Intramuscular sodium tetrathionate as an antidote in a clinically relevant swine model of acute cyanide toxicity.
Intramuscular sodium tetrathionate as an antidote in a clinically relevant swine model of acute cyanide toxicity.
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DOI：
10.1080/15563650.2019.1602272
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发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
Bebarta VS
中科院分区：
文献类型：
--
作者：
Hendry-Hofer TB;Witeof AE;Ng PC;Mahon SB;Brenner M;Boss GR;Bebarta VS
氰化物是一种用于多种工业的代谢性毒物，是一种高威胁化学制剂。目前的解毒剂需要静脉注射，限制了它们在大规模伤亡情况下的作用。四硫酸钠直接与氰化物反应生成硫代硫酸盐和无毒化合物硫氰酸酯。硫代硫酸盐又中和第二个氰化物分子，因此，每摩尔四硫酸钠中和两摩尔氰化物。历史研究考察了其作为氰化物解毒剂的功效，但尚未在临床相关的大型动物模型中进行评估，以前也未通过肌肉注射给药。本研究的目的是评估肌肉注射四硫酸钠对严重氰化物中毒大型猪模型的生存和临床结果的疗效。麻醉猪用仪器连续监测血液动力学，然后在输注氰化钾（0.17 mg/kg/min）之前进行适应和自主呼吸。呼吸暂停后6分钟（无呼吸20秒），终止氰化物输注，给予四硫酸钠（~18 mg/kg）或生理盐水对照。在各个时间点评估临床参数和实验室值，直到死亡或实验结束（治疗后90分钟）。两组在基线和治疗时的实验室值、生命体征和呼吸暂停时间相似。四硫酸钠治疗组的生存率为100%，对照组为17% （P=0.0043）。所有接受四硫酸钠治疗的动物在解药后平均10.85分钟恢复呼吸，除了一个对照组外，所有动物在实验结束时都保持呼吸暂停。四硫酸钠治疗动物在治疗后30分钟开始血乳酸水平有所改善（P≤0.002）。对照组平均死亡时间为63.3±23.2 min。未观察到肌注四硫酸钠的全身或局部不良反应。四硫酸钠显著提高急性氰化物中毒大型猪模型的存活率和临床结果。
Cyanide is a metabolic poison used in multiple industries and is a high threat chemical agent. Current antidotes require intravenous administration, limiting their usefulness in a mass casualty scenario. Sodium tetrathionate reacts directly with cyanide yielding thiosulfate and the non-toxic compound thiocyanate. Thiosulfate in turn neutralizes a second molecule of cyanide, thus, per mole, sodium tetrathionate neutralizes two moles of cyanide. Historical studies examined its efficacy as a cyanide antidote, but it has not been evaluated in a clinically relevant, large animal model, nor has it previously been administered by intramuscular injection. The objective of this study is to evaluate the efficacy of intramuscular sodium tetrathionate on survival and clinical outcomes in a large, swine model of severe cyanide toxicity. Anesthetized swine were instrumented for continuous monitoring of hemodynamics, then acclimated and breathing spontaneously prior to potassium cyanide infusion (0.17 mg/kg/min). At 6-minutes post apnea (no breaths for 20 seconds), the cyanide infusion was terminated, and animals treated with sodium tetrathionate (~18 mg/kg) or normal saline control. Clinical parameters and laboratory values were evaluated at various time points until death, or termination of the experiment (90 minutes post treatment). Laboratory values, vital signs, and time to apnea were similar in both groups at baseline and treatment. Survival in the sodium tetrathionate treated group was 100% and 17% in controls (P=0.0043). All animals treated with sodium tetrathionate returned to breathing at a mean time of 10.85 minutes after antidote, and all but one control remained apneic through end of the experiment. Animals treated with tetrathionate showed improvement in blood lactate (P≤0.002) starting at 30 minutes post treatment. The average time to death in the control group of 63.3 ± 23.2 min. No systemic or localized adverse effects of intramuscular administration of sodium tetrathionate were observed. Sodium tetrathionate significantly improves survival and clinical outcomes in a large, swine model of acute cyanide poisoning.
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DOI：
10.3109/00365513.2011.573573
发表时间：
2011-09-01
影响因子：
2.1
作者：
Carlsson, Christian J.;Hansen, Heidi E.;Szecsi, Pal B.
通讯作者：
Szecsi, Pal B.
影响因子：
--
作者：
GILMAN, A;PHILIPS, FS;STJOHN, E
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STJOHN, E
影响因子：
3.3
作者：
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DOI：
10.1126/science.78.2016.145
发表时间：
1933-08-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Draize, J H
通讯作者：
Draize, J H
影响因子：
6.2
作者：
Bebarta, Vikhyat S.;Tanen, David A.;Boss, Gerry R.
通讯作者：
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