriatric populations most commonly present with new-onset seizure disorder. Drug and or drug withdrawal seizures should be strongly considered in the adult population.
• Predominant sex: Male = Female
Incidence
In the US
• 181,000 people with Ist seizure per year
• 45,000 new cases 15 years of age per year
Prevalence
In the US
• 4 million people have had 1 or more seizures; 2.5 million have a seizure disorder.
• ~600,000 people >65 years of age have a seizure disorder.
• 33% >75 years of age have had at least 1 lifetime seizure.
RISK FACTORS
• Susceptibility to seizures determined by a complex interplay between genetic factors and acquired brain disorders
• Children delivered breech have a prevalence rate of 3.8% compared with 2.2% in children delivered vertex.
Genetics
• Genetically predisposed with variable penetrance
• Family history increases risk 3-fold.
• Much will be understood concerning genetics and seizure disorder in the near future.
ETIOLOGY
• Brain tumor
• Cerebral hypoxia (breath holding, carbon monoxide poisoning, anesthesia)
• Cerebrovascular accident (infarct or hemorrhage)
• Convulsive or toxic agents (lead, alcohol, picrotoxin, strychnine)
• Drug overdose/withdrawal
• Eclampsia
• Exogenous factors (sound, light, cutaneous stimulation)
• Fever (see topic on Febrile seizures)
• Head injury
• Heat stroke
• Infection
• Metabolic disturbances
• Withdrawal from, or hereditary intolerance of, alcohol
ASSOCIATED CONDITIONS
• Infections
• Tumors
• Drug abuse
• Alcohol and drug withdrawal
• Metabolic disorders
• Trauma
DIAGNOSIS
SIGNS AND SYMPTOMS
• General
- Fever: Indicative of infectious etiology
- Focal neurologic finding: May indicate tumor or localized injury to the brain
- Papilledema: Suggestive of increased intracranial pressure
- Hemorrhagic eye grounds: Suggests underlying hypertension
- Meningismus: May be present with meningitis
- Headache: Sometimes associated with infectious or hemorrhagic causes of seizures
• Generalized seizures
- Absence: Loss of consciousness or posture
- Myoclonic: Repetitive muscle contractions
- Tonic-clonic: Sustained contraction followed by rhythmic contractions of all four extremities
• Partial seizures
- Simple: Focal seizures without alteration of awareness/consciousness
- Complex: Focal seizures with alteration of awareness/consciousness
• Febrile seizures (see separate topic)
- Occurs between 3 months and 5 years of age
- Fever without evidence of any other defined cause for seizures
- If febrile seizures occur in the 1st year, the recurrence rate is 51%.
- If febrile seizures occur in the 2nd year, the recurrence rate is 25%.
- 88% of all recurrences of febrile seizures occur in the 1st 2 years.
- The earlier the age of onset, the more likely repetitive febrile seizures will occur.
- Recurrent febrile seizures probably do not increase the risk of epilepsy.
• Status epilepticus (see separate topic)
- Repetitive generalized seizures without return to consciousness between seizures
- Considered a neurological emergency
TESTS
• ECG: A negative ECG does not rule out a seizure disorder. Sleep deprivation is helpful prior to ECG to identify positive spike wave formations.
• Video ECG monitoring is helpful in differentiating psychomotor nonepileptiform seizures.
Lab
• Serum tests: Glucose, sodium, potassium, calcium, phosphorus, magnesium, BUN, ammonia
• Anticonvulsant levels: Inadequate level of anticonvulsant medication is the most common cause of recurrent seizures in children and many adults.
• Drug and toxic screens, include alcohol
• CBC helpful in evaluating infection
• Drugs that may alter lab results
- Anticonvulsant therapy may dramatically affect the ECG results.
- Levels of anticonvulsants may be altered by a variety of common medications such as erythromycin, sulfonamides, warfarin, and cimetidine, as well as alcohol.
• Disorders that may alter lab results: Pregnancy decreases serum concentration. Frequent monitoring and dosage adjustments are necessary.
Imaging
• MRI of brain: Superior in evaluation of the temporal lobes
• CT scan of brain: Indicated routinely in workup of tonic-clonic seizures
Diagnostic Procedures/Surgery
Stereotactic investigation may prove beneficial for the 10% of seizures recalcitrant to pharmaceutical therapy.
Pathological Findings
MRI may identify a lesion responsible (i.e., a nidus) for seizure activity.
DIFFERENTIAL DIAGNOSIS
• Infancy (0-2)
- Perinatal hypoxia
- Birth injury
- Metabolichypoglycemia, hypocalcemia, hypomagnesemia, vitamin B6 deficiency, phenylketonuria
- Acute infection
• Childhood (2-10)
- Febrile seizure
- Idiopathic
- Acute infection
- Trauma
• Adolescent (10-18)
- Idiopathic
- Trauma
- Drug and alcohol withdrawal
- Arteriovenous malformations
- Conversion disorderpseudoseizure
• Early adulthood (18-25)
- Idiopathic
- Drug and alcohol withdrawal
- Trauma
- Conversion disorderpseudoseizure
• Middle age (25-60)
- Drug and alcohol withdrawal
- Trauma
- Tumor
- Vascular disease
- Conversion disorderpseudoseizure
• Late adulthood (>60)
- Vascular disease
- Tumor
- Degenerative disease
- Metabolic: Hypoglycemia, uremia, hepatic failure, electrolyte abnormality
TREATMENT
STABILIZATION
Outpatient therapy is usually sufficient except for status epilepticus.
GENERAL MEASURES
• Protect the patient's airway.
• If possible, protect the patient from physical harm.
Diet
Regular
Activity
• Individuals with uncontrolled seizures should avoid heights and swimming.
• State driving laws can be located at www.epilepsyfoundation.org
MEDICATION (DRUGS)
First Line
Selection of medications from following seizure groups, with attention toward potential side effects, is preferred, as is monotherapy whenever possible. Systemic reviews found insufficient evidence on which to base a choice among these drugs in terms of seizure control.
• Generalized seizures: Tonic-clonic
- Phenytoin (Dilantin): 200-400 mg/d in 1-3 doses; therapeutic range 10-20 ug/mL
- Carbamazepine (Tegretol) 100-200 mg/d in 1-2 doses; therapeutic range: 4-12 ug/mL
- Valproic acid (Depakene): 750-3,000 mg/d in 1-3 doses; begin at 15 mg/kg/d; therapeutic range 50-150 ug/mL
• Generalized seizuresabsence
- Ethosuximide (Zarontin): 250-1,500 mg/d in 1-2 doses; therapeutic range 40-100 ug/mL
- Valproic acid (see information provided previously)
• Partial seizures
- Phenytoin (Dilantin)
- Carbamazepine (Tegretol)
- Phenobarbital
There is evidence to suggest long-term use of phenobarbitol may impair cognative ability. (1)[C]
• Contraindications: Refer to the manufacturer's profile of each drug.
• Precautions: Doses should be based on individual's response and drug levels where available.
• Significant possible interactions: Refer to the manufacturer's profile of each drug.
Second Line
• Felbamate (Felbatol): 1,200 mg/d in 3-4 divided doses. max 3,600 mg/d
• Gabapentin (Neurontin): 300 mg at bedtime, then 2-3 divided doses, max. 2,400-3,600 mg/d
• Lamotrigine (Lamictal): 25-50 mg/d. Adjust in 100-mg increments every 1-2 weeks to 300- 500 mg/d in 2 divided doses.
• Levetiracetam (Kepra) 500 mg b.i.d. with a max. of 3000 mg/d
• Methsuximide (Celontin): 300 mg/d for 1st week, increase 300 mg/3 weeks, max. 1,200 mg/d
• Oxcarbazepine (Trileptal): 300 mg b.i.d., increase 300 mg/3 days; maintenance 1,200 mg/d
• Pregabalin (Lyrica) 150-600 mg/d in divided doses
• Primidone (Mysoline): 100-125 mg at bedtime adjust to max. 2,000 mg/d in 2 doses
• Tiagabine (Gabitril): 4 mg/d, adjust weekly to max. 56 mg/d
• Topiramate (Topamax): 50 mg/d, adjust weekly to effective 400 mg/d in 2 doses, max. 1,600 mg/d
• Zonisamide (Zonegran) 100 mg/d for 2 weeks, increase 100 mg/d each 2 weeks to a max. of 400 mg/d
SURGERY
Many academic centers are finding success with stereotactic surgery for seizures that fail traditional therapy.
FOLLOW-UP
PROGNOSIS
• Dependent on type of seizure disorder
• Seizure activity may become quiescent.
- After a seizurefree 2-year period, withdrawal of therapy may be considered.
- 33% relapse rate should be expected in the following 3 years.
COMPLICATIONS
Drug toxicity
PATIENT MONITORING
• Regular monitoring of anticonvulsant levels and seizure frequency
• CBC as indicated
• Monitor medication side effects and adverse reactions.
REFERENCES
1. Marson A, Ramaratnam S. Epilepsy Clin Evid Concise. 2005;13:362-364.
2. Chang BS, Lowenstein DH. Epilepsy. N Engl J Med. 2003;349:1257-1266.
3. Annegers JF. The epidemiology of epilepsy. In: Wyllie E, ed. The Treatment of Epilepsy: Principles and Practice. 3rd ed. Philadelphia, PA: Lippincott Williams Wilkins; 2001:131-138.
4. Mengel MB, Schwiebert LB, eds. Ambulatory Medicine: Primary Care Families. 4th ed. New York, NY: McGraw-Hill; 2004.
5. Goldstein LH. Assessment of patients with psychogenic non-epileptiform seizures. J Neurol Neurosurg Psychiatry. 2004;75:667-668.
MISCELLANEOUS
• See also: Seizures, Febrile; Status epilepticus
• Other notes: The International League Against Epilepsy (ILAE) is currently making progress in a new 5-axis classification system for seizure disorder, which will include genetics, characterization, and disability for seizure disorder syndromes.
BASICS
DESCRIPTION
A seizure is a sudden change in cortical electrical activity, manifested through motor, sensory, or behavioral changes, with or without an alteration in consciousness.
• System(s) Affected: Nervous
• Synonym(s): Convulsions; Epilepsy; Fits; Spells; Attacks
ALERT
Geriatric Considerations
Fractures from falls are more common in the osteopenic age range.
Pediatric Considerations
• Breast-feeding is not contraindicated in mothers taking anticonvulsant medication; however, drug levels can be measured if sedation occurs in the infant.
• Pharmaceutical labeling is 1C or 1D, and consideration toward consultation should be entertained.
Pregnancy Considerations
• Serum levels of anticonvulsants may decline; frequent monitoring recommended
• 2-fold increased risk of congenital malformation in mothers taking anticonvulsant medications
• All anticonvulsants recommend against use both during pregnancy and while nursing
GENERAL PREVENTION
Maintain adequate epileptic drug therapy; continue efforts at insuring compliance and/or access to medication.
EPIDEMIOLOGY
• Predominant age: Pediatric and geriatric populations most commonly present with new-onset seizure disorder. Drug and or drug withdrawal seizures should be strongly considered in the adult population.
• Predominant sex: Male = Female
Incidence
In the US
• 181,000 people with Ist seizure per year
• 45,000 new cases 15 years of age per year
Prevalence
In the US
• 4 million people have had 1 or more seizures; 2.5 million have a seizure disorder.
• ~600,000 people >65 years of age have a seizure disorder.
• 33% >75 years of age have had at least 1 lifetime seizure.
RISK FACTORS
• Susceptibility to seizures determined by a complex interplay between genetic factors and acquired brain disorders
• Children delivered breech have a prevalence rate of 3.8% compared with 2.2% in children delivered vertex.
Genetics
• Genetically predisposed with variable penetrance
• Family history increases risk 3-fold.
