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以色列北部吸食被溴鼠灵污染的非法合成大麻素人群中爆发严重凝血功能障碍

An outbreak of severe coagulopathy in northern Israel among users of illicit synthetic cannabinoids adulterated with brodifacoum.

机构信息

Israel Poison Information Center, Rambam Health Care Campus, Haifa, Israel.

Section of Clinical Pharmacology and Toxicology, Rambam Health Care Campus, Haifa, Israel.

出版信息

Clin Toxicol (Phila). 2023 Jun;61(6):429-435. doi: 10.1080/15563650.2023.2215402. Epub 2023 Jun 9.

Abstract

INTRODUCTION

Adulteration of illicit drugs is a well-known phenomenon that may expose consumers to unexpected adverse effects. We report a large outbreak of severe coagulopathy in northern Israel during nine months in 2021-2022 among users of synthetic cannabinoids adulterated with a long-acting anticoagulant, brodifacoum.

METHODS

We performed a retrospective cohort study based on data extracted from the Israeli National Poison Information Center database and from electronic medical patient records at three participating hospitals. Confiscated drug samples and blood samples obtained at admission in a subgroup of patients were tested for the presence of long-acting anticoagulants.

RESULTS

We identified 98 patients affected by the outbreak. All patients had a prolonged international normalized ratio on admission, and in 69%, the blood was non-coagulating. For patients treated in the three participating centers ( = 72), the presenting complaint was overt bleeding in 79% of patients, most commonly in the urinary (53%) and gastrointestinal tracts (50%). The most severe complications were intracranial bleeding (4%), hemothorax (3%), pericardial bleeding (1%), and four patients died. Brodifacoum was detected in all available blood samples (median concentration 207 µg/L, interquartile range 112-349 μg/L, range 45-1,118 µg/L), and the drug samples contained both brodifacoum and the synthetic cannabinoid ADB-BUTINACA. All patients were treated with high-dose phytomenadione (vitamin K) and additionally by packed red blood cell transfusions, fresh frozen plasma, and/or 4-factor prothrombin complex concentrate when indicated. The most frequent phytomenadione (vitamin K) dose regimen was initially 20 mg intravenously every eight hours, and at discharge, 20 mg orally three times daily.

CONCLUSIONS

Outbreaks of severe coagulopathies in users of synthetic cannabinoids adulterated with a long-acting anticoagulant continue to erupt in different regions of the world. Rapid recognition of an outbreak requires a high index of suspicion when confronting young, otherwise healthy subjects with otherwise unexplained severe coagulopathy.

摘要

简介

非法药物掺假是一种众所周知的现象,可能使消费者面临意想不到的不良反应。我们报告了 2021 年至 2022 年期间,在以色列北部,大量吸食掺入长效抗凝剂溴敌隆的合成大麻素的使用者出现严重凝血功能障碍。

方法

我们基于从以色列国家毒物信息中心数据库和三家参与医院的电子病历中提取的数据,进行了一项回顾性队列研究。在亚组患者入院时采集的没收药物样本和血液样本被检测是否存在长效抗凝剂。

结果

我们确定了 98 名受疫情影响的患者。所有患者入院时国际标准化比值均延长,69%的患者血液不凝固。在三家参与中心治疗的 72 名患者中,就诊的主要症状是明显出血,最常见于泌尿系统(53%)和胃肠道(50%)。最严重的并发症包括颅内出血(4%)、血胸(3%)、心包出血(1%)和四名患者死亡。在所有可用的血液样本中均检测到溴敌隆(中位数浓度为 207μg/L,四分位距 112-349μg/L,范围 45-1118μg/L),药物样本中同时含有溴敌隆和合成大麻素 ADB-BUTINACA。所有患者均接受大剂量植物甲萘醌(维生素 K)治疗,根据需要还接受红细胞悬液、新鲜冰冻血浆和/或 4 因子凝血酶原复合物浓缩物治疗。最常见的植物甲萘醌(维生素 K)剂量方案为最初每 8 小时静脉注射 20mg,出院时口服每日 3 次,每次 20mg。

结论

在不同地区,掺入长效抗凝剂的合成大麻素使用者出现严重凝血功能障碍的疫情仍在不断爆发。当面对年轻、健康、病因不明的严重凝血功能障碍患者时,快速识别疫情需要高度怀疑。

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