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peds.reye-syndrome.v1

Reye syndrome

pediatricsacutepediatric
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Care setting:

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

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
4
Actions
0
Advance rule
Set
Advance when

Criteria considered + IEM workup launched in parallel

Patient inputs (18)

FAO defects (MCAD, LCHAD, VLCAD) + urea cycle disorders + organic acidemias mimic Reye (Belay NEJM 1999 — IEM workup mandated since 1980 warning)

Definitive screen for organic acidemias + FAO defects (CDC differential)

Age < 5 yr highest mortality risk (relative risk 1.8 — Belay NEJM 1999 PMID 10228187)

All dosing (hyperosmolar therapy, dextrose, AED loading, vitamin K) weight-based (AAP Red Book 2024-2027, Lexicomp Peds)

Family history of IEM or unexplained infant death raises probability of metabolic mimic (Belay NEJM 1999)

Prodromal viral illness 3-7 days before onset is canonical (Belay NEJM 1999)

Aspirin during viral illness is the historical trigger; 82% of cases had detectable blood salicylates (Belay NEJM 1999)

Hypoglycemia common (depleted glycogen + impaired gluconeogenesis); reversible (Belay NEJM 1999)

Ammonia > 45 mcg/dL → relative risk 3.4 for death (Belay NEJM 1999)

AST/ALT > 3× ULN with minimal jaundice + INR elevation = hepatic synthetic dysfunction (CDC criteria)

Anion gap acidosis flags toxic / metabolic mimic (Belay NEJM 1999)

Confirms aspirin exposure + rules out salicylate toxicity mimic (Belay NEJM 1999)

Lactic acidosis flags mitochondrial / FAO defect mimic (CDC differential)

Cerebral edema visualization + rule out alternative (CDC differential)

Lovejoy/Hurwitz staging anchor; airway protection threshold

Cushing's triad (HTN + bradycardia) signals ICP crisis

Bradycardia in Cushing's triad

Hyperventilation in stage 2; apnea / Cheyne-Stokes in late stages

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (8)

8 need judgement
  • informationallife_threateningsevere_reye_stage_3_to_5
    Lovejoy/Hurwitz stages 3-5: stage 3 obtunded + decorticate posturing; stage 4 deepening coma + decerebrate + brainstem dysfunction; stage 5 flaccid + apneic + areflexic + isoelectric EEG (Belay NEJM 1999)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningtransplant_listing_criteria
    King's College criteria met OR PALF criteria met for liver transplant listing in Reye / IEM-induced ALF (Belay NEJM 1999; PALF cohort)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereaspirin_during_viral_illness_child
    Aspirin or salicylate-containing medication (Pepto-Bismol, oil of wintergreen) given to child < 19 yr during viral illness (influenza, varicella) — sentinel risk feature for Reye syndrome (Belay NEJM 1999 PMID 10228187; CDC)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehyperammonemia_above_45
    Ammonia > 45 mcg/dL (~ 26 mcmol/L) — relative risk 3.4 for death in Reye syndrome (Belay NEJM 1999)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehypoglycemia_in_reye_or_iem_mimic
    Hypoglycemia (glucose < 60 mg/dL infant or < 70 mg/dL child) in suspected Reye / Reye-like illness (Belay NEJM 1999; AAP)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereiem_mimic_workup_required
    Any Reye-like illness in 2020s — IEM mimics (FAO defects, urea cycle disorders, organic acidemias) far more common than true Reye syndrome since 1980 aspirin warning (Belay NEJM 1999)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereseizure_in_reye
    Seizure in Reye syndrome — cerebral edema, hypoglycemia, hyperammonemia, electrolyte derangement; routes to peds.status_epilepticus.v1 if refractory (AES 2016 Glauser PMID 26900382)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverecoagulopathy_in_reye
    Coagulopathy with INR > 1.5 in suspected Reye syndrome (hepatic synthetic dysfunction) (Belay NEJM 1999)
    Trigger could not be auto-evaluated — needs clinician judgement.

