12-phase flow (10)

1. 1FRAME
   Serotonin syndrome HTN crisis = excess 5-HT2A agonism from serotonergic polypharmacy → autonomic instability + neuromuscular hyperactivity (clonus dominant) + altered mental status + HTN crisis ± hyperthermia. Pharmacology pivot: STOP all serotonergic agents IMMEDIATELY; BENZODIAZEPINE FIRST for sympatholysis + neuromuscular + sedation; cyproheptadine (5-HT2A antagonist) for refractory severe SS; cooling for hyperthermia; AVOID droperidol (QTc), nitroprusside (cyanide), succinylcholine (rhabdo hyperK), bromocriptine (worsens SS).
   inputs: sbp, dbp, heart_rate, temperature, serotonergic_medication_review
   advance: serotonin syndrome diagnosis confirmed by Hunter criteria + serotonergic exposure documented
2. 2ENTRY
   Recognize toxidrome (HTN + tachy + diaphoresis + clonus + agitation + hyperthermia); STOP all serotonergic medications; IV access + cardiac monitor + benzo-first
   inputs: age, sbp, temperature
   advance: serotonergic agents discontinued + benzo administered + cooling started if hyperthermic
3. 3CONTEXT
   Comprehensive medication reconciliation incl. OTC (dextromethorphan, St John's wort), supplements (5-HTP, tryptophan), illicit (MDMA, cocaine), and recently discontinued (MAOI 14-d washout); duration of therapy + recent dose changes; co-morbidities (depression, chronic pain, migraine)
   inputs: age, serotonergic_medication_review
   advance: complete med rec + Hunter criteria scored
4. 4RED_FLAGS
   Hyperthermia >40°C → aggressive cooling + paralysis + benzo (life-threatening); refractory clonus/seizures → escalating benzo + intubation; rhabdomyolysis-AKI → IV fluids + alkalinization; concurrent MI/dissection from sympathetic surge
   inputs: sbp, temperature, creatine_kinase, creatinine
   actions: htn_emergency
   advance: RED flags screened + life-threats addressed + diagnosis differentiated from NMS / anticholinergic / sympathomimetic
5. 5INITIAL_WORKUP
   Hunter criteria scoring + complete neuromuscular exam (clonus, rigidity, reflexes); ECG (QTc baseline); CK + Cr + lactate + BMP + Mg + glucose + CBC; UA dipstick (myoglobinuria); CT head if focal deficit (exclude ICH from HTN crisis); UDS to identify illicit serotonergic co-ingestants
   inputs: ecg_12_lead, creatine_kinase, creatinine, clonus_inducible_or_spontaneous, neuromuscular_exam
   actions: panel.cardiac, panel.renal
   advance: workup documented + Hunter criteria documented + alternative dx (NMS, anticholinergic, sympathomimetic, malignant hyperthermia) excluded
6. 6BRANCHING_WORKUP
   Mild-moderate SS (no hyperthermia, manageable clonus): supportive + benzo + observation. Severe SS (temp >40°C, refractory clonus, autonomic instability): ICU + cyproheptadine + paralysis + intubation + cooling.
   advance: severity stratified
7. 7TREATMENT
   STEP 1 — STOP all serotonergic medications (mandatory; resolution within 24-48 h after cessation in 70% per Mason 2000 cohort). STEP 2 — Benzodiazepine IV (lorazepam 1-2 mg IV q5-10 min OR diazepam 5-10 mg IV q5-10 min) for sympatholysis + neuromuscular control + sedation (Boyer NEJM 2005 first-line). STEP 3 — IV fluids (crystalloid) for volume + rhabdomyolysis prophylaxis. STEP 4 — Cooling: passive (remove blankets, fans), active (ice packs, evaporative, surface cooling) if temp >38.5°C; aggressive cooling + sedation/paralysis if >40°C. STEP 5 — BP control with nicardipine IV (5-15 mg/h) OR labetalol IV (10-20 mg q10 min) for sustained HTN after benzo. STEP 6 — Cyproheptadine 12 mg PO load → 2 mg PO q2h until improvement, max 32 mg/24 h (5-HT2A antagonist; reserved for moderate-severe disease per Boyer NEJM 2005; can give via NG tube if intubated). STEP 7 — Severe + refractory: intubation + paralysis (rocuronium, AVOID succinylcholine if rhabdo hyperK) + active cooling. AVOID droperidol (QTc + dystonia), nitroprusside (cyanide can worsen if hyperthermic with rhabdo + hepatic dysfunction), bromocriptine (worsens SS — used for NMS).
   inputs: sbp, dbp, heart_rate, temperature
   advance: serotonergic agents stopped + benzo titrated + BP at target + temp <38.5°C + clonus improving
8. 8DISPOSITION
   ICU for moderate-severe SS (hyperthermia, autonomic instability, severe clonus, intubation, cyproheptadine); telemetry/step-down for mild SS resolving with benzo + cessation; admit minimum 24 h for observation given delayed-resolution risk
   advance: ICU vs floor decision documented
9. 9MONITORING
   Continuous ECG + telemetry; q15-30 min BP + temp until stable; serial neuromuscular exam q2-4h (clonus resolution); CK q6h if rhabdo; UOP target >1 mL/kg/h if rhabdo; mental status reassessment q1h initially
   inputs: sbp, heart_rate, temperature
   actions: panel.cardiac
   advance: BP at target + temp normal + clonus resolved + CK trending down + mental status improving
10. 10FOLLOWUP
    Comprehensive medication review + safer alternatives (e.g., switch tramadol to non-serotonergic analgesic; switch SSRI to bupropion if depression amenable); psychiatry consult if depression/SI driver; pharmacy MTM for SS-prevention education; document SS in allergy/ADR list; pain medicine consult if chronic pain driving tramadol use; if MAOI was on board, mandatory 14-d washout before reintroducing serotonergic agent; outpatient PCP follow-up at 1 week
    advance: medication regimen revised + ADR documented + follow-up booked + patient/caregiver education completed