Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Environmental Hazards and Health Effects, Health Studies Branch, Atlanta, GA, USA.
J Med Toxicol. 2013 Mar;9(1):106-15. doi: 10.1007/s13181-012-0285-4.
During the summer of 2005, multiple cities in the United States began to report outbreaks of fentanyl-associated fatalities among illicit drug users. The objectives of this study were to (1) determine if an outbreak of fentanyl-associated fatalities occurred in mid-2005 to mid-2006 and (2) to examine trends and compare features of fentanyl-contaminated heroin-associated fatalities (FHFs) with non-fentanyl, heroin-associated fatalities (NFHFs) among illicit drug users.
Baseline prevalence of fentanyl- and heroin-associated deaths was estimated from January to May 2005 based on recorded cause of death (determined by the medical examiner (ME)) using the Wayne County, MI, USA toxicology database. The database was then queried for both FHFs and NFHFs between July 1, 2005 and May 12, 2006. A FHF was defined as having fentanyl or norfentanyl (metabolite) detected in any postmortem biological sample and either (1) detection of heroin or its metabolite (6-acetylmorphine) and/or cocaine or its metabolite (benzoylecgonine) in a postmortem biological specimen or (2) confirmation of fentanyl abuse as the cause of death by the ME or a medical history available sufficient enough to exclude prescription fentanyl or other therapeutic opioid use. A NFHF was defined as detection of heroin, 6-acetylmorphine (heroin metabolite) or morphine in any postmortem biological specimen, heroin overdose listed as the cause of death by the ME, and absence of fentanyl detection on postmortem laboratory testing. Information was systematically collected, trended for each group and then compared between the two groups with regard to demographic, exposure, autopsy, and toxicology data. Logistic regression was performed using SAS v 9.1 examining the effects of age, gender, and marital status with fentanyl group status.
Monthly prevalence of fentanyl-associated fatalities among illicit drug users increased from an average of two in early 2005 to a peak of 24 in May, 2006. In total, 101 FHFs and 90 NFHFs were analyzed. The median age of decedents was 46 and 45 years for the fentanyl and non-fentanyl groups, respectively. Fentanyl-contaminated heroin-associated fatalities (FHFs) were more likely to be female (p = 0.003). Women aged over 44 years (OR = 4.67;95 % CI = 1.29-16.96) and divorced/widowed women (OR = 14.18;95 % CI = 1.59-127.01) were more likely to be FHFs when compared to women aged less than 44 years and single, respectively. A significant interaction occurred between gender and age, and gender and marital status. Most FHFs had central (heart) blood samples available for fentanyl testing (n = 96; 95 %): fentanyl was detected in most (n = 91; 95 %). Of these, close to half had no detectable heroin (or 6-acetylmorphine) concentrations (n = 37; 40.7 %). About half of these samples had detectable cocaine concentrations (n = 20; 54 %). Median fentanyl concentration in central blood samples was 0.02 μg/ml (n = 91, range <0.002-0.051 μg/ml) and 0.02 μg/ml (n = 32, range <0.004-0.069 μg/ml) in peripheral blood samples. The geometric mean of the ratio of central to peripheral values was 2.10 (median C/P = 1.75). At autopsy, pulmonary edema was the most frequently encountered finding for both groups (77 %).
Illicit drugs may contain undeclared ingredients that may increase the likelihood of fatality in users. Gender differences in fentanyl-related mortality may be modified by age and/or marital status. These findings may help inform public health and prevention activities if fatalities associated with fentanyl-contaminated illicit drugs reoccur.
2005 年夏天,美国多个城市开始报告与芬太尼有关的非法药物使用者死亡事件。本研究的目的是:(1)确定 2005 年中期至 2006 年中期是否发生了与芬太尼有关的死亡事件;(2)检查趋势并比较与芬太尼有关的海洛因相关死亡(FHF)和非芬太尼、海洛因相关死亡(NFHF)的特征,这些特征在非法药物使用者中。
使用美国密歇根州韦恩县的毒理学数据库,根据记录的死因(由法医确定),从 2005 年 1 月至 5 月估计芬太尼和海洛因相关死亡的基线流行率。然后在 2005 年 7 月 1 日至 2006 年 5 月 12 日期间查询 FHF 和 NFHF。FHF 的定义为在任何死后生物样本中检测到芬太尼或其代谢物(去甲芬太尼),并且(1)在死后生物样本中检测到海洛因或其代谢物(6-乙酰吗啡)和/或可卡因或其代谢物(苯甲酰基海洛因),或者(2)法医或可用的病史足以排除处方芬太尼或其他治疗性阿片类药物的使用来确认芬太尼滥用是死因。NFHF 的定义是在任何死后生物样本中检测到海洛因、6-乙酰吗啡(海洛因代谢物)或吗啡,法医将海洛因过量列为死因,并且死后实验室检测未检测到芬太尼。系统地收集信息,对每个组进行趋势分析,然后比较两组之间的人口统计学、暴露、尸检和毒理学数据。使用 SAS v 9.1 进行逻辑回归,检查年龄、性别和婚姻状况对芬太尼组状态的影响。
非法药物使用者中与芬太尼相关的致命事件的每月流行率从 2005 年初的平均两人增加到 2006 年 5 月的高峰 24 人。共分析了 101 例 FHF 和 90 例 NFHF。死者的中位数年龄分别为 46 岁和 45 岁,分别为芬太尼组和非芬太尼组。与非芬太尼组相比,芬太尼污染的海洛因相关死亡(FHF)更可能是女性(p=0.003)。年龄超过 44 岁的女性(OR=4.67;95%CI=1.29-16.96)和离婚/丧偶的女性(OR=14.18;95%CI=1.59-127.01)与年龄小于 44 岁的女性相比,更有可能成为 FHF。性别和年龄以及性别和婚姻状况之间存在显著的交互作用。大多数 FHF 有中心(心脏)血液样本可用于芬太尼检测(n=96;95%):在大多数(n=91;95%)中检测到芬太尼。其中,近一半没有可检测到的海洛因(或 6-乙酰吗啡)浓度(n=37;40.7%)。这些样本中有一半左右可检测到可卡因浓度(n=20;54%)。中心血样中芬太尼的中位数浓度为 0.02μg/ml(n=91,范围<0.002-0.051μg/ml)和 0.02μg/ml(n=32,范围<0.004-0.069μg/ml)外周血样本。中心与外周值比值的几何平均值为 2.10(中位数 C/P=1.75)。尸检时,两组最常发现肺水肿(77%)。
非法药物可能含有未申报的成分,这可能会增加使用者死亡的可能性。与芬太尼相关的死亡率的性别差异可能会被年龄和/或婚姻状况所改变。如果与芬太尼污染的非法药物相关的死亡事件再次发生,这些发现可能有助于为公共卫生和预防活动提供信息。