Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement.

Importance: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management. Objective: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada. Evidence Review: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023. Findings: The search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed. Conclusions and Relevance: This qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.

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.

Fatal metformin intoxication with markedly elevated blood and liver concentrations.

The highest postmortem metformin concentrations are recorded utilizing a sensitive and specific analytical procedure. The peripheral blood metformin concentration was 240 mg/L, the liver concentration was 240 mg/kg and the gastric concentration was 1,700 mg. Additionally, an antemortem blood sample collected shortly after admission revealed a metformin concentration of 210 mg/L. These data, revealing a liver to peripheral blood ratio of 1.0, provide additional support that metformin is not subject to postmortem redistribution. Intentional self-poisonings with metformin can result in death, despite multiple medical interventions.