Department of Emergency Medicine, School of Medicine, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado.
Brooke Army Medical Center, Ft Sam Houston, San Antonio, Texas.
Ann N Y Acad Sci. 2020 Nov;1479(1):159-167. doi: 10.1111/nyas.14339. Epub 2020 Mar 31.
Hydrogen sulfide (H S), a high-threat chemical agent, occurs naturally in a variety of settings. Despite multiple incidents of exposures and deaths, no FDA-approved antidote exists. A rapid-acting, easy to administer antidote is needed. We conducted a randomized control trial in swine comparing intramuscular administration of aminotetrazole cobinamide (2.9 mL, 18 mg/kg) to no treatment following inhalation of H S gas. We found that aminotetrazole cobinamide administered 2 min after the onset of respiratory depression-defined as a tidal volume of less than 3 mL/kg for 2 consecutive minutes-yielded 100% survival, while all control animals died. Respiratory depression resolved in the treatment group within 3.6 ± 1.5 min (mean ± SD) of cobinamide administration, whereas control animals had intermittent gasping until death. Blood pressure and arterial oxygen saturation (SO ) returned to baseline values within 5 and 10 min, respectively, of cobinamide treatment, and plasma lactate concentration decreased to less than 50% of the highest value by the end of the experiment. In control animals, plasma lactate rose continuously until death. We conclude that intramuscular aminotetrazole cobinamide is effective in a large animal, inhalational model of acute, severe H S poisoning.
硫化氢（H₂S）是一种高危化学物质，在各种环境中自然存在。尽管多次发生暴露和死亡事件，但仍没有获得 FDA 批准的解毒剂。我们需要一种起效迅速、易于使用的解毒剂。我们在猪中进行了一项随机对照试验，比较了吸入 H₂S 气体后肌肉内注射氨甲四氮 Cobinamide（2.9 毫升，18 毫克/千克）与不治疗的效果。我们发现，在呼吸抑制发作后 2 分钟内（定义为连续 2 分钟潮气量小于 3 毫升/千克）给予氨甲四氮 Cobinamide，可使 100%的动物存活，而所有对照动物均死亡。在 Cobinamide 给药后 3.6 ± 1.5 分钟（平均值 ± 标准差），治疗组的呼吸抑制得到缓解，而对照组动物则间歇性喘息直至死亡。血压和动脉血氧饱和度（SO₂）分别在 Cobinamide 治疗后 5 和 10 分钟内恢复到基线值，血浆乳酸浓度在实验结束时降至最高值的 50%以下。在对照组动物中，血浆乳酸持续升高直至死亡。我们的结论是，肌肉内注射氨甲四氮 Cobinamide 可有效治疗急性重度 H₂S 中毒的大型动物吸入模型。
