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tox.sympathomimetic-toxidrome.core.v1

Sympathomimetic toxidrome

toxicologyacuteadultpediatric
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12/12 authored

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

Current phase

Frame

Detailed

Recognize the sympathomimetic toxidrome and triage the hyperthermic/excited-delirium subset (the highest-mortality phenotype) up front [AHA 2024 cocaine cardiovascular statement]

Inputs
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Actions
0
Advance rule
Set
Advance when

Toxidrome recognized; hyperthermic/excited-delirium subset flagged

Patient inputs (18)

Pediatric unintentional ingestion / "body-stuffer" teen; weight-based benzodiazepine and fluid dosing [ACMT]

Weight-based benzodiazepine, fluid, and bicarbonate dosing [ACMT agitation guidance]

Cocaine (Na-channel + vasospasm + unopposed-alpha caution) vs MDMA (hyponatremia + serotonin overlap) vs cathinones (prolonged severe agitation) drives branch-specific therapy [AHA 2024; ACMT]

Body-packer vs body-stuffer changes decontamination (whole-bowel irrigation, NO endoscopic cocaine-packet removal, surgery if rupture/obstruction) [ACMT]

MDMA + SSRI/MAOI/linezolid → serotonin-syndrome overlap; ethanol/opioid co-use alters sedation plan [ACMT]

Cocaine Na-channel blockade → wide QRS (bicarbonate); QT prolongation; ischemia from vasospasm [AHA 2024]

MDMA water intoxication / SIADH → severe hyponatremia with seizures; guides hypertonic-saline decision [ACMT]

Agitation + hyperthermia → rhabdomyolysis; CK trend drives aggressive fluids [ACMT]

Rhabdomyolysis-associated AKI; baseline renal function for fluid/contrast decisions [ACMT]

Metabolic (lactic) acidosis tracks excited-delirium severity and impending cardiovascular collapse [AHA 2024]

Hypoglycemia is a universal AMS mimic; co-screen mandatory [ACMT]

Hyperthermia is the leading mortality driver — drives aggressive active cooling and paralysis/intubation if refractory [AHA 2024]

Sinus tachycardia / arrhythmia severity; benzodiazepine titration target [ACMT]

Severe HTN / hypertensive emergency drives phentolamine/nitrate/CCB; hypotension/collapse signals excited delirium [AHA 2024]

Agitation/psychosis severity drives benzodiazepine dosing; obtundation/collapse = excited-delirium decompensation [ACMT]

DIAPHORESIS (wet skin) is the cardinal pivot vs anticholinergic anhidrotic dry/flushed skin [Goldfrank tox]

Cocaine placental abruption risk; alters imaging and obstetric escalation [AHA 2024]

Cocaine-associated chest pain / myocardial injury workup [AHA 2024]

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

Severity triggers (6)

6 need judgement
  • informationallife_threateninghyperthermia_over_40C
    Core temperature >40°C in a stimulant-toxic patient (sympathomimetic hyperthermia) [AHA 2024]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningexcited_delirium_cardiovascular_collapse
    Extreme agitation + hyperthermia + metabolic acidosis with hemodynamic instability or sudden cardiovascular collapse (excited/agitated delirium) [ACMT agitation guidance]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningcocaine_wide_qrs
    QRS >100–120 ms or ventricular dysrhythmia attributable to cocaine sodium-channel blockade [AHA 2024]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningmdma_severe_hyponatremia_seizure
    MDMA-associated severe hyponatremia with seizure or hyponatremic encephalopathy (water intoxication / SIADH) [ACMT]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverecocaine_associated_acs
    Cocaine-associated chest pain with ischemic ECG / troponin elevation (coronary vasospasm + thrombosis + accelerated atherosclerosis) [AHA 2024]
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererhabdomyolysis_aki
    Markedly elevated CK with rising creatinine / myoglobinuric acute kidney injury [ACMT]
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

RISK_STRATIFICATIONoptionalDrives risk stratification
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Recommended regimen

