Mechanisms of Adverse Reactions to Intravenous Acetylcysteine in Acetaminophen Overdose

Background: Mechanisms involved in adverse reactions (ADRs) to IV acetylcysteine (NAC) are poorly understood. In volunteers changes in clotting factors [Knudsen et al 2005] are reported that relate to ADR severity. We have reported increases in serum histamine related to ADRs from NAC in acetaminophen (AP) overdose (EAPCCT Congress, Seville), and now report endothelial and hemostatic data in this group. Methods: An IR approved prospective study of 22 patients receiving IV NAC for AP overdose was conducted. Concentrations of AP, NAC, tryptase, IL6, CRP, tPA, wWf, and clotting factors were determined pre-NAC and at intervals during treatment. ADRs were pre-categorized as minimal (no or mild GI); moderate (GI requiring anti-emetic and/or mild anaphy-lactoid features); severe (anaphylactoid features requiring cessation NAC). Results: ADR occurence and severity (10 cases minimal, 5 moderate, 7 severe) was unrelated to any measure, despite differential changes in histamine. Factors II, VII, IX, X were significantly reduced by NAC but these changes were not related to ADR severity or AP concentration. NAC concentrations were similar in all three groups but AP levels were lower (p