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Sun-107 - MeRIT Project:  Impact of intertreatment N-acetylcysteine (NAC) dose delays on hepatotoxicity in acetaminophen toxicity: A multicenter retrospective study

Scientific Poster Session II - MeRIT Primer Participants (Completed Research)

MeRIT Primer Participants – Completed Research
  Sunday, October 13, 2024
  12:45 PM–02:15 PM

Abstract

Introduction: Acetaminophen (APAP) toxicity is the leading cause of liver transplantation in the United States. N-acetylcysteine (NAC) restores depleted hepatic glutathione reserves and neutralizes toxic APAP metabolites. Delayed NAC administration can increase the risk of liver failure. However, limited evidence exists on the relationship between intertreatment NAC delays in the 3-bag regimen and patient outcomes.

Research Question or Hypothesis: Delays in intertreatment NAC doses are associated with a higher incidence of hepatotoxicity in APAP toxicity.

Study Design: Multicenter, retrospective, cross-sectional study

Methods: Adult patients from emergency departments, receiving NAC for APAP toxicity were included from July 1, 2019, to June 30, 2022. Exclusions were incomplete NAC regimen administration and baseline hepatotoxicity (AST/ALT >1000 units/L). Data collected included demographics, NAC administration times, and hepatic function test results. The primary endpoint was incidence of hepatotoxicity. Correlations between intertreatment NAC delay times and hepatotoxicity were analyzed using linear regression.

Results: Of 237 patients screened, 127 (53.6%) met inclusion criteria. Median delays between NAC dose 1 and 2 was 28.7 mins (IQR 15.6-82.2), and between NAC dose 2 and 3 was 52.4 mins (IQR 20-97.5). Six patients (4.7%) developed clinically significant hepatotoxicity. Mixed-effects models indicated no associations between NAC dose delays and AST or ALT levels. Estimated effects of the delay between NAC doses 1 and 2 on AST and ALT were -1.54 (p=0.675) and -1.04 (p=0.859) units/L per minute, and between doses 2 and 3 were 0.50 (p=0.272) and 0.12 (p=0.121) units/L per minute.

Conclusion: Delays between NAC doses did not show a significant impact on AST and ALT levels. These findings suggest intertreatment NAC timing may not affect hepatotoxicity development patients with APAP toxicity after initiation of the first dose of a 3-bag regimen. These results may support the exploration of alternative NAC regimens, such as the 1-bag method. Further research may elucidate the impacts on intertreatment NAC delays in APAP toxicity.

Presenting Author

Kevin Mercer PharmD, MPH
The Johns Hopkins Hospital

Authors

Joshua Feinstein MD, FACEP
Memorial Hermann Memorial City Medical Center

Chiemela Ubani PharmD, DABAT
Southeast Texas Poison Center

Mark Winter PhD, DABAT, FAACT
Southeast Texas Poison Center

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