Rosen & Barkin's 5-Minute Emergency Medicine Consult (620 page)

• Gosalakkal JA, Kamoji V. Reye syndrome and Reye-like syndrome.
  Pediatr Neurol
  . 2008;39:198–200.
  
• Hurwitz ES. Reye syndrome. In: Feigin RD, Cherry JD, Demmler-Harrison GJ, et al., eds.
  Feigin & Cherry’s Textbook of Pediatric Infectious Diseases.
  6th ed. Philadelphia, PA: WB Saunders; 2009:693–694.
  
• National Reye’s Syndrome Foundation. Available at
  www.reyessyndrome.org
  . Accessed on January 28, 2013.
  
• Pugliese A, Beltramo T, Torre D. Reye’s and Reye’s-like syndromes.
  Cell Biochem Funct
  . 2008;26:741–746.
  
• Schrör K. Aspirin and Reye syndrome: A review of the evidence.
  Paediatr Drugs
  . 2007;9:195–204.
  

See Also (Topic, Algorithm, Electronic Media Element)

• Altered Mental Status
  
• Coma
  
• Influenza
  
• Varicella
  
• Salicylates
  

CODES

331.81 Reye's syndrome

BASICS

Abnormal systemic release of muscle contents—creatine phosphokinase (CPK), myoglobin, potassium, phosphate, urate—caused by trauma, poisoning, infection, primary muscle disorders, and many other disease states. Complications include:

• Myoglobin-induced renal failure in 15–50% adults, only 5% in children
  
• Hyperkalemia may lead to sudden death
  
• Hypocalcemia and acidosis
  
• Volume loss—fluid sequestration in injured muscle or result of underlying illness
  
• Compartment syndrome of muscles in crush, worsened by IV fluid sequestration in damaged tissue
  
• Hepatic dysfunction in 25%
  
• DIC (Disseminated intravascular coagulation)
  

• 26,000 per year in US
  
• Disaster situations lead to 100s of cases of renal failure.
  

• Inherited myopathy
  
• Alcohol or drug use
  
• Medications as listed below
  
• Overexertion with or without risk factors
  

• Sarcolemma keeps intracellular calcium low.
  
• Etiologies disrupt cell membrane and lead to following cascade.
  
• Breakdown of sarcolemma Na–Ca pumps allows calcium to enter cell.
  
• Calcium-dependent proteases cause destruction.
  
• Ischemia and neutrophils cause damage.
  
• Escape of cell contents: Myoglobin, potassium, phosphate, CPK, lactate, etc.
  
• Myoglobin causes renal damage by direct toxicity in acidic urine.
  
• Myoglobin precipitates with other proteins to obstruct renal tubular flow.
  
• Volume depletion also leads to renal vasoconstriction and failure.
  
• Hyperkalemia can lead to arrhythmias.
  
• Calcium precipitates with phosphate, leading to systemic hypocalcemia.
  

Cause usually obvious, but not always.

Adults: Trauma, toxicity, infection

Children: Viral myositis, trauma

• Muscle injury—due to trauma/crush, burn, electrical shock—most common cause overall.
  
• Muscle exertion: Strenuous exercise; marathon running; exercise in hot, humid conditions; exercise in individuals with an inherited myopathy or with poor physical training; status epilepticus; delirium tremens; tetanus; psychotic agitation
  
• Muscle ischemia: Extensive thrombosis, multiple embolism, generalized shock, sickle cell crisis
  
• Surgery: Immobilization, hypotension, ischemia due to vessel clamping
  
• Massive blood transfusion
  
• Hypothermia, hyperthermia
  
• Prolonged immobile state without trauma
  
• Drugs/toxins: Alcohols, cocaine, amphetamines, and analogs (methamphetamine and ecstasy), toluene, opiates, LSD, phencyclidine (PCP), caffeine, carbon monoxide, snake venom, bee/hornet venom, hemlock, buffalo fish, tetanus toxin, mushroom poisoning (
  Tricholoma equestre
  )
  
• Medications: Most common—haloperidol, phenothiazines, HMG–CoA reductase inhibitors (statins) and other cholesterol-lowering agents, antihistamines, selective serotonin receptor inhibitors (SSRIs).
  