Sympathomimetic toxidrome — benzodiazepine sedation → active cooling → fluids/rhabdo-AKI → cocaine cardiac/HTN → bicarbonate wide-QRS → severe hyponatremia (AHA 2024; ACMT)
axis: sympathomimetic_benzodiazepine_anchored_bundlestep 1 - Step 1 — Liberal titrated benzodiazepine sedation (first-line for agitation, tachycardia, HTN, seizure)
Selected step "Step 1 — Liberal titrated benzodiazepine sedation (first-line for agitation, tachycardia, HTN, seizure)" — Any agitated/hyperadrenergic sympathomimetic patient (cocaine, amphetamine/meth, MDMA, cathinones, Rx stimulant)
  • lorazepam
    first line
    benzodiazepine
    2–4 mg IV, repeat q5–10min titrated to calm/non-agitated; no fixed ceiling — escalate to large cumulative doses • IV/IM • q5–10min PRN titrated
    triggers: agitation, tachycardia, hypertension, seizure, hyperthermia
    ACMT agitation guidance — benzodiazepines are the unifying first-line therapy; reduce central catecholaminergic drive, lower HR/BP/temperature, and abort stimulant-induced seizures
    rxcui 6470
  • diazepam
    first line
    benzodiazepine
    5–10 mg IV q5–10min titrated • IV • q5–10min PRN titrated
    triggers: agitation, seizure, IV_access_available
    Rapid-onset alternative; long active metabolites useful for sustained cathinone agitation
    rxcui 3322
  • midazolam
    first line
    benzodiazepine
    5–10 mg IM (or 0.1 mg/kg) for the undifferentiated severely agitated patient without IV access • IM/IV • q5–10min PRN titrated
    triggers: no_IV_access, extreme_agitation_pre_hospital
    ACMT — fast IM absorption; first-choice when IV access is unsafe in a combative patient
    rxcui 6960
  • ketamine
    rescue
    dissociative_anesthetic
    4–5 mg/kg IM or 1–2 mg/kg IV for benzodiazepine-refractory extreme agitation • IM/IV • single dose; prepare for airway
    triggers: benzodiazepine_refractory_agitation, excited_delirium_with_collapse_risk
    Rescue dissociative sedation for refractory excited delirium when rapid control prevents acidosis/hyperthermia death; have airway/RSI ready
    rxcui 6130

ed playbook — drug actions (7)

  1. 1. lorazepam (or diazepam/midazolam)
    Lorazepam 2–4 mg IV (or midazolam 5–10 mg IM if no IV) • IV/IM • q5–10min titrated, no fixed ceiling
    trigger: Agitation / tachycardia / HTN / seizure (ACMT)
    First-line — calm the patient and lower catecholaminergic drive (ACMT agitation guidance)
  2. 2. active external cooling
    Evaporative/ice-water cooling + cold IV crystalloid • physical • continuous to normothermia
    trigger: Core temp >38.5°C (urgent >40°C) (AHA 2024)
    Hyperthermia is the leading mortality driver; antipyretics do not work (AHA 2024)
  3. 3. isotonic crystalloid
    Resuscitate then maintain brisk UOP • IV • bolus + titrated
    trigger: Volume depletion / elevated CK / hyperthermia (ACMT)
    Rhabdomyolysis/AKI prevention + supports cooling (ACMT)
  4. 4. nitroglycerin ± phentolamine ± aspirin
    NTG SL 0.4 mg q5min then IV; phentolamine 1–2.5 mg IV PRN; ASA 162–325 mg chewed • SL/IV/PO • titrated
    trigger: Cocaine chest pain / hypertensive emergency after benzodiazepines (AHA 2024)
    Reverse vasospasm; AVOID acute nonselective beta-blockers — unopposed alpha (AHA 2024)
  5. 5. sodium bicarbonate
    1–2 mEq/kg IV bolus, repeat to QRS narrowing • IV • bolus repeat PRN
    trigger: Cocaine-related QRS >100–120 ms (AHA 2024)
    Overcomes Na-channel-blockade cardiotoxicity (AHA 2024)
  6. 6. hypertonic 3% saline
    100–150 mL IV bolus, repeat for seizures • IV • bolus for active seizures
    trigger: MDMA severe symptomatic hyponatremia (ACMT)
    Reverse hyponatremic encephalopathy; cap correction rate (ACMT)
  7. 7. ketamine (rescue)
    4–5 mg/kg IM or 1–2 mg/kg IV • IM/IV • single, airway ready
    trigger: Benzodiazepine-refractory excited delirium (ACMT)
    Rescue sedation to prevent acidosis/hyperthermia death (ACMT)

