Intramuscular cobinamide versus saline for treatment of severe hydrogen sulfide toxicity in swine
Intramuscular cobinamide versus saline for treatment of severe hydrogen sulfide toxicity in swine
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DOI：
10.1080/15563650.2018.1504955
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发表时间：
2019-03-04
影响因子：
3.3
通讯作者：
Bebarta, Vikhyat S.
中科院分区：
文献类型：
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作者：
Ng, Patrick C.;Hendry-Hofer, Tara B.;Bebarta, Vikhyat S.
前言：硫化氢存在于石油、天然气和腐烂的有机物中。恐怖组织曾试图在封闭的空间内将其用作化学武器。大规模伤亡情况发生在工业事故和油田现场泄漏的情况下。目前还没有FDA批准的硫化物中毒解毒剂。我们之前已经报道过静脉注射可比胺对硫化物中毒有效。一种快速有效的解毒剂，易于肌肉注射(IM)，将是在院前环境下使用的理想选择。在这项研究中，我们评估了使用IM可比胺治疗硫化物中毒猪的存活率。方法：11只猪，体重45~55 kg，麻醉后插管，连续监测股动脉和肺动脉压。稳定后，调整麻醉，使动物自主呼吸，FiO(2)为0.21。氢化钠(NaHS，8 mg/mL)以0.9 mg/kg.min静脉滴注，直至呼吸暂停或严重低血压。动物被随机分配接受可比胺(4毫克/公斤)，或在呼吸暂停/低血压触发时不进行治疗。NaHS的输注速度在触发后维持1.5min，降至0.2 mg/kg.min，持续10min，然后停止。结果：两组发生呼吸暂停或低血压所需NaHS的量无统计学差异(可比胺：9.0 mg/kg+/-6.1；生理盐水：5.9 mg/kg+/-5.5；平均差值：-3.1，95%CI：-11.3，5.0)。钴胺处理组动物全部存活(5/5)，对照组(0/6)无一存活(p<；.01)。服用钴胺的动物恢复自主呼吸的平均时间为3.2(+/-1.1)分钟。服用可比胺的动物恢复到基线收缩压(+/-5%)的时间为5分钟。结论：肌注钴胺能有效地提高硫化氢重度中毒大猪模型的存活率。
Introduction: Hydrogen sulfide (H2S) 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. Methods: 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(2) 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. Results: 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. Conclusion: Intramuscular cobinamide was effective in improving survival in this large swine model of severe hydrogen sulfide toxicity.