• Much will be understood concerning genetics and seizure disorder in the near future.
ETIOLOGY
• Brain tumor
• Cerebral hypoxia (breath holding, carbon monoxide poisoning, anesthesia)
• Cerebrovascular accident (infarct or hemorrhage)
• Convulsive or toxic agents (lead, alcohol, picrotoxin, strychnine)
• Drug overdose/withdrawal
• Eclampsia
• Exogenous factors (sound, light, cutaneous stimulation)
• Fever (see topic on Febrile seizures)
• Head injury
• Heat stroke
• Infection
• Metabolic disturbances
• Withdrawal from, or hereditary intolerance of, alcohol
ASSOCIATED CONDITIONS
• Infections
• Tumors
• Drug abuse
• Alcohol and drug withdrawal
• Metabolic disorders
• Trauma
DIAGNOSIS
SIGNS AND SYMPTOMS
• General
- Fever: Indicative of infectious etiology
- Focal neurologic finding: May indicate tumor or localized injury to the brain
- Papilledema: Suggestive of increased intracranial pressure
- Hemorrhagic eye grounds: Suggests underlying hypertension
- Meningismus: May be present with meningitis
- Headache: Sometimes associated with infectious or hemorrhagic causes of seizures
• Generalized seizures
- Absence: Loss of consciousness or posture
- Myoclonic: Repetitive muscle contractions
- Tonic-clonic: Sustained contraction followed by rhythmic contractions of all four extremities
• Partial seizures
- Simple: Focal seizures without alteration of awareness/consciousness
- Complex: Focal seizures with alteration of awareness/consciousness
• Febrile seizures (see separate topic)
- Occurs between 3 months and 5 years of age
- Fever without evidence of any other defined cause for seizures
- If febrile seizures occur in the 1st year, the recurrence rate is 51%.
- If febrile seizures occur in the 2nd year, the recurrence rate is 25%.
- 88% of all recurrences of febrile seizures occur in the 1st 2 years.
- The earlier the age of onset, the more likely repetitive febrile seizures will occur.
- Recurrent febrile seizures probably do not increase the risk of epilepsy.
• Status epilepticus (see separate topic)
- Repetitive generalized seizures without return to consciousness between seizures
- Considered a neurological emergency
TESTS
• ECG: A negative ECG does not rule out a seizure disorder. Sleep deprivation is helpful prior to ECG to identify positive spike wave formations.
• Video ECG monitoring is helpful in differentiating psychomotor nonepileptiform seizures.
Lab
• Serum tests: Glucose, sodium, potassium, calcium, phosphorus, magnesium, BUN, ammonia
• Anticonvulsant levels: Inadequate level of anticonvulsant medication is the most common cause of recurrent seizures in children and many adults.
• Drug and toxic screens, include alcohol
• CBC helpful in evaluating infection
• Drugs that may alter lab results
- Anticonvulsant therapy may dramatically affect the ECG results.
- Levels of anticonvulsants may be altered by a variety of common medications such as erythromycin, sulfonamides, warfarin, and cimetidine, as well as alcohol.
• Disorders that may alter lab results: Pregnancy decreases serum concentration. Frequent monitoring and dosage adjustments are necessary.
Imaging
• MRI of brain: Superior in evaluation of the temporal lobes
• CT scan of brain: Indicated routinely in workup of tonic-clonic seizures
Diagnostic Procedures/Surgery
Stereotactic investigation may prove beneficial for the 10% of seizures recalcitrant to pharmaceutical therapy.
Pathological Findings
MRI may identify a lesion responsible (i.e., a nidus) for seizure activity.
DIFFERENTIAL DIAGNOSIS
• Infancy (0-2)
- Perinatal hypoxia
- Birth injury
- Metabolichypoglycemia, hypocalcemia, hypomagnesemia, vitamin B6 deficiency, phenylketonuria
- Acute infection
• Childhood (2-10)
- Febrile seizure
- Idiopathic
- Acute infection
- Trauma
• Adolescent (10-18)
- Idiopathic
- Trauma
- Drug and alcohol withdrawal
- Arteriovenous malformations
- Conversion disorderpseudoseizure
• Early adulthood (18-25)
- Idiopathic
- Drug and alcohol withdrawal
- Trauma
- Conversion disorderpseudoseizure
• Middle age (25-60)
- Drug and alcohol withdrawal
- Trauma
- Tumor
- Vascular disease
- Conversion disorderpseudoseizure
• Late adulthood (>60)
- Vascular disease
- Tumor
- Degenerative disease
- Metabolic: Hypoglycemia, uremia, hepatic failure, electrolyte abnormality
TREATMENT
STABILIZATION
Outpatient therapy is usually sufficient except for status epilepticus.
GENERAL MEASURES
• Protect the patient's airway.
• If possible, protect the patient from physical harm.
Diet
Regular
Activity
• Individuals with uncontrolled seizures should avoid heights and swimming.
• State driving laws can be located at www.epilepsyfoundation.org
MEDICATION (DRUGS)
First Line
Selection of medications from following seizure groups, with attention toward potential side effects, is preferred, as is monotherapy whenever possible. Systemic reviews found insufficient evidence on which to base a choice among these drugs in terms of seizure control.
• Generalized seizures: Tonic-clonic
- Phenytoin (Dilantin): 200-400 mg/d in 1-3 doses; therapeutic range 10-20 ug/mL
- Carbamazepine (Tegretol) 100-200 mg/d in 1-2 doses; therapeutic range: 4-12 ug/mL
- Valproic acid (Depakene): 750-3,000 mg/d in 1-3 doses; begin at 15 mg/kg/d; therapeutic range 50-150 ug/mL
• Generalized seizuresabsence
- Ethosuximide (Zarontin): 250-1,500 mg/d in 1-2 doses; therapeutic range 40-100 ug/mL
- Valproic acid (see information provided previously)
• Partial seizures
- Phenytoin (Dilantin)
- Carbamazepine (Tegretol)
- Phenobarbital
There is evidence to suggest long-term use of phenobarbitol may impair cognative ability. (1)[C]
• Contraindications: Refer to the manufacturer's profile of each drug.
• Precautions: Doses should be based on individual's response and drug levels where available.
• Significant possible interactions: Refer to the manufacturer's profile of each drug.
Second Line
• Felbamate (Felbatol): 1,200 mg/d in 3-4 divided doses. max 3,600 mg/d
• Gabapentin (Neurontin): 300 mg at bedtime, then 2-3 divided doses, max. 2,400-3,600 mg/d
• Lamotrigine (Lamictal): 25-50 mg/d. Adjust in 100-mg increments every 1-2 weeks to 300- 500 mg/d in 2 divided doses.
• Levetiracetam (Kepra) 500 mg b.i.d. with a max. of 3000 mg/d
• Methsuximide (Celontin): 300 mg/d for 1st week, increase 300 mg/3 weeks, max. 1,200 mg/d
• Oxcarbazepine (Trileptal): 300 mg b.i.d., increase 300 mg/3 days; maintenance 1,200 mg/d
• Pregabalin (Lyrica) 150-600 mg/d in divided doses
• Primidone (Mysoline): 100-125 mg at bedtime adjust to max. 2,000 mg/d in 2 doses
• Tiagabine (Gabitril): 4 mg/d, adjust weekly to max. 56 mg/d
• Topiramate (Topamax): 50 mg/d, adjust weekly to effective 400 mg/d in 2 doses, max. 1,600 mg/d
• Zonisamide (Zonegran) 100 mg/d for 2 weeks, increase 100 mg/d each 2 weeks to a max. of 400 mg/d
SURGERY
Many academic centers are finding success with stereotactic surgery for seizures that fail traditional therapy.
FOLLOW-UP
PROGNOSIS
• Dependent on type of seizure disorder
• Seizure activity may become quiescent.
- After a seizurefree 2-year period, withdrawal of therapy may be considered.
- 33% relapse rate should be expected in the following 3 years.
COMPLICATIONS
Drug toxicity
PATIENT MONITORING
• Regular monitoring of anticonvulsant levels and seizure frequency
• CBC as indicated
• Monitor medication side effects and adverse reactions.
REFERENCES
1. Marson A, Ramaratnam S. Epilepsy Clin Evid Concise. 2005;13:362-364.
2. Chang BS, Lowenstein DH. Epilepsy. N Engl J Med. 2003;349:1257-1266.
3. Annegers JF. The epidemiology of epilepsy. In: Wyllie E, ed. The Treatment of Epilepsy: Principles and Practice. 3rd ed. Philadelphia, PA: Lippincott Williams Wilkins; 2001:131-138.
4. Mengel MB, Schwiebert LB, eds. Ambulatory Medicine: Primary Care Families. 4th ed. New York, NY: McGraw-Hill; 2004.
5. Goldstein LH. Assessment of patients with psychogenic non-epileptiform seizures. J Neurol Neurosurg Psychiatry. 2004;75:667-668.
MISCELLANEOUS
• See also: Seizures, Febrile; Status epilepticus
• Other notes: The International League Against Epilepsy (ILAE) is currently making progress in a new 5-axis classification system for seizure disorder, which will include genetics, characterization, and disability for seizure disorder syndromes.
SEIZURE DISORDER, PARTIAL
SEIZURE DISORDER, PARTIAL - Sarah Guzofski, MD; Wylie Hall, MD; Ruben Peralta, MD, FACS
BASICS
DESCRIPTION
• Seizures occur when abnormal synchronous neuronal discharges cause transient cortical dysfunction.
• Generalized seizures involve bilateral cerebral cortex from the seizure's onset.
• Partial seizures originate from a discrete focus in the cerebral cortex.
• Partial seizures are further divided into simple and complex subtypes. If consciousness is impaired during a partial seizure, it is classified as complex; if consciousness is preserved, it is a simple partial seizure.
EPIDEMIOLOGY
Incidence
Partial seizures occur in 20/100,000 in US
RISK FACTORS
Genetics
One form of partial seizure, benign rolandic epilepsy, has an autosomal dominant inheritance pattern with penetrance dependant on multiple factors.
ETIOLOGY
• Partial seizures begin when a localized seizure focus produces an abnormal, synchronized depolarization, which spreads to a discrete portion of the surrounding cortex.
• The area of cortex involved in the seizure determines the symptoms; for example, an epileptogenic focus in motor cortex produces contralateral motor symptoms.
• Some conditions lead to structural abnormalities, which are prone to epileptogenesis. Some common examples include
- Early childhood: Developmental/congenital malformation, trauma
- Young adults: Developmental, infection, trauma
- Adults 40-60: Cerebrovascular, infection, trauma
- Adults >60: Cerebrovascular, trauma, neoplasm
• Complex partial seizures: A common cause is mesial temporal sclerosis
ASSOCIATED CONDITIONS
Epilepsy patients have a higher incidence of depression than does the general population.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Seizure activity usually stereotyped.
• Duration: Seconds to minutes unless status epilepticus develops. Status epilepticus may present as focal or generalized convulsion or altered mental status without convulsion.
• Simple partial seizure
- Simple partial seizures are characterized by localized symptoms. The patient is conscious. Symptoms may involve motor, sensory, or psychic systems.
- Motor: Seizure activity in motor strip causes contraction (tonic) or rhythmic jerking (clonic) movements that may involve 1 entire side of body or may be more localized (i.e., hands, feet, face).
- "Jacksonian march": As discharge spreads through motor cortex, tonic-clonic activity spreads in predictable fashion (i.e., beginning in hand, progressing up arm, to face).
- Sensory/psychic
Todd's paresis: Residual, temporary weakness in the area affected by a motor seizure
Parietal lobe: Sensory loss or paresthesias, dizziness
Temporal lobe: Deja vu, rising sensation in epigastrium, auditory hallucinations or forced memories, unpleasant smell or taste
Occipital: Visual hallucinations
• Complex partial seizure
- May have aura; this is start of seizure.
