Department of Emergency Medicine, School of Medicine, University of Colorado, Aurora, CO, USA.
Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, USA.
Clin Toxicol (Phila). 2020 Jan;58(1):29-35. doi: 10.1080/15563650.2019.1602272. Epub 2019 Apr 22.
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-min post-apnea (no breaths for 20 s), the cyanide infusion was terminated, and animals were 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 min 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 ( = 0.0043). All animals treated with sodium tetrathionate returned to breathing at a mean time of 10.85 min after antidote, and all but one control remained apneic through end of the experiment. Animals treated with tetrathionate showed improvement in blood lactate ( ≤ 0.002) starting at 30 min post-treatment. The average time to death in the control group is 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.
氰化物是一种代谢性毒物，广泛应用于多个行业，同时也是一种高危化学毒剂。目前的解毒剂需要通过静脉注射，这限制了其在大规模人员伤亡情况下的应用。连四硫酸钠可与氰化物直接反应，生成硫代硫酸盐和无毒的硫氰酸盐。而硫代硫酸盐则可以进一步中和第二个氰化物分子，因此，每摩尔连四硫酸钠可以中和两个摩尔的氰化物。历史研究已经检验了其作为氰化物解毒剂的效果，但它尚未在具有临床相关性的大型动物模型中进行评估，也未曾通过肌肉注射给药。本研究的目的是评估肌肉注射连四硫酸钠对严重氰化物中毒大猪模型的生存和临床结局的疗效。麻醉猪接受连续监测血流动力学的仪器植入，然后在进行氰化钾输注（0.17mg/kg/min）前适应并自主呼吸。在呼吸暂停 6 分钟后（20 秒内无呼吸），终止氰化物输注，并给动物使用连四硫酸钠（约 18mg/kg）或生理盐水对照治疗。在不同时间点评估临床参数和实验室值，直至死亡或实验结束（治疗后 90 分钟）。在基线和治疗时，两组的实验室值、生命体征和呼吸暂停时间均相似。在连四硫酸钠治疗组中，生存率为 100%，而对照组为 17%（=0.0043）。所有接受连四硫酸钠治疗的动物在解毒剂后 10.85 分钟平均时间内恢复呼吸，而对照组除一只动物外均在实验结束时仍处于呼吸暂停状态。接受连四硫酸盐治疗的动物的血乳酸水平开始在治疗后 30 分钟有所改善（≤0.002）。对照组的平均死亡时间为 63.3±23.2 分钟。未观察到肌肉注射连四硫酸钠的全身或局部不良反应。在急性氰化物中毒的大猪模型中，连四硫酸钠显著提高了生存率和临床结局。
