A Comparison of Resource Utilization in the Management of Anticholinergic Delirium Between Physostigmine and Nonantidote Therapy

Abstract

Background: Antimuscarinic delirium is associated with significant morbidity, and its management requires substantial resource allocation, including intubation, restraint, and intensive care unit (ICU) placement. There is controversy over the management of these patients. Physostigmine can rapidly reverse antimuscarinic delirium but has been associated with adverse effects. Objective: This study aims to assess the effect of physostigmine use on resource allocation and adverse events. Methods: This is a retrospective chart review of patients with an antimuscarinic toxidrome at a single hospital approved by the local institutional review board. A blinded abstractor recorded data from patient charts. Whether the patient was given physostigmine, intubated, restrained, or admitting to critical care was recorded. We recorded instances of seizure, vomiting, or bradycardia. The primary aim was to compare frequency of intubation as a function of physostigmine administration. Results: A total of 141 patients were identified. We found no difference between the groups in age, gender, or initial heart rate; 65 (46%) were given physostigmine, 45 (32%) were admitted to the ICU, and 29 (20%) were intubated. Patients who received physostigmine in the first 24 hours were less likely to be intubated and less likely to be admitted to an ICU. The instance of bradycardia (n = 16), vomiting (n = 27), and seizures (n = 7) was limited, and there were no significant differences between the groups. There were no associations noted between physostigmine administration and adverse effects. Conclusion and Relevance: This study demonstrated that physostigmine use is associated with decreased resource utilization (including intubation and ICU placement) without increasing rates of bradycardia, vomiting, or seizures.

Physostigmine should be used more readily for antimuscarinic toxicity: PRO

“…The clinical literature is characterised by considerable heterogenicity in causative agents, syndrome severity and to a lesser extent physostigmine dosing. [4][5][6][7][8][9][10][11][12][13][14][15] This heterogenicity supports the use of physostigmine in a range of clinical contexts where antimuscarinic delirium is thought likely.…”

“…Methodologically these responses span from physician assessment to use of more formal tools to score delirium and agitation. [4][5][6][7][8][9][10][11][12][13][14][15] A number of studies have shown that improvement and resolution of delirium were significantly greater with physostigmine than alternative treatments, most frequently benzodiazepines. Burns reported physostigmine-controlled agitation and reversed delirium in 96% and 87% of patients, respectively, whereas benzodiazepines controlled agitation in 24% of patients but were ineffective in reversing delirium.…”

“…Treatment with physostigmine was associated with a decreased likelihood of being intubated (OR = 0.24, 95% confidence interval [CI] = 0.100-0.519) and being admitted to ICU (23% vs 39%, P = .048). 14 Burns found that physostigmine was associated with a lower rate of intubation (1%) compared to benzodiazepine treatment (27%). 6 Watkins found a significant decrease in intubation between patients who received physostigmine only and those who did not of 1.9% vs 8.4%, respectively.…”

“…Published case series with cumulative 1926 patients have not reported deaths associated with physostigmine use. [4][5][6][7][8][9][10][11][12][13][14][15] These series include a large proportion of drugs that lower the seizure threshold and/or have some cardiotoxicity, such as antihistamines and neuroleptics. In these series the rates for seizures 0.73% (CI 0.42-1.1) and any cardiovascular adverse event, mostly bradycardia or ECG changes, 0.62% (CI 0.34-1.06), is low.…”

Physostigmine in Anticholinergic Poisoning: An Old Antidote With Resurgence

“…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. The study further elucidated that this in turn minimizes critical care time and thus decreases resource utilization in the management of an otherwise complicated patient population [7].…”