Auto-drafted A&P note

ed

Subjective

- Possible entry pathways: Reported / suspected cocaine, amphetamine, methamphetamine, MDMA, "bath salts", or prescription stimulant use [ACMT agitation guidance]; Severe agitation / psychosis + tachycardia + hypertension + DIAPHORESIS + mydriasis (sympathomimetic toxidrome cluster) [Goldfrank tox]; Core temperature >38.5°C with agitation/combativeness (excited-delirium / hyperthermic toxidrome) [AHA 2024 cocaine statement].

Objective

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

Assessment

**Sympathomimetic toxidrome** (tox.sympathomimetic-toxidrome.core.v1).
Phenotype framing: Distinguish from anticholinergic toxidrome (DIAPHORETIC vs anhidrotic dry skin; bowel sounds present vs ileus), serotonin syndrome (clonus/hyperreflexia + serotonergic-drug history), NMS, thyroid storm, sepsis, alcohol/sedative withdrawal, salicylate toxicity, hypoglycemia, primary psychiatric agitation [Goldfrank tox; ACMT]
Scope: Recognize the sympathomimetic toxidrome and triage the hyperthermic/excited-delirium subset (the highest-mortality phenotype) up front [AHA 2024 cocaine cardiovascular statement]

No severity triggers fired against current inputs.

Plan

Regimen axis: **Sympathomimetic toxidrome — benzodiazepine sedation → active cooling → fluids/rhabdo-AKI → cocaine cardiac/HTN → bicarbonate wide-QRS → severe hyponatremia (AHA 2024; ACMT)** — step "Step 1 — Liberal titrated benzodiazepine sedation (first-line for agitation, tachycardia, HTN, seizure)".
1. lorazepam 2–4 mg IV, repeat q5–10min titrated to calm/non-agitated; no fixed ceiling — escalate to large cumulative doses IV/IM q5–10min PRN titrated (benzodiazepine, first line) — ACMT agitation guidance — benzodiazepines are the unifying first-line therapy; reduce central catecholaminergic drive, lower HR/BP/temperature, and abort stimulant-induced seizures
2. diazepam 5–10 mg IV q5–10min titrated IV q5–10min PRN titrated (benzodiazepine, first line) — Rapid-onset alternative; long active metabolites useful for sustained cathinone agitation
3. midazolam 5–10 mg IM (or 0.1 mg/kg) for the undifferentiated severely agitated patient without IV access IM/IV q5–10min PRN titrated (benzodiazepine, first line) — ACMT — fast IM absorption; first-choice when IV access is unsafe in a combative patient
4. ketamine 4–5 mg/kg IM or 1–2 mg/kg IV for benzodiazepine-refractory extreme agitation IM/IV single dose; prepare for airway (dissociative_anesthetic, rescue) — Rescue dissociative sedation for refractory excited delirium when rapid control prevents acidosis/hyperthermia death; have airway/RSI ready

