Introduction: Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC.

Methods: We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration.

Results: Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC.

Conclusion: For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy.

Introduction: Epinephrine is the treatment of choice for anaphylaxis. We surveyed emergency department (ED) health care providers regarding 2 methods of intramuscular (IM) epinephrine administration (autoinjector and manual injection) for the management of anaphylaxis and allergic reactions and identified provider perceptions and preferred method of medication delivery.

Methods: This observational study adhered to survey reporting guidelines. It was performed through a Web-based survey completed by health care providers at an academic ED. The participants consisted of all ED providers, including staff physicians, resident physicians, pharmacists, advanced practice providers, and nurses. The primary outcomes were assessment of provider perceptions and identification of the preferred IM epinephrine administration method by ED health care providers.

Results: Of 217 ED health care providers invited to participate, 172 (79%) completed the survey. Overall, 82% of respondents preferred the autoinjector method of epinephrine administration. Providers rated the autoinjector method more favorably with regard to time required for training, ease of use, convenience, satisfaction with weight-based dosing, risk of dosing errors, and speed of administration (P<.001 for all comparisons). However, manual injection use was rated more favorably with regard to risk of provider self-injury and patient cost (P<.001 for both comparisons). Three participants (2%) reported a finger stick injury from an epinephrine autoinjector.

Conclusion: ED health care providers preferred the autoinjector method of IM epinephrine administration for the management of anaphylaxis or allergic reactions. Epinephrine autoinjector use may reduce barriers to epinephrine administration for the management of anaphylaxis in the ED.