- Impaired consciousness by definition
- Amnesia for the event, postictal confusion
- Most often, focus in complex partial seizures is temporal or frontal.
- Motor manifestations may include dystonic posturing or automatisms (simple, repetitive movements of face and hands such as lip smacking, picking or more complex actions such as purposeless walking).
- Frontal lobe seizure is characterized by brief, bilateral complex movements, vocalizations, often with onset during sleep.
History
• A detailed description of the seizure should be obtained from an observer.
• Review medication list for drugs that lower seizure threshold
- Tramadol (Ultram), bupropion, theophylline
Physical Exam
Include neurologic exam with attention to lateralizing signs suggestive of structural lesion.
TESTS
EEG: Spikes/sharp waves over seizure focus
• Yield of EEG increased by obtaining in 1st 24 hours following seizure and by sleep deprivation.
• Frontal lobe seizure focus may be difficult to detect by routine EEG.
• If difficulty with diagnosis, continuous video-EEG monitoring may be appropriate.
Lab
• Serum electrolytes including calcium, magnesium, and phosphorus; hepatic function panel, CBC, drugs of abuse
• If measured within 10-20 minutes after suspected seizure, prolactin level may help differentiate generalized or complex partial seizure from psychogenic seizure.
• CSF exam if infection is suspected
• Urinalysis, chest radiogram, levels of antiepileptic drugs for breakthrough seizure
Imaging
• Emergency evaluation of new seizure: CT to screen for hemorrhage, stroke
• After emergency evaluation, MRI with thin cuts through area of interest
• If planning epilepsy surgery; PET scan and/or interictal SPECT may be of value.
• Magnetoencephalography is an evolving technology for localizing seizure focus.
DIFFERENTIAL DIAGNOSIS
• Nonepileptic seizure
• Syncope/post-anoxic myoclonus
• Hypoglycemia
• For hemiparesis following event
- TIA
- Hemiplegic migraine
TREATMENT
GENERAL MEASURES
• Ask patient to maintain a seizure diary.
• Note potential triggers such as stress, sleep deprivation, drug use, discontinuation of alcohol or benzodiazepines, menses.
Diet
Ketogenic or low-glycemic-index diet may improve seizure control in some patients.
Activity
• Most states have restrictions on driving for those with seizure disorders.
• Depending on seizure manifestation, may recommend against activities such as swimming, climbing to heights, working over open flames, or operating heavy machinery.
SPECIAL THERAPY
• Vagal nerve stimulator: Implanted in neck; provides periodic stimulation to vagus nerve. May induce hoarseness, cough, and dysphagia.
• New technologies being developed include deep brain stimulation.
MEDICATION (DRUGS)
• Some physicians do not start medication after a single seizure if EEG and MRI are normal, and/or a precipitant is clear and avoidable.
• Antiepileptic drugs (AEDs) act on voltage-gated ion channels, affect neuronal inhibition via enhancement of GABA (an inhibitory neurotransmitter), or decrease neuronal excitation. End result is to decrease the abnormal synchronized firing and to prevent seizure propagation.
• ~50% of those with newly diagnosed partial seizures will respond to and tolerate the 1st AED trial (1).
• Choose AED based on seizure type, side effect profile, and patient characteristics
- Increase dose until seizure control obtained or side effects become unacceptable.
• Attempt monotherapy, but many patients will require adjunct agents.
• "Refractory to medications" is defined as failure of at least 3 anticonvulsants to achieve adequate control.
• Several AEDs induce or inhibit cytochrome P450 enzymes (watch for drug interactions).
First Line
• Carbamazepine: Affects sodium channels
- Side effects: GI distress, hyponatremia, diplopia, dizziness; rare pancytopenia/marrow suppression, exfoliative rash
• Oxcarbazepine: Affects sodium channels
- Side effects: Dizziness, diplopia, hyponatremia, headache
• Lamotrigine: Affects sodium channels
- Side effects: Insomnia, dizziness, ataxia
- Risk of Stevens-Johnson reaction (potentially fatal exfoliative rash) especially when given with valproaterequires slow titration
• Levetiracetam: Multiple mechanisms
- Side effects: Sedation, ataxia, irritability
Second Line
• Phenytoin: Affects sodium channels
- Side effects: Ataxia, dizziness, diplopia, tremor, GI upset, gingival hyperplasia, fever
• Phenobarbital: Multiple mechanisms
- Side effects: Sedation, withdrawal seizures
• Valproate: Multiple mechanisms
- Side effects: GI upset, weight gain, alopecia, tremor; less common thrombocytopenia, hepatitis, pancreatitis
• Topiramate: Multiple mechanisms
- Side effects: Anorexia, cognitive slowing, sedation, nephrolithiasis, anhidrosis
• Gabapentin: Multiple mechanisms
- Side effects: Sedation, dizziness, ataxia
• Pregabalin: Affects calcium channels
- Side effects: Sedation, dizziness, weight gain
• Zonisamide: Affects sodium channels
- Side effects: Sedation, anorexia, nausea, dizziness, ataxia, anhidrosis, nephrolithiasis
- Cross reaction with sulfa allergy
ALERT
Pregnancy Considerations
• Several antiepileptic medications induce hepatic metabolism of oral contraceptives, decreasing their efficacy. AED therapy during 1st trimester is associated with doubled risk for major fetal malformations (6% vs. 3%) (2). Phenytoin in pregnancy may result in fetal hydantoin syndrome.
• Fetal insult from seizures following withdrawal of therapy also may be severe. Risk/reward balance should be evaluated with high-risk pregnancy and epileptology consultations. Most patients remain on anticonvulsants.
SURGERY
For refractory partial complex seizures
• Should have identifiable focus
• Preoperative testing, such as Wada test, should be done to decrease likelihood of inducing aphasia and memory loss.
• Workup also may include MRI, video-EEG monitoring, electrocorticography, MEG, ictal SPECT.
• 64% will be seizure free after surgery (with continued medication treatment); 25% will have significant decrease in frequency. 1/3 continue to have disabling seizures (3)[B]
• Goal of surgical intervention is to reduce reliance on medications; most remain on anticonvulsants postoperatively.
FOLLOW-UP
Outpatient follow-up with neurologist
DISPOSITION
Admission Criteria
Generally, outpatient treatment; admission for unremitting seizure (partial or secondary generalized status epilepticus)
Issues for Referral
For refractory seizures, consider referral to an epilepsy specialist.
PROGNOSIS
• Risk of seizure recurrence is ~30% after 1st seizure; 50% of these recurrences will occur in the 1st 6 months; 90% in the 1st 2 years. (4)[B]
• Depends on seizure type. Rolandic epilepsy has a good prognosis; temporal lobe epilepsy more likely to be persistent. (5)[A]
• Long duration of uncontrolled seizure disorder associated with increased cognitive and functional impairments. Early pharmacologic intervention is encouraged. (5)[A]
COMPLICATIONS
• Risk of accidental injury
• SUDEP (Sudden Death in Epilepsy Patients)
PATIENT MONITORING
AED levels if concern over toxicity, noncompliance, or for breakthrough seizures
REFERENCES
1. Kwan P and Brodie MJ. Effectiveness of first anticonvulsant drug. Epilepsia 2001;42:1255-1260.
2. Bromfield EB. Clinical use of anticonvulsants: A neurologist's perspective. Harv Rev Psychiatry 2003;11:257-268.
3. Schmidt D, Loscher W. How effective is surgery to cure epilepsy in drug-resistant temporal lobe epilepsy? Epilepsy Res 2003;56:85-91.
4. Pohlmann-Eden B, Beghi E, Camfield C et al. The first seizure and its management in adults and children. BMJ 2006;322:339-342.
5. Wolf P. Determinants of outcome in childhood epilepsy. Acta Neurol Scand 2005;112:5-8.
BASICS
DESCRIPTION
• Seizures occur when abnormal synchronous neuronal discharges cause transient cortical dysfunction.
• Generalized seizures involve bilateral cerebral cortex from the seizure's onset.
• Partial seizures originate from a discrete focus in the cerebral cortex.
• Partial seizures are further divided into simple and complex subtypes. If consciousness is impaired during a partial seizure, it is classified as complex; if consciousness is preserved, it is a simple partial seizure.
EPIDEMIOLOGY
Incidence
Partial seizures occur in 20/100,000 in US
RISK FACTORS
Genetics
One form of partial seizure, benign rolandic epilepsy, has an autosomal dominant inheritance pattern with penetrance dependant on multiple factors.
ETIOLOGY
• Partial seizures begin when a localized seizure focus produces an abnormal, synchronized depolarization, which spreads to a discrete portion of the surrounding cortex.
• The area of cortex involved in the seizure determines the symptoms; for example, an epileptogenic focus in motor cortex produces contralateral motor symptoms.
• Some conditions lead to structural abnormalities, which are prone to epileptogenesis. Some common examples include
- Early childhood: Developmental/congenital malformation, trauma
- Young adults: Developmental, infection, trauma
- Adults 40-60: Cerebrovascular, infection, trauma
- Adults >60: Cerebrovascular, trauma, neoplasm
• Complex partial seizures: A common cause is mesial temporal sclerosis
ASSOCIATED CONDITIONS
Epilepsy patients have a higher incidence of depression than does the general population.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Seizure activity usually stereotyped.
• Duration: Seconds to minutes unless status epilepticus develops. Status epilepticus may present as focal or generalized convulsion or altered mental status without convulsion.
• Simple partial seizure
- Simple partial seizures are characterized by localized symptoms. The patient is conscious. Symptoms may involve motor, sensory, or psychic systems.
- Motor: Seizure activity in motor strip causes contraction (tonic) or rhythmic jerking (clonic) movements that may involve 1 entire side of body or may be more localized (i.e., hands, feet, face).
- "Jacksonian march": As discharge spreads through motor cortex, tonic-clonic activity spreads in predictable fashion (i.e., beginning in hand, progressing up arm, to face).
- Sensory/psychic
Todd's paresis: Residual, temporary weakness in the area affected by a motor seizure
Parietal lobe: Sensory loss or paresthesias, dizziness
Temporal lobe: Deja vu, rising sensation in epigastrium, auditory hallucinations or forced memories, unpleasant smell or taste
Occipital: Visual hallucinations
• Complex partial seizure
- May have aura; this is start of seizure.
- Impaired consciousness by definition
- Amnesia for the event, postictal confusion
- Most often, focus in complex partial seizures is temporal or frontal.
- Motor manifestations may include dystonic posturing or automatisms (simple, repetitive movements of face and hands such as lip smacking, picking or more complex actions such as purposeless walking).
- Frontal lobe seizure is characterized by brief, bilateral complex movements, vocalizations, often with onset during sleep.
History
• A detailed description of the seizure should be obtained from an observer.
• Review medication list for drugs that lower seizure threshold
- Tramadol (Ultram), bupropion, theophylline
Physical Exam
Include neurologic exam with attention to lateralizing signs suggestive of structural lesion.
TESTS
EEG: Spikes/sharp waves over seizure focus
• Yield of EEG increased by obtaining in 1st 24 hours following seizure and by sleep deprivation.
• Frontal lobe seizure focus may be difficult to detect by routine EEG.
• If difficulty with diagnosis, continuous video-EEG monitoring may be appropriate.
Lab
• Serum electrolytes including calcium, magnesium, and phosphorus; hepatic function panel, CBC, drugs of abuse
• If measured within 10-20 minutes after suspected seizure, prolactin level may help differentiate generalized or complex partial seizure from psychogenic seizure.
