Paracetamol (acetaminophen) poisoning; consensus definitions of poisoning types and outcomes to be used in the clinical toxicology recommendations collaborative systematic review

Abstract

Introduction: Paracetamol (acetaminophen) poisoning is common, and many publications describe various outcomes and treatments. As internationally agreed definitions are non-existent to describe patterns of paracetamol overdose (acute, repeated supratherapeutic, chronic, or staggered), it is difficult to analyze outcomes between studies. The Clinical Toxicology Recommendations Collaborative was tasked to provide guidance on the management of paracetamol poisoning and formed the Paracetamol Workgroup. The Workgroup concluded that an agreed set of terms was needed to perform the systematic review and categorize the evidence.

Methods: A modified Delphi process was employed to establish uniform definitions to categorize various patterns of paracetamol overdose.

Results: Group consensus was reached for each one of the following standard definitions for each pattern of poisoning: acute, staggered, repeated supratherapeutic ingestions, and chronic for use in their upcoming systematic review. "Acute" ingestion represents an excessive amount of paracetamol ingested over a total time (from first paracetamol dose ingested to last paracetamol dose ingested) of less than 8 h. "Staggered" ingestion involves an excessive amount of paracetamol ingested over a total time period of between 8 h and 24 h. "Repeated supratherapeutic ingestion" describes ingestions exceeding the recommended daily dose for more than 24 h, and "chronic" ingestion includes both staggered or repeated supratherapeutic ingestions. "High-risk overdoses" are defined by either an ingested dose, that is greater than 500 mg/kg or 30 g (whichever is less), or an initial serum or plasma paracetamol concentration of greater than 300 mg/L (1,985 µmol/L) at 4 h on the Rumack-Matthew nomogram line.

Discussion: The definitions established by the Paracetamol Workgroup will structure the upcoming systematic review, ensuring consistent categorization of studies within each ingestion pattern to enable clearer comparisons of treatments and outcomes.

Conclusion: We encourage researchers to define overdose patterns and patients at increased risk of hepatotoxicity consistently and to include these definitions in publications to improve research reliability and comparability.

Keywords: Acetaminophen; hepatotoxicity; overdose; paracetamol; poisoning.