Unknown Poisoning with Dilated Pupils: Causes and Management

Step 1: Recognizing the Toxidrome

1. Anticholinergic (Antimuscarinic) Toxidrome

• Antihistamines (diphenhydramine, promethazine)
• Tricyclic antidepressants (amitriptyline, imipramine)
• Atropine, scopolamine
• Antiparkinsonian drugs (benztropine, biperiden)
• Antipsychotics (quetiapine, chlorpromazine)
• Antispasmodics (hyoscine)
• Plants: Datura (Jimsonweed), Atropa belladonna, Hyoscyamus niger, Amanita muscaria mushrooms
• Amantadine, skeletal muscle relaxants

The Essentials of Forensic Medicine and Toxicology, 36th ed., Table 24.2

2. Sympathomimetic Toxidrome

• Cocaine, amphetamines, methamphetamine
• MDMA (ecstasy)
• Caffeine (high dose), theophylline
• Pseudoephedrine, ephedrine

The Essentials of Forensic Medicine and Toxicology, 36th ed.; Katzung's Basic & Clinical Pharmacology, 16th ed.

Key Differentiating Feature: Anticholinergic vs. Sympathomimetic

Rosen's Emergency Medicine, 10th ed.

Step 2: Additional Causes of Mydriasis in Poisoning

Royal Children's Hospital Clinical Guidelines - Toxidromes; The Washington Manual, 36th ed.

Step 3: Immediate Assessment

On Arrival - Simultaneous Actions:

1. ABCs - Airway, Breathing, Circulation. Establish IV access, cardiac monitoring, pulse oximetry.
2. Do not delay treatment to identify the agent - stabilize first.
3. Vital signs pattern - tachycardia? hypertension? hyperthermia?
4. Skin examination - Dry vs. diaphoretic is the single most useful differentiating sign.
5. 12-lead ECG - essential; look for QRS prolongation (TCAs), QTc prolongation, arrhythmias.
6. Blood glucose - rule out hypoglycemia mimicking toxidrome.

Bedside Clue Seeking:

• Odors: garlic (organophosphates, arsenic), bitter almonds (cyanide), fruity/sweet (alcohols), rotten eggs (H2S)
• Any medications, tablets, or bottles found with the patient
• History from witnesses, EMS, family

Step 4: Management

General Measures (All Unknown Poisonings)

Specific Management by Toxidrome

Anticholinergic Toxidrome:

• Agitation/delirium: Benzodiazepines (first-line) - IV lorazepam or diazepam
• Hyperthermia: Active cooling, benzodiazepines to reduce muscle activity
• Tachycardia: Usually resolves with benzodiazepines; avoid antiarrhythmics
• Urinary retention: Bladder catheterization
• Physostigmine: A specific antidote (cholinesterase inhibitor) - use 1-2 mg IV slowly in pure anticholinergic toxicity without TCA co-ingestion (contraindicated in TCA overdose due to risk of bradycardia/asystole); helps reverse delirium, tachycardia, hyperthermia

TCA Overdose (anticholinergic + QRS prolongation):

• Sodium bicarbonate: 1-2 mEq/kg IV bolus for QRS >100 ms, seizures, dysrhythmias, or shock - then infusion; target pH 7.45-7.55
• Seizures: Benzodiazepines (first-line); avoid phenytoin
• DO NOT use physostigmine (risk of asystole)

The Washington Manual of Medical Therapeutics, 37th ed.

Sympathomimetic Toxidrome:

• Agitation/hypertension/hyperthermia: Benzodiazepines are first-line (reduce CNS sympathetic outflow)
• Hyperthermia: Active cooling, sedation; avoid antipyretics (not effective for drug-induced hyperthermia)
• Hypertensive crisis: Benzodiazepines; consider phentolamine or nitroprusside if refractory; avoid pure beta-blockers (risk of unopposed alpha stimulation)
• Seizures: Benzodiazepines
• Cocaine-specific: Consider nitroglycerin or benzodiazepines for chest pain/coronary spasm; avoid beta-blockers

Serotonin Syndrome:

• Cyproheptadine (serotonin antagonist) 4-8 mg PO/NG
• Benzodiazepines for agitation and rigidity
• Active cooling

Step 5: Summary Diagnostic Algorithm

UNKNOWN POISONING + DILATED PUPILS
              |
    Is skin DRY or WET?
    /                \
  DRY               WET (diaphoretic)
  |                      |
Anticholinergic    Is there hyperreflexia/clonus?
toxidrome          /                \
(Datura,         YES               NO
TCAs, AH,    Serotonin      Sympathomimetic
antipsych.)  syndrome       (cocaine, amphetamines)
                            OR withdrawal syndrome

• QRS > 100 ms → TCA until proven otherwise → sodium bicarbonate
• QTc prolongation → multiple agents possible
• Normal ECG → pure anticholinergic or sympathomimetic more likely

• The Essentials of Forensic Medicine and Toxicology, 36th ed. (2026), Table 24.2 - Toxidromes
• Rosen's Emergency Medicine, 10th ed. - Anticholinergic toxidrome case illustration
• The Washington Manual of Medical Therapeutics, 37th ed. - TCA and anticholinergic management
• Katzung's Basic and Clinical Pharmacology, 16th ed. - Mydriasis in drug toxicity
• RCEM April 2025 Guideline on managing patients with unidentified poisoning