• CSF exam if infection is suspected
• Urinalysis, chest radiogram, levels of antiepileptic drugs for breakthrough seizure
Imaging
• Emergency evaluation of new seizure: CT to screen for hemorrhage, stroke
• After emergency evaluation, MRI with thin cuts through area of interest
• If planning epilepsy surgery; PET scan and/or interictal SPECT may be of value.
• Magnetoencephalography is an evolving technology for localizing seizure focus.
DIFFERENTIAL DIAGNOSIS
• Nonepileptic seizure
• Syncope/post-anoxic myoclonus
• Hypoglycemia
• For hemiparesis following event
- TIA
- Hemiplegic migraine
TREATMENT
GENERAL MEASURES
• Ask patient to maintain a seizure diary.
• Note potential triggers such as stress, sleep deprivation, drug use, discontinuation of alcohol or benzodiazepines, menses.
Diet
Ketogenic or low-glycemic-index diet may improve seizure control in some patients.
Activity
• Most states have restrictions on driving for those with seizure disorders.
• Depending on seizure manifestation, may recommend against activities such as swimming, climbing to heights, working over open flames, or operating heavy machinery.
SPECIAL THERAPY
• Vagal nerve stimulator: Implanted in neck; provides periodic stimulation to vagus nerve. May induce hoarseness, cough, and dysphagia.
• New technologies being developed include deep brain stimulation.
MEDICATION (DRUGS)
• Some physicians do not start medication after a single seizure if EEG and MRI are normal, and/or a precipitant is clear and avoidable.
• Antiepileptic drugs (AEDs) act on voltage-gated ion channels, affect neuronal inhibition via enhancement of GABA (an inhibitory neurotransmitter), or decrease neuronal excitation. End result is to decrease the abnormal synchronized firing and to prevent seizure propagation.
• ~50% of those with newly diagnosed partial seizures will respond to and tolerate the 1st AED trial (1).
• Choose AED based on seizure type, side effect profile, and patient characteristics
- Increase dose until seizure control obtained or side effects become unacceptable.
• Attempt monotherapy, but many patients will require adjunct agents.
• "Refractory to medications" is defined as failure of at least 3 anticonvulsants to achieve adequate control.
• Several AEDs induce or inhibit cytochrome P450 enzymes (watch for drug interactions).
First Line
• Carbamazepine: Affects sodium channels
- Side effects: GI distress, hyponatremia, diplopia, dizziness; rare pancytopenia/marrow suppression, exfoliative rash
• Oxcarbazepine: Affects sodium channels
- Side effects: Dizziness, diplopia, hyponatremia, headache
• Lamotrigine: Affects sodium channels
- Side effects: Insomnia, dizziness, ataxia
- Risk of Stevens-Johnson reaction (potentially fatal exfoliative rash) especially when given with valproaterequires slow titration
• Levetiracetam: Multiple mechanisms
- Side effects: Sedation, ataxia, irritability
Second Line
• Phenytoin: Affects sodium channels
- Side effects: Ataxia, dizziness, diplopia, tremor, GI upset, gingival hyperplasia, fever
• Phenobarbital: Multiple mechanisms
- Side effects: Sedation, withdrawal seizures
• Valproate: Multiple mechanisms
- Side effects: GI upset, weight gain, alopecia, tremor; less common thrombocytopenia, hepatitis, pancreatitis
• Topiramate: Multiple mechanisms
- Side effects: Anorexia, cognitive slowing, sedation, nephrolithiasis, anhidrosis
• Gabapentin: Multiple mechanisms
- Side effects: Sedation, dizziness, ataxia
• Pregabalin: Affects calcium channels
- Side effects: Sedation, dizziness, weight gain
• Zonisamide: Affects sodium channels
- Side effects: Sedation, anorexia, nausea, dizziness, ataxia, anhidrosis, nephrolithiasis
- Cross reaction with sulfa allergy
ALERT
Pregnancy Considerations
• Several antiepileptic medications induce hepatic metabolism of oral contraceptives, decreasing their efficacy. AED therapy during 1st trimester is associated with doubled risk for major fetal malformations (6% vs. 3%) (2). Phenytoin in pregnancy may result in fetal hydantoin syndrome.
• Fetal insult from seizures following withdrawal of therapy also may be severe. Risk/reward balance should be evaluated with high-risk pregnancy and epileptology consultations. Most patients remain on anticonvulsants.
SURGERY
For refractory partial complex seizures
• Should have identifiable focus
• Preoperative testing, such as Wada test, should be done to decrease likelihood of inducing aphasia and memory loss.
• Workup also may include MRI, video-EEG monitoring, electrocorticography, MEG, ictal SPECT.
• 64% will be seizure free after surgery (with continued medication treatment); 25% will have significant decrease in frequency. 1/3 continue to have disabling seizures (3)[B]
• Goal of surgical intervention is to reduce reliance on medications; most remain on anticonvulsants postoperatively.
FOLLOW-UP
Outpatient follow-up with neurologist
DISPOSITION
Admission Criteria
Generally, outpatient treatment; admission for unremitting seizure (partial or secondary generalized status epilepticus)
Issues for Referral
For refractory seizures, consider referral to an epilepsy specialist.
PROGNOSIS
• Risk of seizure recurrence is ~30% after 1st seizure; 50% of these recurrences will occur in the 1st 6 months; 90% in the 1st 2 years. (4)[B]
• Depends on seizure type. Rolandic epilepsy has a good prognosis; temporal lobe epilepsy more likely to be persistent. (5)[A]
• Long duration of uncontrolled seizure disorder associated with increased cognitive and functional impairments. Early pharmacologic intervention is encouraged. (5)[A]
COMPLICATIONS
• Risk of accidental injury
• SUDEP (Sudden Death in Epilepsy Patients)
PATIENT MONITORING
AED levels if concern over toxicity, noncompliance, or for breakthrough seizures
REFERENCES
1. Kwan P and Brodie MJ. Effectiveness of first anticonvulsant drug. Epilepsia 2001;42:1255-1260.
2. Bromfield EB. Clinical use of anticonvulsants: A neurologist's perspective. Harv Rev Psychiatry 2003;11:257-268.
3. Schmidt D, Loscher W. How effective is surgery to cure epilepsy in drug-resistant temporal lobe epilepsy? Epilepsy Res 2003;56:85-91.
4. Pohlmann-Eden B, Beghi E, Camfield C et al. The first seizure and its management in adults and children. BMJ 2006;322:339-342.
5. Wolf P. Determinants of outcome in childhood epilepsy. Acta Neurol Scand 2005;112:5-8.
SEIZURE DISORDER, ABSENCE
SEIZURE DISORDER, ABSENCE - Wyley Hall, MD
BASICS
DESCRIPTION
• Pediatric epilepsy type with brief seizures characterized by lapses of consciousness
• Often mistaken for daydreaming/inattention
• Childhood absence: 80% of cases
- Onset age 4-8
- 30% develop tonic-clonic seizures
- 10-20% experience status epilepticus
• Juvenile absence: 20% of cases
- Onset averages age 12
- 80% develop tonic-clonic seizures
- 40% experience status epilepticus
• Also divided into typical and atypical absence
• Typical absence
- Abrupt onset unresponsiveness/behavior arrest without aura or postictal state
- Rarely last >0 seconds
- May occur hundreds of times daily
- May include automatisms, tonic or atonic features, eyelid or facial clonus
• Atypical absence
- More gradual on and offset
- Often last >0 seconds
- Often with tonic, atonic, myoclonic features
- Associated with more severe epilepsy syndromes such as Lennox-Gastaut
EPIDEMIOLOGY
Incidence
1.9-8 per 100,000 Population
Prevalence
Accounts for 3-4% of epilepsies
RISK FACTORS
Genetics
• 64% concordance occurs in monozygotic twins or clinical epilepsy; 82% share EEG features.
• 33% concordance among 1st-degree relatives.
• 16-45% have family history of epilepsy.
• Girls are affected twice as often as boys.
• Likely autosomal dominant inheritance with incomplete penetrance
• For childhood absence, genes/loci implicated include 6q, 8q24, 5q14.
• For juvenile absence, chromosomes 5, 8, 18, 21 may have genes involved.
• Mutations of GABA-A receptor also are implicated.
PATHOPHYSIOLOGY
Corticoreticular theory implicates abnormal activity in thalamocortical circuits
• Reticular nucleus sends -aminobutyric acid (GABA)ergic neurons to thalamic relay nuclei.
• These neurons affect low-threshold calcium currents.
• These circuits can fire in oscillatory/rhythmic fashion or tonic bursts
- Tonic firing present during awake state
- Alertness suppressed by oscillatory firing
• Absence seizure potentiates rhythmic firing and produces lapse of consciousness.
ASSOCIATED CONDITIONS
• Multiple genetic syndromes exist
- Lennox-Gastaut most recognizable, severe
• May evolve into juvenile myoclonic epilepsy
DIAGNOSIS
PRE HOSPITAL
Seizures are often so brief that untrained observers are not aware of diagnosis
SIGNS AND SYMPTOMS
History
Frequently diagnosed in children being evaluated for poor school performance
• Teachers report child seems to daydream or "zone out" frequently
• Child will forget portions of conversations
• Child with normal IQ underperforms in school
Physical Exam
• Unless child has other genetic or acquired abnormality, neurologic examination is usually normal
• Seizures may be frequent enough to be observed during physical examination
- Manifest by behavior arrest: Child will stop speaking in mid-sentence, stare blankly, etc.
- Automatisms (repetitive stereotyped behaviors) may be present.
- Child resumes previous activity and may attempt to "cover up" lapse in awareness.
• Seizures may be induced by hyperventilation
- Have child blow on a piece of paper or similar exercise until seizure occurs.
- Photic stimulation may also evoke seizure although less frequently than hyperventilation.
• Patient manifests unresponsiveness, but retains postural tone in a typical absence seizure.
• Patients with associated tonic-clonic seizures are at risk of injury due to falls, similar to patients with partial and generalized epilepsy subtypes.
TESTS
• EEG is standard for diagnosis.
• Typical absence features 3.0-Hz spike-and-wave activity on normal EEG background
- Seizures feature bursts of 3-4 Hz spike-and-wave activity, which may slow to 2.5-3 Hz during seizure
- Seizure is usually evident clinically if bursts last >3 seconds; subtle changes of "transient cognitive impairment" may be evident with briefer seizures.
• Atypical absence seizures feature 0.5-2.5 Hz slow spike-and-wave activity superimposed on an abnormal background EEG pattern.
• Hyperventilation and occasionally photic stimulation are performed and may induce seizure, thus confirming diagnosis of typical absence epilepsy
- Atypical absence seizures generally are not inducible.
Lab
• No specific hematological workup
• Follow blood chemistry, hepatic function, blood counts specific to drug regimen.
• Drug levels useful to evaluate symptoms of toxicity or for breakthrough seizures; less useful for routine monitoring
Imaging
• Not routinely indicated in children with typical absence and normal neurologic examination and IQ
• Brain MRI is indicated in atypical absence and in children with mixed seizure types when combined with abnormal neurologic examination or low IQ.
DIFFERENTIAL DIAGNOSIS
• Temporal lobe epilepsy with complex partial seizures
- Differentiate by longer duration (>30 seconds vs. 10 in absence) and presence of postictal confusion
• Frontal lobe complex partial seizures
- More difficult to distinguish on EEG due to rapid spread to bilateral cortex
- Difference in duration and postictal state applies as in temporal lobe seizures
TREATMENT
GENERAL MEASURES
Activity
• Patients with associated tonic-clonic seizures should avoid high places, swimming alone.
• Absence rarely persists into adulthood, but affected adults may be restricted from driving, working over open flames, etc., as with other generalized and partial epilepsy subtypes.