• Sports supplements including ephedra, caffeine, androgenic steroids, creatine, diuretics
  
• Neuroleptic malignant syndrome (idiosyncratic and not dose-related)
  
• Metabolic disorders: Hypokalemia, hypophosphatemia, hypocalcemia, hyper- and hyponatremia, diabetic ketoacidosis, hyperosmolar state, hypoxia, hyperthyroid state (rare), pheochromocytoma (rare)
  
• Infections:
  
  • Viral: Coxsackievirus, herpesviruses, HIV, influenza B, cytomegalovirus, Epstein–Barr virus, adeno/echovirus
    
  • Bacterial: Legionnaires’ disease, pyomyositis, salmonellosis, shigellosis,
    Staphylococcus, Streptococcus, Listeria,
    tetanus, toxic shock syndrome, tularemia, gas gangrene,
    Bacillus cereus
    
  • Parasitic (
    Plasmodium falciparum
    ), protozoan (leptospirosis), rickettsial
    
  • Inherited myopathic disorders: McArdle disease, Tarui disease, CPT deficiency.
    
• Immunologic disorders: Dermatomyositis, polymyositis
  
• Idiopathic
  

• Crush syndrome
  
• Compartment syndrome
  
• Alcohol and drug abuse
  
• Elderly and acutely immobile (found on floor)
  

DIAGNOSIS

• Can vary dramatically, reflecting underlying disease process.
  
• Trauma or crush usually obvious.
  
• Consider nonaccidental trauma with unclear details of history.
  
• If no trauma, consider in drug toxicity, heat illness, immobilization, or overexertion states.
  
• Ask about reddish brown urine and decreased urine output
  
• Most nontraumatic cases in children <9 yr old are due to viral illness with myositis
  

• Hypothermia/hyperthermia
  
• Alert/obtunded
  
• Muscle pain (only 40–50%)
  
• Neurovascular status of involved muscle groups if compartment syndrome is suspected.
  
• Hypovolemic state, dry mucous membranes, poor skin turgor, tachycardia, hypotension
  
• Decreased urine output
  
• Urine color (tea-colored) is early sign
  
• Children more often have absent physical findings
  

Initial lab tests

• History and physical exam are insensitive in making the diagnosis
  
• Serum and urine myoglobin levels often normal due to rapid metabolism and excretion.
  
• Serum CPK level >1,000 (standard) considered positive
  
• CPK level not always predictive of renal failure but most often associated with level >15,000
  
• Urine dipstick test positive for heme but absent for RBCs suggests rhabdomyolysis
  
• Microscopic urinalysis to look for pigmented tubular casts
  
• Because of rapid urinary excretion of myoglobin, some patients with rhabdomyolysis have negative urine dipstick test.
  
• In children, heme <2+ on urine dip correlates with reduced risk of acute renal failure (ARF)
  
• Serum electrolytes (potassium, calcium, magnesium, phosphorus, BUN, creatinine, uric acid, bicarbonate)
  
• In addition to above consider:
  
  • Arterial and venous blood gases (ABG/VBG) (baseline pH if considering bicarbonate therapy).
    
  • Urine/serum myoglobin, but may be too transient to be useful
    
  • Serum glucose
    
  • LFTs including GGTP, LDH, albumin
    
  • Toxicology screen in absence of physical injury
    
  • PT/PTT, platelet count, fibrinogen, fibrin split products if DIC is suspected
    

• Renal US to rule out long-standing renal failure (small, shrunken kidneys) or renal obstruction (hydronephrosis)
  
• MRI is 90–95% sensitive in visualizing muscle injury but does not change initial ED treatment.
  
• Other imaging as indicated
  

• Early ECG: Hyperkalemia or hypocalcemia before serum levels available
  
• Measure compartment pressure if compartment syndrome is suspected.
  

Conditions that may present with elevated serum CPK but are not rhabdomyolysis:

• Nontraumatic myopathies including muscular dystrophies and inherited myopathies
  
• Chronic renal failure
  
• IM injections
  
• Myocardial injury
  
• Stroke
  

TREATMENT