The designer-benzodiazepine concentrations reported in 21 Norwegian autopsies were descriptive findings, not established lethal ranges. Heide and colleagues explicitly lacked the causes of death for those cases. Their separate evidence about impairment came from living people and cannot be transferred directly to a decedent’s autopsy blood.
Separate the 21 autopsies from the 554 living cases
The study included 575 positive forensic cases submitted between 1 June 2016 and 30 September 2019: 554 living cases involving suspected impaired driving or other offenses, and 21 medicolegal autopsies. Flualprazolam entered the analytical repertoire only in December 2018, so its observation period was shorter.
The living-case concentration summary in Table II is not the autopsy dataset. For example, its 334 diclazepam findings and median of 0.0096 mg/L describe living cases. Table IV separately reports 13 autopsy diclazepam findings, with a median of 0.0032 mg/L.
The autopsy specimens were femoral venous whole blood collected into 25 mL polystyrene tubes containing 0.3 mL of 67% weight/volume potassium fluoride solution. Living blood used 5 mL glass tubes containing 20 mg sodium fluoride and 143 IU heparin. Samples were refrigerated at 4°C for up to two weeks while analyses were completed. Those handling descriptions do not establish analyte stability, and the paper did not provide a uniform postmortem collection interval.
What the autopsy table actually reported
| Drug | Autopsy findings | Median, mg/L | Reported range, mg/L |
|---|---|---|---|
| Diclazepam | 13 | 0.0032 | 0.0018–0.032 |
| Etizolam | 2 | 0.026 | 0.022–0.029 |
| Flubromazolam | 1 | Single value: 0.052 | Not a population range |
| Phenazepam | 5 | 0.0059 | 0.0051–0.052 |
Clonazolam, flualprazolam and flubromazepam were not detected in these autopsies. That absence in this small, selected series does not establish their absence from other deaths or a universal laboratory detection capability.
Other drugs were detected in 20 of the 21 cases. Phenazepam was the only detected drug in one case. Because the investigators did not know the causes of death, even that single-drug finding cannot be described from this paper as a proven phenazepam fatality.
Quantitative methods still had defined reporting limits
Blood screening used UHPLC–MS/MS, followed by quantitative confirmation using a different chromatographic procedure. Methods and instrumentation changed during the study. Duplicate analyses and independent quality controls supported the reported quantitative results.
The stated reporting cutoffs included 0.0016 mg/L for diclazepam, 0.014 mg/L for etizolam, 0.00037 mg/L for flubromazolam and 0.0017 mg/L for phenazepam. These analytical cutoffs were at or above the respective quantitation limits. They are not concentrations at which impairment or death begins.
What the living-person impairment analysis added
In 25 living cases, one designer benzodiazepine was the only drug judged relevant to impairment. This definition allowed other detected drugs considered below relevant concentrations; it did not mean every specimen was chemically free of all other substances. Physicians judged 19 of these people impaired and six not impaired.
For the 16 diclazepam cases in that subgroup, the impaired-versus-not-impaired concentration comparison was not statistically significant, with p = 0.133. A separate analysis found a significant association between concentration and degree of impairment, with Spearman’s rho = 0.561 and p = 0.024. Both results matter: an association with an ordered clinical assessment does not create a sharp individual impairment threshold. Other compounds had too few such cases for statistical analysis.
Why the numbers cannot reconstruct the concentration during life
The study did not include paired antemortem and postmortem specimens to quantify concentration change. Blood-to-plasma ratios were also unknown for the seven designer benzodiazepines. A postmortem blood result therefore cannot simply be matched to a plasma effect range or treated as an earlier driving concentration.
Use the autopsy values as limited historical context with their small drug-specific denominators. They do not independently establish dose, impairment or cause of death. The broader limitations of comparing therapeutic plasma ranges with autopsy blood apply here as well.
Primary source
Heide G, Høiseth G, Middelkoop G, Øiestad ÅML. Blood Concentrations of Designer Benzodiazepines: Relation to Impairment and Findings in Forensic Cases. Journal of Analytical Toxicology. 2020;44:905–914. doi:10.1093/jat/bkaa043.
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