Giorgetti Arianna, Pascali Jennifer, Montisci Massimo, Amico Irene, Bonvicini Barbara, Fais Paolo, Viero Alessia, Giorgetti Raffaele, Cecchetto Giovanni, Viel Guido
DIMEC, Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy.
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35121 Padova, Italy.
Metabolites. 2021 Mar 22;11(3):189. doi: 10.3390/metabo11030189.
Methadone-related deaths are characterized by a wide range of post-mortem blood concentrations, due to the high pharmacokinetic/dynamic inter-individual variability, the potential subjective tolerance state and to other risk factors or comorbidities, which might enhance methadone acute toxicity. In the present study, the association among pre-existing and external conditions and diseases and the resultant methadone death capacity have been investigated. Beside a systematic literature review, a retrospective case-control study was done, dividing cases in which methadone was the only cause of death (controls), and those with associated clinical-circumstantial (naive/non-tolerant state), pathological (pulmonary or cardiovascular diseases) or toxicological (other drugs detected) conditions. Methadone concentrations were compared between the two groups and the association with conditions/diseases was assessed by multiple linear and binomial logistic regressions. Literature cases were 139, in house 35, consisting of 22 controls and 152 cases with associated conditions/diseases. Mean methadone concentrations were 2122 ng/mL and 715 ng/mL in controls and cases respectively, with a statistically significant difference ( < 0.05). Lower methadone concentrations (by 24, 19 and 33% respectively) were detected in association with naive/non-tolerant state, pulmonary diseases and presence of other drugs, and low levels of methadone (<600 ng/mL) might lead to death in the presence of the above conditions/diseases.
美沙酮相关死亡的特点是死后血液浓度范围广泛，这是由于药代动力学/药效学个体间差异大、潜在的主观耐受状态以及其他可能增强美沙酮急性毒性的风险因素或合并症所致。在本研究中，调查了既往存在的和外部的状况及疾病与由此导致的美沙酮致死能力之间的关联。除了进行系统的文献综述外，还开展了一项回顾性病例对照研究，将病例分为美沙酮是唯一死因的情况（对照组）以及伴有临床情况（初治/非耐受状态）、病理情况（肺部或心血管疾病）或毒理学情况（检测到其他药物）的情况。比较了两组的美沙酮浓度，并通过多元线性回归和二项逻辑回归评估了与各种状况/疾病的关联。文献病例有139例，本院病例有35例，其中包括22例对照和152例伴有相关状况/疾病的病例。对照组和美沙酮相关死亡病例组的美沙酮平均浓度分别为2122纳克/毫升和715纳克/毫升，差异具有统计学意义（<0.05）。与初治/非耐受状态、肺部疾病和存在其他药物相关的美沙酮浓度较低（分别降低24%、19%和33%），并且在存在上述状况/疾病的情况下，低水平的美沙酮（<600纳克/毫升）可能导致死亡。