MEDICATION (DRUGS)
Certain common anticonvulsants may exacerbate absence: Carbamazepine, tiagabine, vigabatrin, and gabapentin.
First Line
• Ethosuximide blocks T-type calcium channels
- 1st line, except in absence patients with tonic-clonic seizures (lacks efficacy).
- Side effects: Headache, hiccups, behavior changes, tremor
- Adverse effects: Rare blood dyscrasias (monitor CBC)
• Lamotrigine affects sodium channels
- Side effects: Headache, insomnia, dizziness
- Adverse effects: Rare Stevens-Johnson rash, more often when coadministered with valproic acid
• Valproic acid has multiple mechanisms
- 1st choice in absence patients with tonic-clonic, myoclonic, mixed seizure types
- Side effects: Weight gain, alopecia, sedation
- Adverse effects: Thrombocytopenia, rare fulminant hepatic failure (especially in children 2 years)
Second Line
• Topiramate affects GABA and excitatory neurotransmission
- FDA approved for Lennox-Gastaut syndrome
- Side effects: Psychomotor slowing
- Adverse effects: Weight loss, renal stones, myopia, glaucoma (rare), anhidrosis
• Zonisamide, Levetiracetam also are used off label.
ALERT
Pregnancy Considerations
Anticonvulsants, especially valproic acid, are associated with an increase in fetal malformations. Use of valproic acid in women who are or are likely to become pregnant generally is contraindicated. Obtain specialty consultation.
FOLLOW-UP
Patients should be monitored periodically by a neurologist for evolution of absence epilepsy into tonic-clonic or other seizure types.
DISPOSITION
Admission Criteria
• Absence epilepsy rarely requires admission.
• Tonic-clonic status epilepticus requires inpatient management.
Discharge Criteria
Resolution of status epilepticus
PROGNOSIS
• In typical absence epilepsy without tonic-clonic seizures, 65-70% remit by adulthood.
• 35% of patients with tonic-clonic seizures experience complete remission of absence.
• 15% of patients develop juvenile myoclonic epilepsy (JME).
• Decreased IQ, abnormal EEG background, resistance to medications, positive family history of epilepsy, presence of myoclonic seizures all associated with poorer prognosis for remission.
REFERENCES
1. Bouma PA, Westendorp RG et al. The outcome of absence epilepsy: A meta-analysis. Neurology. 1996;47:802-808.
2. Camfield P, Camfield C. Epileptic syndromes in childhood: Clinical features, outcomes, and treatment. Epilepsia. 2002;43(3):27-32.
3. Crunelli V, Leresche N. Childhood absence epilepsy: Genes, channels, neurons, and networks. Nat Rev Neuro. 2002;3:371-382.
4. Delgado-Escueta AV, Treiman DM, Walsh GO. The treatable epilepsies. N Engl J Med. 1983;308:1508-1514.
5. Nordli DR. Idiopathic generalized epilepsies recognized by the International League Against Epilepsy. Epilepsia. 2005;46(9):48-56.
MISCELLANEOUS
Other uncommon absence subtypes exist
• Micturition absence
- Detrusor spasm during seizures
- Problematic due to frequency of seizures Children are always wet, causing social issues.
• Myoclonic absence
- Arms ratchet upwards at 3 Hz, retain posture
- Associated with mental retardation
- Resistant to therapy
• Absence with eyelid myoclonia
- Prominent upper facial spasm
- Resistant to therapy, autosomal dominant
BASICS
DESCRIPTION
• Pediatric epilepsy type with brief seizures characterized by lapses of consciousness
• Often mistaken for daydreaming/inattention
• Childhood absence: 80% of cases
- Onset age 4-8
- 30% develop tonic-clonic seizures
- 10-20% experience status epilepticus
• Juvenile absence: 20% of cases
- Onset averages age 12
- 80% develop tonic-clonic seizures
- 40% experience status epilepticus
• Also divided into typical and atypical absence
• Typical absence
- Abrupt onset unresponsiveness/behavior arrest without aura or postictal state
- Rarely last >0 seconds
- May occur hundreds of times daily
- May include automatisms, tonic or atonic features, eyelid or facial clonus
• Atypical absence
- More gradual on and offset
- Often last >0 seconds
- Often with tonic, atonic, myoclonic features
- Associated with more severe epilepsy syndromes such as Lennox-Gastaut
EPIDEMIOLOGY
Incidence
1.9-8 per 100,000 Population
Prevalence
Accounts for 3-4% of epilepsies
RISK FACTORS
Genetics
• 64% concordance occurs in monozygotic twins or clinical epilepsy; 82% share EEG features.
• 33% concordance among 1st-degree relatives.
• 16-45% have family history of epilepsy.
• Girls are affected twice as often as boys.
• Likely autosomal dominant inheritance with incomplete penetrance
• For childhood absence, genes/loci implicated include 6q, 8q24, 5q14.
• For juvenile absence, chromosomes 5, 8, 18, 21 may have genes involved.
• Mutations of GABA-A receptor also are implicated.
PATHOPHYSIOLOGY
Corticoreticular theory implicates abnormal activity in thalamocortical circuits
• Reticular nucleus sends -aminobutyric acid (GABA)ergic neurons to thalamic relay nuclei.
• These neurons affect low-threshold calcium currents.
• These circuits can fire in oscillatory/rhythmic fashion or tonic bursts
- Tonic firing present during awake state
- Alertness suppressed by oscillatory firing
• Absence seizure potentiates rhythmic firing and produces lapse of consciousness.
ASSOCIATED CONDITIONS
• Multiple genetic syndromes exist
- Lennox-Gastaut most recognizable, severe
• May evolve into juvenile myoclonic epilepsy
DIAGNOSIS
PRE HOSPITAL
Seizures are often so brief that untrained observers are not aware of diagnosis
SIGNS AND SYMPTOMS
History
Frequently diagnosed in children being evaluated for poor school performance
• Teachers report child seems to daydream or "zone out" frequently
• Child will forget portions of conversations
• Child with normal IQ underperforms in school
Physical Exam
• Unless child has other genetic or acquired abnormality, neurologic examination is usually normal
• Seizures may be frequent enough to be observed during physical examination
- Manifest by behavior arrest: Child will stop speaking in mid-sentence, stare blankly, etc.
- Automatisms (repetitive stereotyped behaviors) may be present.
- Child resumes previous activity and may attempt to "cover up" lapse in awareness.
• Seizures may be induced by hyperventilation
- Have child blow on a piece of paper or similar exercise until seizure occurs.
- Photic stimulation may also evoke seizure although less frequently than hyperventilation.
• Patient manifests unresponsiveness, but retains postural tone in a typical absence seizure.
• Patients with associated tonic-clonic seizures are at risk of injury due to falls, similar to patients with partial and generalized epilepsy subtypes.
TESTS
• EEG is standard for diagnosis.
• Typical absence features 3.0-Hz spike-and-wave activity on normal EEG background
- Seizures feature bursts of 3-4 Hz spike-and-wave activity, which may slow to 2.5-3 Hz during seizure
- Seizure is usually evident clinically if bursts last >3 seconds; subtle changes of "transient cognitive impairment" may be evident with briefer seizures.
• Atypical absence seizures feature 0.5-2.5 Hz slow spike-and-wave activity superimposed on an abnormal background EEG pattern.
• Hyperventilation and occasionally photic stimulation are performed and may induce seizure, thus confirming diagnosis of typical absence epilepsy
- Atypical absence seizures generally are not inducible.
Lab
• No specific hematological workup
• Follow blood chemistry, hepatic function, blood counts specific to drug regimen.
• Drug levels useful to evaluate symptoms of toxicity or for breakthrough seizures; less useful for routine monitoring
Imaging
• Not routinely indicated in children with typical absence and normal neurologic examination and IQ
• Brain MRI is indicated in atypical absence and in children with mixed seizure types when combined with abnormal neurologic examination or low IQ.
DIFFERENTIAL DIAGNOSIS
• Temporal lobe epilepsy with complex partial seizures
- Differentiate by longer duration (>30 seconds vs. 10 in absence) and presence of postictal confusion
• Frontal lobe complex partial seizures
- More difficult to distinguish on EEG due to rapid spread to bilateral cortex
- Difference in duration and postictal state applies as in temporal lobe seizures
TREATMENT
GENERAL MEASURES
Activity
• Patients with associated tonic-clonic seizures should avoid high places, swimming alone.
• Absence rarely persists into adulthood, but affected adults may be restricted from driving, working over open flames, etc., as with other generalized and partial epilepsy subtypes.
MEDICATION (DRUGS)
Certain common anticonvulsants may exacerbate absence: Carbamazepine, tiagabine, vigabatrin, and gabapentin.
First Line
• Ethosuximide blocks T-type calcium channels
- 1st line, except in absence patients with tonic-clonic seizures (lacks efficacy).
- Side effects: Headache, hiccups, behavior changes, tremor
- Adverse effects: Rare blood dyscrasias (monitor CBC)
• Lamotrigine affects sodium channels
- Side effects: Headache, insomnia, dizziness
- Adverse effects: Rare Stevens-Johnson rash, more often when coadministered with valproic acid
• Valproic acid has multiple mechanisms
- 1st choice in absence patients with tonic-clonic, myoclonic, mixed seizure types
- Side effects: Weight gain, alopecia, sedation
- Adverse effects: Thrombocytopenia, rare fulminant hepatic failure (especially in children 2 years)
Second Line
• Topiramate affects GABA and excitatory neurotransmission
- FDA approved for Lennox-Gastaut syndrome
- Side effects: Psychomotor slowing
- Adverse effects: Weight loss, renal stones, myopia, glaucoma (rare), anhidrosis
• Zonisamide, Levetiracetam also are used off label.
ALERT
Pregnancy Considerations
Anticonvulsants, especially valproic acid, are associated with an increase in fetal malformations. Use of valproic acid in women who are or are likely to become pregnant generally is contraindicated. Obtain specialty consultation.
FOLLOW-UP
Patients should be monitored periodically by a neurologist for evolution of absence epilepsy into tonic-clonic or other seizure types.
DISPOSITION
Admission Criteria
• Absence epilepsy rarely requires admission.
• Tonic-clonic status epilepticus requires inpatient management.
Discharge Criteria
Resolution of status epilepticus
PROGNOSIS
• In typical absence epilepsy without tonic-clonic seizures, 65-70% remit by adulthood.
• 35% of patients with tonic-clonic seizures experience complete remission of absence.
• 15% of patients develop juvenile myoclonic epilepsy (JME).
• Decreased IQ, abnormal EEG background, resistance to medications, positive family history of epilepsy, presence of myoclonic seizures all associated with poorer prognosis for remission.
REFERENCES
1. Bouma PA, Westendorp RG et al. The outcome of absence epilepsy: A meta-analysis. Neurology. 1996;47:802-808.
2. Camfield P, Camfield C. Epileptic syndromes in childhood: Clinical features, outcomes, and treatment. Epilepsia. 2002;43(3):27-32.
3. Crunelli V, Leresche N. Childhood absence epilepsy: Genes, channels, neurons, and networks. Nat Rev Neuro. 2002;3:371-382.
4. Delgado-Escueta AV, Treiman DM, Walsh GO. The treatable epilepsies. N Engl J Med. 1983;308:1508-1514.
5. Nordli DR. Idiopathic generalized epilepsies recognized by the International League Against Epilepsy. Epilepsia. 2005;46(9):48-56.
MISCELLANEOUS
Other uncommon absence subtypes exist
• Micturition absence
- Detrusor spasm during seizures
- Problematic due to frequency of seizures Children are always wet, causing social issues.
