Timing and Frequency of Physostigmine Redosing for Antimuscarinic Toxicity

Abstract

We sought to determine how frequently antimuscarinic-poisoned patients receiving physostigmine receive multiple doses of physostigmine, the length of time between physostigmine doses, and what impact multiple doses of physostigmine have on the disposition and total length of hospital stay. We performed a retrospective chart review of patients given physostigmine for likely antimuscarinic toxicity. A total of 45 patients met inclusion criteria. We abstracted patient demographics, vital signs, physical exam findings, electrocardiograms, the timing and dose of physostigmine, the implicated antimuscarinic agents, and disposition from the hospital. We counted the number of patients who required multiple physostigmine doses and calculated the time to repeat dosing. Fourteen of the 45 patients (31%) given physostigmine for antimuscarinic toxicity received multiple doses: nine patients (20%) received two doses, three patients (6.6%) received three doses, and two patients (4.4%) received four doses. Less than 5.5 h elapsed between sequential physostigmine doses, and less than 6.5 h elapsed between the first and last dose. Forty-five percent of patients receiving one dose of physostigmine were discharged from the emergency department (ED) and 36% of patients receiving more than one dose of physostigmine were discharged from the ED. Whether admitted or discharged, there was no statistically significant difference in the length of hospital stay between patients receiving one or multiple doses of physostigmine.Repeated physostigmine administration is not frequently needed in medication-induced antimuscarinic toxicity. Patients are not likely to require further physostigmine redosing more than 6.5 h from their first dose.

Physostigmine in Anticholinergic Poisoning: An Old Antidote With Resurgence

“…Without the need for endotracheal intubation, our patient's length of hospital stay was drastically reduced. A study conducted in 2010 evaluating physostigmine use in anticholinergic delirium and hospital stay showed that 42% of patients were discharged directly from the emergency department, 31% were admitted to the general medical floors, and 27% were admitted to the intensive care unit with an average length of stay being 3.59 days [ 6 ]. A more recent retrospective study conducted in 2019 evaluated 141 patients in whom physostigmine was used demonstrated reduced intubation rates without increased incidence of dangerous adverse events including bradycardia and seizures.…”

Physostigmine use in clozapine intoxication from adulterated heroin: an atypical toxidrome with an effective antidote

“…Physostigmine is a short-acting acetylcholinesterase inhibitor, which increases synaptic concentrations of acetylcholine for competition with the toxic muscarinic antagonist for the acetylcholine receptor. It is a tertiary amine, allowing for crossing of the blood brain barrier for reversal of central antimuscarinic effects [1,11]. Its first documented use for reversing anticholinergic delirium was in 1864 by Kleinwachter, who treated patients that had mistakenly consumed atropine [1,12,13].…”

“…Yet, practice patterns vary widely with regard to the dosing and rate of administration of physostigmine [1]. When dosed appropriately, however, most patients who receive physostigmine in the ED require only a single dose [11]. To avoid toxicity and prevent unnecessary redosing, recent recommendations suggest a single dose of 0.5 to 1 mg of physostigmine given intravenously with a minimum delay of 10-15 min before redosing [1].…”

Pharmacological management of anticholinergic delirium ‐ theory, evidence and practice

“…In complete responders the rate of delirium recurrence requiring repeated doses of physostigmine ranges from 31 to 90% . The frequency and timing of relapse appears to be due to the shorter half‐life and duration of action of physostigmine compared with many anticholinergic agents.…”