University Hospital of Padova, Legal Medicine and Toxicology, Via Falloppio 50, Padova, Italy.
Polizia di Stato, Rome, Italy.
Forensic Sci Int. 2022 Jan;330:111097. doi: 10.1016/j.forsciint.2021.111097. Epub 2021 Nov 6.
BACKGROUND & OBJECTIVES: This study reports the prevalence and concentrations of sedative-hypnotic drugs as exemplified by benzodiazepines (BZD) and zolpidem (Z-hypnotic) in blood samples from drivers involved in road traffic accidents (RTA) in the Padova region of Italy. Another aim of the study was to estimate the prevalence of these drugs with concentrations in blood above the therapeutic intervals and above specific per se limits.
A total of 4066 blood samples collected from drivers involved in RTA were analysed for the presence of alcohol, drugs of abuse and medicinal drugs with sedative-hypnotic properties. Prevalence of drivers positive for BZDs and zolpidem were reported according to the reporting limit of our laboratory (1 ng/mL) in a sort of zero tolerance approach and compared with the prevalence according to analytical cut-offs used in the "European Union's research project on Driving Under the Influence of Drugs, Alcohol and Medicines" (DRUID). The impairment-based, per se limits adopted in Norway and in England and Wales and the values used to define "therapeutic ranges" in blood and in plasma/serum were also applied to the case study.
175 blood samples were positive for sedative-hypnotics above 1 ng/mL, with the following prevalence: diazepam 44%, nordazepam 41.8%, lorazepam 32.6%, zolpidem 28%, oxazepam 25.6%, alprazolam 16%, delorazepam 11,6%, lormetazepam 11,6%, temazepam 11.6%, clonazepam 11.6%, triazolam 6.9%, N-desalkylflurazepam 4.6%, bromazepam 2.3%. When applying DRUID analytical cut-offs, the prevalence of BZDs and zolpidem sharply decreases. Applying the impairing cut-offs used in Norway, 56% of positive samples were above the limits equivalent to a BAC of 0.2 g/L, 39% above the limits corresponding to 0.5 g/L, and 23% above the cut-off corresponding to 1.2 g/L. Only 1% of the drivers had drug concentrations above the per se concentration limits adopted in England and Wales [26]. When comparing blood levels with therapeutic ranges in plasma, bromazepam, lormetazepam and delorazepam were often found above the highest limits. The adjustment of the concentrations with the plasma-to-blood ratios causes a significant increase of cases above the therapeutic ranges in plasma.
Sedative-hypnotic drugs are medicinal substances frequently identified in drivers involved in RTA, commonly in concentrations associated with driving impairment. Besides the concentrations of drugs in blood, several factors have to be considered to conclude that a driver was impaired. The frequent association with alcohol, cocaine and other BZDs, confirms the abuse potential of these medications.
本研究报告了在意大利帕多瓦地区涉及道路交通碰撞（RTA）的司机血液样本中，苯二氮䓬类（BZD）和唑吡坦（Z-催眠药）等镇静催眠药物的流行率和浓度。本研究的另一个目的是估计这些药物的流行率，以及血液中浓度超过治疗区间和特定法定限量的情况。
对 4066 份涉及 RTA 的司机血液样本进行了酒精、滥用药物和具有镇静催眠特性的药物检测。报告了根据我们实验室的报告限值（1ng/mL）呈 BZD 和唑吡坦阳性的司机的流行率，这是一种零容忍的方法，并与“欧盟药物、酒精和药物对驾驶影响研究项目”（DRUID）中使用的分析截止值进行了比较。还对挪威和英格兰和威尔士采用的基于损伤的法定限量以及用于定义血液和血浆/血清中“治疗范围”的值进行了应用。
175 份血液样本中镇静催眠药物浓度超过 1ng/mL，其流行率为：地西泮 44%、去甲西泮 41.8%、劳拉西泮 32.6%、唑吡坦 28%、奥沙西泮 25.6%、阿普唑仑 16%、去氯羟安定 11.6%、氯米帕明 11.6%、替马西泮 11.6%、氯硝西泮 11.6%、三唑仑 6.9%、N-去烷基氟西泮 4.6%、溴西泮 2.3%。当应用 DRUID 分析截止值时，BZD 和唑吡坦的流行率急剧下降。应用挪威采用的损伤截止值，56%的阳性样本浓度超过相当于 0.2g/L 血液酒精浓度的限量，39%超过相当于 0.5g/L 的限量，23%超过相当于 1.2g/L 的限量。只有 1%的司机的药物浓度超过了英格兰和威尔士采用的法定浓度限量[26]。当比较血液浓度与血浆中的治疗范围时，常发现溴西泮、氯米帕明和去氯羟安定的浓度超过最高限量。根据血浆与血液的比值调整浓度会导致超过血浆治疗范围的病例显著增加。
镇静催眠药物是在涉及 RTA 的司机中经常发现的药物，通常与驾驶障碍有关。除了血液中药物的浓度外，还有几个因素需要考虑才能得出司机受到影响的结论。与酒精、可卡因和其他 BZD 的频繁关联，证实了这些药物的滥用潜力。
