Analphylatoid reaction is caused by non-IgE mediated histamine released. Intravenous N-acetylcysteine (NAC) infusion is well known to cause analphylatoid reaction. However, it’s incidence is unknown.

Recently, a large retrospective study of all patients who received 21-hour IV NAC in 34 Canadian hospitals (1980 to 2005) was performed. 

Anaphylactoid reaction was documented in 528 (8.2%) of 6455 treatment courses

• Cutaneous reaction (urticarial, pruritus and angioedema) occurred in 398 (75.4%)
• Systemic reaction (respiratory symptoms or hypotension): 34 (6.4%)
• Both reactions: 96 (18.2%)

Over 90% patients developed analphylatoid reaction within 5 hours.

Onset of reaction: 

• 1^stNAC dosing (150 mg/kg over 1 hour): 133/528
• 2^ndNAC dosing (50 mg/kg over 4 hours): 371/528
• 3^rdNAC dosing (100 mg/kg over 16 hours): 24/528

Administered medication for treatment

• Antihistamine: 371
• Beta-2 agonist: 15
• Epinephrine: 10
• Corticosteroids: 7

Patient characteristics that were associated with higher incidence of Anaphylactoid reaction includes

• Female
• Single acute ingestion
• Low serum acetaminophen level.

 

Bottom line

1. Anaphylactoid reaction to NAC is uncommon
2. Cutaneous symptoms are most common
3. Female, single acute ingestion and low serum acetaminophen levels are associated with incidence of anaphylactoid reaction. 

References

Yarema M et al. Anaphylactoid reactions to intravenous N-acetylcysteine during treatment for acetaminophen poisoning. J Med Toxicol 2018: Jun;14(2):120-127. doi: 10.1007/s13181-018-0653-9. Epub 2018 Feb 8.