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CONTEXTrequiredDrives severity classification
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Recommended regimen

Reye syndrome — supportive ICU bundle (NO specific antidote) (Belay NEJM 1999 PMID 10228187)
axis: peds_reye_supportive_icu
Selected axis "Reye syndrome — supportive ICU bundle (NO specific antidote) (Belay NEJM 1999 PMID 10228187)" by default fallback (first axis)
  • PICU admission + early transfer to pediatric liver transplant center
    first line
    critical_care_consultation
    Mandatory PICU + early transfer to facility with pediatric liver transplant capability; involve pediatric hepatology, metabolism, genetics, neurology, neurosurgery, transplant teams
    triggers: suspected_Reye_or_Reye_like_illness
    Belay NEJM 1999 PMID 10228187 — 31% case-fatality even with treatment; early transplant-center transfer is mandatory
  • IEM workup in parallel with treatment
    first line
    metabolic_workup
    Plasma amino acids + acylcarnitine profile + urine organic acids + acylglycines + carnitine + VLCFA + biotinidase; consult metabolism / genetics
    triggers: suspected_Reye_or_Reye_like_illness
    Belay NEJM 1999 — since 1980 aspirin warning, IEM mimics far more likely than true Reye; do not delay workup
  • mannitol
    rescue
    osmotic_diuretic
    0.25-1 g/kg IV q4-6h PRN for ICP crisis • IV • PRN q4-6h (max: max 4 g/kg/day cumulative; monitor serum osm < 320)
    triggers: ICP_crisis_or_herniation_or_GCS_drop
    ICS pediatric severe TBI consensus — hyperosmolar therapy for cerebral edema in PALF / Reye / metabolic encephalopathy (AAP Red Book 2024-2027, Lexicomp Peds)
    rxcui 6628
  • hypertonic saline 3% NaCl
    rescue
    osmotic_agent
    3-5 mL/kg IV bolus over 10-15 min for ICP crisis; may follow with continuous infusion 0.1-1 mL/kg/h titrated to serum Na 145-155 mEq/L • IV • bolus + infusion
    triggers: ICP_crisis_or_herniation_features
    ICS pediatric severe TBI consensus — preferred over mannitol when hypovolemic / hypotensive (Lexicomp Peds; AAP Red Book 2024-2027) — listed as non_pharm because 3% NaCl is a compounded concentration not a single RxCUI
  • glucose
    first line
    simple_sugar
    D10W or D25W 5 mL/kg IV bolus for hypoglycemia, then D10W continuous infusion GIR 6-8 mg/kg/min titrated to glucose 100-200 mg/dL • IV • bolus then continuous (max: use D10W for peripheral access; D25/D50 only via central or large IV with caution)
    triggers: hypoglycemia_or_high_anion_gap_acidosis_or_FAO_defect_concern
    Reverses hypoglycemia + suppresses lipolysis in suspected FAO defects (e.g., MCAD) — D10W at GIR 6-8 mg/kg/min is the standard metabolic-crisis backbone (AAP Red Book 2024-2027, Lexicomp Peds)
    rxcui 4850
  • phytonadione (vitamin K1)
    first line
    vitamin_K_for_coagulopathy_reversal
    0.3 mg/kg IV/IM/SC slow IV (max 10 mg single dose); for vitamin-K-dependent coagulopathy from hepatic synthetic dysfunction • IV/IM/SC • single dose; may repeat per INR (max: max 10 mg single dose per AAP Red Book 2024-2027 / Lexicomp Peds)
    triggers: coagulopathy_INR_above_1_5_or_active_bleeding
    Reverses vitamin-K-dependent coagulopathy from hepatic synthetic dysfunction; slow IV due to anaphylactoid risk (AAP Red Book 2024-2027, Lexicomp Peds)
    rxcui 8308
  • fresh frozen plasma + cryoprecipitate
    rescue
    blood_product_coagulopathy_reversal
    FFP 10-15 mL/kg IV for INR > 1.5 with bleeding OR pre-procedure; cryoprecipitate 1 unit / 5-10 kg for fibrinogen < 100 • IV • per coagulopathy + bleeding
    triggers: active_bleeding_with_coagulopathy
    AAP transfusion guidance — blood-product reversal for active bleeding with hepatic synthetic dysfunction
  • lactulose
    first line
    osmotic_laxative_ammonia_reducer
    1 mL/kg PO/PR q2-4h titrated to 2-3 soft stools/day • PO/PR • q2-4h titrated (max: max 30 mL/kg/day)
    triggers: hepatic_encephalopathy_or_hyperammonemia_above_1_5x_ULN
    Reduces serum ammonia via gut acidification + ammonia trapping; first-line for hepatic encephalopathy (AAP Red Book 2024-2027, Lexicomp Peds)
    rxcui 6218
  • lorazepam
    rescue
    benzodiazepine_seizure_abortive
    0.1 mg/kg IV (max 4 mg per dose) • IV • q5 min x 2 (max: max 4 mg per dose, 8 mg cumulative)
    triggers: active_seizure
    AES 2016 Glauser PMID 26900382 — first-line acute seizure abortive; routes to peds.status_epilepticus.v1 if recurrent
    rxcui 6470
  • levetiracetam
    first line
    AED_no_hepatic_toxicity
    20-40 mg/kg IV load over 15 min, then 30-60 mg/kg/day divided BID • IV/PO • BID after load (max: max 3000 mg per dose, max 60 mg/kg/day per AAP Lexicomp Peds)
    triggers: Reye_with_seizures_or_seizure_prophylaxis_per_neuro
    AES 2016 Glauser PMID 26900382 — levetiracetam preferred (no hepatic toxicity); AVOID valproate (worsens mitochondrial dysfunction + hepatotoxicity); AVOID phenytoin (hepatic enzyme inducer) (AAP Red Book 2024-2027, Lexicomp Peds)
    rxcui 114477

