Brenner Matthew, Azer Sarah M, Oh Kyung-Jin, Han Chang Hoon, Lee Jangwoen, Mahon Sari B, Du Xiaohua, Mukai David, Burney Tanya, Saidian Mayer, Chan Adriano, Straker Derek I, Bebarta Vikhyat S, Boss Gerry R
Beckman Laser Institute, University of California, Irvine, California, USA.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, California, USA.
J Clin Toxicol. 2017 Jun;7(3). doi: 10.4172/2167-7972.1000355. Epub 2017 Jun 27.
Accidental or intentional cyanide ingestion is an-ever present danger. Rapidly acting, safe, inexpensive oral cyanide antidotes are needed that can neutralize large gastrointestinal cyanide reservoirs. Since humans cannot be exposed to cyanide experimentally, we studied oral cyanide poisoning in rabbits, testing oral sodium thiosulfate with and without gastric alkalization.
University research laboratory.
New Zealand white rabbits.
Seven animal groups studied; Groups 1-5 received high dose oral NaCN (50 mg, >LD100) and were treated immediately with oral ( nasogastric tube): 1) saline, 2) glycine, 3) sodium thiosulfate or 4) sodium thiosulfate and glycine, or 5) after 2 min with intramuscular injection of sodium nitrite and sodium thiosulfate plus oral sodium thiosulfate and glycine. Groups 6-7 received moderate dose oral NaCN (25 mg, LD70) and delayed intramuscular 6) saline or 7) sodium nitrite-sodium thiosulfate.
All animals in the high dose NaCN group receiving oral saline or glycine died very rapidly, with a trend towards delayed death in glycine-treated animals; saline glycine-treated animals died at 10.3+3.9 and 14.6+5.9 min, respectively (p=0.13). In contrast, all sodium thiosulfate-treated high dose cyanide animals survived (p<0.01), with more rapid recovery in animals receiving both thiosulfate and glycine, compared to thiosulfate alone (p<0.03). Delayed intramuscular treatment alone in the moderate cyanide dose animals increased survival over control animals from 30% to 71%. Delayed treatment in high dose cyanide animals was not as effective as immediate treatment, but did increase survival time and rescued 29% of animals (p<0.01 cyanide alone).
Oral sodium thiosulfate with gastric alkalization rescued animals from lethal doses of ingested cyanide. The combination of oral glycine and sodium thiosulfate may have potential for treating high dose acute cyanide ingestion and merits further investigation. The combination of systemic and oral therapy may provide further options.
意外或故意摄入氰化物是一直存在的危险。需要有能迅速起效、安全且廉价的口服氰化物解毒剂,以中和胃肠道中大量的氰化物蓄积。由于无法在人体上进行氰化物实验暴露,我们研究了家兔口服氰化物中毒情况,测试了口服硫代硫酸钠以及联合胃碱化的效果。
大学研究实验室。
新西兰白兔。
研究了7个动物组;第1 - 5组给予高剂量口服氰化钠(50毫克,>半数致死量的100%),并立即经口服(鼻胃管)治疗:1)生理盐水,2)甘氨酸,3)硫代硫酸钠,4)硫代硫酸钠和甘氨酸,或5)2分钟后肌肉注射亚硝酸钠和硫代硫酸钠加口服硫代硫酸钠和甘氨酸。第6 - 7组给予中等剂量口服氰化钠(25毫克,半数致死量的70%),并延迟肌肉注射6)生理盐水或7)亚硝酸钠 - 硫代硫酸钠。
高剂量氰化钠组中接受口服生理盐水或甘氨酸的所有动物均很快死亡,接受甘氨酸治疗的动物有延迟死亡的趋势;生理盐水和甘氨酸治疗的动物分别在10.3±3.9分钟和14.6±5.9分钟死亡(p = 0.13)。相比之下,所有接受硫代硫酸钠治疗的高剂量氰化物动物均存活(p<0.01),与单独使用硫代硫酸钠相比,同时接受硫代硫酸钠和甘氨酸治疗的动物恢复更快(p<0.03)。中等剂量氰化物动物单独采用延迟肌肉注射治疗后,存活率从对照组的30%提高到了71%。高剂量氰化物动物的延迟治疗不如立即治疗有效,但确实延长了存活时间,挽救了29%的动物(与单独使用氰化物相比,p<0.01)。
口服硫代硫酸钠联合胃碱化可使动物从致死剂量的摄入性氰化物中毒中获救。口服甘氨酸和硫代硫酸钠的联合应用可能对治疗高剂量急性氰化物摄入有潜在价值,值得进一步研究。全身治疗与口服治疗联合应用可能会提供更多选择。