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Intramuscular aminotetrazole cobinamide as a treatment for inhaled hydrogen sulfide poisoning in a large swine model
Annals of the New York Academy of Sciences ( IF 5.2 ) Pub Date : 2020-03-31 , DOI: 10.1111/nyas.14339
Tara B. Hendry-Hofer 1 , Patrick C. Ng 1, 2 , Alison M. McGrath 3 , David Mukai 4 , Matthew Brenner 4 , Sari Mahon 4 , Joseph K. Maddry 2, 5 , Gerry R. Boss 6 , Vikhyat S. Bebarta 1, 7
Affiliation  

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.

中文翻译:

肌肉注射氨基四唑协同胺治疗大型猪模型吸入硫化氢中毒

硫化氢 (H2S) 是一种高威胁化学试剂,在各种环境中自然存在。尽管发生了多起暴露和死亡事件,但不存在 FDA 批准的解毒剂。需要一种速效、易于给药的解毒剂。我们在猪中进行了一项随机对照试验,比较肌肉注射氨基四唑协同胺(2.9 mL,18 mg/kg)与吸入 H2S 气体后不进行治疗。我们发现,在呼吸抑制开始后 2 分钟(定义为连续 2 分钟的潮气量低于 3 mL/kg)给予氨基四唑协同胺可产生 100% 的存活率,而所有对照动物均死亡。治疗组的呼吸抑制在服用 cobinamide 的 3.6 ± 1.5 分钟(平均值 ± SD)内消退,而对照组动物间歇性喘气直至死亡。血压和动脉血氧饱和度 (SO2) 分别在服用 cobinamide 后 5 分钟和 10 分钟内恢复到基线值,并且血浆乳酸浓度在实验结束时降至最高值的 50% 以下。在对照动物中,血浆乳酸持续上升直至死亡。我们得出结论,肌内注射氨基四唑 cobinamide 在急性、严重 H2S 中毒的大型动物吸入模型中是有效的。
更新日期:2020-03-31
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