Pettie Janice M, Caparrotta Thomas M, Hunter Robert W, Morrison Emma E, Wood David M, Dargan Paul I, Thanacoody Ruben H, Thomas Simon H L, Elamin Muhammad E M O, Francis Ben, Webb David J, Sandilands Euan A, Eddleston Michael, Dear James W
NPIS Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK.
Pharmacology, Toxicology and Therapeutics, Centre for Cardiovascular Science, University of Edinburgh, UK.
EClinicalMedicine. 2019 May 2;11:11-17. doi: 10.1016/j.eclinm.2019.04.005. eCollection 2019 May-Jun.
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.
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.
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)).
In clinical use the SNAP regimen has similar efficacy as standard therapy for preventing liver injury and produces fewer adverse reactions.
对乙酰氨基酚过量服用后,乙酰半胱氨酸(NAC)可有效预防肝损伤。苏格兰和纽卡斯尔对乙酰氨基酚中毒的抗呕吐预处理(SNAP)研究表明,与标准的21小时给药方案相比,12小时NAC给药方案的药物不良反应更少。在此,我们描述SNAP NAC给药方案的临床疗效。
SNAP给药方案为静脉注射NAC,2小时内注射100mg/kg,然后10小时内注射200mg/kg,该方案被引入爱丁堡皇家医院、纽卡斯尔皇家维多利亚医院和伦敦圣托马斯医院,用于治疗所有对乙酰氨基酚过量服用的患者。在治疗方案改变前后,对患者数据进行前瞻性和系统性收集(患者总数N = 3340,21小时组N = 1488,SNAP组N = 1852)。通过健康记录链接来确定患者出院后的结局。
两种给药方案在肝损伤或肝脏合成功能障碍方面无差异。21小时组和SNAP组分别有64例(4.3%)和67例(3.6%)患者出现肝毒性(谷丙转氨酶峰值>1000 U/L)(绝对差异 -0.7%,95%置信区间 -2.1至0.6)。多变量逻辑回归未将治疗方案确定为与结局相关的因素。出院后30天内,无患者因肝衰竭再次入院或死亡。21小时给药方案组有163例(11.0%)患者接受了抗组胺治疗(用于NAC类过敏药物反应),SNAP给药方案组有37例(2.0%)患者接受了该治疗(绝对差异9.0%(95%置信区间7.3至10.7))。
在临床应用中,SNAP给药方案在预防肝损伤方面与标准疗法疗效相似,且不良反应更少。