a Bundeswehr Institute of Pharmacology and Toxicology , Munich , Germany.
Clin Toxicol (Phila). 2019 May;57(5):343-349. doi: 10.1080/15563650.2018.1520241. Epub 2018 Oct 11.
In a military or terrorist scenario, combination of organophosphorus compounds (OP) poisoning with physical trauma requiring surgical treatment and thus general anaesthesia are possible. Previous in vitro studies showed an altered potency of relevant anaesthetics during cholinergic crisis. Hence, it is not clear, which anaesthetics are suitable to achieve the necessary stage of surgical anaesthesia in OP poisoning.
In the present study, different anaesthetic regimens (ketamine-midazolam, propofol-fentanyl, thiopental-fentanyl), relevant in military emergency medicine, were examined in soman-poisoned rats. Clinical signs and cardiovascular variables were recorded continuously. Blood samples for acetylcholinesterase (AChE) activity were drawn. After euthanasia or death of the animals, brain and diaphragm were collected for cholinesterase assays.
Propofol-fentanyl and thiopental-fentanyl resulted in surgical anaesthesia throughout the experiments. With ketamine-midazolam, surgical anaesthesia without respiratory impairment could not be achieved in pilot experiments (no soman challenge) and was therefore not included in the study. Soman-poisoned and control animals required a comparable amount of propofol-fentanyl or thiopental-fentanyl. In combination with atropine, significantly less propofol was needed. Survival rate was higher with thiopental compared to propofol. Atropine improved survival in both groups. Blood and tissue AChE activities were strongly inhibited after soman administration with and without atropine treatment.
The current in vivo study did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning. Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals.
Further experiments in in vivo models closer to human pharmaco- and toxicokinetics (e.g., swine) are required for confirmation of the initial findings and for improving extrapolation to humans.
在军事或恐怖主义场景中,有机磷化合物(OP)中毒与需要手术治疗的身体创伤相结合,因此可能需要全身麻醉。以前的体外研究表明,在胆碱能危象期间,相关麻醉剂的效力发生了变化。因此,尚不清楚在 OP 中毒时哪种麻醉剂适合达到必要的手术麻醉阶段。
在本研究中,检查了军事急诊医学中相关的几种不同麻醉方案(氯胺酮-咪达唑仑、异丙酚-芬太尼、硫喷妥钠-芬太尼)在梭曼中毒大鼠中的作用。连续记录临床体征和心血管变量。抽取血液样本以测定乙酰胆碱酯酶(AChE)活性。动物安乐死或死亡后,采集脑和膈肌进行胆碱酯酶测定。
异丙酚-芬太尼和硫喷妥钠-芬太尼在整个实验过程中均导致手术麻醉。在氯胺酮-咪达唑仑的初步实验(无梭曼挑战)中,无法实现无呼吸损害的手术麻醉,因此未纳入研究。梭曼中毒和对照动物需要相同量的异丙酚-芬太尼或硫喷妥钠-芬太尼。与阿托品联合使用时,所需的异丙酚明显减少。与丙泊酚相比,硫喷妥钠的存活率更高。阿托品可提高两组的存活率。在给予和不给予阿托品治疗后,梭曼给药后血液和组织 AChE 活性均受到强烈抑制。
目前的体内研究并未证实由于梭曼中毒,现有麻醉方案(如丙泊酚或硫喷妥钠加芬太尼)的效力发生变化的担忧。尽管存在严重的胆碱能危象,但所有动物都能达到足够的麻醉深度。
需要在更接近人类药代动力学和毒代动力学的体内模型中进行进一步实验(例如,猪),以确认初步发现并改善对人类的推断。