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识别毒理学分析未检测到6-乙酰吗啡(6-AM)的海洛因中毒病例。

Identifying cases of heroin toxicity where 6-acetylmorphine (6-AM) is not detected by toxicological analyses.

作者信息

Ellis Ashley D, McGwin Gerald, Davis Gregory G, Dye Daniel W

机构信息

Virginia Commonwealth University School of Medicine, 1101 E. Marshall Street, PO Box 980662, Richmond, VA, 23298, USA.

University of Alabama at Birmingham, 1515 6th Ave. S, Birmingham, AL, 35233, USA.

出版信息

Forensic Sci Med Pathol. 2016 Sep;12(3):243-7. doi: 10.1007/s12024-016-9780-2. Epub 2016 Apr 25.

Abstract

PURPOSE

Heroin has a half-life of 2-6 min and is metabolized too quickly to be detected in autopsy samples. The presence of 6-acetylmophine (6-AM) in urine, blood, or other samples is convincing evidence of heroin use by a decedent, but 6-AM itself has a half-life of 6-25 min before it is hydrolyzed to morphine, so 6-AM may not be present in sufficient concentration to detect in postmortem samples. Codeine is often present in heroin preparations as an impurity and is not a metabolite of heroin. Studies report that a ratio of morphine to codeine greater than one indicates heroin use. We hypothesize that the ratio of morphine to codeine in our decedents abusing drugs intravenously will be no different in individuals with 6-AM present than in individuals where no 6-AM is detected, and we report our study of this hypothesis.

METHODS

All accidental deaths investigated by the Jefferson County Coroner/Medical Examiner Office from 2010 to 2013 with morphine detected in blood samples collected at autopsy were reviewed. Five deaths where trauma caused or contributed to death were excluded from the review. The presence or absence of 6-AM and the concentrations of morphine and codeine were recorded for each case. The ratio of morphine to codeine was calculated for all decedents. Any individual in whom no morphine or codeine was detected in a postmortem sample was excluded from further study. Absence or presence of drug paraphernalia or evidence of intravascular (IV) drug use was documented in each case to identify IV drug users. The proportion of the IV drug users with and without 6-AM present in a postmortem sample was compared to the M/C ratio for the individuals.

RESULTS

Of the 230 deaths included in the analysis, 103 IV drug users with quantifiable morphine and codeine in a postmortem sample were identified allowing for calculation of an M/C ratio. In these IV drug users, the M/C ratio was greater than 1 in 98 % of decedents. When controlling for the absence or presence of 6-AM there was no statistically significant difference in the proportion of IV drug users when compared to non IV drug users with an M/C ratio of greater than 1 (p = 1.000).

CONCLUSION

The M/C ratio in IV drug users, if greater than 1, is seen in deaths due to heroin toxicity where 6-AM is detected in a postmortem sample. This study provides evidence that a M/C ratio greater than one in an IV drug user is evidence of a death due to heroin toxicity even if 6-AM is not detected in the blood. Using the M/C ratio, in addition to scene and autopsy findings, provides sufficient evidence to show heroin is the source of the morphine and codeine. Listing heroin as a cause or contributing factor in deaths with evidence of IV drug abuse and where the M/C ratio exceeds 1 will improve identification of heroin fatalities, which will allow better allocation of resources for public health initiatives.

摘要

目的

海洛因的半衰期为2 - 6分钟,代谢速度过快,以至于在尸检样本中无法检测到。尿液、血液或其他样本中6 - 乙酰吗啡(6 - AM)的存在是死者使用过海洛因的确凿证据,但6 - AM本身在水解为吗啡之前的半衰期为6 - 25分钟,因此在死后样本中6 - AM的浓度可能不足以被检测到。可待因常作为杂质存在于海洛因制剂中,并非海洛因的代谢产物。研究报告称,吗啡与可待因的比值大于1表明使用过海洛因。我们推测,静脉吸毒的死者中,存在6 - AM的个体与未检测到6 - AM的个体相比,吗啡与可待因的比值并无差异,我们报告了对此假设的研究。

方法

回顾了2010年至2013年杰斐逊县验尸官/法医办公室调查的所有意外死亡案例,这些案例的尸检血液样本中检测到了吗啡。5例因创伤导致或促成死亡的案例被排除在回顾范围之外。记录每个案例中6 - AM的有无以及吗啡和可待因的浓度。计算所有死者的吗啡与可待因比值。死后样本中未检测到吗啡或可待因的个体被排除在进一步研究之外。记录每个案例中是否存在吸毒用具或血管内(IV)吸毒的证据,以识别静脉吸毒者。将死后样本中存在和不存在6 - AM的静脉吸毒者的比例与个体的M/C比值进行比较。

结果

在纳入分析的230例死亡案例中,有103例死后样本中吗啡和可待因可量化的静脉吸毒者,从而能够计算M/C比值。在这些静脉吸毒者中,98%的死者M/C比值大于1。在控制6 - AM的有无后,与M/C比值大于1的非静脉吸毒者相比,静脉吸毒者的比例在统计学上无显著差异(p = 1.000)。

结论

静脉吸毒者中,若M/C比值大于1,在死后样本中检测到6 - AM的情况下,可见于海洛因中毒死亡案例。本研究提供了证据,表明静脉吸毒者M/C比值大于1是海洛因中毒死亡的证据,即使血液中未检测到6 - AM。除现场和尸检结果外,使用M/C比值提供了充分证据,表明海洛因是吗啡和可待因的来源。在有静脉吸毒证据且M/C比值超过1的死亡案例中,将海洛因列为死因或促成因素,将改善海洛因致死案例的识别,从而为公共卫生举措更好地分配资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7fd/4967084/41b0dce69954/12024_2016_9780_Fig1_HTML.jpg

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