12-phase flow (12)

1. 1FRAME
   Recognize serotonin toxicity as a clinical diagnosis (Hunter criteria) on a serotonergic exposure, and triage the hyperthermic/rigid life-threatening subset up front [Boyer & Shannon NEJM 2005]
   inputs: core_temperature, clonus_and_reflexes
   advance: Serotonin toxicity pattern recognized; severe hyperthermic/rigid subset flagged
2. 2ENTRY
   Capture trigger — serotonergic dose change/combination with neuromuscular excitation, hyperthermia with clonus, AMS after a serotonergic agent, or a known serotonergic interaction/overdose [ACMT serotonin toxicity guidance]
   inputs: age
   advance: Trigger captured
3. 3CONTEXT
   Catalogue ALL serotonergic agents and the timing of the most recent change/addition (onset usually <24h); explicitly screen dopamine-blocker exposure (NMS pivot); capture weight, intent, co-ingestants [Dunkley QJM 2003; Boyer & Shannon NEJM 2005]
   inputs: weight_kg, serotonergic_agents, timing_of_serotonergic_change, dopamine_blocker_exposure
   advance: Serotonergic agent(s) + timing + dopamine-blocker status classified
4. 4RED_FLAGS
   Hyperthermia >38.5–41°C, rigidity with respiratory compromise, rapidly rising temperature, seizures, rhabdomyolysis → AKI, DIC, severe autonomic instability — any positive triggers resuscitation/ICU [Boyer & Shannon NEJM 2005]
   inputs: core_temperature, clonus_and_reflexes, rigidity_and_hypertonia, mental_status_agitation, skin_moisture_and_bowel, hr
   actions: workup.hyperthermic_toxidromes, calc.news2
   advance: Red flags screened; ICU/resuscitation triggered for any positive
5. 5INITIAL_WORKUP
   Serotonin syndrome is a CLINICAL diagnosis via Hunter criteria (no confirmatory assay) — apply workup.hyperthermic_toxidromes and exclude mimics; send CK, renal panel, LFTs, coags, CO2/bicarbonate, lactate, glucose, CBC, UDS + serotonergic co-screen (APAP/salicylate/ethanol), ECG [Dunkley QJM 2003; Boyer & Shannon NEJM 2005]
   inputs: creatine_kinase, creatinine, venous_or_arterial_ph, glucose, ecg_12_lead
   actions: workup.hyperthermic_toxidromes, panel.metabolic, panel.tox_screen, panel.cardiac, panel.renal, panel.cbc
   advance: Hunter criteria applied and end-organ panel resulted
6. 6BRANCHING_WORKUP
   Branch by dominant feature: severe agitation/AMS → delirium/agitation workup; first seizure → neuro workup + glucose/Na; psychosis-like agitation → acute-psychosis workup; wide-complex tachycardia (TCA/citalopram co-ingestion) → Na-channel/QT pathway [ACMT serotonin toxicity guidance]
   inputs: mental_status_agitation, ecg_12_lead
   actions: workup.severe_agitation, workup.delirium, workup.first_seizure, workup.acute_psychosis, workup.wide_complex_tach
   advance: Dominant-feature branch(es) selected
7. 7DIFFERENTIAL
   Distinguish from NMS (dopamine-blocker exposure, BRADYreflexia, lead-pipe rigidity, slow onset/resolution), anticholinergic toxidrome (DRY skin, normal reflexes, NO clonus, ileus), sympathomimetic toxidrome, malignant hyperthermia (anesthetic trigger), thyroid storm, meningoencephalitis, status epilepticus [Boyer & Shannon NEJM 2005]
   inputs: clonus_and_reflexes, skin_moisture_and_bowel, dopamine_blocker_exposure, timing_of_serotonergic_change
   advance: Serotonin toxicity confirmed as principal driver; mimics excluded
8. 8RISK_STRATIFICATION
   Stratify mild (tremor/hyperreflexia, afebrile) vs moderate (clonus + autonomic + temp ≤40°C) vs life-threatening (temp >38.5–41°C, severe rigidity, respiratory compromise, seizures, rhabdo/AKI/DIC); qSOFA/NEWS2 for instability and ICU disposition [Boyer & Shannon NEJM 2005]
   inputs: core_temperature, rigidity_and_hypertonia, venous_or_arterial_ph, creatine_kinase
   actions: calc.qsofa, calc.news2
   advance: Severity tier assigned; ICU disposition decided
9. 9TREATMENT
   STOP all serotonergic agents (cornerstone) + supportive care (IV fluids, continuous monitoring); benzodiazepines first-line for agitation/tremor and to blunt autonomic/neuromuscular drive (mild–moderate); aggressive ACTIVE COOLING + benzodiazepines for hyperthermia; cyproheptadine (oral/NG 5-HT2A antagonist) for moderate-severe not responding; for SEVERE hyperthermia/rigidity → deep sedation + NON-DEPOLARIZING neuromuscular PARALYSIS (e.g., rocuronium — NOT succinylcholine if rhabdo/hyperK) + intubation (the definitive treatment for life-threatening hyperthermia/rigidity; antipyretics ineffective — fever is muscular); manage rhabdomyolysis/AKI; AVOID physical restraints alone (worsen hyperthermia/rhabdo/lactate); most resolve within 24h after removal of the cause + supportive care [Boyer & Shannon NEJM 2005; ACMT serotonin toxicity guidance]
   inputs: serotonergic_agents, core_temperature, mental_status_agitation, rigidity_and_hypertonia
   advance: Serotonergic agents stopped + benzodiazepine sedation + active cooling in flight; cyproheptadine/paralysis escalated per severity
10. 10DISPOSITION
    Discharge mild cases after observation once asymptomatic off offending agent; admit/observe moderate; ICU for hyperthermia, severe rigidity/respiratory compromise, autonomic instability, seizures, rhabdo/AKI/DIC, or need for paralysis; toxicology + poison-center consult; psychiatry/SUD if intentional [ACMT serotonin toxicity guidance]
    advance: Disposition + consults assigned
11. 11MONITORING
    Continuous core-temperature + telemetry, RASS/agitation score, serial clonus/reflex exam for resolution, q4–6h CK + renal until trending down, coags if DIC concern, lactate/bicarbonate clearance, UOP, capnography if intubated/paralyzed [Boyer & Shannon NEJM 2005]
    inputs: core_temperature, clonus_and_reflexes, creatine_kinase, hr
    actions: panel.metabolic, panel.renal, panel.cardiac
    advance: Normothermic, clonus/reflexes resolving, agitation controlled, no end-organ deterioration
12. 12FOLLOWUP
    Medication reconciliation to remove/avoid the offending serotonergic combination (durable allergy/interaction flag), pharmacist review of MAOI/linezolid/methylene-blue washout intervals, psychiatry safety plan if intentional, nephrology if AKI, return precautions for re-exposure [ACMT serotonin toxicity guidance]
    advance: Medication reconciliation + interaction flag + psych/SUD follow-up documented