Multiple Aminotransferase Peak Levels After Acute Acetaminophen Overdose in Three Patients Sean H. Rhyee, M.D., M.P.H., Jason Hoppe, D.O., and Kennon Heard, M.D. After acetaminophen overdose, typical trends of aspartate and alanine aminotransferase (AST and ALT, respectively) levels consist of a single peak followed by a decrease to baseline. Based on this pattern, declining AST or ALT levels have been proposed as a criterion for when to discontinue N- acetylcysteine therapy in patients with acetaminophen overdose. We describe three patients who experienced multiple aminotransferase peak levels after acetaminophen overdose. In each case, an initial peak was followed by a 20% or greater decrease in AST or ALT level, then a second, higher peak exceeding 1000 U/L. In two cases, the second peak correlated with encephalopathy or coagulopathy. Two patients were treated with a continuous infusion of intravenous N-acetylcysteine, with treatment interrupted for 4 hours in one of them. As observed in the three patients, multiple aminotransferase peak levels can occur after acetaminophen overdose. Although declining levels typically coincide with clinical improvement, the presence of other markers of liver injury, such as coagulopathy or encephalopathy, should prompt continued N-acetylcysteine treatment. Key Words: acetaminophen, overdose, N-acetylcysteine, aminotransferases, aspartate aminotransferase, alanine aminotransferase, AST, ALT. (Pharmacotherapy 2010;30(10):1084–1088) Typical trends of aspartate and alanine aminotransferase (AST and ALT, respectively) levels after acetaminophen overdose consist of a steady increase to a single peak, followed by a decrease to baseline. 1 This decrease usually corresponds with clinical recovery. Based on this pattern, some authors have proposed using declining AST or ALT levels as one of the criteria for when to discontinue N -acetylcysteine treatment. 2, 3 In this case report, however, we describe three patients with acetaminophen overdose who each experienced a decline in aminotransferase levels after an initial peak level, followed by a second, higher peak that correlated with evidence of hepatic failure. Case Reports Patient No. 1 A 33-year-old woman was brought to the emergency department approximately 24 hours after acute ingestion of acetaminophen and quetiapine (doses unknown). Her mental status was normal. Her medical history was remarkable for schizoaffective disorder, epilepsy, Gilbert’s From the Division of Medical Toxicology, Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, Massachusetts (Dr. Rhyee); the Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado (Drs. Hoppe and Heard); and Rocky Mountain Poison and Drug Center, Denver Health, Denver, Colorado (Dr. Heard). Dr. Rhyee is a contract consultant for Teva Neuroscience. The subject matter of this contract does not relate in any way to the content of this manuscript. Dr. Heard received funding from the National Institute on Drug Abuse (grant DA 020573-04). Presented in part as an abstract at the North American Congress of Clinical Toxicology, New Orleans, Louisiana, October 19–24, 2007. For reprints, visit http://www.atypon-link.com/PPI/loi/phco. For questions or comments, contact Sean H. Rhyee, M.D., M.P.H., Department of Emergency Medicine, UMass Memorial Medical Center, 55 Lake Avenue North, LA-202, Worcester, MA 01655.