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Safety and effectiveness of physostigmine: a 10-year retrospective review.
Clin Toxicol (Phila). 2018 02; 56(2):101-107.CT

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.

Authors+Show Affiliations

a Department of Emergency Medicine , Hennepin County Medical Center , Minneapolis , MN , USA. b Department of Emergency Medicine , University of California San Francisco , San Francisco , CA , USA.c Department of Clinical Pharmacy , University of California San Francisco , San Francisco , CA , USA.d Department of Emergency Medicine , Sultan Qaboos University Hospital , Muscat , Oman.d Department of Emergency Medicine , Sultan Qaboos University Hospital , Muscat , Oman. e Department of Medicine , University of California San Francisco , San Francisco , CA , USA.b Department of Emergency Medicine , University of California San Francisco , San Francisco , CA , USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28703024

Citation

Arens, Ann M., et al. "Safety and Effectiveness of Physostigmine: a 10-year Retrospective Review." Clinical Toxicology (Philadelphia, Pa.), vol. 56, no. 2, 2018, pp. 101-107.
Arens AM, Shah K, Al-Abri S, et al. Safety and effectiveness of physostigmine: a 10-year retrospective review. Clin Toxicol (Phila). 2018;56(2):101-107.
Arens, A. M., Shah, K., Al-Abri, S., Olson, K. R., & Kearney, T. (2018). Safety and effectiveness of physostigmine: a 10-year retrospective review. Clinical Toxicology (Philadelphia, Pa.), 56(2), 101-107. https://doi.org/10.1080/15563650.2017.1342828
Arens AM, et al. Safety and Effectiveness of Physostigmine: a 10-year Retrospective Review. Clin Toxicol (Phila). 2018;56(2):101-107. PubMed PMID: 28703024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and effectiveness of physostigmine: a 10-year retrospective review. AU - Arens,Ann M, AU - Shah,Krishna, AU - Al-Abri,Suad, AU - Olson,Kent R, AU - Kearney,Tom, Y1 - 2017/07/13/ PY - 2017/7/14/pubmed PY - 2019/3/30/medline PY - 2017/7/14/entrez KW - Physostigmine KW - anticholinergic KW - antidote KW - delirium SP - 101 EP - 107 JF - Clinical toxicology (Philadelphia, Pa.) JO - Clin Toxicol (Phila) VL - 56 IS - 2 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. SN - 1556-9519 UR - https://wwww.unboundmedicine.com/medline/citation/28703024/Safety_and_effectiveness_of_physostigmine:_a_10_year_retrospective_review_ L2 - https://www.tandfonline.com/doi/full/10.1080/15563650.2017.1342828 DB - PRIME DP - Unbound Medicine ER -