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peds.reye-syndrome.v1

Reye syndrome

pediatricsacutepediatricacuteinpatient
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NEW pediatric dossier (lane-D 2026-05-26). Manifest authored at prisma/seed/manifests/peds.reye-syndrome.v1.ts. All RxCUIs RxNav-verified (forward + reverse) on 2026-05-26: mannitol 6628, glucose (dextrose) 4850, phytonadione (vitamin K1) 8308, lactulose 6218, lorazepam 6470, levetiracetam 114477. Hypertonic saline 3% and FFP / cryoprecipitate are non_pharm composites (no single RxCUI). PMIDs verified via PubMed MCP on 2026-05-26: 10228187 Belay NEJM 1999 CDC surveillance Reye syndrome 1981-1997 (canonical post-aspirin-warning epidemiology + risk factors); 26900382 Glauser AES 2016 pediatric status epilepticus (cross-reference for Reye-induced seizures with valproate + phenytoin avoidance). Workup IDs omitted as not in registry: reye_syndrome, iem_screen, hyperammonemia, acute_liver_failure — used safe registry workups: workup.encephalopathy, workup.first_seizure, workup.pediatric_fever. Calculator gaps: Lovejoy/Hurwitz stages, King's College criteria for transplant not in registry; used calc.gcs + calc.anion_gap + calc.meld_na (adult-validated, supplemental use) for severity / risk stratification. Largely supportive workflow — no specific antidote per Belay NEJM 1999; treatment is hyperosmolar for cerebral edema, aggressive dextrose for hypoglycemia, vitamin K + FFP for coagulopathy, lactulose for hyperammonemia, transfer to pediatric liver transplant center. Safety: NEVER give valproate (FDA black box for Reye + mitochondrial); AVOID phenytoin (hepatic enzyme inducer); levetiracetam preferred AED. Sibling differentiation from peds.toxic-ingestions.v1 (toxic ALF) and peds.status_epilepticus.v1 (with valproate / phenytoin contraindications).

Entry points (4)

  • symptom
    Intractable vomiting + altered MS in child / adolescent 3-7 days after viral illness (especially influenza B / varicella) (Belay NEJM 1999 PMID 10228187)
    intractable_vomiting_after_viral_illness
  • symptom
    Progressive encephalopathy + behavior change + lethargy in child post-viral (Belay NEJM 1999)
    progressive_encephalopathy_child
  • history
    Aspirin or salicylate-containing medication (Pepto-Bismol, oil of wintergreen) given during viral illness in child < 19 yr (Belay NEJM 1999)
    aspirin_use_during_viral_illness_child
  • lab_abnormality
    Elevated AST/ALT > 3× ULN + ammonia > 1.5× ULN + minimal jaundice in child — Reye-syndrome differential (CDC surveillance criteria)
    elevated_lft_ammonia_no_jaundice_child

Required inputs (18)

