Helander Anders, Bäckberg Matilda, Signell Patrick, Beck Olof
a Department of Laboratory Medicine , Karolinska Institutet , Stockholm , Sweden.
b Clinical Pharmacology, Karolinska University Laboratory , Stockholm , Sweden.
Clin Toxicol (Phila). 2017 Jul;55(6):589-599. doi: 10.1080/15563650.2017.1303141. Epub 2017 Mar 28.
The number of new psychoactive substances (NPS) introduced through the online recreational drugs market increases continuously. This report from the Swedish STRIDA project describes analytically confirmed intoxications involving the novel fentanyl analogs acrylfentanyl, 4-chloroisobutyrfentanyl (4Cl-iBF), 4-fluoroisobutyrfentanyl (4F-iBF), and tetrahydrofuranfentanyl (THF-F), and cyclopentylfentanyl in a drug product.
Patients with suspected NPS exposure presenting in emergency departments (ED) or intensive care units (ICU) in Sweden and requiring hospital care are invited to the STRIDA project. NPS analysis of serum and urine samples was performed by multi-component liquid chromatography-mass spectrometry. Data on clinical features were retrieved from telephone consultations with the Swedish Poisons Information Centre and from medical records.
Between April and October 2016, eleven intoxications involving acrylfentanyl (8 cases), acrylfentanyl together with 4Cl-iBF (1), 4F-iBF (1), and THF-F (1) were analytically confirmed. Patients were aged 19-51 (median 28) years and 91% were men. Six (55%) were monitored at the ED, and five admitted to the ICU. Typical clinical features were decreased consciousness, respiratory depression, and miosis. In 8 cases, the antidote naloxone was administered to counter the opioid effects. The 4F-iBF positive patient eventually died of brain edema. The serum acrylfentanyl concentration (n = 8) ranged 0.5-2.1 (median 0.9) ng/mL, and in urine (n = 9) 0.2-10.5 (mean 4.6, median 5.2) μg/mmol creatinine. For 4Cl-iBF, 4F-iBF, and THF-F (n = 1 each), higher serum (5-45 ng/mL) and urine (11-136 μg/mmol creatinine) concentrations were found. Other NPS (e.g., flunitrazolam) and/or classical drugs were detected in five cases. In early 2016, nasal sprays with a claimed content of acrylfentanyl brought to hospital by patients or obtained by test purchase were demonstrated to instead contain fentanyl.
Potentially life-threatening opioid toxicity was seen in 11 acute intoxications involving the fentanyl analogs acrylfentanyl, 4Cl-iBF, 4F-iBF, and THF-F, which are available through open Internet trading. All patients were supported with acute and intensive hospital care, and naloxone was effective to reverse the opioid symptoms. One patient died of brain edema.
通过在线娱乐性毒品市场引入的新型精神活性物质（NPS）数量持续增加。这份来自瑞典STRIDA项目的报告分析了经证实的涉及新型芬太尼类似物丙烯酰芬太尼、4-氯异丁酰芬太尼（4Cl-iBF）、4-氟异丁酰芬太尼（4F-iBF）、四氢呋喃芬太尼（THF-F）以及环戊基芬太尼在一种药品中的中毒情况。
邀请在瑞典急诊科（ED）或重症监护病房（ICU）就诊且疑似接触NPS并需要住院治疗的患者参与STRIDA项目。通过多组分液相色谱 - 质谱法对血清和尿液样本进行NPS分析。临床特征数据从与瑞典毒物信息中心的电话咨询以及病历中获取。
在2016年4月至10月期间，经分析证实了11例中毒事件，其中涉及丙烯酰芬太尼（8例）、丙烯酰芬太尼与4Cl-iBF（1例）、4F-iBF（1例）以及THF-F（1例）。患者年龄在19至51岁（中位数28岁）之间，91%为男性。6例（55%）在急诊科接受监测，5例入住重症监护病房。典型的临床特征为意识减退、呼吸抑制和瞳孔缩小。8例患者使用了解毒剂纳洛酮来对抗阿片类药物的作用。4F-iBF阳性的患者最终死于脑水肿。血清丙烯酰芬太尼浓度（n = 8）范围为0.5至2.1（中位数0.9）ng/mL，尿液中（n = 9）为0.2至10.5（均值4.6，中位数5.2）μg/mmol肌酐。对于4Cl-iBF、4F-iBF和THF-F（各n = 1），血清（5至45 ng/mL）和尿液（11至136 μg/mmol肌酐）中发现了更高的浓度。在5例病例中检测到了其他NPS（如氟硝西泮）和/或经典药物。2016年初，患者带到医院或通过试购获得的声称含有丙烯酰芬太尼的鼻喷雾剂经证实实际含有芬太尼。
在11例涉及通过公开互联网交易可得的芬太尼类似物丙烯酰芬太尼、4Cl-iBF、4F-iBF和THF-F的急性中毒事件中，观察到了潜在的危及生命的阿片类药物毒性。所有患者均接受了急性和重症住院治疗，纳洛酮有效地逆转了阿片类药物症状。1例患者死于脑水肿。