ed playbook — drug actions (7)

  1. 1. ABC + airway protection if GCS ≤ 8 + IV access
    RSI ketamine + rocuronium preferred • IV • as needed
    trigger: Severe Reye with GCS ≤ 8 or respiratory compromise
    PALS 2020 — secure airway before transport / imaging if at risk
  2. 2. D10W 5 mL/kg IV bolus for hypoglycemia, then continuous infusion GIR 6-8 mg/kg/min
    D10W 5 mL/kg bolus then GIR 6-8 mg/kg/min titrated to glucose 100-200 • IV • bolus then continuous
    trigger: Hypoglycemia OR anion gap acidosis OR suspected FAO defect
    Mandatory metabolic-crisis backbone; suppresses lipolysis in FAO defects
  3. 3. hypertonic saline 3% NaCl 3-5 mL/kg IV bolus OR mannitol 0.5-1 g/kg IV
    HS 3% 3-5 mL/kg over 10-15 min OR mannitol 0.5-1 g/kg over 20 min • IV • PRN, may repeat
    trigger: ICP crisis (Cushing's triad, GCS drop, posturing, fixed pupil) OR stage 3-5 Reye
    ICS pediatric severe TBI consensus — time-critical for ICP rescue
  4. 4. vitamin K 0.3 mg/kg IV slow (max 10 mg) for coagulopathy reversal
    0.3 mg/kg IV slow (max 10 mg) • IV • single, may repeat per INR
    trigger: INR > 1.5 OR active bleeding
    Reverses vitamin-K-dependent coagulopathy from hepatic synthetic dysfunction
  5. 5. FFP 10-15 mL/kg IV for active bleeding with coagulopathy
    10-15 mL/kg IV • IV • per coags
    trigger: Active bleeding + INR > 1.5
    AAP transfusion guidance
  6. 6. lorazepam 0.1 mg/kg IV for active seizure abortive (max 4 mg)
    0.1 mg/kg IV (max 4 mg) • IV • q5 min x 2
    trigger: Active seizure
    AES 2016 Glauser PMID 26900382 — routes to peds.status_epilepticus.v1 if refractory
  7. 7. lactulose 1 mL/kg PO/PR q2-4h for hyperammonemia + hepatic encephalopathy
    1 mL/kg PO/PR q2-4h titrated to 2-3 soft stools/day • PO/PR • q2-4h
    trigger: Ammonia > 1.5× ULN or hepatic encephalopathy
    AAP Red Book 2024-2027 — first-line ammonia reducer

