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

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 (150mg/kg over 1h) 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: 200mg/kg over 4h (50mg/kg/h) and second bag: (100mg/kg over 16h).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 150mg/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.