The anticholinergic toxidrome is best illustrated by the mnemonic: hot as a hare, blind as a bat, mad as a hatter, red as a beet, and dry as a bone. As the etiology reflects central and peripheral muscarinic receptor blockade, it is more accurately termed an antimuscarinic toxidrome. A centrally mediated delirium may occur, which is typically not violent but is associated with mumbling speech and persistent “picking” behaviors. Other manifestations include hyperthermia, mydriasis, dry mucus membranes and axillae, tachycardia, decreased gastrointestinal motility, erythematous skin, and urinary retention.
Many xenobiotics are antimuscarinic. One of the more common is diphenhydramine. Tricyclic antidepressants, phenothiazines, cyclobenzaprine, carbamazepine, atropine, scopolamine, glycopyrrolate, and belladonna alkaloids all have antimuscarinic properties. Plants such as jimson weed contain belladonna alkaloids and may be used recreationally.
Management and Disposition
Initial assessments of the vital signs and the duration of the QRS on ECG are important. Since many antimuscarinic xenobiotics are also sodium channel blockers, QRS interval should be monitored. Hyperthermia occasionally occurs and is treated with evaporative cooling. Most of these patients require only supportive care, with the administration of benzodiazepines for agitation. A Foley catheter may be needed for treatment of the urinary retention. Occasionally, physostigmine is used as a diagnostic reversal agent for antimuscarinic poisoning, but its risks versus benefits must be considered. The half-life of physostigmine is only about 20 minutes.
Anticholinergic Mydriasis. Mydriasis and flushing are some of the characteristic findings of anticholinergic toxidrome. (Photo contributor: Matthew D. Sztajnkrycer, MD, PhD.)
The antihistamine diphenhydramine has sodium channel–blocking properties and may cause QRS widening.
Physostigmine inhibits acetylcholinesterase, resulting in increased acetylcholine at the muscarinic synapses. Physostigmine crosses the blood-brain barrier, so it improves the antimuscarinic delirium; however, the improvement may be delayed by a few minutes after its administration given the mechanism of action.
Since the anticholinergic toxidrome may mimic the sympathomimetic toxidrome, the best physical examination finding to distinguish the two is presence or absence of sweat. Antimuscarinic patients are “dry as a bone.”
Anticholinergic Delirium. Anticholinergic delirium is manifested by agitation, confusion, and a “picking” behavior. (Photo contributor: Matthew D. Sztajnkrycer, MD, PhD.)
Anticholinergic Delirium. Prior to treatment with physostigmine, a patient suffering acute anticholinergic delirium drew the clock on the left. Following physostigmine administration, the patient drew the clock on the right. (Photo contributor: Division of Medical Toxicology, University of California, San Diego.)