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.

Efficacy of a two bag acetylcysteine regimen to treat paracetamol overdose (2NAC study)

“…This included gastrointestinal, cutaneous and systemic reactions. Similarly, the SNAP regimen studies which decreased the infusion rate of the loading-dose over the first hour have shown similar findings [10,11]. Some previous studies assessing safety of the two-bag regimen did not find a difference in the incidence of gastrointestinal reactions [12,13], but in this larger efficacy study, these were significantly less frequent that with the three-bag regimen.…”

“…The incidence of peak INR >2.0 was 6.9% (n = 23) with the two-bag regimen vs 7.4% (n = 15) with the three-bag regimen (Difference: À0.5, 95% CI À5.1 to 3.9). The median time from paracetamol ingestion to start of acetylcysteine was 14 h (11,18) in the twobag group vs 13 h (11,17) in the three-bag group (p = 0.1). Fulminant hepatic failure developed in four patients (1.2%) receiving the twobag regimen and three patients (1.5%) receiving the three-bag regimen (Difference: À0.3, 95% CI À2.3 to 1.7).…”

“…In addition, this can lead to treatment interruption and/or premature cessation of acetylcysteine. Previous studies involving the SNAP (Scottish and Newcastle Antiemetic Pretreatment) regimen [10] and a recent study by Pettie et al [11] have shown that by infusing the initial loading dose over two hours, it can decrease the number of adverse effects related to acetylcysteine. In addition, recent studies involving hundreds of patients have shown that a two-bag 20 h regimen (200 mg/kg IV loading dose of acetylcysteine infused over four hours, with a further 100 mg/kg infused over 16-h) reduces the incidence and severity of non-allergic anaphylactic reactions, compared to the three-bag regimen administering the same total dose over a similar time-frame [12À15].…”

Acute liver failure

“…8 Although the recent SNAP study showed that for POD presenting to the emergency department, a new 12-hour 300 mg/kg NAC regimen was better tolerated and non-inferior to an older 21-hour regimen in terms of consequent hepatic injury and ALF, there is still a lack of clarity regarding the optimal duration of NAC infusion once ALF has developed. 9 Furthermore, caution is required in extrapolating the findings of this trial to delayed or staggered overdoses where outcomes tend to be worse.…”

Direct detection of circulating microRNA-122 using dynamic chemical labelling with single molecule detection overcomes stability and isomiR challenges for biomarker qualification

“…17,18 Currently all patients deemed to need treatment receive the same dose of acetylcysteine, a practice which results in significant patient numbers being under or over treated. 19 can be included as a biomarker of hepatocellular injury in short--term rat toxicology studies and its use adds benefit in detecting hepatotoxicity in this species. 20 miR--122 is also a new biomarker for liver disease in dogs that is gaining traction in clinical veterinary practice.…”