Safety and Efficacy of the SNAP 12-hour Acetylcysteine Regimen for the Treatment of Paracetamol Overdose

Abstract

Background: Acetylcysteine (NAC) is effective at preventing liver injury after paracetamol overdose. The Scottish and Newcastle Anti-emetic Pre-treatment for Paracetamol Poisoning (SNAP) Study demonstrated that a 12 h NAC regimen was associated with fewer adverse drug reactions compared with the standard 21 h regimen. Here, we describe the clinical effectiveness of the SNAP NAC regimen.

Methods: The SNAP regimen, consisting of intravenous NAC 100 mg/kg over 2 h then 200 mg/kg over 10 h, was introduced to treat all paracetamol overdose patients at the Royal Infirmary of Edinburgh, the Royal Victoria Infirmary, Newcastle and St Thomas' Hospital, London. Patient data were prospectively and systematically collected before and after the change in treatment (total patients N = 3340, 21 h N = 1488, SNAP N = 1852). Health record linkage was used to determine patient outcome after hospital discharge.

Findings: There was no difference in liver injury or liver synthetic dysfunction between regimens. Hepatotoxicity (peak ALT > 1000 U/L) occurred in 64 (4.3%) and 67 (3.6%) patients, respectively, in the 21 h and SNAP groups (absolute difference - 0.7%, 95% CI - 2.1 to 0.6). Multivariable logistic regression did not identify treatment regimen as an outcome-associated factor. No patients were readmitted to hospital with, or died from, liver failure within 30 days of discharge. Anti-histamine treatment (for NAC anaphylactoid drug reactions) was prescribed for 163 (11.0%) patients with the 21 h regimen and 37 (2.0%) patients with the SNAP regimen (absolute difference 9.0% (95% CI 7.3 to 10.7)).

Interpretation: In clinical use the SNAP regimen has similar efficacy as standard therapy for preventing liver injury and produces fewer adverse reactions.

Keywords: ALT, Alanine transaminase activity; Acute liver failure; Clinical practice; Drug-induced liver injury; INR, International normalised ratio; MHRA, Medicines and Healthcare Products Regulatory Agency's; NAC; NAC, Acetylcysteine; NAPQI, N‑acetyl‑p‑benzoquinone imine; Paracetamol; RIE, Royal Infirmary of Edinburgh; RVI, The Royal Victoria Infirmary, Newcastle; SNAP, Scottish and Newcastle Anti-emetic Pre-treatment for Paracetamol Poisoning; STH, St Thomas' Hospital, London.

Fig. 1

The difference in the frequency of liver injury between the 21 h NAC regimen and the SNAP regimen. A range of cut-off values for serum ALT activity and INR are presented. Extended treatment refers to having NAC treatment continued after the regimen finishes. Data are presented as the absolute differences (%) with the error bars representing the 95% confidence intervals. All patients are included from the 3 hospital sites.

Fig. 2

The difference in the frequency of liver injury between the 21 h NAC regimen and the SNAP regimen when the population is sub-divided by overdose pattern. Liver injury is presented as ALT > 1000 U/L (A) and INR > 2 (B). Acute single overdoses are sub-divided by the time from overdose to starting NAC treatment. The unknown group took a single overdose at an unknown time. Staggered and therapeutic excess patterns are also presented. Data are presented as the absolute differences (%) with the error bars representing the 95% confidence intervals. Patients without baseline ALT or INR values and those reaching the endpoints before starting NAC were excluded. Patients from all 3 sites are included.