Auto-drafted A&P note

ed

Subjective

- Possible entry pathways: Intractable vomiting + altered MS in child / adolescent 3-7 days after viral illness (especially influenza B / varicella) (Belay NEJM 1999 PMID 10228187); Progressive encephalopathy + behavior change + lethargy in child post-viral (Belay NEJM 1999); Aspirin or salicylate-containing medication (Pepto-Bismol, oil of wintergreen) given during viral illness in child < 19 yr (Belay NEJM 1999).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Reye syndrome** (peds.reye-syndrome.v1).
Phenotype framing: 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)
Scope: 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)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Reye syndrome — supportive ICU bundle (NO specific antidote) (Belay NEJM 1999 PMID 10228187)**.
1. PICU admission + early transfer to pediatric liver transplant center Mandatory PICU + early transfer to facility with pediatric liver transplant capability; involve pediatric hepatology, metabolism, genetics, neurology, neurosurgery, transplant teams (critical_care_consultation, first line) — Belay NEJM 1999 PMID 10228187 — 31% case-fatality even with treatment; early transplant-center transfer is mandatory
2. IEM workup in parallel with treatment Plasma amino acids + acylcarnitine profile + urine organic acids + acylglycines + carnitine + VLCFA + biotinidase; consult metabolism / genetics (metabolic_workup, first line) — Belay NEJM 1999 — since 1980 aspirin warning, IEM mimics far more likely than true Reye; do not delay workup
3. mannitol 0.25-1 g/kg IV q4-6h PRN for ICP crisis IV PRN q4-6h (osmotic_diuretic, rescue) — ICS pediatric severe TBI consensus — hyperosmolar therapy for cerebral edema in PALF / Reye / metabolic encephalopathy (AAP Red Book 2024-2027, Lexicomp Peds)
4. hypertonic saline 3% NaCl 3-5 mL/kg IV bolus over 10-15 min for ICP crisis; may follow with continuous infusion 0.1-1 mL/kg/h titrated to serum Na 145-155 mEq/L IV bolus + infusion (osmotic_agent, rescue) — ICS pediatric severe TBI consensus — preferred over mannitol when hypovolemic / hypotensive (Lexicomp Peds; AAP Red Book 2024-2027) — listed as non_pharm because 3% NaCl is a compounded concentration not a single RxCUI
5. glucose D10W or D25W 5 mL/kg IV bolus for hypoglycemia, then D10W continuous infusion GIR 6-8 mg/kg/min titrated to glucose 100-200 mg/dL IV bolus then continuous (simple_sugar, first line) — Reverses hypoglycemia + suppresses lipolysis in suspected FAO defects (e.g., MCAD) — D10W at GIR 6-8 mg/kg/min is the standard metabolic-crisis backbone (AAP Red Book 2024-2027, Lexicomp Peds)
6. phytonadione (vitamin K1) 0.3 mg/kg IV/IM/SC slow IV (max 10 mg single dose); for vitamin-K-dependent coagulopathy from hepatic synthetic dysfunction IV/IM/SC single dose; may repeat per INR (vitamin_K_for_coagulopathy_reversal, first line) — Reverses vitamin-K-dependent coagulopathy from hepatic synthetic dysfunction; slow IV due to anaphylactoid risk (AAP Red Book 2024-2027, Lexicomp Peds)
7. fresh frozen plasma + cryoprecipitate FFP 10-15 mL/kg IV for INR > 1.5 with bleeding OR pre-procedure; cryoprecipitate 1 unit / 5-10 kg for fibrinogen < 100 IV per coagulopathy + bleeding (blood_product_coagulopathy_reversal, rescue) — AAP transfusion guidance — blood-product reversal for active bleeding with hepatic synthetic dysfunction
8. lactulose 1 mL/kg PO/PR q2-4h titrated to 2-3 soft stools/day PO/PR q2-4h titrated (osmotic_laxative_ammonia_reducer, first line) — Reduces serum ammonia via gut acidification + ammonia trapping; first-line for hepatic encephalopathy (AAP Red Book 2024-2027, Lexicomp Peds)
9. lorazepam 0.1 mg/kg IV (max 4 mg per dose) IV q5 min x 2 (benzodiazepine_seizure_abortive, rescue) — AES 2016 Glauser PMID 26900382 — first-line acute seizure abortive; routes to peds.status_epilepticus.v1 if recurrent
10. levetiracetam 20-40 mg/kg IV load over 15 min, then 30-60 mg/kg/day divided BID IV/PO BID after load (AED_no_hepatic_toxicity, first line) — AES 2016 Glauser PMID 26900382 — levetiracetam preferred (no hepatic toxicity); AVOID valproate (worsens mitochondrial dysfunction + hepatotoxicity); AVOID phenytoin (hepatic enzyme inducer) (AAP Red Book 2024-2027, Lexicomp Peds)

