Department of Forensic Sciences, Oslo University Hospital, PO Box 4950 Nydalen, Oslo 0424, Norway; Department of Pharmacology, Oslo University Hospital, PO Box 4950 Nydalen, Oslo 0424, Norway; Division of Medicine, Department of Acute Medicine and Department of Pulmonary Medicine, Oslo University Hospital, Ullevål, PO Box 4950 Nydalen, Oslo 0424, Norway.
Department of Forensic Sciences, Oslo University Hospital, PO Box 4950 Nydalen, Oslo 0424, Norway; Center for Psychopharmacology, Diakonhjemmet Hospital, PO Box 85, Vinderen, Oslo 0319, Norway; Norwegian Center for Addiction Research, University of Oslo, PO Box 1039 Blindern, Oslo 0315, Norway.
Forensic Sci Int. 2021 Apr;321:110726. doi: 10.1016/j.forsciint.2021.110726. Epub 2021 Feb 15.
Unexpected death caused by diabetic or alcoholic ketoacidosis is easily overlooked due to the non-specific symptoms. Although the acid betahydroxybutyrate (BHB) is the most abundant ketone body formed in conditions with ketoacidosis, routine analysis in postmortem investigations often only includes the neutral ketone body acetone. This study aims to evaluate the usefulness of implementing routine BHB analysis in postmortem cases, by investigating the relationship between BHB and acetone concentrations in postmortem blood and the main cause of death. From our database of forensic autopsy cases examined from 2012 to 2015, there were 376 cases with BHB and/or acetone detected in postmortem blood that could be paired with data from the Norwegian Cause of Death Registry. Cases were categorized into three groups based on cause of death: "Diabetes-related" (n = 38), "Alcohol-related" (n = 35) and "Other" (n = 303). Analysis of BHB in blood was performed using UHPLC-MS/MS (limit of quantification (LOQ) 52 mg/L) and of acetone using HS-GC-FID (LOQ 87 mg/L). For the purpose of the study, the acetone method was also validated for a LOQ of 23 mg/L. The median BHB concentration was significantly higher in the group of diabetes-related deaths (671 mg/L, range 68-1311 mg/L) compared to the group of alcohol-related (304 mg/L, range 65-1555 mg/L, p <0.001) and other causes of deaths (113 mg/L, range 0-1402 mg/L, p <0.001). In seven deaths (1.9%), the BHB blood concentration was above the suggested pathological threshold of 250 mg/L, without detection of acetone in blood above 23 mg/L. In 15% of deaths by other causes than diabetes or alcohol, a pathologically significant BHB blood concentration was detected. Our results indicate that BHB is a more reliable marker of pathologically significant ketoacidosis than acetone, and we suggest that BHB should be routinely analyzed in postmortem investigations.
由于非特异性症状，糖尿病或酒精性酮症酸中毒引起的意外死亡很容易被忽视。虽然β-羟丁酸（BHB）是酮症酸中毒时形成的最丰富的酮体，但常规分析在尸检调查中通常只包括中性酮体丙酮。本研究旨在通过研究 BHB 与死后血液中丙酮浓度以及主要死因之间的关系，评估在尸检中常规分析 BHB 的有用性。从 2012 年至 2015 年检查的法医尸检案例数据库中，有 376 例死后血液中检测到 BHB 和/或丙酮，这些案例可以与挪威死因登记处的数据相匹配。根据死因将病例分为三组：“糖尿病相关”（n=38）、“酒精相关”（n=35）和“其他”（n=303）。使用 UHPLC-MS/MS （定量下限 (LOQ) 52mg/L）分析血液中的 BHB，使用 HS-GC-FID（LOQ 87mg/L）分析丙酮。为了本研究的目的，还对丙酮方法进行了验证，LOQ 为 23mg/L。与酒精相关（304mg/L，范围 65-1555mg/L，p<0.001）和其他死因（113mg/L，范围 0-1402mg/L，p<0.001）相比，糖尿病相关死亡组的 BHB 浓度中位数明显更高（671mg/L，范围 68-1311mg/L）。在 7 例死亡（1.9%）中，BHB 血液浓度高于 250mg/L 的建议病理阈值，而血液中丙酮未超过 23mg/L。在 15%的非糖尿病或酒精引起的死亡中，检测到具有病理意义的 BHB 血液浓度。我们的结果表明，BHB 是比丙酮更可靠的病理意义上的酮症酸中毒标志物，我们建议在尸检中常规分析 BHB。
