Clinical Commander

All dossiers
tox.neuroleptic-malignant-syndrome.core.v1

Neuroleptic malignant syndrome

toxicologyacuteadultpediatricacuteinpatient
Start encounter →Print handoutPRODUCTION

manifest pointer is a PLACEHOLDER reusing prisma/seed/manifests/tox.salicylate-overdose.core.v1.ts — a dedicated tox.neuroleptic-malignant-syndrome manifest is NOT yet authored (tracked in design-brief Open gaps). No problem-package folder / atom manifests on disk; design brief authored alongside this dossier. Regimen drugs intentionally carry NO rxcui — RxNav validation deferred (Stage-A API checklist in brief); non_pharm:true set for offending-agent discontinuation, dopaminergic restoration, active cooling, supportive monitoring, RRT, ECT, sedation/intubation/paralysis, precipitant management, and the rechallenge-safety plan. workup ids (workup.hyperthermic_toxidromes / workup.delirium / workup.severe_agitation), calculators (calc.qsofa, calc.news2), and panels (panel.metabolic/renal/cbc/abg/tox_screen/cardiac) drawn from the authorized whitelist; cascade.electrolyte used for rhabdomyolysis-driven electrolyte derangement. Withdrawal-type NMS (parkinsonism-hyperpyrexia syndrome) encoded explicitly as a distinct precipitant with the opposite cornerstone (RESTART dopaminergic therapy) — separate severity trigger + contraindication rule. Sibling differentiation §5.5.2 pivots authored vs serotonin syndrome (tox.serotonin-syndrome.core.v1) and anticholinergic toxidrome (tox.anticholinergic-toxidrome.core.v1); malignant catatonia + malignant hyperthermia handled in overlap_handling. Bayesian likelihood-ratio enrichment for the rigidity / clonus / bowel-sound / tempo discriminators deferred — see brief Open gaps. Authored 2026-05-16: 8-step stop-trigger + supportive + tiered-antidotal regimen ladder (cause removal → supportive ICU + cooling → fluids/rhabdo-AKI → benzodiazepine → dantrolene ± bromocriptine/amantadine → ECT → sedation+intubation±paralysis → safe later rechallenge), ED + ICU playbooks, 6 severity triggers.

Entry points (5)

  • medication
    Recent start / dose increase of an antipsychotic or dopamine-blocking antiemetic (metoclopramide, prochlorperazine, promethazine) [Strawn 2007 NMS consensus]
    dopamine_antagonist_exposure
  • medication
    Abrupt withdrawal / dose reduction / malabsorption of levodopa, amantadine, or a dopamine agonist in Parkinson disease (parkinsonism-hyperpyrexia syndrome) [DSM-5; critical-care tox review]
    dopaminergic_withdrawal
  • symptom
    Lead-pipe rigidity + hyperthermia + autonomic instability + altered mental status evolving over 1–3 days [Strawn 2007; DSM-5 NMS criteria]
    rigidity_hyperthermia_autonomic_ams_tetrad
  • vital_abnormality
    Core temperature >38°C with generalized muscular rigidity in a patient on a dopamine antagonist [Strawn 2007]
    hyperthermia_with_rigidity
  • lab_abnormality
    Markedly elevated creatine kinase (often >1000 IU/L) with rigidity/AMS on a neuroleptic [DSM-5 NMS criteria]
    marked_ck_elevation_on_antipsychotic

Required inputs (18)

