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Reye Syndrome, Emergency Medicine

Basics

Description

- 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

- 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

- No focal neurologic signs - Hepatomegaly in 40% of cases - Pancreatitis - Clinical staging of Reye syndrome with Lovejoy classification: - Stage 0: - Stage I: - Vomiting - Lethargy - Sleepiness

- 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

- 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

- Interventions aimed at lowering ICP: - Stage III or greater - Stage II with serum ammonia >300 Όg/L: - Intubation using rapid-sequence protocol - Hyperventilation - Fluid restriction - Barbiturate coma

- Osmotically active agents: - Monitor ICP: - Subarachnoid bolt - Intraventricular cannula

  • Reversible clinicopathologic syndrome of unknown etiology
  • Primary mitochondrial injury
  • Decreased enzyme activity:Krebs cycleGluconeogenesisUrea biosynthesis
  • Fatty infiltration:Liver:Hyperammonemia due to decreased conversion from ammonia to ureaHepatorenal syndrome may be the end result.Rapid recovery of liver function in survivorsBrain:Encephalopathy of unclear etiologyCytotoxic edemaDeteriorating level of consciousness reflects increasing intracranial pressure (ICP).Herniation is the most common cause of death.Normal recovery of neurologic function in survivorsSkeletal and myocardial muscleFatty infiltration and distorted mitochondria
  • <10% of cases occur before the age of 1 yr:Average age is 7 yrPeak age is 4 " 11 yrExtremely rare in age >18 yr.
  • Regional differences:Highest incidence in the Midwestern statesLower 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

Etiology

  • Not known with certainty
  • Multifactorial causes have been epidemiologically implicated:Antecedent viral syndromeInfluenza A or BVaricellaDiarrhea illnessGenetic predispositionExposure to salicylatesOther undefined factors

Diagnosis

Signs and Symptoms

  • Usually the patient is afebrile.
  • Tachycardia
  • Hyperventilation

History

  • 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

Physical Exam

  • No focal neurologic signs
  • Hepatomegaly in 40% of cases
  • Pancreatitis
  • Clinical staging of Reye syndrome with Lovejoy classification:Stage 0:Stage I:VomitingLethargySleepinessStage II:DisorientationDeliriumCombative/stuporousHyperventilationHyperreflexiaAppropriate response to noxious stimuliStage III:ObtundedComaHyperventilationInappropriate response to noxious stimuliDecorticate posturingPreservation of pupillary light reflexesPreservation of oculovestibular light reflexesStage IV:Deeper comaDecerebrate rigidityLoss of oculovestibular reflexesDilated, fixed pupilsDisconjugate eye movements in response to caloric stimulationStage V:SeizuresAbsent deep tendon reflexesRespiratory arrestFlaccid paralysisNo papillary response
  • Infants: Atypical presentation:TachypneaApneaIrritabilitySeizuresHypoglycemia

Essential Workup

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

Diagnosis Tests & Interpretation

Lab

  • Liver function tests: ≥3 rise in aspartate aminotransferase, alanine aminotransferaseSerum ammonia level >1.5 " 3 normal:Transient 24 " 48 hr after mental status changesLevel >300 Όg/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

Imaging

Head CT scan:

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

Diagnostic Procedures/Surgery

  • Lumbar puncture:Perform after head CTMeasure opening pressure<8 leukocytes/mm3
  • Percutaneous liver biopsy:Useful in patients with atypical presentation (1 yr old, recurrent, familial)

Differential Diagnosis

  • Inborn errors of metabolism:Disorders of the urea cycleDisorders of fatty acid oxidationSystemic carnitine deficiencyOrganic acidemiasDisorders of the electron transport chain
  • Hypoglycemia
  • Toxin exposure:Toxic encephalopathy without liver dysfunction (Gall syndrome)LeadHydrocarbons
  • Drug intoxication:AcetaminophenSalicylatesEthanol
  • Infection:SepsisMeningitisEncephalitisVaricella hepatitis
  • Trauma, head

Treatment

Pre-Hospital

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

Initial Stabilization/Therapy

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

Ed Treatment/Procedures

  • Institute treatment before the liver biopsy.
  • Vitamin K:Indicated if prothrombin time is elevated.
  • Fresh-frozen plasma:To control bleedingTo correct a severe coagulopathy
  • Interventions aimed at lowering ICP:Stage III or greaterStage II with serum ammonia >300 Όg/L:Intubation using rapid-sequence protocolHyperventilationFluid restrictionBarbiturate coma
  • Osmotically active agents:
  • Monitor ICP:Subarachnoid boltIntraventricular cannula

Medication

  • D50W: 1 " 2 mL/kg/dose (0.5 " 1 g/kg) IV for age >3 yr
  • D25W: 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

Disposition

Admission Criteria

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

Discharge Criteria

Hospital discharge criteria are individualized for each case:

  • Mental status and lab values have improved and stabilized.

Issues for Referral

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

Followup Recommendations

Long-term psychological and neuropsychological testing

Pearls and Pitfalls

  • 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.

Additional Reading

  • 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 & Cherrys 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.
  • Schr Άr 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

ICD9

331.81 Reyes syndrome

ICD10

G93.7 Reyes syndrome

SNOMED

  • 74351001 Reyes syndrome (disorder)