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Adducts post acetaminophen overdose treated with a 12-hour vs 20-hour acetylcysteine infusion

Journal of Medical Toxicology Jan 23, 2020

Wong A, et al. - Given the value of acetaminophen protein adducts in the circulation as a specific biomarker of acetaminophen oxidation, and its possible value as a more sensitive measure of impending hepatic injury following overdose than alanine transaminase (ALT), researchers conducted an exploratory analytical substudy of adducts during a clinical trial (NACSTOP) of abbreviated (12-hour) vs control (20-hour) acetylcysteine to recognize any signal of reduced antidotal effectiveness with shortened therapy. Adducts were measured at 0, 12, and 20 hours in a convenience sample of individuals who were recruited in the cluster-controlled NACSTOP trial evaluating a 12-hour (“abbreviated”; 200 mg/kg over 4 hours, 50 mg/kg over 8 hours) vs 20-hour acetylcysteine regimen (“control”; 200 mg/kg over 4 hours, 100 mg/kg over 16 hours). At 20 hours following the initiation of acetylcysteine, median ALT of 12 U/L (IQR 8,14) was identified in the abbreviated 12-hour regimen group (N = 8), compared with the control group 16 U/L (IQR 11,21; N = 21). Observations revealed the detection of minimal to no acetaminophen protein adducts. This provides further support to discontinuation of acetylcysteine when acetaminophen concentrations are low and liver function tests normal after 12 hours of treatment.
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