• Myoclonic absence
- Arms ratchet upwards at 3 Hz, retain posture
- Associated with mental retardation
- Resistant to therapy
• Absence with eyelid myoclonia
- Prominent upper facial spasm
- Resistant to therapy, autosomal dominant
SEASONAL AFFECTIVE DISORDER
SEASONAL AFFECTIVE DISORDER - Christopher C. White, MD, JD
BASICS
DESCRIPTION
• Seasonal Affective Disorder (SAD) is a heterogeneous mood disorder with depressive episodes associated with winter months (possibly due to changes in light) with full remissions in the spring and summer.
• Although noted to occur decades ago, it was not formally named until the 1980s.
• Ranges from a milder form causing discomfort often called "winter blues" or sub-syndromal SAD to a seriously disabling illness
• Must separate out patients with other mood disorders (such as major depressive disorder and bipolar affective disorder) whose symptoms persist during spring and summer months
GENERAL PREVENTION
• Individuals with prior episodes should either begin daily light therapy in October or spend increased time outside during winter.
• Patients may consider moving to a more southern location to decrease symptoms.
EPIDEMIOLOGY
• Predominant age: Can occur at any age, but peak is 20s-30s (1)
• Predominant sex: Female > Male (3:1)
Incidence
• Affects up to 500,000 people every winter
• Up to 30% of patients visiting a PCP during winter may report winter depressive symptoms.
Prevalence
• 1-2% of the general population (2)
• 10-20% of patients identified as having mood symptoms will have a seasonal component.
RISK FACTORS
• Most common during winter months of January and February
- Patients frequently visiting PCP during winter months complaining of recurrent flu, chronic fatigue, and unexplained weight gain should be screened for SAD.
• Women and young people at increased risk
• Decreased risk for those who live within 30 of equator
• Working in a building without windows or other environment without exposure to sunlight
Genetics
• Some twin studies have suggested a genetic component, but further study is needed.
• Increased incidence of depression and alcoholism in close relatives
PATHOPHYSIOLOGY
The major theories currently involve the interplay of phase-shifted circadian rhythms, genetic vulnerability, and serotonin dysregulation. (3)
ETIOLOGY
• Melatonin produced by the pineal gland at increased levels in the dark has been linked to depressive symptoms.
- Light therapy on the retina acts to inhibit melatonin secretion.
• Serotonin dysregulation, because it is secreted at lower levels during winter months, must be present for light therapy to work, and treatment with SSRIs appears to reverse SAD symptoms.
ASSOCIATED CONDITIONS
Some with SAD have a weakened immune system and may be more vulnerable to infections.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Symptoms of depression (SIGECAPS) meeting the criteria for major depressive disorder
- Sleep disturbanceeither too much or too little
- Interest (lack of)in life and absence of pleasure from hobbies/activities
- Guiltfeelings of guilt or worthlessness
- Energyfatigue or constantly feeling tired
- Concentrationdifficulty with concentration and memory
- Appetitechanges in appetite and weight
- Psychomotor retardationpatients may feel slowed down with decreased activity
- Suicidal thoughtspatients may report thoughts of suicide
• In SAD hypersomnia, hyperphagia (craving for carbohydrates and sweets), and weight gain usually predominates. Despite sleeping more, patients report daytime sleepiness and fatigue. Cravings may lead to binge eating and weight gains >20 lbs.
• Remission of symptoms during spring and summer
- Patients may report hypomanic episodes upon re-exposure to sunlight during spring.
• Symptoms have occurred the past 2 years
• Seasonal episodes associated with winter months substantially outnumber any nonseasonal depressive episodes.
History
• Obtain collateral history if patient is unable to provide insight into the seasonal component.
• Carefully document the presence or absence of prior manic episodes.
• Screen for the existence of any suicidal ideation and safety risk factors.
Physical Exam
Use the physical exam to exclude other organic causes for the symptoms. Focal neurological deficits, signs of endocrine dysfunction, or stigmata of substance abuse should prompt further testing and examination.
TESTS
Lab
• TSH to rule out hypothyroidism
• CBC to rule out anemia
• Renal to examine electrolytes and glucose dysregulation
• 25 OH Vitamin D level
• BHCG for women of childbearing potential
• Urine tox screen if substance abuse is a concern
Imaging
Generally not very useful unless focal neurological finding on physical exam or looking to exclude an organic cause
DIFFERENTIAL DIAGNOSIS
• Similar to that of major depressive disorder meaning organic causes of low energy and fatigue such as hypothyroidism, anemia, and mononucleosis (or other viral syndromes) accounting for the low energy and fatigue need to be considered
• Other mood disorders without a seasonal component such as major depression, bipolar disorder, adjustment disorder, or dysthymia
• Symptoms should not be better accounted for by seasonal psychosocial stressors, which often accompany the winter holiday seasons.
• Substance abuse
TREATMENT
GENERAL MEASURES
Work to reduce stress levels through meditation, progressive relaxation exercises, and/or lifestyle modification.
Activity
• Increase time outdoors during daylight.
• Rearrange home or work environment to get more direct sunlight through windows.
SPECIAL THERAPY
Vitamin D supplementation has been found to be more effective than phototherapy in small studies.
• Phototherapy using special light sources has been shown to be effective in 60-90% of patients often providing relief within a few sessions. (2,4)[B]
- Variables which can regulate effect are
Light intensityAlthough the minimum light source intensity is under investigation, 2,500 lux is suggested (domestic lights emit on average 200-500 lux). There is good evidence for 10,000 lux as the recommended source. (4)[A]
Treatment durationexposure time varies on intensity of light source with daily sessions of 30 minutes to a few hours.
Time of treatmentmost patients respond better by using the light therapy early in the morning.
- Light box is placed on table several feet away and the light is allowed to shine onto the patient's eyes (sunglasses should be avoided). Ensure light box has a UV filter.
- Most common side effects are eye strain and headache. Insomnia can result if the light box is used too late in the day.
- Dawn simulation machines gradually increase illumination while the patient sleeps simulating sunrise while using a significantly less intense light source.
MEDICATION (DRUGS)
There is a lack of evidence to determine whether light therapy or medication should be the 1st-line agent. It depends on the acuity of the patient and the comfort level of the prescribing clinician with each treatment modality, [C].
First Line
Vitamin D supplementation may be beneficial.
• SSRIs such as sertraline (Zoloft), paroxetine (Paxil), fluoxetine (Prozac), citalopram (Celexa) in their traditional antidepressant doses (2)[B]
FOLLOW-UP
Regular monitoring by PCP or psychiatrist for response to treatment. Patients may become manic when treated with SSRIs or light therapy.
DISPOSITION
Admission Criteria
If the patient develops suicidal ideation as part of their depression or mania after treatment is initiated, hospitalization should be considered.
Issues for Referral
• Patients with a history of ocular disease should be referred for an ophthalmologic exam before phototherapy and for serial monitoring.
• Patients who fail to respond to a medication trial or phototherapy should be considered for psychiatric referral.
PROGNOSIS
Symptoms, if untreated, generally remit within 5 months with exposure to spring light only to return in subsequent winters. If treated, patients usually respond within 2-3 weeks.
COMPLICATIONS
Development of suicidal ideation or mania are 2 outcomes which the clinician needs to monitor.
PATIENT MONITORING
Patients should be seen in the outpatient clinic weekly to bi-weekly when initiating light or pharmacotherapy to monitor treatment results, side effects, and any increased suicidal thoughts if using SSRIs. [B]
REFERENCES
1. Saeed SA, Brucw TJ. Seasonal affective disorders. American Family Physician. 1998: 57.
2. Lam RW. Seasonal affective disorder: Diagnosis and management. Primary Care Psychiatry. 1998;4:63-74.
3. Lam RW, Levitan RD. Pathophysiology of seasonal affective disorder: A review. J Psychiatry Neurosci. 2000;25:469-480.
4. Terman M, Terman JS. Light therapy for seasonal and nonseasonal depression: Efficacy, protocol, safety, and side effects. CNS Spectr. 2005;10:647-663.
MISCELLANEOUS
See also: Bipolar disorder
BASICS
DESCRIPTION
• Seasonal Affective Disorder (SAD) is a heterogeneous mood disorder with depressive episodes associated with winter months (possibly due to changes in light) with full remissions in the spring and summer.
• Although noted to occur decades ago, it was not formally named until the 1980s.
• Ranges from a milder form causing discomfort often called "winter blues" or sub-syndromal SAD to a seriously disabling illness
• Must separate out patients with other mood disorders (such as major depressive disorder and bipolar affective disorder) whose symptoms persist during spring and summer months
GENERAL PREVENTION
• Individuals with prior episodes should either begin daily light therapy in October or spend increased time outside during winter.
• Patients may consider moving to a more southern location to decrease symptoms.
EPIDEMIOLOGY
• Predominant age: Can occur at any age, but peak is 20s-30s (1)
• Predominant sex: Female > Male (3:1)
Incidence
• Affects up to 500,000 people every winter
• Up to 30% of patients visiting a PCP during winter may report winter depressive symptoms.
Prevalence
• 1-2% of the general population (2)
• 10-20% of patients identified as having mood symptoms will have a seasonal component.
RISK FACTORS
• Most common during winter months of January and February
- Patients frequently visiting PCP during winter months complaining of recurrent flu, chronic fatigue, and unexplained weight gain should be screened for SAD.
• Women and young people at increased risk
• Decreased risk for those who live within 30 of equator
• Working in a building without windows or other environment without exposure to sunlight
Genetics
• Some twin studies have suggested a genetic component, but further study is needed.
• Increased incidence of depression and alcoholism in close relatives
PATHOPHYSIOLOGY
The major theories currently involve the interplay of phase-shifted circadian rhythms, genetic vulnerability, and serotonin dysregulation. (3)
ETIOLOGY
• Melatonin produced by the pineal gland at increased levels in the dark has been linked to depressive symptoms.
- Light therapy on the retina acts to inhibit melatonin secretion.
• Serotonin dysregulation, because it is secreted at lower levels during winter months, must be present for light therapy to work, and treatment with SSRIs appears to reverse SAD symptoms.
ASSOCIATED CONDITIONS
Some with SAD have a weakened immune system and may be more vulnerable to infections.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Symptoms of depression (SIGECAPS) meeting the criteria for major depressive disorder
- Sleep disturbanceeither too much or too little
- Interest (lack of)in life and absence of pleasure from hobbies/activities
- Guiltfeelings of guilt or worthlessness
- Energyfatigue or constantly feeling tired
- Concentrationdifficulty with concentration and memory
- Appetitechanges in appetite and weight
- Psychomotor retardationpatients may feel slowed down with decreased activity
- Suicidal thoughtspatients may report thoughts of suicide
• In SAD hypersomnia, hyperphagia (craving for carbohydrates and sweets), and weight gain usually predominates. Despite sleeping more, patients report daytime sleepiness and fatigue. Cravings may lead to binge eating and weight gains >20 lbs.
• Remission of symptoms during spring and summer
- Patients may report hypomanic episodes upon re-exposure to sunlight during spring.
• Symptoms have occurred the past 2 years
• Seasonal episodes associated with winter months substantially outnumber any nonseasonal depressive episodes.
History
• Obtain collateral history if patient is unable to provide insight into the seasonal component.
• Carefully document the presence or absence of prior manic episodes.
• Screen for the existence of any suicidal ideation and safety risk factors.
Physical Exam
Use the physical exam to exclude other organic causes for the symptoms. Focal neurological deficits, signs of endocrine dysfunction, or stigmata of substance abuse should prompt further testing and examination.