  • agerequired
    demographic • used at CONTEXT
    Young agitated males overrepresented for antipsychotic NMS; elderly Parkinson patients for withdrawal-type; weight-based dantrolene/benzodiazepine/fluid dosing
  • sex
    demographic • used at CONTEXT
    Male sex is a recognized risk factor; alters pretest probability
  • offending_dopamine_antagonistrequired
    medication • used at CONTEXT
    Identifying the precise causative neuroleptic / antiemetic (high-potency, parenteral, depot, rapidly titrated) is the cornerstone — it must be STOPPED [Strawn 2007]
  • dopaminergic_therapy_statusrequired
    medication • used at CONTEXT
    Abrupt levodopa/amantadine/agonist withdrawal or malabsorption precipitates parkinsonism-hyperpyrexia syndrome — the agent must be RESTARTED, not stopped [critical-care tox review]
  • serotonergic_co_medicationsrequired
    medication • used at CONTEXT
    Serotonergic agents (SSRI/SNRI/MAOI/linezolid) raise the competing serotonin-syndrome diagnosis — the key sibling differential [Strawn 2007]
  • prior_nms_or_catatoniarequired
    history • used at CONTEXT
    Prior NMS episode and pre-existing catatonia are major risk factors and shift treatment toward benzodiazepines/ECT (malignant-catatonia overlap)
  • agitation_dehydration_restraintrequired
    history • used at CONTEXT
    Psychomotor agitation, dehydration, and physical restraint use are modifiable precipitants and worsen rhabdomyolysis
  • core_temperaturerequired
    vital • used at RED_FLAGS
    Hyperthermia is a defining feature and the leading mortality driver — drives aggressive active cooling
  • hrrequired
    vital • used at RED_FLAGS
    Tachycardia is part of autonomic instability; tracks severity and dysautonomia
  • sbprequired
    vital • used at RED_FLAGS
    Labile BP / autonomic instability → autonomic collapse; guides ICU escalation
  • rrrequired
    vital • used at RED_FLAGS
    Tachypnea, chest-wall rigidity → respiratory failure / aspiration risk; airway watch
  • muscle_rigidity_characterrequired
    symptom • used at RED_FLAGS
    Generalized LEAD-PIPE rigidity (± tremor/dystonia) is the cardinal pivot vs serotonin-syndrome clonus/hyperreflexia and anticholinergic absence of rigidity
  • mental_statusrequired
    symptom • used at RED_FLAGS
    Stupor/coma/mutism severity; catatonic features signal malignant-catatonia overlap
  • creatine_kinaserequired
    lab • used at INITIAL_WORKUP
    Markedly elevated CK (often >1000) supports NMS and drives rhabdomyolysis/AKI fluid management [DSM-5 criteria]
  • creatininerequired
    lab • used at INITIAL_WORKUP
    Myoglobinuric AKI from rhabdomyolysis; baseline renal function for fluid plan and RRT decision
  • venous_or_arterial_phrequired
    lab • used at INITIAL_WORKUP
    Metabolic acidosis tracks severity and impending autonomic/cardiopulmonary collapse
  • wbc
    lab • used at INITIAL_WORKUP
    Leukocytosis is characteristic and must be reconciled against an infectious differential (sepsis/CNS infection)
  • serum_iron
    lab • used at INITIAL_WORKUP
    Low serum iron is a supportive associated finding in NMS

12-phase flow (12)

