A Systematic review and meta-analysis to compare the effectiveness of shorter 12-hour N-Acetylcysteine (NAC) regimen VS 20-21-hour NAC regimen in management of paracetamol poisoning

Abstract

Abstract Background: Paracetamol poisoning due to unrecommended doses is a leading cause of acute liver failure (ALF) globally, resulting in significant medical consequences. N-Acetylcysteine (NAC) is the standard antidote for paracetamol poisoning, administered through a 20-21 hour 3-bag infusion since 1980. However, this regimen has been associated with adverse reactions, prompting the investigation of shorter NAC regimens like the 12-hour version. A comparison of evidence on the effectiveness and safety between the two interventions is lacking, necessitating this research. Aims and Objectives: A meta-analysis to compare the effectiveness of a 12-hour NAC regimen with the longer 20-21hour regimen in managing paracetamol poisoning. Methods: A quantitative systematic review of Randomized Controlled Trials (RCTs) and observational studies was performed, using PICO criteria to search databases Medline, Web of Science, PubMed, Cochrane and Clinical trials.com from 2008 to 2023. The extracted data were analyzed separately for RCTs and observational studies. Results: Eight studies, including three RCTs and five observational studies involving 10,924 patients, were analyzed. The primary outcome, hepatic injury, showed an insignificant reduction with the 20-21hour NAC regimen (odds ratio= 1.53, 95% CI 0.69-3.40, p=0.29) in RCTs and with the 12-hour NAC regimen (odds ratio= 0.88, 95% CI 0.70-1.11, p=0.29) in observational studies. The secondary outcome, adverse reactions (anaphylactoid reaction), showed a statistically significant reduction with the 12-hour NAC regimen (odds ratio= 0.37, 95% CI 0.20-0.68, p=0.001) in RCTs and (odds ratio= 0.16, 95% CI 0.12-0.22, p=0.00001) in the observational studies. Conclusions: This study suggests that the 12-hour NAC regimen is as effective as the 20-21hour regimen in managing paracetamol poisoning, but with fewer adverse reactions. However, further research is needed to explore the impact of factors like late presentation and delayed infusion on adverse reactions.