Fieler Melanie, Eich Christoph, Becke Karin, Badelt Gregor, Leimkühler Klaus, Messroghli Leila, Boethig Dietmar, Sümpelmann Robert
From the Clinic for Anaesthesiology and Intensive Care Medicine, Hanover Medical School (MF, RS), Department of Anaesthesia, Paediatric Intensive Care and Emergency Medicine, Auf der Bult Children[Combining Acute Accent]s Hospital, Hanover (CE), Department of Anaesthesiology and Intensive Care Medicine, Cnopf[Combining Acute Accent]sche Kinderklinik/Klinik Hallerwiese, Nuremberg (KB), Department of Anaesthesiology and Paediatric Anaesthesiology, Krankenhaus Barmherzige Brüder Regensburg/Klinik St. Hedwig, Regensburg (GB), Department of Anaesthesiology, Intensive Care and Emergency Medicine, Protestant Hospital Bielefeld, Bielefeld (KL), Department of Anaesthesiology, Intensive-Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main (LM), and Clinic for Cardiac, Thoracic, Transplant and Vascular Surgery, Hanover Medical School, Hanover, Germany (DB).
Eur J Anaesthesiol. 2015 Dec;32(12):839-43. doi: 10.1097/EJA.0000000000000272.
Due to possible serious adverse drug reactions (ADRs), the use of metamizole for postoperative pain therapy in children is a subject of debate. Safety studies with large sample sizes have not been published as yet.
The aim of this study was to evaluate the use of metamizole in children aged up to 6 years undergoing surgery with a particular focus on serious ADRs such as haemodynamic, anaphylactic or respiratory reactions and agranulocytosis.
A multicentre, prospective, noninterventional, observational postauthorisation safety study (PASS).
The study was conducted in six different paediatric centres from September 2013 to September 2014.
One thousand one hundred and seventy-seven children aged up to six years (American Society of Anesthesiologists' physical status class I to III) receiving a single dose of metamizole for postoperative pain therapy were enrolled.
Patient demographics, main and secondary diagnoses, surgical procedures performed, metamizole dose, haemodynamic data, use of other analgesics and regional blocks, results of pain measurement (Children and Infants Postoperative Pain Scale, ChIPPS) and ADR incidence were documented using a standardised case report form.
Of the 1177 children observed at six paediatric centres, 1145 were included for analysis [age 35.8 ± 18.1 (0.1 to 72) months]. The mean metamizole dose was 17.3 ± 2.9 (8.3 to 29.4) mg kg(-1). Mean arterial pressure (MAP) remained stable during metamizole infusion [baseline 55.7 ± 1.3 (25 to 98) and after infusion 56.6 ± 11.3 (25 to 99) mmHg; P < 0.01]. Pruritus, swelling and exanthema were observed in one patient each (total 0.3%). No respiratory adverse events directly related to the metamizole administration and no clinical signs of agranulocytosis were reported. All data are mean ± SD (range).
Single intravenous doses of metamizole used for the prevention or treatment of postoperative pain were well tolerated in more than 1000 children aged up to 6 years. The probability of serious ADRs (haemodynamic, anaphylactic or respiratory reactions) is lower than 0.3%. The sample size and follow-up was not sufficient to detect episodes of agranulocytosis.
由于可能出现严重的药物不良反应（ADR），安乃近用于儿童术后疼痛治疗一直存在争议。目前尚未发表大样本量的安全性研究。
本研究旨在评估安乃近在6岁及以下接受手术儿童中的应用情况，特别关注严重的ADR，如血流动力学、过敏或呼吸反应以及粒细胞缺乏症。
一项多中心、前瞻性、非干预性、观察性上市后安全性研究（PASS）。
该研究于2013年9月至2014年9月在六个不同的儿科中心进行。
纳入1177名6岁及以下（美国麻醉医师协会身体状况分级I至III级）接受单剂量安乃近进行术后疼痛治疗的儿童。
使用标准化病例报告表记录患者人口统计学资料、主要和次要诊断、所进行的外科手术、安乃近剂量、血流动力学数据、其他镇痛药和区域阻滞的使用情况、疼痛测量结果（儿童和婴儿术后疼痛量表，ChIPPS）以及ADR发生率。
在六个儿科中心观察的1177名儿童中，1145名纳入分析[年龄35.8±18.1（0.1至72）个月]。安乃近平均剂量为17.3±2.9（8.3至29.4）mg/kg。安乃近输注期间平均动脉压（MAP）保持稳定[基线时55.7±1.3（25至98），输注后56.6±11.3（25至99）mmHg；P<0.01]。分别有一名患者出现瘙痒、肿胀和皮疹（共0.3%）。未报告与安乃近给药直接相关的呼吸不良事件，也未出现粒细胞缺乏症的临床体征。所有数据均为平均值±标准差（范围）。
1000多名6岁及以下儿童单剂量静脉注射安乃近预防或治疗术后疼痛耐受性良好。严重ADR（血流动力学、过敏或呼吸反应）的发生率低于0.3%。样本量和随访不足以检测到粒细胞缺乏症的发作。
