Intramuscular aminotetrazole cobinamide as a treatment for inhaled hydrogen sulfide poisoning in a large swine model
Intramuscular aminotetrazole cobinamide as a treatment for inhaled hydrogen sulfide poisoning in a large swine model
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DOI：
10.1111/nyas.14339
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发表时间：
2020-03-31
影响因子：
5.2
通讯作者：
Bebarta，Vikhyat S.
中科院分区：
文献类型：
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作者：
Hendry-Hofer，Tara B.;Ng，Patrick C.;Bebarta，Vikhyat S.
硫化氢 (H2S) 是一种高威胁化学剂，在各种环境中自然产生。尽管发生了多起接触和死亡事件，但尚无 FDA 批准的解毒剂。需要一种起效快、易于给药的解毒剂。我们在猪身上进行了一项随机对照试验，比较了吸入 H2S 气体后肌肉注射氨基四唑钴酰胺（2.9 mL，18 mg/kg）与不进行治疗的情况。我们发现，在呼吸抑制（定义为连续 2 分钟潮气量小于 3 mL/kg）发作 2 分钟后给予氨基四唑可滨酰胺，可实现 100% 的存活，而所有对照动物均死亡。治疗组的呼吸抑制在给予可宾酰胺后 3.6 ± 1.5 分钟（平均值 ± 标准差）内消失，而对照组动物则出现间歇性喘气直至死亡。血压和动脉氧饱和度 (SO2) 分别在 Cobinamide 治疗后 5 分钟和 10 分钟内恢复到基线值，并且在实验结束时血浆乳酸浓度降至最高值的 50% 以下。在对照动物中，血浆乳酸持续升高直至死亡。我们得出的结论是，肌肉注射氨基四唑可联酰胺对大型动物急性、严重 H2S 中毒吸入模型有效。
Hydrogen sulfide (H2S), 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 H2S 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 (SO2) 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 H2S poisoning.