Acetaminophen Overdose in Intensive Care Practice: Pathophysiological Mechanisms and Treatment Methods

Introduction . Acetaminophen overdose (AM) is a common cause of toxicity with a high risk of acute kidney injury and death. Provision of emergency care and development of alternative methods of intensive therapy of AM overdose is a vital area of interest for critical care medicine. Aim — to assess the current knowledge of the pathogenesis, manifestations and intensive therapy of acute AM overdose and discuss new and experimental treatments. Materials and methods . Relevant publications were found in the Cochrane Library, PubMed and Medscape using the following terms: “acetaminophen”, “overdose”, “intensive therapy”, “N-acetylcysteine”, “mitochondrial dysfunction”, “oxidative stress”. 76 papers were selected for review. Results and discussion . The pathogenesis of hepatic and renal injury in acute AM overdose is driven by mitochondrial oxidative stress, inflammation, autophagy, apoptosis, and disruption of endoplasmic reticulum. Clinical manifestations include 4 main stages, starting with nausea and vomiting with gradually worsening acute kidney injury, proceeding to cerebral and cardiac insufficiency and sometimes death. Emergency care in AM overdose is provided in the ICU and includes detoxification, hemodynamic maintenance, and treatment of cerebral edema. The only antidote with proven efficacy approved for AM poisoning is N-acetylcysteine. New treatments are being developed to mitigate mitochondrial stress and endoplasmic reticulum disruption, curb inflammation and activate autophagy. Conclusion. The low efficacy of pathogenesis-driven intensive therapy of acute AM poisoning indicates the need for in-depth research in order to improve the quality of emergency care for these patients.