title: Comparing the Therapeutic Effectiveness of N-acetylcysteine with the Combination of N-acetyl Cysteine and Cimetidine in Acute Acetaminophen Toxicity: A Double-Blinded Clinical Trial.
abstract: BACKGROUND
  N-acetylcysteine (NAC) has been used as a classic treatment for hepatotoxicity induced by N-acetyl-p-benzoquinone imine (NAPQI) as a metabolite of acetaminophen. However, cimetidine theoretically can reduce the production of toxic metabolites through the inhibition of cytochrome p450, and it recently was proposed as a complementary treatment for acetaminophen toxicity.
  
  
  OBJECTIVE
  The aim of this study was to compare the effects of treating acute acetaminophen toxicity with NAC alone and with a combination of NAC and cimetidine.
  
  
  METHODS
  From October 2013 to March 2014, 105 patients suspected of acetaminophen toxicity who had paraclinical confirmation of toxicity requiring medical treatment (based on the risk assessment nomogram of acetaminophen serum level) were enrolled in this double-blind, randomized, controlled trial at Imam Reza Hospital in Mashhad, Iran. The patients were divided into two groups, i.e., 1) patients who were treated with NAC alone (group A) and 2) patients who were treated with a combination of NAC and cimetidine (group B). The primary outcomes were 1) the serum level of acetaminophen and 2) the serum level of aminotransferases at the time of admission and 4, 12, 24, and 48 hours after admission. Exclusion criteria included multiple toxicities, concurrent diseases that could affect liver enzymes, the use of other drugs, and dissatisfaction with the project. For measuring quantitative data, SPSS version 16 was used for t-test analysis and for analyzing the qualitative data with chi-squared analysis.
  
  
  RESULTS
  Sixty patients (32 females and 28 males) with a mean age of 25.2 ± 7.3 years were classified in two groups of 30.. There was no difference between the groups in terms of their admission information. The average levels of acetaminophen in both groups at admission, 12, 24, and 48 hours after hospitalization were not significantly different from each other. Twelve hours after hospitalization, the aspartate aminotransferase (AST) level in the group treated with NAC was significantly higher than in the group treated with the combination of NAC and cimetidine (IU/L30.1 ± 110.0 versus IU/L26.38 ± 94.93, p = 0.044). At the other times that the level of liver enzymes was assessed, the serum levels of urea and creatinine were not significantly different in the two groups (p > 0.05).
  
  
  CONCLUSIONS
  The intravenous administration of 300 mg of cimetidine every six hours with NAC did not improve the level of hepatoprotective action significantly compared with the NAC treatment protocol alone.
authors.affiliation: Emergency Medicine Department, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Ebrahimi
authors.affiliation: Medical Toxicology Research Center, Department of Clinical Toxicology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Reza
authors.initials: SR
authors.lastname: Mousavi
authors.affiliation: Addiction Research Center, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Alireza Ghassemi
authors.initials: AG
authors.lastname: Toussi
authors.affiliation: Emergency Medicine Department, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Reihani
authors.affiliation: Emergency Medicine Department, Peymanieh Hospital, Jahrom University of Medical Sciences, Jahrom, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Bagherian
keywords: acetaminophen; acetylcysteine; cimetidine; toxicity