Fewer adverse effects with a modified two-bag acetylcysteine protocol in paracetamol overdose

Clin Toxicol (Phila). 2018 Jul;56(7):618-621. doi: 10.1080/15563650.2017.1408812. Epub 2017 Dec 8.

Abstract

Objective: Acetylcysteine (NAC), an effective antidote for paracetamol poisoning, is commonly associated with adverse reactions. This has been postulated to be related to the rapid initial infusion rate (150 mg/kg over 1 h) of the traditional three-bag protocol. We hypothesized that a slower rate would result in fewer adverse reactions. Our institution in Western Sydney moved to a modified two-bag protocol in February 2015 - first bag: 200 mg/kg over 4 h (50 mg/kg/h) and second bag: (100 mg/kg over 16 h).

Methods: Data was extracted from our database on paracetamol overdoses treated with NAC from August 2010 to September 2016. We compared adverse reactions in patients receiving the modified two-bag protocol with a historical control (traditional three-bag regimen with initial bolus of 150 mg/kg/h).

Results: Over the study period 1011 paracetamol poisonings presented to our toxicology service, of which 476 required NAC (three-bag = 313, two-bag = 163). Demographic characteristics of the two groups were similar. Fewer anaphylactoid reactions (itch, rash, and swelling) occurred using the two-bag regimen (14% versus 5%, p = .002), a relative reduction of 66%. Similarly, there were fewer prescriptions of anti-allergy medications in the two-bag group (11% versus 4%, p = .01). There was no difference in incidence of hepatotoxicity.

Conclusions: Adverse reactions to NAC were less common with the two-bag regimen. These results add to the accumulating evidence that reducing the initial NAC infusion rate reduces the risk of adverse reactions.

Keywords: Acetylcysteine; adverse drug reaction; anaphylactoid reactions; paracetamol overdose.

MeSH terms

  • Acetaminophen / poisoning*
  • Acetylcysteine / administration & dosage
  • Acetylcysteine / adverse effects*
  • Adult
  • Anaphylaxis / chemically induced
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Drug Overdose / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged

Substances

  • Acetaminophen
  • Acetylcysteine