TESTS
Lab
• TSH to rule out hypothyroidism
• CBC to rule out anemia
• Renal to examine electrolytes and glucose dysregulation
• 25 OH Vitamin D level
• BHCG for women of childbearing potential
• Urine tox screen if substance abuse is a concern
Imaging
Generally not very useful unless focal neurological finding on physical exam or looking to exclude an organic cause
DIFFERENTIAL DIAGNOSIS
• Similar to that of major depressive disorder meaning organic causes of low energy and fatigue such as hypothyroidism, anemia, and mononucleosis (or other viral syndromes) accounting for the low energy and fatigue need to be considered
• Other mood disorders without a seasonal component such as major depression, bipolar disorder, adjustment disorder, or dysthymia
• Symptoms should not be better accounted for by seasonal psychosocial stressors, which often accompany the winter holiday seasons.
• Substance abuse
TREATMENT
GENERAL MEASURES
Work to reduce stress levels through meditation, progressive relaxation exercises, and/or lifestyle modification.
Activity
• Increase time outdoors during daylight.
• Rearrange home or work environment to get more direct sunlight through windows.
SPECIAL THERAPY
Vitamin D supplementation has been found to be more effective than phototherapy in small studies.
• Phototherapy using special light sources has been shown to be effective in 60-90% of patients often providing relief within a few sessions. (2,4)[B]
- Variables which can regulate effect are
Light intensityAlthough the minimum light source intensity is under investigation, 2,500 lux is suggested (domestic lights emit on average 200-500 lux). There is good evidence for 10,000 lux as the recommended source. (4)[A]
Treatment durationexposure time varies on intensity of light source with daily sessions of 30 minutes to a few hours.
Time of treatmentmost patients respond better by using the light therapy early in the morning.
- Light box is placed on table several feet away and the light is allowed to shine onto the patient's eyes (sunglasses should be avoided). Ensure light box has a UV filter.
- Most common side effects are eye strain and headache. Insomnia can result if the light box is used too late in the day.
- Dawn simulation machines gradually increase illumination while the patient sleeps simulating sunrise while using a significantly less intense light source.
MEDICATION (DRUGS)
There is a lack of evidence to determine whether light therapy or medication should be the 1st-line agent. It depends on the acuity of the patient and the comfort level of the prescribing clinician with each treatment modality, [C].
First Line
Vitamin D supplementation may be beneficial.
• SSRIs such as sertraline (Zoloft), paroxetine (Paxil), fluoxetine (Prozac), citalopram (Celexa) in their traditional antidepressant doses (2)[B]
FOLLOW-UP
Regular monitoring by PCP or psychiatrist for response to treatment. Patients may become manic when treated with SSRIs or light therapy.
DISPOSITION
Admission Criteria
If the patient develops suicidal ideation as part of their depression or mania after treatment is initiated, hospitalization should be considered.
Issues for Referral
• Patients with a history of ocular disease should be referred for an ophthalmologic exam before phototherapy and for serial monitoring.
• Patients who fail to respond to a medication trial or phototherapy should be considered for psychiatric referral.
PROGNOSIS
Symptoms, if untreated, generally remit within 5 months with exposure to spring light only to return in subsequent winters. If treated, patients usually respond within 2-3 weeks.
COMPLICATIONS
Development of suicidal ideation or mania are 2 outcomes which the clinician needs to monitor.
PATIENT MONITORING
Patients should be seen in the outpatient clinic weekly to bi-weekly when initiating light or pharmacotherapy to monitor treatment results, side effects, and any increased suicidal thoughts if using SSRIs. [B]
REFERENCES
1. Saeed SA, Brucw TJ. Seasonal affective disorders. American Family Physician. 1998: 57.
2. Lam RW. Seasonal affective disorder: Diagnosis and management. Primary Care Psychiatry. 1998;4:63-74.
3. Lam RW, Levitan RD. Pathophysiology of seasonal affective disorder: A review. J Psychiatry Neurosci. 2000;25:469-480.
4. Terman M, Terman JS. Light therapy for seasonal and nonseasonal depression: Efficacy, protocol, safety, and side effects. CNS Spectr. 2005;10:647-663.
MISCELLANEOUS
See also: Bipolar disorder
SCLERODERMA
SCLERODERMA - Jeremy Golding, MD
BASICS
DESCRIPTION
• Scleroderma (systemic sclerosis [SSc]) is a chronic disease of unknown cause, characterized by diffuse fibrosis, degenerative changes, and vascular abnormalities in the skin, articular structures, and other organs (kidneys, lung, heart, gastrointestinal and skeletal muscles).
• Most manifestations have vascular features (e.g., Raynaud phenomenon), but frank vasculitis is rarely seen. It can range from a mild disease, affecting the skin, to a systemic disease that can cause death in a few months.
• The disease is categorized into 2 major clinical variants
- Diffuse
Distal and maximal extremity and truncal skin thickening
- Limited
Restricted to the fingers, hands, and face
CREST syndrome (calcinosis, Raynaud phenomenon, poor esophageal mobility, sclerodactyly, telangiectasia) closely analogous with limited scleroderma
• System(s) Affected: Cardiovascular; Gastrointestinal; Musculoskeletal; Pulmonary; Renal/Urologic; Skin/Exocrine
• Synonym(s): Progressive systemic sclerosis (PSS); Morphea
ALERT
Geriatric Considerations
Uncommon >75 years of age
Pediatric Considerations
Rare in this age group
GENERAL PREVENTION
None
EPIDEMIOLOGY
• Predominant age
- Young adult (16-40 years); middle-aged (40-75 years)
- Symptoms usually appear in the 3rd-5th decades.
• Predominant sex: Female > Male (4:1)
Incidence
In the US: 1-2 per 100,00
Prevalence
In the US: 1-25 per 100,000
RISK FACTORS
Unknown
Genetics
Familial clustering is rare, but has been seen.
ETIOLOGY
• Unknown
• Possible alterations in immune response
• Possibly some association with exposure to quartz mining, quarrying, vinyl chloride, hydrocarbons, toxin exposure, and rapeseed oil
• Treatment with bleomycin has caused a sclerodermalike syndrome.
ASSOCIATED CONDITIONS
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Polymyositis
• Overlap (and mixed) connective tissue disease
DIAGNOSIS
SIGNS AND SYMPTOMS
• Skin
- Digital ulcerations
- Tightness, swelling, thickening of digits
- Hyperpigmentation
- Hypopigmentation
- Narrowed oral aperture
- Pruritus
- Scaling of skin
- Subcutaneous calcinosis
• Peripheral vascular system
- Raynaud phenomenon (differentiate from Raynaud disease, generally affecting younger individuals, and without digital ulcers)
- Telangiectasia
• Joints, tendons, and bones
- Flexion contractures
- Friction rub on tendon movement
- Hand swelling
- Joint stiffness
- Polyarthralgia
- Sclerodactyly
• Muscle
- Proximal muscle weakness
- Weakness
• Gastrointestinal tract
- Dysphagia
- Esophageal reflux due to dysmotility (most common systemic sign in diffuse disease)
- Malabsorptive diarrhea
- Nausea and vomiting
- Weight loss
- Xerostomia
• Kidney
- Hypertension
- May develop scleroderma renal crisis: Acute renal failure
• Pulmonary
- Dry crackles at lung bases
- Dyspnea
• Nervous system
- Peripheral neuropathy
- Trigeminal neuropathy
TESTS
• ECG
- Low voltage; possibly nonspecific abnormalities
• Lung function tests
- Decreased diffusion and vital capacity
• Nail fold capillary loop abnormalities
Lab
• Increased ESR
• Normocytic anemia
• Normochromic anemia
• Positive antinuclear antibody (ANA), often with a nucleolar pattern
• Anticentromere antibody (usually associated with limited cutaneous disease)
• Anti-Scl-70 (topoisomerase antibody) is highly specific for systemic disease.
• Albuminuria
• Microscopic hematuria
• Eosinophilia
• Hemolysis
• Hypergammaglobulinemia
• Decreased maximum breathing capacity
• Increased residual volume
• Diffusion defect
• Positive rheumatoid factor test (33%)
Imaging
• Hand radiograph
- Actor-osteolysis
- Soft tissue atrophy
- Subcutaneous calcinosis
• Upper gastrointestinal
- Distal esophageal dilatation
- Atonic esophagus
- Esophageal dysmotility
- Duodenal diverticula
• Barium enema
- Colonic diverticula
- Megacolon
• Chest radiograph
- Diffuse reticular pattern
- Bilateral basilar pulmonary fibrosis
• Gallium67 lung scan
- Can be positive in early interstitial disease
• High-resolution CT scan for detecting alveolitis
- Ground-glass appearance or honeycomb pattern in fibrosis
Diagnostic Procedures/Surgery
• Skin biopsy
- Compact collagen fibers in the reticular dermis and hyalinization and fibrosis of arterioles
- Thinning of epidermis with loss of rete pegs and atrophy of dermal appendages
- Accumulation of mononuclear cells is also seen.
• Right heart catheterization
- Pulmonary hypertension is an ominous prognostic feature.
Pathological Findings
• Skin
- Edema, fibrosis, or atrophy (late stage)
- Lymphocytic infiltrate around sweat glands
- Loss of capillaries
- Endothelial proliferation
- Hair follicle atrophy
• Synovium
- Pannus formation
- Fibrin deposits in tendons
• Kidney
- Small kidneys
- Intimal proliferation in interlobular arteries
• Heart
- Endocardial thickening
- Myocardial interstitial fibrosis
- Ischemic band necrosis
- Enlarged heart
- Cardiac hypertrophy
• Lung
- Interstitial pneumonitis
- Cyst formation
- Interstitial fibrosis
- Bronchiectasis
• Esophagus
- Esophageal atrophy
- Fibrosis
DIFFERENTIAL DIAGNOSIS
• Sclerodermatomyositis
• Mixed connective tissue disease
• Toxic oil syndrome (Madrid, 1981, affecting 20,000 people)
• Eosinophilia-myalgia syndrome
• Diffuse fasciitis with eosinophilia
• Scleredema of Buschke
TREATMENT
GENERAL MEASURES
• Treatment is symptomatic and supportive.
• Esophageal dilatation may be used for strictures.
• Avoid cold; dress appropriately for the weather; be wary of air conditioning.
• Avoid smoking (crucial)
• For chronic digital ulcerations
- Debridement after soaking in 1/2-strength hydrogen peroxide solution
- Digital plaster to immobilize
• Avoid finger sticks (e.g., blood tests).
• Elevate of the head of the bed during sleep to help relieve gastrointestinal symptoms.
• Skin
- Use softening lotions, ointments, and bath oils to help prevent dryness and cracking.
• Dialysis may be necessary in renal crisis.
Diet
• Soft, bland diet with frequent small meals
• Drink plenty of fluids with meals.
Activity
Stay as active as possible, but avoid fatigue.
Physical Therapy
• Physical therapy to maintain function and promote strength
• Heat therapy to relieve joint stiffness
MEDICATION (DRUGS)
First Line
• Few drug therapies have proven value, except for angiotensin-converting enzyme (ACE) inhibitors for hypertensive renal crisis.
• Corticosteroids: For disabling myositis, pulmonary alveolitis, or mixed connective tissue disease
• NSAIDs: For joint or tendon symptoms
• Antibiotics: For secondary infections in bowel
• Antacids or cimetidine: For gastric reflux
• Dipyridamole (Persantine) or aspirin: Antiplatelet therapy
• Hydrophilic skin ointments: Skin therapy
• Topical clindamycin or erythromycin or silver sulfadiazine (Silvadene) cream may prevent recurrent infectious cutaneous ulcers.
- Use systemic antibiotic therapy for active infections.
• Consider immunosuppressives
- Used alone or with plasmapheresis for treatment of life-threatening or potentially crippling scleroderma or interstitial pneumonitis
• Avoidance of caffeine, nicotine, and sympathomimetics may ease Raynaud symptoms
• Vasoactive agents (nitrates) and antihypertensives (dihydropyridine calcium channel blockers): For Raynaud phenomenon
• Penicillamine (D-penicillamine): To reduce skin thickening and delay the rate of new visceral involvement (anecdotally)
• ACE (captopril): For kidney disease
• PDE-5 antagonists (e.g., sildenafil), prostanoids, and endothelin-1 antagonists are changing management of pulmonary hypertension
• Contraindications: Refer to the manufacturer's literature.
