Treatment of paracetamol overdose with a 12 hour acetylcysteine regimen (SNAP): report of safety and efficacy in clinical practice

J. M. Pettie¹, E. Sandilands¹, T. Caparrotta², E. Morrison², M. Dow¹, E. Brogan¹, E. McCrae¹, A. Veiraiah¹, J. Wraight¹, D. J. Webb², M. Eddleston², J. W. Dear². ¹NPIS Edinburgh, Edinburgh, United Kingdom, ²Edinburgh University, Edinburgh, United Kingdom.

Introduction: Acetylcysteine (NAC) is effective at preventing liver injury after paracetamol overdose. The standard 21h intravenous regimen is associated with adverse events, particularly anaphylactoid reactions, which cause treatment interruption and prolong hospital admission. The SNAP trial demonstrated that a modified 12h NAC regimen (‘SNAP regimen’) was associated with substantially fewer adverse events. (1) This trial was not powered to determine efficacy with regard to preventing liver injury. The SNAP regimen is now standard clinical practice for treating paracetamol overdose in all patients at the Royal Infirmary of Edinburgh. Here we report its safety and efficacy.

Method: The SNAP regimen was introduced on 28^th September 2015. This regimen consists of intravenous NAC 100mg/kg over 2h then 200 mg/kg over 10h. At the end of the second bag, treatment was discontinued if: INR <1.3; AND ALT <100 U/L and not more than doubled from admission; AND paracetamol concentration <20mg/L. If these criteria were not reached then NAC was continued at 200mg/kg over 10h. Therefore, higher risk patients received more NAC (500mg/kg) compared with the standard 21h regimen (300mg/kg). Irrespective of whether NAC was continued or discontinued, patients had further blood sampling 21h after starting NAC to determine the need for extended treatment (at the equivalent time to, and using the same criteria as, the standard regimen). Data were audited prospectively for all patients over 18-month periods before and after the regimen change.

Results: There were 985 paracetamol overdose admissions in the pre-change period, of which 786 received the standard 21h NAC regimen and there were 984 admissions post-change, of which 855 received the SNAP regimen. Anaphylactoid reactions occurred in 88 (11%) patients in the 21h regimen group compared with 12 (2%) in the SNAP treatment group (absolute reduction 10%, 95%CI 8-12. NNT 10). Extended treatment beyond 21h was needed for 81 (10%) patients in the 21h regimen group compared to 88 (10%) with SNAP treatment (absolute difference 0%, 95%CI -3-3). Hepatotoxicity (ALT>1000U/L) occurred in 23 patients (3%) pre-change and 24 patients (3%) with SNAP (absolute difference 0%, 95%CI -2-2).

Conclusions: Clinical adoption of the SNAP NAC regimen resulted in substantially fewer anaphylactoid reactions. This study builds on the SNAP trial by demonstrating enhanced safety in an unselected patient population. The SNAP regimen has comparable efficacy to standard therapy with regard to preventing liver injury after paracetamol overdose.

References:

1. Bateman DN et al. (2014). Lancet 383:697-704.