Prevalence and concentrations of sedative-hypnotic drugs in blood of drivers involved in road traffic crashes in the Padova region of Italy – not so easy to interpret

•Use of benzodiazepine receptor agonists while driving is dangerous.•Benzodiazepines and zolpidem were found in 5% of drivers involved in road-traffic accidents.•Different cut-off levels were applied including zero tolerance.•Only a minority of drivers had drug concentrations in blood above the therapeutic ranges.•Adjusting concentrations with the plasma-to-blood ratios was considered. 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 plas