Rosen & Barkin's 5-Minute Emergency Medicine Consult (619 page)

• Reversible clinicopathologic syndrome of unknown etiology
  
• Primary mitochondrial injury
  
• Decreased enzyme activity:
  
  • Krebs cycle
    
  • Gluconeogenesis
    
  • Urea biosynthesis
    
• Fatty infiltration:
  
  • Liver:
    
    • Hyperammonemia due to decreased conversion from ammonia to urea
      
    • Hepatorenal syndrome may be the end result.
      
    • Rapid recovery of liver function in survivors
      
  • Brain:
    
    • Encephalopathy of unclear etiology
      
    • Cytotoxic edema
      
    • Deteriorating level of consciousness reflects increasing intracranial pressure (ICP).
      
    • Herniation is the most common cause of death.
      
    • Normal recovery of neurologic function in survivors
      
  • Skeletal and myocardial muscle
    
  • Fatty infiltration and distorted mitochondria
    
• <10% of cases occur before the age of 1 yr:
  
  • Average age is 7 yr
    
  • Peak age is 4–11 yr
    
  • Extremely rare in age >18 yr.
    
• Regional differences:
  
  • Highest incidence in the Midwestern states
    
  • Lower incidence in the states of the Southeast and far West
    
• More common in whites than in blacks
  
• Peak incidence in winter and early spring
  
• Reye-like syndrome:
  
  • Describes conditions resulting in defects in urea and fatty acid metabolism, toxicologic injury, and impaired gluconeogenesis
    

• Not known with certainty
  
• Multifactorial causes have been epidemiologically implicated:
  
  • Antecedent viral syndrome
    
  • Influenza A or B
    
  • Varicella
    
  • Diarrhea illness
    
  • Genetic predisposition
    
  • Exposure to salicylates
    
  • Other undefined factors
    

DIAGNOSIS

• Usually the patient is afebrile.
  
• Tachycardia
  
• Hyperventilation
  

• Biphasic history marked by an infectious phase (viral illness or prodrome) followed by an encephalopathic stage
  
• Profuse and repeated vomiting:
  
  • Typically 4–5 days after the start of the viral illness
    
• Marked behavioral changes, including delirium and combativeness, disorientation, and hallucination
  

• No focal neurologic signs
  
• Hepatomegaly in 40% of cases
  
• Pancreatitis
  
• Clinical staging of Reye syndrome with Lovejoy classification:
  
  • Stage 0:
    
    • Wakeful
      
  • Stage I:
    
    • Vomiting
      
    • Lethargy
      
    • Sleepiness
      
  • Stage II:
    
    • Disorientation
      
    • Delirium
      
    • Combative/stuporous
      
    • Hyperventilation
      
    • Hyperreflexia
      
    • Appropriate response to noxious stimuli
      
  • Stage III:
    
    • Obtunded
      
    • Coma
      
    • Hyperventilation
      
    • Inappropriate response to noxious stimuli
      
    • Decorticate posturing
      
    • Preservation of pupillary light reflexes
      
    • Preservation of oculovestibular light reflexes
      
  • Stage IV:
    
    • Deeper coma
      
    • Decerebrate rigidity
      
    • Loss of oculovestibular reflexes
      
    • Dilated, fixed pupils
      
    • Disconjugate eye movements in response to caloric stimulation
      
  • Stage V:
    
    • Seizures
      
    • Absent deep tendon reflexes
      
    • Respiratory arrest
      
    • Flaccid paralysis
      
    • No papillary response
      
• Infants: Atypical presentation:
  
  • Tachypnea
    
  • Apnea
    
  • Irritability
    
  • Seizures
    
  • Hypoglycemia
    

• Establish the presence of encephalopathy and liver abnormalities.
  
• Lab testing to assess for characteristic biochemical abnormalities
  
• Liver biopsy confirms the diagnosis.
  

• Liver function tests:
  
  • ≥3× rise in aspartate aminotransferase, alanine aminotransferase
    
  • Serum ammonia level >1.5–3× normal:
    
    • Transient 24–48 hr after mental status changes
      
    • Level >300 μg/dL is associated with poor prognosis.
      
