a Rocky Mountain Poison and Drug Center , Denver Health and Hospital Authority , Denver , CO , USA.
b Department of Emergency Medicine , University of Colorado, School of Medicine , Aurora , CO , USA.
Clin Toxicol (Phila). 2019 Mar;57(3):189-196. doi: 10.1080/15563650.2018.1504955. Epub 2018 Nov 15.
Hydrogen sulfide (HS) is found in petroleum, natural gas, and decaying organic matter. Terrorist groups have attempted to use it in enclosed spaces as a chemical weapon. Mass casualty scenarios have occurred from industrial accidents and release from oil field sites. There is no FDA approved antidote for sulfide poisoning. We have previously reported that intravenous cobinamide is effective for sulfide poisoning. A rapid-acting antidote that is easy to administer intramuscularly (IM) would be ideal for use in a prehospital setting. In this study, we assessed survival in sulfide-poisoned swine treated with IM cobinamide.
Eleven swine (45-55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. After stabilization, anesthesia was adjusted such that animals ventilated spontaneously with a FiO of 0.21. Sodium hydrosulfide (NaHS, 8 mg/mL) was infused intravenously at 0.9 mg/kg.min until apnea or severe hypotension. Animals were randomly assigned to receive cobinamide (4 mg/kg), or no treatment at the apnea/hypotension trigger. The NaHS infusion rate was sustained for 1.5 min post trigger, decreased to 0.2 mg/kg.min for 10 min, and then discontinued.
The amount of NaHS required to produce apnea or hypotension was not statistically different in both groups (cobinamide: 9.0 mg/kg ±6.1; saline: 5.9 mg/kg ±5.5; mean difference: -3.1, 95% CI: -11.3, 5.0). All of the cobinamide treated animals survived (5/5), none of the control (0/6) animals survived (p < .01). Mean time to return to spontaneous ventilation in the cobinamide treated animals was 3.2 (±1.1) min. Time to return to baseline systolic blood pressure (±5%) in cobinamide-treated animals was 5 min.
Intramuscular cobinamide was effective in improving survival in this large swine model of severe hydrogen sulfide toxicity.
硫化氢（HS）存在于石油、天然气和腐烂的有机物质中。恐怖组织曾试图在封闭空间中使用它作为化学武器。工业事故和油田泄漏会导致大量人员伤亡。目前还没有 FDA 批准的硫化物中毒解毒剂。我们之前曾报道过，静脉注射 cobinamide 可有效治疗硫化物中毒。一种起效迅速且易于肌肉内（IM）给药的解毒剂，将非常适合在院前环境中使用。在这项研究中，我们评估了 IM cobinamide 治疗的硫化物中毒猪的存活率。
11 头猪（45-55kg）麻醉、插管并进行连续股动脉和肺动脉压力监测。稳定后，调整麻醉使动物在 FiO 为 0.21 的情况下自主呼吸。静脉输注硫氢化钠（NaHS，8mg/mL），速度为 0.9mg/kg.min，直至出现呼吸暂停或严重低血压。动物随机接受 cobinamide（4mg/kg）或在呼吸暂停/低血压触发时不接受治疗。在触发后 1.5 分钟内维持 NaHS 输注速度，持续 10 分钟后降至 0.2mg/kg.min，然后停止。
两组产生呼吸暂停或低血压所需的 NaHS 量无统计学差异（ cobinamide：9.0mg/kg ±6.1；生理盐水：5.9mg/kg ±5.5；平均差异：-3.1，95%CI：-11.3，5.0）。所有 cobinamide 治疗的动物均存活（5/5），对照组（0/6）动物均未存活（p<0.01）。 cobinamide 治疗动物恢复自主呼吸的平均时间为 3.2（±1.1）分钟。 cobinamide 治疗动物恢复基线收缩压（±5%）的时间为 5 分钟。
在这项大型猪严重硫化氢毒性模型中，肌肉内 cobinamide 可有效提高存活率。
