Management of Anaphylactoid Reactions to Intravenous N-Acetylcysteine,☆☆,,★★,

Presented in part at the North American Congress of Clinical Toxicology, Portland, OR, October 1996.
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Abstract

Study Objective: To develop management guidelines for the treatment of anaphylactoid reactions to intravenous N-acetylcysteine (NAC) and to assess the safety of restarting the infusion after a reaction. Methods: In phase 1, we used a 6-year retrospective case series of hospitalized patients and a review of the literature to develop the management guidelines for anaphylactoid reactions to intravenous NAC. In phase 2, these guidelines were evaluated prospectively in our poison-control center. Results: In phase 1, the charts of 11 patients with anaphylactoid reactions (9 cutaneous and 2 systemic) were reviewed. In most cases, no treatment or treatment with diphenhydramine alone or with salbutamol was sufficient to continue or restart NAC infusion safely. On the basis of our findings in those patients and on published experience, we concluded that anaphylactoid reactions to intravenous NAC are dose-related and that antihistamines are useful in controlling and in preventing recurrence of anaphylactoid symptoms. We developed the following guidelines: flushing requires no treatment, urticaria should be treated with diphen hydramine, and NAC infusion should be continued in both cases. Angioedema and respiratory symptoms each require the administration of diphenhydramine and symptomatic therapy. In these cases, NAC infusion should be stopped but, when necessary, can be restarted 1 hour after the administration of diphenhydramine in the absence of symptoms. In phase 2, 50 patients (31 cutaneous and 19 systemic reactions) were treated prospectively with the use of these guidelines. Recurrence of symptoms occurred in only one case involving a deviation from the guidelines. The NAC infusion was restarted immediately after the administration of diphenhydramine in a patient who sustained a systemic reaction. Conclusion: Non–life-threatening anaphylactoid reactions to intravenous NAC are treated easily and the infusion may be continued or restarted safely after the administration of diphenhydramine. [Bailey B, McGuigan MA: Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med June 1998;31: 710-715.]

Section snippets

INTRODUCTION

N-Acetylcysteine (NAC) is an effective antidote for acute acetaminophen poisoning.1 It is usually given orally in a 72-hour treatment protocol or intravenously in either a 20-hour or a 48-hour treatment protocol.1 When used intravenously, NAC can cause anaphylactoid reactions involving flushing, urticaria, angioedema, bronchospasm, and other respiratory symptoms or a combination of them.1

In no study has the management of these reactions and the continuation of intravenous NAC been assessed.

Phase 1: Retrospective study and guidelines development

We reviewed the charts of all patients hospitalized in our pediatric hospital with a diagnosis of acetaminophen overdose between January 1, 1990, and December 31, 1995, to identify adverse reactions to intravenous NAC and the treatment used. In an attempt to detect all reactions, we reviewed medical progress notes, nursing progress notes, and medication prescription and delivery forms. Adverse reactions to NAC were defined as the presence of symptoms or signs of anaphylactoid reactions.

Phase 1: Retrospective study and guidelines development

Over the 6 years studied, 60 patients received at least one dose of NAC (more than one protocol was sometimes carried out in the same overdose). Forty-three patients were exposed to at least the first and the beginning of the second infusion of the 20-hour intravenous-NAC protocol, 5 patients were exposed at least to the first dose of the 48-hour intra venous-NAC protocol, and 16 patients were exposed to the first dose of the 72-hour oral-NAC protocol.

Adverse reactions to NAC developed in 11

DISCUSSION

Most adverse reactions to NAC are said to be anaphylactoid in nature because the reaction is clinically similar to an anaphylactic reaction in that it is caused by release of histamine but generally not IgE-mediated. Very rarely these reactions may have been associated with hypotension and death.7, 16, 19 The role of NAC in the reported deaths is not clear: In all of them an alternative cause of death was possible. Furthermore, in three of four, an incorrect dose of NAC was administered.7, 16,

Acknowledgements

We thank all the poison-information specialists who identified cases.

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  • Cited by (0)

    From the Section of Clinical Pharmacology and Toxicology* and Emergency Section, Department of Pediatrics, Hôpital Sainte-Justine, Montreal, Quebec; and the Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children and the Ontario Regional Poison Information Centre, Toronto, Ontario, Canada.§

    ☆☆

    Received for publication April 9, 1997. Revisions received July 28, 1997, and January 28, 1998. Accepted for publication February 26, 1998.

    Dr Bailey was supported by a fellowship from the R. Samuel McLaughlin Foundation and the Canadian Society for Clinical Pharmacology.

    ★★

    Address for reprints: Benoit Bailey, MD, MSc, Department of Pediatrics, Hôpital Sainte Justine, 3175 Côte Sainte-Catherine, Montreal, Quebec, H3T 1C5 , Canada

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