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


CONCLUSIONS
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.
Pakravan
Nasrin
N
National Poisons Information Service Edinburgh, University ofEdinburgh, Edinburgh, UK.
Waring
W Stephen
WS
Sharma
Sushma
S
Ludlam
Christopher
C
Megson
Ian
I
Bateman
D Nicholas
DN
D000082:Acetaminophen / Q000097:blood / Q000506:poisoning*; D000111:Acetylcysteine / Q000009:adverse effects*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000506:poisoning*; D000707:Anaphylaxis / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D000931:Antidotes / Q000009:adverse effects*; D001779:Blood Coagulation Factors / Q000378:metabolism; D062787:Drug Overdose / Q000188:drug therapy; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D010375:Pedigree; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D001779:Blood Coagulation Factors; D018836:Inflammation Mediators; D000082:Acetaminophen; D000111:Acetylcysteine