• Precautions: Refer to the manufacturer's literature.
• Significant possible interactions: Refer to the manufacturer's literature.
Second Line
Many other drugs are currently under investigation, but no evidence of real benefits have emerged yet.
SURGERY
• Some success with gastroplasty for correction of gastroesophageal reflux
• Limited role for sympathectomy for Raynaud
FOLLOW-UP
DISPOSITION
Outpatient care
Admission Criteria
Inpatient may be considered possibly for some surgical procedures.
PROGNOSIS
• Variable
• Possible improvement, but incurable
• Prognosis is poor if cardiac, pulmonary, or renal manifestations present early.
COMPLICATIONS
• Renal failure
• Respiratory failure
• Flexion contractures
• Disability
• Esophageal dysmotility
• Reflux esophagitis
• Arrhythmia
• Megacolon
• Pneumatosis intestinalis
• Obstructive bowel
• Cardiomyopathy
• Possible association with lung and other cancers
• Death
PATIENT MONITORING
Frequent monitoring of end-organ involvement and medications, and encouragement
REFERENCES
1. Kelley WN, et al., eds. Textbook of Rheumatology, 7th ed. Philadelphia: WB Saunders, 2005.
2. Reveille JD. Evidence-based guidelines for the use of immunologic tests: Anticentromere, SCL-70, and nucleolar antibodies. Arthritis Rheum. 2003;49(3):399-412.
3. Kippel JH, Dippe PR, eds. Rheumatology. St. Louis, MO: Mosby, 1994.
4. Koopman WJ, ed. Arthritis and Allied Disorders, 13th ed. Philadelphia: Lea Febiger, 1997
BASICS
DESCRIPTION
• Scleroderma (systemic sclerosis [SSc]) is a chronic disease of unknown cause, characterized by diffuse fibrosis, degenerative changes, and vascular abnormalities in the skin, articular structures, and other organs (kidneys, lung, heart, gastrointestinal and skeletal muscles).
• Most manifestations have vascular features (e.g., Raynaud phenomenon), but frank vasculitis is rarely seen. It can range from a mild disease, affecting the skin, to a systemic disease that can cause death in a few months.
• The disease is categorized into 2 major clinical variants
- Diffuse
Distal and maximal extremity and truncal skin thickening
- Limited
Restricted to the fingers, hands, and face
CREST syndrome (calcinosis, Raynaud phenomenon, poor esophageal mobility, sclerodactyly, telangiectasia) closely analogous with limited scleroderma
• System(s) Affected: Cardiovascular; Gastrointestinal; Musculoskeletal; Pulmonary; Renal/Urologic; Skin/Exocrine
• Synonym(s): Progressive systemic sclerosis (PSS); Morphea
ALERT
Geriatric Considerations
Uncommon >75 years of age
Pediatric Considerations
Rare in this age group
GENERAL PREVENTION
None
EPIDEMIOLOGY
• Predominant age
- Young adult (16-40 years); middle-aged (40-75 years)
- Symptoms usually appear in the 3rd-5th decades.
• Predominant sex: Female > Male (4:1)
Incidence
In the US: 1-2 per 100,00
Prevalence
In the US: 1-25 per 100,000
RISK FACTORS
Unknown
Genetics
Familial clustering is rare, but has been seen.
ETIOLOGY
• Unknown
• Possible alterations in immune response
• Possibly some association with exposure to quartz mining, quarrying, vinyl chloride, hydrocarbons, toxin exposure, and rapeseed oil
• Treatment with bleomycin has caused a sclerodermalike syndrome.
ASSOCIATED CONDITIONS
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Polymyositis
• Overlap (and mixed) connective tissue disease
DIAGNOSIS
SIGNS AND SYMPTOMS
• Skin
- Digital ulcerations
- Tightness, swelling, thickening of digits
- Hyperpigmentation
- Hypopigmentation
- Narrowed oral aperture
- Pruritus
- Scaling of skin
- Subcutaneous calcinosis
• Peripheral vascular system
- Raynaud phenomenon (differentiate from Raynaud disease, generally affecting younger individuals, and without digital ulcers)
- Telangiectasia
• Joints, tendons, and bones
- Flexion contractures
- Friction rub on tendon movement
- Hand swelling
- Joint stiffness
- Polyarthralgia
- Sclerodactyly
• Muscle
- Proximal muscle weakness
- Weakness
• Gastrointestinal tract
- Dysphagia
- Esophageal reflux due to dysmotility (most common systemic sign in diffuse disease)
- Malabsorptive diarrhea
- Nausea and vomiting
- Weight loss
- Xerostomia
• Kidney
- Hypertension
- May develop scleroderma renal crisis: Acute renal failure
• Pulmonary
- Dry crackles at lung bases
- Dyspnea
• Nervous system
- Peripheral neuropathy
- Trigeminal neuropathy
TESTS
• ECG
- Low voltage; possibly nonspecific abnormalities
• Lung function tests
- Decreased diffusion and vital capacity
• Nail fold capillary loop abnormalities
Lab
• Increased ESR
• Normocytic anemia
• Normochromic anemia
• Positive antinuclear antibody (ANA), often with a nucleolar pattern
• Anticentromere antibody (usually associated with limited cutaneous disease)
• Anti-Scl-70 (topoisomerase antibody) is highly specific for systemic disease.
• Albuminuria
• Microscopic hematuria
• Eosinophilia
• Hemolysis
• Hypergammaglobulinemia
• Decreased maximum breathing capacity
• Increased residual volume
• Diffusion defect
• Positive rheumatoid factor test (33%)
Imaging
• Hand radiograph
- Actor-osteolysis
- Soft tissue atrophy
- Subcutaneous calcinosis
• Upper gastrointestinal
- Distal esophageal dilatation
- Atonic esophagus
- Esophageal dysmotility
- Duodenal diverticula
• Barium enema
- Colonic diverticula
- Megacolon
• Chest radiograph
- Diffuse reticular pattern
- Bilateral basilar pulmonary fibrosis
• Gallium67 lung scan
- Can be positive in early interstitial disease
• High-resolution CT scan for detecting alveolitis
- Ground-glass appearance or honeycomb pattern in fibrosis
Diagnostic Procedures/Surgery
• Skin biopsy
- Compact collagen fibers in the reticular dermis and hyalinization and fibrosis of arterioles
- Thinning of epidermis with loss of rete pegs and atrophy of dermal appendages
- Accumulation of mononuclear cells is also seen.
• Right heart catheterization
- Pulmonary hypertension is an ominous prognostic feature.
Pathological Findings
• Skin
- Edema, fibrosis, or atrophy (late stage)
- Lymphocytic infiltrate around sweat glands
- Loss of capillaries
- Endothelial proliferation
- Hair follicle atrophy
• Synovium
- Pannus formation
- Fibrin deposits in tendons
• Kidney
- Small kidneys
- Intimal proliferation in interlobular arteries
• Heart
- Endocardial thickening
- Myocardial interstitial fibrosis
- Ischemic band necrosis
- Enlarged heart
- Cardiac hypertrophy
• Lung
- Interstitial pneumonitis
- Cyst formation
- Interstitial fibrosis
- Bronchiectasis
• Esophagus
- Esophageal atrophy
- Fibrosis
DIFFERENTIAL DIAGNOSIS
• Sclerodermatomyositis
• Mixed connective tissue disease
• Toxic oil syndrome (Madrid, 1981, affecting 20,000 people)
• Eosinophilia-myalgia syndrome
• Diffuse fasciitis with eosinophilia
• Scleredema of Buschke
TREATMENT
GENERAL MEASURES
• Treatment is symptomatic and supportive.
• Esophageal dilatation may be used for strictures.
• Avoid cold; dress appropriately for the weather; be wary of air conditioning.
• Avoid smoking (crucial)
• For chronic digital ulcerations
- Debridement after soaking in 1/2-strength hydrogen peroxide solution
- Digital plaster to immobilize
• Avoid finger sticks (e.g., blood tests).
• Elevate of the head of the bed during sleep to help relieve gastrointestinal symptoms.
• Skin
- Use softening lotions, ointments, and bath oils to help prevent dryness and cracking.
• Dialysis may be necessary in renal crisis.
Diet
• Soft, bland diet with frequent small meals
• Drink plenty of fluids with meals.
Activity
Stay as active as possible, but avoid fatigue.
Physical Therapy
• Physical therapy to maintain function and promote strength
• Heat therapy to relieve joint stiffness
MEDICATION (DRUGS)
First Line
• Few drug therapies have proven value, except for angiotensin-converting enzyme (ACE) inhibitors for hypertensive renal crisis.
• Corticosteroids: For disabling myositis, pulmonary alveolitis, or mixed connective tissue disease
• NSAIDs: For joint or tendon symptoms
• Antibiotics: For secondary infections in bowel
• Antacids or cimetidine: For gastric reflux
• Dipyridamole (Persantine) or aspirin: Antiplatelet therapy
• Hydrophilic skin ointments: Skin therapy
• Topical clindamycin or erythromycin or silver sulfadiazine (Silvadene) cream may prevent recurrent infectious cutaneous ulcers.
- Use systemic antibiotic therapy for active infections.
• Consider immunosuppressives
- Used alone or with plasmapheresis for treatment of life-threatening or potentially crippling scleroderma or interstitial pneumonitis
• Avoidance of caffeine, nicotine, and sympathomimetics may ease Raynaud symptoms
• Vasoactive agents (nitrates) and antihypertensives (dihydropyridine calcium channel blockers): For Raynaud phenomenon
• Penicillamine (D-penicillamine): To reduce skin thickening and delay the rate of new visceral involvement (anecdotally)
• ACE (captopril): For kidney disease
• PDE-5 antagonists (e.g., sildenafil), prostanoids, and endothelin-1 antagonists are changing management of pulmonary hypertension
• Contraindications: Refer to the manufacturer's literature.
• Precautions: Refer to the manufacturer's literature.
• Significant possible interactions: Refer to the manufacturer's literature.
Second Line
Many other drugs are currently under investigation, but no evidence of real benefits have emerged yet.
SURGERY
• Some success with gastroplasty for correction of gastroesophageal reflux
• Limited role for sympathectomy for Raynaud
FOLLOW-UP
DISPOSITION
Outpatient care
Admission Criteria
Inpatient may be considered possibly for some surgical procedures.
PROGNOSIS
• Variable
• Possible improvement, but incurable
• Prognosis is poor if cardiac, pulmonary, or renal manifestations present early.
COMPLICATIONS
• Renal failure
• Respiratory failure
• Flexion contractures
• Disability
• Esophageal dysmotility
• Reflux esophagitis
• Arrhythmia
• Megacolon
• Pneumatosis intestinalis
• Obstructive bowel
• Cardiomyopathy
• Possible association with lung and other cancers
• Death
PATIENT MONITORING
Frequent monitoring of end-organ involvement and medications, and encouragement
REFERENCES
1. Kelley WN, et al., eds. Textbook of Rheumatology, 7th ed. Philadelphia: WB Saunders, 2005.
2. Reveille JD. Evidence-based guidelines for the use of immunologic tests: Anticentromere, SCL-70, and nucleolar antibodies. Arthritis Rheum. 2003;49(3):399-412.
3. Kippel JH, Dippe PR, eds. Rheumatology. St. Louis, MO: Mosby, 1994.
4. Koopman WJ, ed. Arthritis and Allied Disorders, 13th ed. Philadelphia: Lea Febiger, 1997