Setting playbook (ed) — Recognize the toxidrome, achieve rapid benzodiazepine sedation + active cooling, identify cocaine cardiac / wide-QRS / hyponatremia / excited-delirium subsets, and triage ICU disposition (ACMT; AHA 2024)
5. lorazepam (or diazepam/midazolam) Lorazepam 2–4 mg IV (or midazolam 5–10 mg IM if no IV) IV/IM q5–10min titrated, no fixed ceiling — Agitation / tachycardia / HTN / seizure (ACMT) (First-line — calm the patient and lower catecholaminergic drive (ACMT agitation guidance))
6. active external cooling Evaporative/ice-water cooling + cold IV crystalloid physical continuous to normothermia — Core temp >38.5°C (urgent >40°C) (AHA 2024) (Hyperthermia is the leading mortality driver; antipyretics do not work (AHA 2024))
7. isotonic crystalloid Resuscitate then maintain brisk UOP IV bolus + titrated — Volume depletion / elevated CK / hyperthermia (ACMT) (Rhabdomyolysis/AKI prevention + supports cooling (ACMT))
8. nitroglycerin ± phentolamine ± aspirin NTG SL 0.4 mg q5min then IV; phentolamine 1–2.5 mg IV PRN; ASA 162–325 mg chewed SL/IV/PO titrated — Cocaine chest pain / hypertensive emergency after benzodiazepines (AHA 2024) (Reverse vasospasm; AVOID acute nonselective beta-blockers — unopposed alpha (AHA 2024))
9. sodium bicarbonate 1–2 mEq/kg IV bolus, repeat to QRS narrowing IV bolus repeat PRN — Cocaine-related QRS >100–120 ms (AHA 2024) (Overcomes Na-channel-blockade cardiotoxicity (AHA 2024))
10. hypertonic 3% saline 100–150 mL IV bolus, repeat for seizures IV bolus for active seizures — MDMA severe symptomatic hyponatremia (ACMT) (Reverse hyponatremic encephalopathy; cap correction rate (ACMT))
11. ketamine (rescue) 4–5 mg/kg IM or 1–2 mg/kg IV IM/IV single, airway ready — Benzodiazepine-refractory excited delirium (ACMT) (Rescue sedation to prevent acidosis/hyperthermia death (ACMT))

Non-pharmacologic actions:
- Continuous cardiac monitor + SpO2 + continuous core-temperature probe (AHA 2024)
- Active cooling: evaporative mist + fans or ice-water immersion, ice packs to groin/axillae/neck, cold IV fluids (AHA 2024)
- AVOID prolonged physical restraint without chemical sedation — worsens hyperthermia/acidosis/rhabdomyolysis and risks sudden death (ACMT)
- Foley for hourly UOP if rhabdomyolysis/hyperthermia (ACMT)
- Whole-bowel irrigation for asymptomatic confirmed body-packers; NO endoscopic cocaine-packet removal; surgery if rupture/obstruction (ACMT)
- If refractory hyperthermia: RSI with rocuronium + deep sedation, continue cooling (AHA 2024)
- Early toxicology / regional poison-center consult (ACMT)

AVOID / contraindication checks:
- Avoid_acute_nonselective_beta_blockers_in_cocaine_unopposed_alpha_risk (AHA 2024 cocaine cardiovascular statement) — evidence is evolving and the labetalol/combined alpha beta debate is unresolved; default to benzodiazepines + nitrates + phentolamine + CCB
- Antipsychotic_monotherapy_avoided_lowers_seizure_threshold_impairs_heat_dissipation_prolongs_QT (ACMT agitation guidance)
- Physical_restraint_only_without_chemical_sedation_worsens_hyperthermia_acidosis_rhabdomyolysis_and_sudden_death (ACMT agitation guidance)
- Antipyretics_ineffective_for_sympathomimetic_hyperthermia_use_active_cooling (AHA 2024)
- No_endoscopic_removal_of_cocaine_body_packets_rupture_risk_use_WBI_or_surgery (ACMT)
- Cap_hyponatremia_correction_to_avoid_osmotic_demyelination (ACMT)
- Avoid_succinylcholine_in_rhabdomyolysis_hyperkalemia_use_rocuronium (AHA 2024)

Monitoring

Regimen monitoring:
- continuous telemetry and core temperature (AHA 2024)
- vitals q15-30min during active cooling and sedation titration (ACMT)
- serial ECG until QRS and QTc normalize (AHA 2024)
- CK and renal function q4-6h until trending down (ACMT)
- serial sodium if MDMA hyponatremia correction rate capped (ACMT)
- lactate clearance and acid base (AHA 2024)
- urine output hourly for rhabdomyolysis (ACMT)
- continuous capnography if intubated or paralyzed (AHA 2024)
- sedation depth and agitation score (ACMT)

Setting (ed) monitoring:
- Vitals + core temp q15min during active cooling/sedation (AHA 2024)
- Serial ECG for QRS/QTc evolution (AHA 2024)
- Glucose, CK, Na, lactate on arrival and serially (ACMT)
- Agitation/sedation score q15–30min (ACMT)
- Hourly UOP if rhabdomyolysis (ACMT)

