Anticholinergic drugs have been used as chemical-warfare (CW) agents (1). They are classified as incapacitating agents (ie, designed not to cause serious injury or death but rather to cause sufficient disorientation to prevent military personnel from carrying out their missions). One anticholinergic chemical-warfare agent is 3-quinuclidinyl benzilate, North Atlantic Treaty Organization (NATO) code BZ.
BZ is a solid that can be disseminated by heat-generating artillery rounds without being inactivated. It can persist in the environment for 3 to 4 weeks. Mass casualties due to BZ exposure would likely result from inhalation of aerosolized BZ, although the compound can also be dissolved in a solvent and placed on an environmental surface from which it can be absorbed through the skin following contact.
(See also Overview of Chemical-Warfare Agents.)
General reference
1. Emetarom C, Barrueto F, Nelson LS. Antimuscarinic Agent Attack. In Ciottone's Disaster Medicine 2024 Jan 1 (pp. 705-707). Elsevier.
Pathophysiology of Anticholinergic Chemical-Warfare Injuries
BZ binds to muscarinic cholinergic receptors in the central nervous system (CNS), smooth muscle, and exocrine glands and blocks acetylcholine (ACh) at these sites. The decrease in cholinergic stimulation produces the anticholinergic toxidrome (see table Common Toxic Syndromes).
Symptoms and Signs of Anticholinergic Chemical-Warfare Injuries
Patients have dry mouth and skin, dilated pupils (causing blurring of vision), usually tachycardia, and may develop hyperthermia. Cholinergic blockade in the CNS causes first lethargy and then characteristic anticholinergic illusions and hallucinations; hallucinations may be visual or auditory and are typically concrete and easily describable (eg, voices of known contacts, imaginary television programs, sharing of imaginary cigarettes, odd shapes) in contrast to the abstract, geometric, and ineffable nature of psychedelic hallucinations. Anticholinergic visual hallucinations may also be lilliputian (ie, items hallucinated decrease in size over time—eg, a cow transforms into a dog and then into a mouse or a butterfly). Speech may be slurred, and patients exhibit stereotypical picking or plucking motions (woolgathering) and may confabulate. Stupor and coma may last hours to days, with gradual recovery.
Diagnosis of Anticholinergic Chemical-Warfare Injuries
Clinical evaluation
Sometimes diagnostic challenge with physostigmine
Diagnosis is made by recognizing the typical anticholinergic toxidrome. No common laboratory tests detect BZ exposure. Although many drugs and plants have anticholinergic effects (see table Common Toxic Syndromes), the simultaneous appearance of an anticholinergic toxidrome in many individuals who did not all ingest an anticholinergic drug or plant suggests an intentional or CW exposure. Physostigmine, a cholinergic drug, can be used as a diagnostic challenge; reduction of anticholinergic manifestations after physostigmine is given strongly suggests an anticholinergic compound.
Triage
Most patients exposed to BZ can be triaged as delayed.
Treatment of Anticholinergic Chemical-Warfare Injuries
Supportive care, including cooling as needed
Rarely physostigmine (1, 2)
Patients are usually quiet but may become disruptive and may need to be reassured and in some cases restrained. Patients with elevated body temperature require cooling (see Heatstroke: Cooling techniques). Most patients do not require drug treatment, but those who are disruptive or who are markedly distressed as a result of hallucinations may benefit from being given physostigmine slowly; dose is 0.5 to 20 mg IV in adults and 0.02 mg/kg IV in children (see tableSymptoms and Treatment of Specific Poisons). Exceeding recommended doses may cause cholinergic effects, including seizures.
Treatment references
1. Saadi R, Bohnenberger K. Physostigmine for Antimuscarinic Toxicity.J Emerg Nurs. 2020;46(1):126-128. doi:10.1016/j.jen.2019.09.002
2. Serrano WC, Maldonado J. The Use of Physostigmine in the Diagnosis and Treatment of Anticholinergic Toxicity After Olanzapine Overdose: Literature Review and Case Report.J Acad Consult Liaison Psychiatry. 2021;62(3):285-297. doi:10.1016/j.jaclp.2020.12.013
