Correction to: Adverse Effects of Physostigmine.

In "Adverse Effects of Physostigmine" by Arens et al in the July 2019 issue of JMT, reference #27 contains an error.

Adverse Effects of Physostigmine.

INTRODUCTION: Physostigmine is a tertiary amine carbamate acetylcholinesterase inhibitor. Its ability to cross the blood-brain barrier makes it an effective antidote to reverse anticholinergic delirium. Physostigmine is underutilized following the publication of patients with sudden cardiac arrest after physostigmine administration in patients with tricyclic antidepressant (TCA) overdoses. We completed a narrative literature review to identify reported adverse effects associated with physostigmine administration. DISCUSSION: One hundred sixty-one articles and a total of 2299 patients were included. Adverse effects occurred in 415 (18.1%) patients. Hypersalivation (206; 9.0%) and nausea and vomiting (96; 4.2%) were the most common adverse effects. Fifteen (0.61%) patients had seizures, all of which were self-limited or treated successfully without complication. Symptomatic bradycardia occurred in 8 (0.35%) patients including 3 patients with bradyasystolic arrests. Ventricular fibrillation occurred in one (0.04%) patient with underlying coronary artery disease. Of the 394 patients with TCA overdose, adverse effects were described in 14 (3.6%). Adverse effects occurred in 7.7% of patients treated with an overdose of an anticholinergic agent compared with 20.6% of patients with non-anticholinergic agents. Five (0.22%) fatalities were identified. CONCLUSIONS: In conclusion, significant adverse effects associated with the use of physostigmine were infrequently reported. Seizures were self-limited or resolved with benzodiazepines, and all patients recovered neurologically intact. Physostigmine should be avoided in patients with QRS prolongation on EKG, and caution should be used in patients with a history of coronary artery disease and overdoses with QRS prolonging medications. Based upon our review, physostigmine is a safe antidote to treat anticholinergic overdose.

An 11-year retrospective review of cyproheptadine use in serotonin syndrome cases reported to the California Poison Control System.

WHAT IS KNOWN: Cyproheptadine is a serotonin and histamine antagonist that has been suggested as a treatment for serotonin syndrome in case reports. OBJECTIVE: We sought to examine the differences between outcomes and treatment recommendations in patients who received and did not receive cyproheptadine for a probable serotonin syndrome. METHODS: A retrospective review of cases reported to the California Poison Control System between 2006 and 2017 involving cyproheptadine administration or consideration for treatment of a probable serotonin syndrome. RESULTS AND DISCUSSION: A total of 1420 cases were identified and 288 cases met the inclusion criteria. Of these, 68 (23.1%) patients received cyproheptadine treatment and were significantly older (mean age 49.7 vs 33.5 years, P < 0.00001), intubated (n = 35, 51% vs n = 62, 28%, P < 0.05) and, although not statistically significant, were more frequently admitted to a critical care unit (n = 56, 82.3% vs n = 154, 70.0%, P = 0.09). There were no significant differences in serious outcomes (moderate or worse effects) or hospitalization rates (OR, 1.09, 95% CI, 0.49-2.64 and OR, 1.99, 95% CI, 0.86-4.58). There were eight fatalities, of which two patients received cyproheptadine. All fatalities were acute polypharmacy ingestions and had manifested severe symptoms (seizures, hypotension or hyperthermia) either prior to the administration or consideration of cyproheptadine therapy. Cyproheptadine was not administered in 138 (48%) cases primarily due to minimal clinical severity and patient improvement (43%), and not recommended in 82 (28%) cases for reasons from waiting for response to other supportive measures (30%), limited evidence of efficacy (28%) and undetermined diagnosis (14.6%). WHAT IS NEW AND CONCLUSION: The benefits of and indications for cyproheptadine are uncertain and questionable for the management of a serotonin syndrome. Future recommendations on its use should be based on diagnostic criteria, severity of symptoms and management in conjunction with other supportive measures.

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

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.

Dietary supplement adverse events: report of a one-year poison center surveillance project.

BACKGROUND: The safety and efficacy of dietary supplements is of growing concern to regulators, health-care providers and consumers. Few scientific data exist on clinical effects and potential toxicities of marketed products. Harmful supplements may not be identified for months or years with existing adverse event monitoring mechanisms. Retrospective review of poison center statistics to capture supplement-associated toxicity also has limitations. METHODS: We collaborated with the FDA Center for Food Safety and Nutrition (CFSAN) to conduct a 1-year prospective surveillance study of dietary supplement-related poison control center calls in 2006. Prompt follow-up of symptomatic cases, laboratory analysis of implicated dietary supplements, and causality assessment by a case review expert panel were performed. RESULTS: Of 275 dietary supplements calls, 41% involved symptomatic exposures; and two-thirds were rated as probably or possibly related to supplement use. Eight adverse events required hospital admission. Sympathomimetic toxicity was most common, with caffeine products accounting for 47%, and yohimbe products accounting for 18% of supplement-related symptomatic cases. Suspected drug-herb interactions occurred in 6 cases, including yohimbe co-ingested with buproprion (1) and methamphetamine (3), and additive anticoagulant/antiplatelet effects of NSAIDs taken with fish oils (1) and ginkgo (1). Laboratory analysis identified a pharmacologically active substance in 4 cases; supplement toxicity was ruled unlikely when analytical testing was negative in 5 cases. CONCLUSION: Most supplement-related adverse events were minor. Clinically significant toxic effects were most frequently reported with caffeine and yohimbe-containing products. Active surveillance of poison control center reports of dietary supplement adverse events enables rapid detection of potentially harmful products, which may facilitate regulatory oversight.