STUDY OBJECTIVE: We determine whether the incidence of adverse events caused by intravenous N -acetylcysteine is significantly less when the initial dose is infused over a 60-minute period compared with the standard infusion period of 15 minutes. A secondary objective is to assess the efficacy of the 2 treatment arms. METHODS: This was a multicenter, randomized, prospective trial of patients who presented with acetaminophen poisoning and who were treated with N -acetylcysteine and had no history of hypersensitivity to N-acetylcysteine. Patients were randomly assigned to receive the initial dose of N-acetylcysteine over a 15-minute or 60-minute period. Baseline signs and symptoms and adverse events were serially evaluated before and during administration of N -acetylcysteine. Tests of liver injury and coagulation were collected at baseline and then at 12-hour intervals. RESULTS: The study was designed with an 80% power to detect a halving of the incidence of adverse events. Of 180 evaluable patients, 109 patients were randomized to the 15-minute group and 71 patients were randomized to the 60-minute group. The incidence of drug-related adverse events was 45% in the 15-minute group and 38% in the 60-minute group (95% confidence interval -8% to 22%). The study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. Incidence of maximum alanine aminotransferase levels indicating hepatotoxicity (serum level >1,000 IU/L) was 6.8% (5.6% for 15-minute, 8.7% for 60-minute). The difference did not attain statistical significance. CONCLUSION: This study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. The study also confirmed that early treatment with N -acetylcysteine (within 8 hours of ingestion) is more effective than later treatment.
RCT Entities:
STUDY OBJECTIVE: We determine whether the incidence of adverse events caused by intravenous N -acetylcysteine is significantly less when the initial dose is infused over a 60-minute period compared with the standard infusion period of 15 minutes. A secondary objective is to assess the efficacy of the 2 treatment arms. METHODS: This was a multicenter, randomized, prospective trial of patients who presented with acetaminophenpoisoning and who were treated with N -acetylcysteine and had no history of hypersensitivity to N-acetylcysteine. Patients were randomly assigned to receive the initial dose of N-acetylcysteine over a 15-minute or 60-minute period. Baseline signs and symptoms and adverse events were serially evaluated before and during administration of N -acetylcysteine. Tests of liver injury and coagulation were collected at baseline and then at 12-hour intervals. RESULTS: The study was designed with an 80% power to detect a halving of the incidence of adverse events. Of 180 evaluable patients, 109 patients were randomized to the 15-minute group and 71 patients were randomized to the 60-minute group. The incidence of drug-related adverse events was 45% in the 15-minute group and 38% in the 60-minute group (95% confidence interval -8% to 22%). The study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. Incidence of maximum alanine aminotransferase levels indicating hepatotoxicity (serum level >1,000 IU/L) was 6.8% (5.6% for 15-minute, 8.7% for 60-minute). The difference did not attain statistical significance. CONCLUSION: This study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. The study also confirmed that early treatment with N -acetylcysteine (within 8 hours of ingestion) is more effective than later treatment.
Authors: Vikhyat S Bebarta; Louise Kao; Blake Froberg; Richard F Clark; Eric Lavonas; Ming Qi; Joao Delgado; John McDonagh; Tom Arnold; Oladapo Odujebe; Gerry O'Malley; Claudia Lares; Elizabeth Aguilera; Richard Dart; Kennon Heard; Chriss Stanford; Jamie Kokko; Greg Bogdan; Carrie Mendoza; Sara Mlynarchek; Sean Rhyee; Jason Hoppe; William Haur; Hock Heng Tan; Nguyen Nguyen Tran; Shawn Varney; Amy Zosel; Jennifer Buchanan; Mohammed Al-Helial Journal: Clin Toxicol (Phila) Date: 2010-06 Impact factor: 4.467
Authors: Mark Yarema; Puja Chopra; Marco L A Sivilotti; David Johnson; Alberto Nettel-Aguirre; Benoit Bailey; Charlemaigne Victorino; Sophie Gosselin; Roy Purssell; Margaret Thompson; Daniel Spyker; Barry Rumack Journal: J Med Toxicol Date: 2018-02-08
Authors: Sara Martinez de Lizarrondo; Clément Gakuba; Bradley A Herbig; Yohann Repessé; Carine Ali; Cécile V Denis; Peter J Lenting; Emmanuel Touzé; Scott L Diamond; Denis Vivien; Maxime Gauberti Journal: Circulation Date: 2017-05-09 Impact factor: 29.690
Authors: Hoi Yan Tong; Nicolás Medrano; Alberto Manuel Borobia; José Antonio Ruiz; Ana María Martínez; Julia Martín; Manuel Quintana; Santos García; Antonio José Carcas; Elena Ramírez Journal: World J Pediatr Date: 2016-07-15 Impact factor: 2.764