Toxidromes in the ICU

ICU Toxidromes — Quick-Reference Comparison

This table summarizes the hallmark clinical patterns (“toxidromes”) you’ll encounter in critical-care toxicology, with key physiologic clues and first-line treatments.

Toxidrome	Common Agents	Classic Signs & Symptoms	Pupils / Skin	Key Labs / ECG	First-Line Treatment(s)
Anticholinergic	Diphenhydramine, TCA, atropine, jimson weed	“Dry as a bone, hot as a hare, red as a beet, blind as a bat, mad as a hatter”: dry mucosa, urinary retention, tachycardia, hyperthermia, delirium	Mydriasis; dry, flushed skin	± QRS > 100 ms (TCA), metabolic acidosis	IV fluids, active cooling, benzodiazepines for agitation; physostigmine 0.5–2 mg IV only if severe & no conduction delay; NaHCO3 for TCA QRS > 120 ms
Sympathomimetic	Cocaine, amphetamines, MDMA, synthetic cathinones	Severe agitation, tachycardia, hypertension, diaphoresis, hyperthermia, seizures	Mydriasis; moist skin, profuse sweat	Troponin, CK↑, lactate↑; ECG: ischemia, wide QRS if Na+ channel block (cocaine)	Large-dose benzodiazepines, fluids, active cooling; avoid β-blockers alone (unopposed α); vasodilators or phentolamine for refractory HTN
Opioid	Heroin, fentanyl, oxycodone, methadone, loperamide (abuse)	CNS depression, bradypnea/apnea, hypotension, hypothermia	Pinpoint (miosis); skin usually normal	Respiratory acidosis, hypercapnia; QT prolongation (methadone)	Naloxone 0.04–2 mg IV/IN titrated; airway & ventilation support; consider infusion for long-acting opioids
Sedative-Hypnotic	Benzodiazepines, barbiturates, zolpidem, ethanol	CNS depression, ataxia, slurred speech, hypoventilation, hypotension (barbs), hypothermia	Normal – slightly miotic pupils; cool/clammy skin	↓ RR/PaO2; barbs → hypo-Na/HCO3	Airway/ventilation, fluids/pressors; flumazenil only if isolated benzo OD and no seizure risk; consider HD for phenobarb
Cholinergic (Muscarinic & Nicotinic)	Organophosphates, carbamates, nerve agents, physostigmine overdose	Muscarinic: SLUDGE – salivation, lacrimation, urination, diarrhea, GI cramps, emesis; bronchorrhea/bronchospasm. Nicotinic: fasciculations, muscle weakness, paralysis	Miosis; diaphoresis	↓ Cholinesterase activity; hypoxia, mixed acidosis	Atropine 1–3 mg IV q5 min until secretions dry; pralidoxime 2 g IV over 30 min (repeat q1 h then infusion); airway + high-dose benzos for seizures
Serotonin Syndrome	SSRI/SNRI, MAOI, linezolid, tramadol, MDMA; combos	Agitation, hyperreflexia, inducible/sustained clonus, tremor, hyperthermia	Mydriasis; diaphoretic skin	Mild CK↑, metabolic acidosis; ECG usually normal	Stop serotonergic drugs; large-dose benzodiazepines, active cooling; cyproheptadine 12 mg load then 2 mg q2 h (max 32 mg/24 h)

Clinical Pearls

• Mydriasis + dry skin → think anticholinergic; if sweaty, consider sympathomimetic.
• Pinpoint pupils + bradypnea strongly favors opioid toxidrome—even if patient is restless (fentanyl chest-wall rigidity).
• Cholinergic crises kill by airway flooding & paralysis—titrate atropine until secretions dry, not until HR normalizes.
• Wide QRS (>100 ms) after TCA or cocaine = give sodium bicarbonate 1–2 mEq/kg.

Selected References

1. Goldfrank’s Toxicologic Emergencies, 12th ed. 2024.
2. Tintinalli, Emergency Medicine, Ch. Toxicology, 2023.
3. UpToDate. Approach to the poisoned patient. 2025.
4. American Heart Association. 2020 ACLS Toxicology Algorithms.

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