Toxicology
A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning

Presented at the North American Congress of Clinical Toxicology annual meeting, St. Louis, MO, October 1997.
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Abstract

Study objective: To compare the efficacy and safety of physostigmine with benzodiazepines for the treatment of agitation and delirium associated with anticholinergic poisoning. Methods: We conducted a retrospective study of 52 consecutive patients referred to a university hospital toxicology consultation service who were treated with physostigmine, benzo-diazepines, or both for anticholinergic agitation and delirium. Patients treated with physostigmine were compared with those treated with benzodiazepines with respect to demographics, severity of poisoning, response to treatment, side effects of treatment, and complications. Results: Physostigmine controlled agitation and reversed delirium in 96% and 87% of patients, respectively. Benzodiazepines controlled agitation in 24% of patients but were ineffective in reversing delirium. Initial treatment with physostigmine (n=30) resulted in a significant decrease in the incidence of agitation (P <.001) and level of central nervous system stimulation (P <.001), whereas initial treatment with benzodiazepines (n=22) did not (P =.03 and P =.05, respectively). Patients treated initially with physostigmine had a significantly lower incidence of complications (7% versus 46%; P <.002) and a shorter time to recovery (median, 12 versus 24 hours; P =.004) than those treated initially with benzodiazepines. There were no significant differences between these groups in the incidence of side effects (7% versus 14%; P =0.6) and length of stay (median, 32 versus 39 hours; P =.15). Conclusion: Results suggest that physostigmine is more effective and safer than benzodiazepines for the treatment of anticholinergic agitation and delirium. A prospective controlled study is necessary to confirm such findings. [Burns MJ, Linden CH, Graudins A, Brown RM, Fletcher KE. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med. April 2000;35:374-381.]

Introduction

Physostigmine, a short-acting acetylcholinesterase inhibitor, increases synaptic acetylcholine concentrations and can overcome the postsynaptic muscarinic receptor blockade produced by anticholinergic agents. As a tertiary amine, it can pass freely into the central nervous system (CNS) and reverse both central and peripheral anticholinergic effects.

Physostigmine has been shown to be effective and safe when used to treat anticholinergic poisoning.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 It was neither consistently effective nor safe when used as an antidote for undifferentiated drug-induced coma and tricyclic antidepressant (TCA) poisoning.5, 6, 10, 11, 12, 13, 14, 15, 16 Although seizures were more common than asystole when physostig-mine was used for patients with TCA poisoning,10, 11, 14, 15 the latter occurrence has led some to categorically dismiss physostigmine as a treatment option when overdose with TCAs is known or suspected.16, 17, 18

In 1997, US poison centers reported that only 2% of more than 7,000 patients treated in health care facilities with moderate to severe effects from anticholinergic agents other than TCAs received physostigmine.19 Fear of potential toxicity is probably responsible for its apparent current underutilization in this setting. Although physostigmine remains the most rational treatment for anticholinergic poisoning, benzodiazepines have been recommended as the preferred therapy for agitation and delirium.18, 20 We report our experience with physostigmine and benzodiazepines for the treatment of anticholinergic agitation and delirium.

Section snippets

Materials and Methods

Patients with a diagnosis of anticholinergic poisoning (International Classification of Diseases–ninth revision , code 971.1) were identified by reviewing toxicology consultations and discharge diagnoses at the University of Massachusetts Medical Center from April 1986 through July 1997.

Those who had agitation or delirium and were treated with physostigmine, benzodiazepines, or both were included in the study. Data abstracted from the medical record included patient demographics; drug exposure;

Results

Seventy-one patients with a diagnosis of anticholinergic poisoning were identified. Sixteen patients were excluded because they did not receive physostigmine or benzodiazepines. Three patients were excluded because they were subsequently determined not to have anticholinergic poisoning. Of the remaining 52 patients, 45 (86%) were treated with physostigmine and 26 (50%) with benzodiazepines. Additional sedating agents (eg, haloperidol) were used to control agitation in 4 (8%) patients.

Median age

Discussion

We found physostigmine to be more effective than benzodiazepines for the control of agitation and reversal of CNS stimulation and delirium associated with anticholinergic poisoning. Results were similar when physostigmine and benzodiazepines were compared as initial therapy, at separate times in the same patient, or using the blinded abstractor’s data. Although the incidence and time of initial relapse was similar between patients treated with either drug, those treated with physostigmine had

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    Address for reprints: Michael J. Burns, MD, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215; 617-667-5198; E-mail[email protected] .

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