Emergency Medicine Hub / Toxicology & Environmental • 3 min read • 2 sections

Anticholinergic Toxicity & Physostigmine

Comprehensive emergency evaluation and protocolized management of anticholinergic/antimuscarinic overdoses: diphenhydramine, atropine, scopolamine, benztropine, Jimson weed (*Datura stramonium*), and belladonna alkaloids; classic toxidrome ('blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone'), differentiating central vs. peripheral toxicity, differentiating anticholinergic from sympathomimetic states, urinary bladder catheterization, and cautious indications for physostigmine salicylate with 12-lead ECG contraindication screening.

Resuscitation Quick Actions • First 2 Minutes

High-Acuity

Differentiating Pearl

Axillae and groin are BONE DRY in anticholinergic poisoning; profuse diaphoresis indicates sympathomimetic toxicity

First-Line Sedation

Lorazepam 2–4 mg IV or Midazolam 5–10 mg IM/IV titrated for agitation, delirium, and hyperthermia prevention

Bladder Decompression

Place Foley catheter immediately; urinary retention often holds 1,000–1,500+ mL of urine and worsens agitation

Physostigmine Dose

1–2 mg slow IV push over 5 minutes in adults (pediatric 0.02 mg/kg); have atropine and cardiac monitor ready at bedside

ECG Contraindication

Screen 12-lead ECG first: PR prolongation or QRS > 100 ms (TCA ingestion) is an ABSOLUTE CONTRAINDICATION to physostigmine (causes asystole)

Active Cooling

Evaporative misting and fans for severe hyperthermia (> 104°F/40°C) from impaired sweating

Bottom-Line Clinical Pearl

Anticholinergic poisoning presents with tachycardia, hyperthermia, mydriasis, anhidrosis, flushed dry skin, delirium ('muttering delirium' and picking at invisible objects), and urinary retention. Differentiate from sympathomimetics by examining sweat glands: anticholinergics produce bone-dry axillae and groin, whereas sympathomimetics cause drenched diaphoresis. First-line medical therapy is titrated benzodiazepines and Foley catheterization. Physostigmine (1–2 mg IV over 5 min) is an acetylcholinesterase inhibitor that crosses the blood-brain barrier and rapidly reverses central delirium, but is strictly contraindicated if there is concurrent TCA overdose or QRS/PR prolongation on ECG due to risk of fatal asystole.

1. Pathophysiology: Muscarinic Receptor Blockade

Anticholinergic syndrome results from competitive antagonism of acetylcholine at central and peripheral muscarinic receptors (M1–M5). Common culprits include first-generation antihistamines (diphenhydramine, hydroxyzine, chlorpheniramine), antiparkinsonian agents (benztropine, trihexyphenidyl), antispasmodics (dicyclomine, oxybutynin), mydriatics (cyclopentolate, tropicamide, scopolamine patches), and solanaceous plants containing belladonna alkaloids (Datura stramonium [Jimson weed, thorn apple], Atropa belladonna [deadly nightshade], and Hyoscyamus niger).

Classic Mnemonic Component	Clinical Manifestation	Underlying Pathophysiology
'Blind as a bat'	Mydriasis (dilated pupils) with loss of visual accommodation	Pupillary sphincter and ciliary muscle paralysis (cycloplegia)
'Mad as a hatter'	Agitated delirium, tactile/visual hallucinations, mumbling speech, purposeless plucking at bedsheets	Central M1 receptor blockade in cerebral cortex and hippocampus
'Red as a beet'	Cutaneous vasodilation, intense facial and truncal flushing	Compensatory vascular shunting to radiate heat in the absence of sweating
'Hot as a hare'	Hyperpyrexia (temperatures frequently exceeding 39–40°C)	Total cessation of evaporative cooling from sweat gland paralysis
'Dry as a bone'	Extreme xerostomia, cracked lips, absent bowel sounds, bone-dry axillae and groin	Postganglionic muscarinic blockade of salivary, sweat, and bronchial glands
'Full as a flask'	Massive urinary retention and bladder distension	Detrusor muscle relaxation coupled with internal urethral sphincter contraction

2. Differentiating Anticholinergic from Sympathomimetic Toxidromes

Both toxidromes share tachycardia, hypertension, mydriasis, hyperthermia, and agitation. The single most reliable physical exam differentiator is sweat production: check the patient's axillae, groin, and palm creases. Anticholinergic toxicity produces dry, warm skin and absent bowel sounds; sympathomimetic toxicity (cocaine, amphetamines, synthetic cathinones) presents with profuse diaphoresis and hyperactive bowel sounds.

Critical Pitfall / Contraindication

PHYSOSTIGMINE CONTRAINDICATIONS & ASYSTOLE RISK: Physostigmine salicylate is a tertiary amine carbamate that crosses the blood-brain barrier to inhibit acetylcholinesterase, dramatically reversing delirium. However, it MUST NOT be given if tricyclic antidepressant (TCA) toxicity is suspected, or if the ECG demonstrates QRS widening (> 100 ms) or PR prolongation. In patients with sodium-channel blocker cardiotoxicity, physostigmine can precipitate catastrophic intractable bradyasystolic cardiac arrest.

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