Safety and effectiveness of physostigmine: a 10-year retrospective review*

Ann M. Arens, Krishna Shah, Suad Al-Abri, Kent R. Olson, Tom Kearney

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Physostigmine has long been recognized as an antidote to reverse anticholinergic delirium. However, its effectiveness, safety profile, and dosing have been disputed. Objectives: To describe effectiveness, adverse events, and dosing associated with the use of physostigmine to reverse anticholinergic delirium. Methods: A retrospective cohort study of hospitalized patients reported to a regional poison center system between 2003 and 2012 who received physostigmine to reverse an anticholinergic toxidrome. Data extraction of a priori defined variables were recorded with concurrence of investigators. The cases were stratified by the primary ingestant as the presumed causative agent and associations for response were performed using odds ratios (ORs), 95% confidence intervals (CI’s), and p values. Results: Of the 1422 cases identified, 191 met the inclusion criteria. Patients exposed to non-diphenhydramine antihistamines (n = 14), antipsychotics (n = 4), and tricyclic antidepressants (n = 3) had 100% response to physostigmine, whereas anticholinergic plants (n = 46/67; 68.7%, OR: 0.70; CI: 0.36–1.35), diphenhydramine (n = 43/56; 64.2%, OR: 1.30; CI: 0.63–2.68), and combination products (n = 8/10; 80%, OR: 1.48; CI: 0.30–7.24) had partial response rates. Of the included patients, 142 (74.3%) were treated with physostigmine alone, and 16 (8.4%) of these patients were discharged directly from the emergency department (ED). Discussion: Most patients, 182 (95.3%), had no documented adverse effects. Four patients (2.1%) experienced emesis, two experienced QTc prolongation (1.0%), and two experienced seizures (1.0%). There was a single fatality 6 h after physostigmine administration. Average initial total doses of physostigmine ranged from 1.0 to 1.75 mg. Most patients were admitted to the ICU (n = 110; 57.6%), however, 36 (18.8%) patients were discharged directly from the ED. Conclusions: In this retrospective cohort study, physostigmine administration to reverse anticholinergic delirium had a good safety profile, and often improved or resolved anticholinergic delirium when administered in doses less than 2 mg.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalClinical Toxicology
DOIs
Publication statusAccepted/In press - Jul 13 2017

Fingerprint

Physostigmine
Cholinergic Antagonists
Safety
Delirium
Odds Ratio
Confidence Intervals
Hospital Emergency Service
Cohort Studies
Retrospective Studies
Diphenhydramine
Intensive care units
Antidotes
Tricyclic Antidepressive Agents
Poisons
Histamine Antagonists
Antipsychotic Agents
Vomiting
Seizures
Research Personnel

Keywords

  • anticholinergic
  • antidote
  • delirium
  • Physostigmine

ASJC Scopus subject areas

  • Toxicology

Cite this

Safety and effectiveness of physostigmine : a 10-year retrospective review*. / Arens, Ann M.; Shah, Krishna; Al-Abri, Suad; Olson, Kent R.; Kearney, Tom.

In: Clinical Toxicology, 13.07.2017, p. 1-7.

Research output: Contribution to journalArticle

Arens, Ann M. ; Shah, Krishna ; Al-Abri, Suad ; Olson, Kent R. ; Kearney, Tom. / Safety and effectiveness of physostigmine : a 10-year retrospective review*. In: Clinical Toxicology. 2017 ; pp. 1-7.
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N2 - Background: Physostigmine has long been recognized as an antidote to reverse anticholinergic delirium. However, its effectiveness, safety profile, and dosing have been disputed. Objectives: To describe effectiveness, adverse events, and dosing associated with the use of physostigmine to reverse anticholinergic delirium. Methods: A retrospective cohort study of hospitalized patients reported to a regional poison center system between 2003 and 2012 who received physostigmine to reverse an anticholinergic toxidrome. Data extraction of a priori defined variables were recorded with concurrence of investigators. The cases were stratified by the primary ingestant as the presumed causative agent and associations for response were performed using odds ratios (ORs), 95% confidence intervals (CI’s), and p values. Results: Of the 1422 cases identified, 191 met the inclusion criteria. Patients exposed to non-diphenhydramine antihistamines (n = 14), antipsychotics (n = 4), and tricyclic antidepressants (n = 3) had 100% response to physostigmine, whereas anticholinergic plants (n = 46/67; 68.7%, OR: 0.70; CI: 0.36–1.35), diphenhydramine (n = 43/56; 64.2%, OR: 1.30; CI: 0.63–2.68), and combination products (n = 8/10; 80%, OR: 1.48; CI: 0.30–7.24) had partial response rates. Of the included patients, 142 (74.3%) were treated with physostigmine alone, and 16 (8.4%) of these patients were discharged directly from the emergency department (ED). Discussion: Most patients, 182 (95.3%), had no documented adverse effects. Four patients (2.1%) experienced emesis, two experienced QTc prolongation (1.0%), and two experienced seizures (1.0%). There was a single fatality 6 h after physostigmine administration. Average initial total doses of physostigmine ranged from 1.0 to 1.75 mg. Most patients were admitted to the ICU (n = 110; 57.6%), however, 36 (18.8%) patients were discharged directly from the ED. Conclusions: In this retrospective cohort study, physostigmine administration to reverse anticholinergic delirium had a good safety profile, and often improved or resolved anticholinergic delirium when administered in doses less than 2 mg.

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