  1. 1FRAME
    Recognize NMS as an idiosyncratic dopamine-blockade (or dopaminergic-withdrawal) hyperthermic emergency and triage the hyperthermic/rigidity-with-respiratory-compromise subset up front [Strawn 2007 NMS consensus; DSM-5]
    inputs: core_temperature, muscle_rigidity_character
    advance: NMS pattern recognized; life-threatening hyperthermic/rigidity subset flagged
  2. 2ENTRY
    Capture trigger — dopamine-antagonist exposure, dopaminergic withdrawal, the rigidity/hyperthermia/autonomic/AMS tetrad, hyperthermia with rigidity, or marked CK elevation on a neuroleptic [DSM-5 NMS criteria]
    inputs: age
    advance: Trigger captured
  3. 3CONTEXT
    Identify the precise offending dopamine antagonist (high-potency / parenteral / depot / rapid titration / antiemetic) vs dopaminergic-withdrawal etiology; capture serotonergic co-meds, prior NMS/catatonia, agitation/dehydration/restraint, and recent dose changes [Strawn 2007]
    inputs: sex, offending_dopamine_antagonist, dopaminergic_therapy_status, serotonergic_co_medications, prior_nms_or_catatonia, agitation_dehydration_restraint
    advance: Causative agent (or dopaminergic-withdrawal etiology) and risk context classified
  4. 4RED_FLAGS
    Hyperthermia / hypermetabolic crisis, rigidity with respiratory failure / aspiration, rhabdomyolysis with AKI, DIC, autonomic collapse, VTE from immobility, renal failure — any one mandates ICU-level resuscitation [Strawn 2007; DSM-5]
    inputs: core_temperature, hr, sbp, rr, muscle_rigidity_character, mental_status
    actions: workup.hyperthermic_toxidromes, calc.news2
    advance: Red flags screened; ICU/resuscitation triggered for any positive
  5. 5INITIAL_WORKUP
    CK, CMP + Cr, lactate/VBG, CBC (leukocytosis), serum iron, coagulation panel (DIC), CK-trend, UA/myoglobin, lactate; ECG; CXR; cultures + LP/CT head to exclude CNS infection; medication-administration record review; toxicology co-screen [Strawn 2007; DSM-5]
    inputs: creatine_kinase, creatinine, venous_or_arterial_ph, wbc, serum_iron
    actions: workup.hyperthermic_toxidromes, panel.metabolic, panel.cbc, panel.renal, panel.abg, panel.tox_screen
    advance: CK + renal + acid-base + CBC resulted and CNS-infection workup initiated
  6. 6BRANCHING_WORKUP
    Branch by precipitant and overlap: dopamine-antagonist NMS vs dopaminergic-withdrawal parkinsonism-hyperpyrexia; catatonic features → malignant-catatonia pathway; encephalopathy/seizure → CNS-infection/status pathway; agitation/psychosis driving exposure → psychiatric pathway [Strawn 2007]
    inputs: offending_dopamine_antagonist, dopaminergic_therapy_status, mental_status
    actions: workup.delirium, workup.acute_psychosis, workup.severe_agitation, workup.first_seizure
    advance: Precipitant branch + overlap pathway(s) selected
  7. 7DIFFERENTIAL
    Distinguish from SEROTONIN SYNDROME (serotonergic agent, onset <24h, clonus/HYPERreflexia/myoclonus, hyperactive bowel), malignant hyperthermia (anesthetic/succinylcholine, intra-operative), malignant catatonia (a continuum), anticholinergic toxidrome (dry, no rigidity), sympathomimetic toxidrome, severe acute dystonia, heat stroke, CNS infection / status epilepticus, thyroid storm, and drug-induced parkinsonism [Strawn 2007; DSM-5]
    inputs: muscle_rigidity_character, serotonergic_co_medications
    advance: NMS confirmed as principal driver against the hyperthermic-toxidrome differential
  8. 8RISK_STRATIFICATION
    Stratify by temperature tier, rigidity severity with respiratory compromise, CK magnitude / rhabdomyolysis-AKI, acidosis depth, DIC, autonomic instability, and mental-status depth; qSOFA/NEWS2 for collapse risk and ICU disposition [Strawn 2007]
    inputs: core_temperature, creatine_kinase, venous_or_arterial_ph
    actions: calc.qsofa, calc.news2
    advance: Severity tier (mild → life-threatening) assigned; ICU disposition decided
  9. 9TREATMENT
    STOP the offending dopamine antagonist (or RESTART the dopaminergic agent if withdrawal-precipitated) — the cornerstone; aggressive supportive ICU care with ACTIVE COOLING + isotonic fluids + rhabdomyolysis/AKI management + electrolyte correction + VTE prophylaxis + airway watch; benzodiazepines (lorazepam) for agitation/mild disease and catatonia overlap; moderate–severe: DANTROLENE and/or BROMOCRIPTINE or amantadine (restore dopamine tone); ECT for refractory disease / malignant-catatonia overlap; severe: deep sedation + intubation ± paralysis; do NOT re-challenge with the same agent acutely [Strawn 2007; DSM-5]
    inputs: offending_dopamine_antagonist, dopaminergic_therapy_status, core_temperature, muscle_rigidity_character, mental_status
    advance: Offending agent stopped (or dopaminergic restarted) + active cooling + fluids/rhabdo-AKI in flight; severity-tiered pharmacotherapy started
  10. 10DISPOSITION
    ICU for all moderate–severe NMS (hyperthermia, autonomic instability, rhabdomyolysis/AKI, respiratory compromise, depressed consciousness); toxicology/poison-center + psychiatry + neurology consults; medicine for AKI/electrolytes [Strawn 2007]
    advance: Disposition + consults assigned
  11. 11MONITORING
    Continuous core-temperature + telemetry, q1h vitals during cooling, serial CK + renal function + electrolytes + coagulation (DIC) until trending down, lactate clearance, hourly UOP for rhabdomyolysis, daily rigidity / mental-status resolution scoring, VTE surveillance, capnography if intubated/paralyzed [Strawn 2007]
    inputs: core_temperature, creatine_kinase, creatinine
    actions: panel.metabolic, panel.renal, panel.cbc
    advance: Normothermic, rigidity/mental status resolving, CK/renal trending to baseline, no DIC/VTE
  12. 12FOLLOWUP
    Document the offending agent as an allergy/adverse-reaction; defer ANY antipsychotic rechallenge ≥2 weeks after full recovery, then use a lower-potency / different-class agent with slow titration and close monitoring; restore steady-state dopaminergic therapy for Parkinson patients; psychiatry/neurology continuity, nephrology if AKI, patient/family NMS education and return precautions [Strawn 2007]
    advance: Adverse-reaction documented + safe rechallenge / dopaminergic plan and specialty follow-up arranged