Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of adverse drug reactions

Context: Adverse reactions to intravenous (IV) acetylcysteine treatment in paracetamol overdose, are common. Previous studies suggest the incidence and severity of non-allergic anaphylactic reactions (NAARs) are influenced by the rate of acetylcysteine infusion. Objective: We compared the incidence of adverse drug events of a two-bag IV acetylcysteine regimen with that of the traditional three-bag regimen. Materials and methods: This was a retrospective analysis of patients presenting with paracetamol overdose requiring treatment with acetylcysteine to three emergency departments. We prospectively identified all presentations where IV acetylcysteine was administered using a 20 h, two-bag regimen (200mg/kg over 4 h followed by 100mg/kg over 16 h) from February 2014 to June 2015. We compared this to an historical cohort treated with the 21 h three-bag IV regimen (150mg/kg over 1 h, 50mg/kg over 4 h and 100mg/kg over 16 h) from October 2009 to October 2013. Medical and nursing notes were searched retrospectively for entries suggesting the presence of an adverse reaction. The primary outcome was incidence of NAARs and gastrointestinal reactions in each group. Results: 389 presentations were treated with the three-bag regimen and 210 presentations received the two-bag regimen. NAARs were recorded more commonly with the three-bag acetylcysteine regimen than the two-bag regimen (10% vs 4.3%, p=0.02, OR 2.5, 95% CI 1.1-5.8). There was no difference in reports of gastrointestinal reactions between cohorts (three-bag 39% vs two-bag 41%, p=0.38, OR 1.17 95% CI (0.83-1.65)). Discussion: The incidence of NAARs was significantly reduced by combining the first two bags of the traditional three-bag regimen and infusing these over 4 h at 50mg/kg/hr. Simplifying the administration of acetylcysteine may have other benefits such as better utilisation of nursing time and reduced infusion administration errors. Conclusions: A two-bag 20 h acetylcysteine regimen was well tolerated and resulted in significantly fewer and milder NAARs than the standard three-bag regimen.