Söderberg Carl, Wernvik Emma, Jönsson Anna K, Druid Henrik
Department of Oncology-Pathology, Karolinska Institutet, Retzius v. 3, KI Campus Solna, 171 77 Stockholm, Sweden; Department of Forensic Medicine, National Board of Forensic Medicine, Artillerigatan 12, 587 58 Linköping, Sweden.
Department of Forensic Medicine, National Board of Forensic Medicine, Artillerigatan 12, 587 58 Linköping, Sweden.
Forensic Sci Int. 2017 Aug;277:207-214. doi: 10.1016/j.forsciint.2017.06.007. Epub 2017 Jun 15.
The main recipients of lithium, people diagnosed with bipolar disorder, show an increased mortality in both natural and unnatural causes of death. Based on international data persons diagnosed with bipolar disorder comprise 2.3-9.6% of all suicidal deaths. In cases of suicide among those suffering from bipolar disorder, 17-53% are due to fatal intoxications. Diagnosing fatal intoxications is often challenging, particularly when the reference information needed to interpret the concentration of a drug is lacking or scarce.
The aim of this study was to establish postmortem femoral blood reference concentrations of lithium, providing both fatal and "normal" postmortem concentrations, as well as to investigate the impact of the mode of intoxication and to study the co-detection of lithium and antidepressant drugs in intoxications and controls.
In Sweden, forensic autopsies are performed in unnatural and obscure deaths. This study included all autopsies in which lithium was found during the study period (1992-2010). Lithium was not included in the regular drug screen, but analysed upon request using flame photometry, ion-selective electrode detection or atomic absorption spectrophotometry. Each case was evaluated according to an established strategy, with strict inclusion and exclusion criteria followed by a multi-observer manual review (Fig. 1, Table 1). The cases included were classified as single intoxications (group A), multi-drug intoxications (group B) or controls (group C). The control group only included cases where death by intoxication and antemortem incapacitation by drugs could be ruled out.
During the study period, lithium was found in 124 cases. After application of inclusion and exclusion criteria and the subsequent manual review, 21 cases were classified as group A (n=4), group B, (n=7) and group C (n=10). The femoral blood lithium concentrations in group A (median 2.69mmol/l) and group B (median 2.10mmol/l) were significantly different (p=0.01) compared to group C (median 0.2mmol/l). There were however no statistically significant difference between the concentrations in groups A and B. The most common mode of death in intoxications was acute-on-chronic (n=10), but the impact of chronic use on the fatal blood concentrations could not be evaluated since there was just one case without previous use. There was no difference in the proportion of co-detections of lithium and antidepressants between intoxication cases and controls.
锂的主要使用者，即被诊断为双相情感障碍的人，在自然死亡和非自然死亡原因中的死亡率均有所上升。根据国际数据，被诊断为双相情感障碍的人占所有自杀死亡人数的2.3 - 9.6%。在双相情感障碍患者的自杀案例中，17 - 53%是由于致命中毒。诊断致命中毒往往具有挑战性，尤其是在缺乏或难以获取用于解释药物浓度所需的参考信息时。
本研究的目的是确定锂的死后股静脉血参考浓度，提供致命和“正常”的死后浓度，研究中毒方式的影响，并研究中毒和对照案例中锂与抗抑郁药物的共同检测情况。
在瑞典，对非自然死亡和不明原因死亡进行法医尸检。本研究纳入了研究期间（1992 - 2010年）所有发现锂的尸检案例。锂未包含在常规药物筛查中，而是根据请求使用火焰光度法、离子选择性电极检测法或原子吸收分光光度法进行分析。每个案例根据既定策略进行评估，遵循严格的纳入和排除标准，随后进行多观察者人工复查（图1，表1）。纳入的案例分为单一中毒（A组）、多药中毒（B组）或对照（C组）。对照组仅包括可以排除中毒死亡和药物生前失能情况的案例。
在研究期间，124例案例中发现了锂。应用纳入和排除标准并随后进行人工复查后，21例案例被分类为A组（n = 4）、B组（n = 7）和C组（n = 10）。A组（中位数2.69mmol/l）和B组（中位数2.10mmol/l）的股静脉血锂浓度与C组（中位数0.2mmol/l）相比有显著差异（p = 0.01）。然而，A组和B组的浓度之间没有统计学上的显著差异。中毒案例中最常见的死亡方式是慢性基础上急性发作（n = 10），但由于只有1例无既往用药史，无法评估长期用药对致命血药浓度的影响。中毒案例和对照案例中锂与抗抑郁药物共同检测的比例没有差异。
