a The Swedish Poisons Information Centre , Stockholm , Sweden.
b Department of Laboratory Medicine, Division of Clinical Pharmacology , Karolinska Institutet , Stockholm , Sweden.
Clin Toxicol (Phila). 2019 Mar;57(3):203-212. doi: 10.1080/15563650.2018.1506130. Epub 2018 Oct 22.
In recent years, many unclassified benzodiazepines (BZD) have appeared through online sale as new psychoactive substances (NPS). This study describes bioanalytical and clinical data related to intoxications involving NPS BZD ("designer BZD") in the Swedish STRIDA project.
Case series of consecutive patients with admitted or suspected intake of NPS presenting to hospitals all over Sweden for emergency treatment in 2012-2016.
Urine samples collected in the STRIDA project were analyzed for 28 NPS BZD, using immunoassay and liquid chromatography-high-resolution mass spectrometry . Data of patient's age, gender, reported substance exposure, clinical signs, and treatment were obtained from medical and Poisons Information Center (PIC) records.
A total of fifteen different NPS BZD were analytically confirmed in 217 of 1913 (11%) cases involving patients (81% men) aged 15-66 (mean 28) years. The frequency of positive samples increased from 4% in 2012 to 19% in 2015. Etizolam (20 cases) was the first detected NPS BZD (January 2012), and it was followed by metizolam (four cases), estazolam (two), pyrazolam (33), flubromazepam (33), nifoxipam (five), diclazepam (four), meclonazepam (26), bromazepam (one), flubromazolam (92), deschloroetizolam (one), clonazolam (16), 3-hydroxyphenazepam (eight), ketazolam (one), and phenazepam (one). Most cases (89%) also involved other drugs. Use of NPS BZD was rarely (15%) reported during PIC consultation. In 24 patients exposed only to NPS BZD, CNS depression was the most prominent clinical sign, seven were observed in the intensive care unit, and they responded positively to flumazenil treatment.
An increasing use of NPS BZD in Sweden was detected in acute intoxication cases, sometimes leading to intensive care monitoring and support needs.
近年来,许多未经分类的苯二氮䓬类药物(BZD)通过网络销售作为新的精神活性物质(NPS)出现。本研究描述了瑞典 STRIDA 项目中涉及 NPS BZD(“设计 BZD”)中毒的生物分析和临床数据。
这是一项连续的病例系列研究,纳入了 2012 年至 2016 年期间因疑似摄入 NPS 而在瑞典各地医院接受急诊治疗的患者。
STRIDA 项目中收集的尿液样本使用免疫测定法和液相色谱-高分辨率质谱法分析了 28 种 NPS BZD。从医疗和毒物信息中心(PIC)记录中获取了患者的年龄、性别、报告的物质暴露、临床体征和治疗数据。
在涉及年龄 15-66 岁(平均 28 岁)的 1913 例患者(81%为男性)中,有 217 例(11%)病例通过分析确认了 15 种不同的 NPS BZD。阳性样本的频率从 2012 年的 4%增加到 2015 年的 19%。艾司唑仑(20 例)是第一个被检测到的 NPS BZD(2012 年 1 月),其次是甲咪唑仑(4 例)、依替唑仑(2 例)、吡唑仑(33 例)、氟马西泮(33 例)、硝西泮(5 例)、地西泮(4 例)、美克洛仑(26 例)、溴马唑仑(1 例)、氟马西泮(92 例)、去氯艾司唑仑(1 例)、氯硝西泮(16 例)、3-羟基苯并二氮䓬(8 例)、凯他唑仑(1 例)和苯并二氮䓬(1 例)。大多数病例(89%)还涉及其他药物。在 PIC 咨询中,仅有 NPS BZD 暴露的报告很少(15%)。在仅暴露于 NPS BZD 的 24 例患者中,中枢神经系统抑制是最突出的临床体征,其中 7 例在重症监护病房观察到,他们对氟马西尼治疗反应良好。
在瑞典急性中毒病例中检测到 NPS BZD 的使用不断增加,有时需要重症监护监测和支持。