Mark Yarema1,2,3, Puja Chopra4, Marco L A Sivilotti5,6, David Johnson7,8, Alberto Nettel-Aguirre8,9,10, Benoit Bailey11, Charlemaigne Victorino12, Sophie Gosselin13, Roy Purssell14, Margaret Thompson6, Daniel Spyker15, Barry Rumack16. 1. Poison and Drug Information Service, Foothills Medical Centre, 1403-29th St NW, Calgary, Alberta, T2N 2T9, Canada. mark.yarema@albertahealthservices.ca. 2. Section of Clinical Pharmacology and Toxicology, Alberta Health Services, Calgary, AB, Canada. mark.yarema@albertahealthservices.ca. 3. Department of Emergency Medicine, University of Calgary, Calgary, AB, Canada. mark.yarema@albertahealthservices.ca. 4. Department of Emergency Medicine, University of Calgary, Calgary, AB, Canada. 5. Departments of Emergency Medicine, and of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada. 6. Ontario Poison Centre, Toronto, ON, Canada. 7. Poison and Drug Information Service, Foothills Medical Centre, 1403-29th St NW, Calgary, Alberta, T2N 2T9, Canada. 8. Department of Pediatrics, University of Calgary, Calgary, AB, Canada. 9. Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada. 10. Alberta Children's Hospital Research Institute for Child and Maternal Health, Calgary, AB, Canada. 11. Division of Emergency Medicine, Department of Pediatrics, CHU Sainte Justine, Montréal, Quebec, Canada. 12. Prairie Regional Research Data Centre, Statistics Canada, Calgary, AB, Canada. 13. Centre Antipoison du Québec, Québec City, Québec, Canada. 14. Department of Emergency Medicine, University of British Columbia, Vancouver, BC, Canada. 15. Department of Emergency Medicine, Oregon Health Sciences University, Portland, OR, USA. 16. Department of Pediatrics, University of Colorado School of Medicine, Denver, CO, USA.
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.
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 acetaminophenoverdose. METHODS: This retrospective medical record review included all patients initiated on the 21-h IV NAC protocol for acetaminophenpoisoning 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.
Entities:
Keywords:
Acetaminophen; Adverse drug event; N-acetylcysteine; Paracetamol
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