Anaphylactoid Reactions to Intravenous N-Acetylcysteine during Treatment for Acetaminophen Poisoning

Abstract

Background: Anaphylactoid reactions to intravenous (IV) N-acetylcysteine (NAC) are well-recognized adverse events during treatment for acetaminophen (APAP) poisoning. Uncertainty exists regarding their incidence, severity, risk factors, and management. We sought to determine the incidence, risk factors, and treatment of anaphylactoid reactions to IV NAC in a large, national cohort of patients admitted to hospital for acetaminophen overdose.

Methods: This retrospective medical record review included all patients initiated on the 21-h IV NAC protocol for acetaminophen poisoning in 34 Canadian hospitals between February 1980 and November 2005. The primary outcome was any anaphylactoid reaction, defined as cutaneous (urticaria, pruritus, angioedema) or systemic (hypotension, respiratory symptoms). We examined the incidence, severity and timing of these reactions, and their association with patient and overdose characteristics using multivariable analysis.

Results: An anaphylactoid reaction was documented in 528 (8.2%) of 6455 treatment courses, of which 398 (75.4%) were cutaneous. Five hundred four (95.4%) reactions occurred during the first 5 h. Of 403 patients administered any medication for these reactions, 371 (92%) received an antihistamine. Being female (adjusted OR 1.24 [95%CI 1.08, 1.42]) and having taken a single, acute overdose (1.24 [95%CI 1.10, 1.39]) were each associated with more severe reactions, whereas higher serum APAP concentrations were associated with fewer reactions (0.79 [95%CI 0.68, 0.92]).

Conclusion: Anaphylactoid reactions to the 21-h IV NAC protocol were uncommon and involved primarily cutaneous symptoms. While the protective effects of higher APAP concentrations are of interest in understanding the pathophysiology, none of the associations identified are strong enough to substantially alter the threshold for NAC initiation.

Keywords: Acetaminophen; Adverse drug event; N-acetylcysteine; Paracetamol.

Fig. 1

Time-weighted risk of developing an anaphylactoid reaction during the three phases of intravenous N-acetylcysteine infusion. The absolute risk for experiencing a reaction during each of the three dosing phases (150 mg/kg over 15 to 60 min, 50 mg/kg over 4 h, 100 mg/kg over 16 h) is shown, divided by the duration of the phase. Thus, the area of each rectangle is proportional to the actual number of cases. The large, open rectangles bounded by solid lines show the risk had all patients been administered the loading dose over 60 min and is therefore a very conservative estimate of the risk rate during the loading phase. The gray rectangles show a closer (yet also conservative) approximation under the null hypothesis that the risk of reaction is independent of the duration of the loading phase