  • agerequired
    demographic • used at CONTEXT
    Age < 5 yr highest mortality risk (relative risk 1.8 — Belay NEJM 1999 PMID 10228187)
  • weightrequired
    demographic • used at CONTEXT
    All dosing (hyperosmolar therapy, dextrose, AED loading, vitamin K) weight-based (AAP Red Book 2024-2027, Lexicomp Peds)
  • recent_viral_illness_timingrequired
    history • used at FRAME
    Prodromal viral illness 3-7 days before onset is canonical (Belay NEJM 1999)
  • aspirin_or_salicylate_exposurerequired
    history • used at FRAME
    Aspirin during viral illness is the historical trigger; 82% of cases had detectable blood salicylates (Belay NEJM 1999)
  • family_history_metabolic_diseaserequired
    history • used at CONTEXT
    Family history of IEM or unexplained infant death raises probability of metabolic mimic (Belay NEJM 1999)
  • gcsrequired
    vital • used at RED_FLAGS
    Lovejoy/Hurwitz staging anchor; airway protection threshold
  • sbprequired
    vital • used at RED_FLAGS
    Cushing's triad (HTN + bradycardia) signals ICP crisis
  • hrrequired
    vital • used at RED_FLAGS
    Bradycardia in Cushing's triad
  • rrrequired
    vital • used at RED_FLAGS
    Hyperventilation in stage 2; apnea / Cheyne-Stokes in late stages
  • glucose_fingerstickrequired
    lab • used at INITIAL_WORKUP
    Hypoglycemia common (depleted glycogen + impaired gluconeogenesis); reversible (Belay NEJM 1999)
  • ammoniarequired
    lab • used at INITIAL_WORKUP
    Ammonia > 45 mcg/dL → relative risk 3.4 for death (Belay NEJM 1999)
  • lft_inrrequired
    lab • used at INITIAL_WORKUP
    AST/ALT > 3× ULN with minimal jaundice + INR elevation = hepatic synthetic dysfunction (CDC criteria)
  • bmp_anion_gaprequired
    lab • used at INITIAL_WORKUP
    Anion gap acidosis flags toxic / metabolic mimic (Belay NEJM 1999)
  • salicylate_levelrequired
    lab • used at INITIAL_WORKUP
    Confirms aspirin exposure + rules out salicylate toxicity mimic (Belay NEJM 1999)
  • lactaterequired
    lab • used at INITIAL_WORKUP
    Lactic acidosis flags mitochondrial / FAO defect mimic (CDC differential)
  • plasma_acylcarnitine_amino_acidsrequired
    lab • used at BRANCHING_WORKUP
    FAO defects (MCAD, LCHAD, VLCAD) + urea cycle disorders + organic acidemias mimic Reye (Belay NEJM 1999 — IEM workup mandated since 1980 warning)
  • urine_organic_acids_acylglycinesrequired
    lab • used at BRANCHING_WORKUP
    Definitive screen for organic acidemias + FAO defects (CDC differential)
  • head_ct_then_mrirequired
    imaging • used at INITIAL_WORKUP
    Cerebral edema visualization + rule out alternative (CDC differential)

12-phase flow (12)

