Kintz P, Villain M, Dumestre V, Cirimele V
X'pertise Consulting, 3 rue Grüninger, 67400 Illkirch, France.
Forensic Sci Int. 2005 Oct 4;153(1):81-4. doi: 10.1016/j.forsciint.2005.04.033.
Chemical dependency is a disease that can affect all professions. Among the health care professionals, anesthesiologists represent a specific group. Numerous factors have been proposed to explain the high incidence of drug abuse among anesthesiologists. These include: easy access to potent drugs, particularly narcotics, highly addictive potential of agents with which they are in contact, and easy diversion of these agents since only small doses will initially provide an effect desired by the abuser. Opioids are the drugs of choice for anesthesiologists, and among them fentanyl and sufentanil are the most commonly used. Alcohol is mostly abused by older anesthesiologists. Propofol, ketamine, thiopental and midazolam are also abused. In fact, all but quaternary ammonium drugs can be observed. Signs and symptoms of addiction in the hospital workplace include: unusual changes in behavior, desire to work alone, refusal of lunch relief or breaks, volunteer for extra cases, call, come in early and leave late, frequent restroom breaks, weight loss and pale skin, malpractice, behind on charts .... Toxicological investigations are difficult, as the drugs of interest are difficult to test for. In most cases, half-lives of the compounds are short, and the circulating concentrations weak. It is, therefore, necessary to develop tandem mass spectrometry procedures to satisfy the criteria of identification and quantitation. In most cases, blood and/or urine analyses are not useful to document impairment, as these specimens are collected at inadequate moments. Hair analysis appears, therefore, as the unique choice to evidence chronic exposure. Depending the length of the hair shaft, it is possible to establish an historical record, associated to the pattern of drug use, considering a growth rate of about 1cm/month. An original procedure was developed to test for fentanyl derivatives. After decontamination with methylene chloride, drugs are extracted from the hair by liquid/liquid extraction after incubation in pH 8.4 phosphate buffer. Fentanyl derivatives are analyzed by GC-MS/MS. The following cases are included in this paper: Case 1: 50-year-old anesthetist, positive for fentanyl (644 pg/mg); Case 2: 42-year-old anesthetist, positive for fentanyl (101 pg/mg) and sufentanil (2 pg/mg); Case 3: 40-year-old anesthetist, positive for codeine (210 pg/mg), alfentanil (30 pg/mg) and midazolam (160 pg/mg); Case 4: 46-year-old nurse, found dead, positive for alfentanil (2 pg/mg) and fentanyl (8 pg/mg). In these cases, the combination of an alternative specimen (hair) and hyphenated analytical techniques (tandem mass spectrometry) appears to be a pre-requisite.
药物依赖是一种会影响所有职业的疾病。在医疗保健专业人员中,麻醉医生是一个特殊群体。人们提出了许多因素来解释麻醉医生中药物滥用的高发生率。这些因素包括:容易获取强效药物,尤其是麻醉药品;他们接触的药物具有高度成瘾性;而且这些药物很容易被挪用,因为最初只需小剂量就能产生滥用者想要的效果。阿片类药物是麻醉医生的首选药物,其中芬太尼和舒芬太尼是最常用的。酒精大多被年长的麻醉医生滥用。丙泊酚、氯胺酮、硫喷妥钠和咪达唑仑也被滥用。事实上,除季铵类药物外的所有药物都可能被滥用。医院工作场所成瘾的迹象和症状包括:行为异常变化、喜欢独自工作、拒绝午餐休息或休息时间、主动要求做额外的病例、接听电话、早来晚走、频繁去洗手间、体重减轻和皮肤苍白以及医疗事故、病历滞后……毒理学调查很困难,因为感兴趣的药物很难检测。在大多数情况下,这些化合物的半衰期很短,循环浓度很低。因此,有必要开发串联质谱程序以满足鉴定和定量的标准。在大多数情况下,血液和/或尿液分析对于记录损伤情况并无帮助,因为这些样本是在不合适的时间采集的。因此,毛发分析似乎是证明长期接触药物的唯一选择。根据毛干的长度,考虑到大约每月1厘米的生长速度,可以建立与药物使用模式相关的历史记录。开发了一种检测芬太尼衍生物的原始程序。用二氯甲烷去污后,将毛发在pH 8.4的磷酸盐缓冲液中孵育,然后通过液液萃取从毛发中提取药物。芬太尼衍生物通过气相色谱 - 串联质谱法进行分析。本文包括以下病例:病例1:50岁麻醉师,芬太尼检测呈阳性(644皮克/毫克);病例2:42岁麻醉师,芬太尼检测呈阳性(101皮克/毫克),舒芬太尼检测呈阳性(2皮克/毫克);病例3:40岁麻醉师,可待因检测呈阳性(210皮克/毫克),阿芬太尼检测呈阳性(30皮克/毫克),咪达唑仑检测呈阳性(160皮克/毫克);病例4:46岁护士,被发现死亡,阿芬太尼检测呈阳性(2皮克/毫克),芬太尼检测呈阳性(8皮克/毫克)。在这些病例中,替代样本(毛发)和联用分析技术(串联质谱法)的结合似乎是一个先决条件。