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Clin Toxicol (Phila). 2008 Sep;46(8):697-702. doi: 10.1080/15563650802245497.

Risk factors and mechanisms of anaphylactoid reactions to acetylcysteine in acetaminophen overdose.

Author information

1
National Poisons Information Service Edinburgh, University ofEdinburgh, Edinburgh, UK.

Abstract

BACKGROUND:

Adverse effects to N-acetylcysteine (NAC) are well recognized, but their etiology and incidence are unclear.

METHODS:

The nature and severity of adverse effects were prospectively studied in 169 patients and potential reaction mediators studied in 22 patients.

RESULTS:

Adverse effects were minimal in 101 (59.8%), moderate in 51 (30.2%), and severe in 17 (10.1%). Features were nausea (70.4%), vomiting (60.4%), flushing (24.9%), pruritus (20.1%), dyspnea (13.6%), chest pain (7.1%), dizziness (7.7%), fever (4.7%), wheeze and bronchospasm (7.1%), and rash and urticaria (3.6%). Serum acetaminophen concentration was lower in patients with severe adverse effects: median (IQR) 46 mg/L (0 to 101 mg/L), moderate 108 mg/L (54 to 178 mg/L), and minimal 119 mg/L (77 to 174 mg/L), p = 0.002. Family history of allergy and female gender were independent risk factors for adverse effects. Severity of adverse effects was associated with histamine release: AUC for change from baseline histamine was -6 ng/mL min (-60 to 11 ng/mL min) in the minimal group, 26 ng/mL min (3-129 ng/mL min) in the moderate group, and 49 ng/mL min (21-68 ng/mL min) in the severe group (p = 0.01). There was no increase in tryptase and no differences between groups for NAC concentrations or hemostatic and inflammatory variables (factors II, VII, IX, X, vWF, tPA, IL6, and CRP).

CONCLUSION:

Severity of adverse effects correlates with the extent of histamine release. Histamine release appears independent of tryptase suggesting a non-mast cell source. Acetaminophen is protective against adverse effects of NAC, and mechanisms by which acetaminophen might lessen histamine release require further attention.

PMID:
18803085
DOI:
10.1080/15563650802245497
[Indexed for MEDLINE]

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