  1. 1FRAME
    Confirm CDC surveillance criteria: encephalopathy + acute non-inflammatory hepatopathy (AST/ALT > 3× ULN OR ammonia > 1.5× ULN OR microvesicular fatty hepatocellular changes on biopsy) + no other reasonable explanation; aspirin exposure during preceding viral illness (Belay NEJM 1999 PMID 10228187)
    inputs: recent_viral_illness_timing, aspirin_or_salicylate_exposure, lft_inr, ammonia
    advance: Criteria considered + IEM workup launched in parallel
  2. 2ENTRY
    Intractable vomiting + altered MS + behavior change in child / adolescent 3-7 days after viral illness (Belay NEJM 1999)
    inputs: age
    advance: Entry trigger captured + ICU notified
  3. 3CONTEXT
    Age (peak 4-12 yr; < 5 yr worst prognosis), prodromal viral illness (influenza B, varicella), aspirin / salicylate exposure including Pepto-Bismol + oil of wintergreen, family history of IEM (Belay NEJM 1999)
    inputs: weight, family_history_metabolic_disease
    advance: Context complete
  4. 4RED_FLAGS
    Lovejoy/Hurwitz stages 1-5: Stage 1 quiet + vomiting → Stage 2 deep coma + hyperventilation + hyperreflexia → Stage 3 obtunded + decorticate posturing → Stage 4 deepening coma + decerebrate + brainstem dysfunction → Stage 5 flaccid + apneic + areflexic + isoelectric EEG (death); Cushing's triad; rising ammonia (Belay NEJM 1999)
    inputs: gcs, sbp, hr, rr, ammonia
    advance: Stage assigned + life-threatening features identified + ABC addressed
  5. 5INITIAL_WORKUP
    Comprehensive metabolic panel (glucose, BMP, anion gap); LFTs + ammonia + INR; CBC; ABG; salicylate level; acetaminophen level; urine + serum toxicology; lactate; CK; head CT (then MRI); lumbar puncture (after CT) to rule out meningoencephalitis; consider liver biopsy (microvesicular fatty change) if diagnosis uncertain (Belay NEJM 1999; CDC surveillance criteria)
    inputs: glucose_fingerstick, ammonia, lft_inr, bmp_anion_gap, salicylate_level, lactate, head_ct_then_mri
    actions: workup.encephalopathy, panel.lft, panel.cbc, panel.renal, panel.coag, panel.metabolic, panel.abg
    advance: Baseline labs returned + IEM workup launched + transfer to transplant center considered
  6. 6BRANCHING_WORKUP
    MANDATORY metabolic workup to exclude IEM: plasma amino acids + plasma acylcarnitine profile + urine organic acids + urine acylglycines + free and total carnitine + very-long-chain fatty acids + biotinidase + repeat ammonia + lactate-to-pyruvate ratio; muscle / liver biopsy if persistent diagnostic uncertainty; MRI brain (Belay NEJM 1999 — IEM workup mandated since aspirin warning)
    inputs: plasma_acylcarnitine_amino_acids, urine_organic_acids_acylglycines
    advance: Metabolic workup launched + metabolism / genetics consulted
  7. 7DIFFERENTIAL
    Reye syndrome (rare in 2020s; presumes aspirin exposure) vs MCAD deficiency vs other FAO defects (LCHAD, VLCAD, CPT) vs urea cycle disorders (OTC) vs organic acidemias (propionic, methylmalonic) vs Reye-like illness without aspirin trigger vs toxin-induced ALF (APAP, mushroom) vs viral encephalitis vs MELAS / mitochondrial vs glutaric aciduria (Belay NEJM 1999; CDC differential)
    advance: Differential narrowed + IEM mimics actively investigated
  8. 8RISK_STRATIFICATION
    Lovejoy / Hurwitz stages 1-5; ammonia > 45 mcg/dL relative risk 3.4 for death; age < 5 yr relative risk 1.8 (Belay NEJM 1999); PALF King's College transplant criteria if hepatic failure
    inputs: ammonia, age
    advance: Risk tier + stage documented
  9. 9TREATMENT
    Largely supportive; NO specific antidote. Step 1: PICU admission + ABC; Step 2: hyperosmolar therapy for cerebral edema (mannitol 0.25-1 g/kg IV q4-6h OR hypertonic saline 3% NaCl 3-5 mL/kg IV bolus); Step 3: aggressive hypoglycemia management — D10W 5 mL/kg IV bolus then GIR 6-8 mg/kg/min titrated to glucose 100-200; Step 4: FFP + cryoprecipitate + vitamin K 0.3 mg/kg IV/IM/SC max 10 mg for coagulopathy; Step 5: lactulose 1 mL/kg PO/PR q2-4h for hyperammonemia / hepatic encephalopathy; Step 6: seizure management (lorazepam 0.1 mg/kg IV abortive → levetiracetam 20-40 mg/kg IV load + 30-60 mg/kg/day BID; AVOID valproate — worsens mitochondrial); Step 7: early transfer to pediatric liver transplant center (Belay NEJM 1999; AES 2016 Glauser PMID 26900382)
    inputs: weight, glucose_fingerstick, ammonia
    advance: Supportive plan documented + transplant center contacted
  10. 10DISPOSITION
    PICU mandatory; transfer to pediatric liver transplant center; CDC notification (Reye syndrome historically reportable; surveillance system continues per CDC) (Belay NEJM 1999)
    advance: Disposition + transfer documented
  11. 11MONITORING
    q1h neuro + ICP if bolt + glucose q1h + ammonia trend + LFT/INR trend + cEEG if intubated + K+ trend (Belay NEJM 1999; AES 2016)
    advance: Monitoring orders documented
  12. 12FOLLOWUP
    Pediatric hepatology + neurology (cognitive impairment in significant fraction of survivors per Belay 1999) + genetics + metabolism (lifetime IEM monitoring even if initial workup negative) + family education (NEVER give aspirin to children < 19 yr unless specifically prescribed) + school re-entry plan (Belay NEJM 1999; CDC)
    advance: Follow-up + family education + IEM monitoring plan documented