Follow-up plan: Substance-use disorder referral + harm reduction (naloxone co-prescription if opioid co-use), cardiology follow-up for cocaine-associated myocardial injury, nephrology if AKI, psychiatry safety plan if intentional, social work [AHA 2024; ACMT]
- Close-out criterion: Disposition plan + SUD/psych follow-up documented

Monitoring phase: Continuous telemetry + core-temp monitoring, q15–30min vitals during cooling/sedation, serial ECG until QRS/QTc normalize, q4–6h CK + renal until trending down, serial Na if MDMA hyponatremia, lactate clearance, UOP, capnography if intubated [AHA 2024]

Disposition

Current setting: ed — Recognize the toxidrome, achieve rapid benzodiazepine sedation + active cooling, identify cocaine cardiac / wide-QRS / hyponatremia / excited-delirium subsets, and triage ICU disposition (ACMT; AHA 2024)

Disposition criteria:
- Discharge after observation: mild toxicity, normothermic, calm off sedation, normal ECG, no end-organ injury, reliable follow-up, psych cleared if intentional (ACMT)
- Admit ward: resolving toxicity needing monitoring, mild rhabdomyolysis without AKI (ACMT)
- Admit ICU: hyperthermia, excited delirium, refractory agitation, wide-QRS, cocaine ACS, severe hyponatremia, or significant end-organ injury (AHA 2024)

Escalation triggers (move to higher acuity):
- Core temp >40°C or not falling with cooling + benzodiazepines → ICU + paralysis/intubation (AHA 2024)
- Excited delirium with metabolic acidosis / impending collapse → ICU + aggressive sedation + resuscitation (ACMT)
- Cocaine wide-QRS / ventricular dysrhythmia → ICU + sodium bicarbonate (AHA 2024)
- Cocaine ACS / refractory ischemia → cath lab + cardiology (AHA 2024)
- Severe MDMA hyponatremia with seizures → ICU + hypertonic saline (ACMT)
- Body-packer with obstruction or suspected rupture → emergent surgery (ACMT)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Core temperature >40°C in a stimulant-toxic patient (sympathomimetic hyperthermia) [AHA 2024]
- [LIFE_THREATENING] Extreme agitation + hyperthermia + metabolic acidosis with hemodynamic instability or sudden cardiovascular collapse (excited/agitated delirium) [ACMT agitation guidance]
- [LIFE_THREATENING] QRS >100–120 ms or ventricular dysrhythmia attributable to cocaine sodium-channel blockade [AHA 2024]

Citations

- AHA Cocaine-Associated Cardiovascular Disease Scientific Statement (2024-2025) + ACMT stimulant / acute-agitation guidance + 2024-2025 critical-care toxicology reviews of sympathomimetic poisoning and excited delirium [PMID:38226471](https://pubmed.ncbi.nlm.nih.gov/38226471/)
- Cited evidence (PMID 33352076) [PMID:33352076](https://pubmed.ncbi.nlm.nih.gov/33352076/)
- Cited evidence (PMID 32118049) [PMID:32118049](https://pubmed.ncbi.nlm.nih.gov/32118049/)
- Cited evidence (PMID 30447800) [PMID:30447800](https://pubmed.ncbi.nlm.nih.gov/30447800/)
- Cited evidence (PMID 28988075) [PMID:28988075](https://pubmed.ncbi.nlm.nih.gov/28988075/)

Last reconciled with current guidelines: 2026-05-16.
References
  • AHA Cocaine-Associated Cardiovascular Disease Scientific Statement (2024-2025) + ACMT stimulant / acute-agitation guidance + 2024-2025 critical-care toxicology reviews of sympathomimetic poisoning and excited delirium — PMID:38226471
  • Cited evidence (PMID 33352076) — PMID:33352076
  • Cited evidence (PMID 32118049) — PMID:32118049
  • Cited evidence (PMID 30447800) — PMID:30447800
  • Cited evidence (PMID 28988075) — PMID:28988075