Comparison of Two-Bag Versus Three-Bag N-Acetylcysteine Regimens for Pediatric Acetaminophen Toxicity

Ann Pharmacother. 2023 Jan;57(1):36-43. doi: 10.1177/10600280221097700. Epub 2022 May 19.

Abstract

Background: Acetaminophen overdose is a leading cause of liver failure, and a leading cause of pediatric poisoning requiring hospital admission. The antidote, N-acetylcysteine (NAC), is traditionally administered as a three-bag intravenous infusion. Despite its efficacy, NAC is associated with high incidence of nonallergic anaphylactoid reactions (NAARs). Adult evidence demonstrates that alternative dosing regimens decrease NAARs and medication errors (MEs).

Objectives: To compare NAARs and MEs associated with two- versus three-bag NAC for acetaminophen overdose in a pediatric population.

Methods: This is a retrospective observational cohort study comparing pediatric patients who received three- versus two-bag NAC for acetaminophen toxicity. The primary outcome was incidence of NAARs. Secondary outcomes were rates of MEs and relevant hospital outcomes (length of stay [LOS], intensive care unit (ICU) admission, liver transplant, death).

Results: Two hundred forty-three patients met inclusion criteria (median age of 15 years): 150 (62%) three-bag NAC and 93 (38%) two-bag NAC. There was no difference in overall NAARs (p = 0.54). Fewer cutaneous NAARs were observed in the two-bag group, three-bag: 15 (10%), two-bag: 2 (2%), p = 0.02. MEs were significantly decreased with the two-bag regimen, three-bag: 59 (39%), two-bag: 21 (23%), p = 0.01. No statistical differences were observed in LOS, ICU admissions, transplant, or death.

Conclusion and relevance: A significant decrease in cutaneous NAARs and MEs was observed in pediatric patients by combining the first two bags of the traditional three-bag NAC regimen. In pediatric populations, a two-bag NAC regimen for acetaminophen overdose may improve medication tolerance and safety.

Keywords: N-acetylcysteine; NAC; acetaminophen; adverse events; medication errors; nonanaphylactoid allergic reactions.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / therapeutic use
  • Acetylcysteine / therapeutic use
  • Adolescent
  • Adult
  • Analgesics, Non-Narcotic* / therapeutic use
  • Antidotes / therapeutic use
  • Child
  • Cohort Studies
  • Drug Overdose* / drug therapy
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Retrospective Studies

Substances

  • Acetylcysteine
  • Acetaminophen
  • Antidotes
  • Analgesics, Non-Narcotic