Setting playbook (ed) — ABC + emergency dextrose for hypoglycemia + ICP rescue + IEM workup + early transfer to pediatric liver transplant center
11. ABC + airway protection if GCS ≤ 8 + IV access RSI ketamine + rocuronium preferred IV as needed — Severe Reye with GCS ≤ 8 or respiratory compromise (PALS 2020 — secure airway before transport / imaging if at risk)
12. D10W 5 mL/kg IV bolus for hypoglycemia, then continuous infusion GIR 6-8 mg/kg/min D10W 5 mL/kg bolus then GIR 6-8 mg/kg/min titrated to glucose 100-200 IV bolus then continuous — Hypoglycemia OR anion gap acidosis OR suspected FAO defect (Mandatory metabolic-crisis backbone; suppresses lipolysis in FAO defects)
13. hypertonic saline 3% NaCl 3-5 mL/kg IV bolus OR mannitol 0.5-1 g/kg IV HS 3% 3-5 mL/kg over 10-15 min OR mannitol 0.5-1 g/kg over 20 min IV PRN, may repeat — ICP crisis (Cushing's triad, GCS drop, posturing, fixed pupil) OR stage 3-5 Reye (ICS pediatric severe TBI consensus — time-critical for ICP rescue)
14. vitamin K 0.3 mg/kg IV slow (max 10 mg) for coagulopathy reversal 0.3 mg/kg IV slow (max 10 mg) IV single, may repeat per INR — INR > 1.5 OR active bleeding (Reverses vitamin-K-dependent coagulopathy from hepatic synthetic dysfunction)
15. FFP 10-15 mL/kg IV for active bleeding with coagulopathy 10-15 mL/kg IV IV per coags — Active bleeding + INR > 1.5 (AAP transfusion guidance)
16. lorazepam 0.1 mg/kg IV for active seizure abortive (max 4 mg) 0.1 mg/kg IV (max 4 mg) IV q5 min x 2 — Active seizure (AES 2016 Glauser PMID 26900382 — routes to peds.status_epilepticus.v1 if refractory)
17. lactulose 1 mL/kg PO/PR q2-4h for hyperammonemia + hepatic encephalopathy 1 mL/kg PO/PR q2-4h titrated to 2-3 soft stools/day PO/PR q2-4h — Ammonia > 1.5× ULN or hepatic encephalopathy (AAP Red Book 2024-2027 — first-line ammonia reducer)

Non-pharmacologic actions:
- PICU consult STAT (Belay NEJM 1999)
- Pediatric hepatology consult STAT (Belay NEJM 1999)
- Pediatric metabolism / genetics consult STAT for IEM workup (Belay NEJM 1999)
- Early transfer to pediatric liver transplant center (Belay NEJM 1999)
- Pediatric neurosurgery for ICP bolt consideration if stage 3-5 (ICS pediatric TBI)
- Family education on aspirin avoidance in children < 19 yr (Belay NEJM 1999; CDC)
- AVOID further hepatotoxins (acetaminophen, valproate, phenytoin) (Lexicomp Peds; FDA black box for VPA)

AVOID / contraindication checks:
- NEVER_give_aspirin_to_children_under_19_yr_during_viral_illness (Belay NEJM 1999 PMID 10228187; CDC)
- NEVER_give_valproate_in_Reye_syndrome_or_suspected_mitochondrial_disease_FDA_black_box (FDA; AES 2016)
- AVOID_phenytoin_hepatic_enzyme_inducer_use_levetiracetam (AES 2016)
- AVOID_acetaminophen_during_acute_Reye_hepatic_failure (Lexicomp Peds)
- Mannitol_monitor_serum_osm_avoid_above_320 (Lexicomp Peds)
- Hypertonic_saline_target_serum_Na_145_to_155_avoid_CPM (ICS pediatric TBI)
- Vitamin_K_slow_IV_anaphylactoid_risk (Lexicomp Peds)
- Lactulose_titrate_to_2_to_3_soft_stools_avoid_dehydration (Lexicomp Peds)
- Any_Reye_like_illness_workup_for_IEM_mimics_FAO_urea_cycle_organic_acidemia (Belay NEJM 1999)

