Bernard Jean-Paul, Khiabani Hassan Z, Hilberg Thor, Karinen Ritva, Slørdal Lars, Waal Helge, Mørland Jørg
Norwegian Institute of Public Health, Division of Forensic Sciences, Oslo, Norway; Centre for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
Norwegian Institute of Public Health, Division of Forensic Sciences, Oslo, Norway; Oslo University Hospital, Rikshospitalet, Department of Pharmacology, Oslo, Norway.
J Forensic Leg Med. 2015 Nov;36:114-20. doi: 10.1016/j.jflm.2015.09.011. Epub 2015 Sep 25.
There are currently over 7000 patients enrolled in opioid maintenance treatment (OMT) programs in Norway. A rise in methadone-related deaths proportional to increasing methadone sales over the period 2000-2006 has been observed, but the causative factors for these fatalities have been elusive. In the present study, individual characteristics, methadone concentrations and additional toxicological findings were analyzed. Methadone intoxication deaths (n = 264) were divided into 3 groups according to toxicological findings in whole blood: group 1 - methadone detected alone, or together with one additional drug at low or therapeutic levels, or a low concentration of ethanol (<1 g/L) (n = 21); group 2 - multiple additional drugs/substances detected below lethal levels (n = 175); group 3 - one or more additional drugs/substances detected at lethal levels, or ethanol >3 g/L (n = 55). Methadone blood concentrations in decedents who had been enrolled in OMT were higher than for decedents not in treatment, in all groups. Blood methadone concentrations around 1 mg/L were present in fatal multi-drug intoxications in OMT patients. Results suggest that some patients may be at risk of dying when combining therapeutic concentrations of methadone with other psychoactive substances. Somatic disease was a common finding among deceased OMT patients. Concentrations in methadone users not enrolled in OMT were predominantly between 0.3 and 0.4 mg/L and were not related to the presence of other drugs. However, methadone concentrations below 0.1 mg/L may be associated with intoxication following methadone use, both alone and in combination with other drugs. Younger male users (mean age 34 years) seemed to have a higher susceptibility to methadone intoxication.
目前，挪威有超过7000名患者参加了阿片类药物维持治疗（OMT）项目。在2000年至2006年期间，已观察到与美沙酮相关的死亡人数随着美沙酮销售量的增加而成比例上升，但这些死亡的致病因素一直难以捉摸。在本研究中，分析了个体特征、美沙酮浓度和其他毒理学发现。根据全血中的毒理学发现，将美沙酮中毒死亡病例（n = 264）分为3组：第1组 - 仅检测到美沙酮，或与另一种低水平或治疗水平的药物一起检测到，或乙醇浓度低（<1 g/L）（n = 21）；第2组 - 检测到多种低于致死水平的其他药物/物质（n = 175）；第3组 - 检测到一种或多种处于致死水平的其他药物/物质，或乙醇>3 g/L（n = 55）。在所有组中，参加OMT的死者的美沙酮血药浓度均高于未接受治疗的死者。OMT患者致命多药中毒时的血美沙酮浓度约为1 mg/L。结果表明，一些患者在将治疗浓度的美沙酮与其他精神活性物质合用时可能有死亡风险。躯体疾病是已故OMT患者的常见发现。未参加OMT的美沙酮使用者的浓度主要在0.3至0.4 mg/L之间，且与其他药物的存在无关。然而，美沙酮浓度低于0.1 mg/L可能与美沙酮单独使用或与其他药物合用时的中毒有关。年轻男性使用者（平均年龄34岁）似乎对美沙酮中毒更敏感。