  • Serum bilirubin should be normal or slightly elevated.
    
• Hypoglycemia may be present, especially in infants.
  
• Elevated BUN
  
• Ketonuria
  
• The prothrombin time may be prolonged due to decreased liver-dependent clotting factors (II, VII, IX, X).
  
• Normal platelet count and blood smear
  
• Negative toxicology screen
  

Head CT scan:

• May show diffuse cerebral edema
  
• Edema is diffuse, and lumbar puncture is not contraindicated.
  

• Lumbar puncture:
  
  • Perform after head CT
    
  • Measure opening pressure
    
  • <8 leukocytes/mm
    ³
    
• Percutaneous liver biopsy:
  
  • Useful in patients with atypical presentation (1 yr old, recurrent, familial)
    

• Inborn errors of metabolism:
  
  • Disorders of the urea cycle
    
  • Disorders of fatty acid oxidation
    
  • Systemic carnitine deficiency
    
  • Organic acidemias
    
  • Disorders of the electron transport chain
    
• Hypoglycemia
  
• Toxin exposure:
  
  • Toxic encephalopathy without liver dysfunction (Gall syndrome)
    
  • Lead
    
  • Hydrocarbons
    
• Drug intoxication:
  
  • Acetaminophen
    
  • Salicylates
    
  • Ethanol
    
• Infection:
  
  • Sepsis
    
  • Meningitis
    
  • Encephalitis
    
  • Varicella hepatitis
    
• Trauma, head
  

TREATMENT

• Decreased mental status:
  
  • Glucose
    
  • Narcan
    
• Coma:
  
  • Assist respirations with bag-valve mask.
    

• Place on a cardiorespiratory monitor.
  
• Supplemental oxygen
  
• Rapid-sequence intubation if airway management required
  
• Glucose if mental status is altered:
  
  • 10% glucose solution IV
    
  • Rate of 2/3 maintenance requirement after dehydration is corrected
    
  • Follow serum glucose hourly; maintain glucose 125–175 mg/dL.
    
• Avoid early overhydration.
  

• Institute treatment before the liver biopsy.
  
• Vitamin K:
  
  • Indicated if prothrombin time is elevated.
    
• Fresh-frozen plasma:
  
  • To control bleeding
    
  • To correct a severe coagulopathy
    
• Interventions aimed at lowering ICP:
  
  • Stage III or greater
    
  • Stage II with serum ammonia >300 μg/L:
    
    • Intubation using rapid-sequence protocol
      
    • Hyperventilation
      
    • Fluid restriction
      
    • Barbiturate coma
      
• Osmotically active agents:
  
  • Mannitol
    
  • Furosemide
    
• Monitor ICP:
  
  • Subarachnoid bolt
    
  • Intraventricular cannula
    

• D
  ₅₀
  W: 1–2 mL/kg/dose (0.5–1 g/kg) IV for age >3 yr
  
• D
  ₂₅
  W: 2–4 mL/kg/dose (0.5–1 mg/kg) IV for age of <3 yr; maintenance infusion 10% dextrose solution at a rate of 2/3 maintenance
  
• Fresh-frozen plasma: 10 mL/kg/dose q12–24h IV or PRN
  
• Lasix: 1 mg/kg IV
  
• Mannitol: 0.25–1 g/kg IV q4–6h
  
• Pentobarbital: 3–5 mg/kg IV slowly while monitoring BP; maintenance infusion 1–2 mg/kg/h; maintain level at 2–5 mg/L
  
• Vitamin K: 1–2 mg/dose IV slowly (infants and children); 2–10 mg/dose IV (adolescents)
  

FOLLOW-UP

• All children with suspected Reye syndrome should be admitted to the ICU.
  
• Hospital capable of ICP monitoring
  

Hospital discharge criteria are individualized for each case:

• Mental status and lab values have improved and stabilized.
  

Close follow-up with specialists in gastroenterology (hepatology) and neurology

Long-term psychological and neuropsychological testing

• Aspirin and salicylates are found in many medications and combination products.
  
• All efforts must be directed at identifying other possible causes of illness in the patient with suspected Reye syndrome.
  
• Monitoring and control of intracranial pressure is a key component of treatment.