Cerebral edema and brain death following intravenous N-acetylcysteine overdose: a case report

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Abstract

N-acetylcysteine (NAC) infusions are rarely associated with cerebral edema. We present a patient that received 1242.2 mg/kg intravenous NAC over 8.3 h who developed seizures, cerebral edema, and died. A 17-24-year-old female (48.3 kg) presented after an acute acetaminophen ingestion. Their initial presumed 5 h acetaminophen concentration was 591.7 μmol/L. Initial alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were 16 and 21 IU/L, respectively. Due to inconsistencies in the time of ingestion, IV NAC was initiated as a two-step protocol of 150 mg/kg over 1 h followed by 15 mg/kg/h for 20 h. During treatment, the patient developed vomiting, flushing, and a maculopapular rash. It was discovered that NAC had been administered continuously at 150 mg/kg/h for 8.3 h and was stopped. The patient became confused and agitated and subsequently developed seizures. They were treated with lorazepam, phenytoin, intubation, and propofol. Neuroimaging demonstrated cerebral edema with cerebellar tonsillar herniation. Despite neurocritical care, the patient died 86 h post-ingestion. The patient's ALT and AST remained normal. Investigations including lumbar puncture and post-mortem toxicology analysis were unremarkable. Clinicians must be aware of the clinical features of supratherapeutic IV NAC dosing errors and potential adverse effects.

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Hartmann, R. J., Pradhan, S., Bylyku, D., Markieta, K., Scozzafava, J., Lucyk, S., & Yarema, M. (2026). Cerebral edema and brain death following intravenous N-acetylcysteine overdose: a case report. Canadian Journal of Physiology and Pharmacology, 104, 1–5. https://doi.org/10.1139/cjpp-2025-0341

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