Monitoring

Regimen monitoring:
- Continuous neuro q1h + GCS + pupil exam (Belay NEJM 1999)
- Continuous cardiac + SpO2 + ETCO2 + ICP monitoring if neurosurgical bolt (Belay NEJM 1999)
- Glucose q1h initially, then q2h once stable (Belay NEJM 1999)
- Ammonia trend q4h until trending down + < 100 mcmol/L (Belay NEJM 1999)
- LFT + INR trend q6-12h (Belay NEJM 1999)
- Continuous EEG if intubated + sedated or witnessed seizure (AES 2016 Glauser PMID 26900382)
- K+ q1-2h on dextrose infusion (Lexicomp Peds)
- Serum Na + osm q4-6h on hyperosmolar therapy (ICS pediatric TBI)
- Strict I/O (Belay NEJM 1999)

Setting (ed) monitoring:
- Continuous cardiac + SpO2 + ETCO2 (PALS 2020)
- Continuous neuro q15-30 min initially (PALS 2020)
- Pupil checks q15-30 min (PALS 2020)
- Glucose q1h (Belay NEJM 1999)

Follow-up plan: 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)
- Close-out criterion: Follow-up + family education + IEM monitoring plan documented

Monitoring phase: q1h neuro + ICP if bolt + glucose q1h + ammonia trend + LFT/INR trend + cEEG if intubated + K+ trend (Belay NEJM 1999; AES 2016)

Disposition

Current setting: ed — ABC + emergency dextrose for hypoglycemia + ICP rescue + IEM workup + early transfer to pediatric liver transplant center

Disposition criteria:
- PICU mandatory: any suspected Reye syndrome (Belay NEJM 1999)
- Transfer to pediatric liver transplant center: any patient with hepatic dysfunction + encephalopathy (Belay NEJM 1999)

Escalation triggers (move to higher acuity):
- GCS drop or new herniation features → hyperosmolar therapy + neurosurgery + ICP bolt + PICU (ICS pediatric TBI)
- Active seizure → lorazepam + route to peds.status_epilepticus.v1 (AES 2016 Glauser PMID 26900382)
- Hyperammonemia > 300-500 mcmol/L despite lactulose → CRRT / HD per nephrology + transplant team (AAP / IPNA pediatric ammonia management)
- Cardiac arrest → PALS resuscitation (PALS 2020)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Lovejoy/Hurwitz stages 3-5: stage 3 obtunded + decorticate posturing; stage 4 deepening coma + decerebrate + brainstem dysfunction; stage 5 flaccid + apneic + areflexic + isoelectric EEG (Belay NEJM 1999)
- [LIFE_THREATENING] King's College criteria met OR PALF criteria met for liver transplant listing in Reye / IEM-induced ALF (Belay NEJM 1999; PALF cohort)
- [SEVERE] Aspirin or salicylate-containing medication (Pepto-Bismol, oil of wintergreen) given to child < 19 yr during viral illness (influenza, varicella) — sentinel risk feature for Reye syndrome (Belay NEJM 1999 PMID 10228187; CDC)

Citations

- Belay NEJM 1999 PMID 10228187 (CDC surveillance Reye syndrome 1981-1997) + CDC clinical case definition + AES 2016 Glauser PMID 26900382 (status epilepticus cross-reference) + ICS pediatric severe TBI consensus + PALS 2020 [PMID:10228187](https://pubmed.ncbi.nlm.nih.gov/10228187/)
- Cited evidence (PMID 26900382) [PMID:26900382](https://pubmed.ncbi.nlm.nih.gov/26900382/)

Last reconciled with current guidelines: 2026-05-26.
References
  • Belay NEJM 1999 PMID 10228187 (CDC surveillance Reye syndrome 1981-1997) + CDC clinical case definition + AES 2016 Glauser PMID 26900382 (status epilepticus cross-reference) + ICS pediatric severe TBI consensus + PALS 2020 — PMID:10228187
  • Cited evidence (PMID 26900382) — PMID:26900382