Clinical Pharmacology and Toxicology Unit, Carmel Medical Center, Haifa, Israel.
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Clin Toxicol (Phila). 2021 Aug;59(8):734-739. doi: 10.1080/15563650.2020.1856382. Epub 2020 Dec 4.
In this proof-of-concept study, the aim was to evaluate the short-term clinical effectiveness of isosorbide dinitrate (ISDN) oral spray in non-anaesthetized cyanide-poisoned swine.
A comparative study was conducted using domestic swine. Animals were intravenously poisoned with potassium cyanide (KCN), either 2 mg/kg or 4 mg/kg dose. Two control groups (one for each cyanide dose) were not further treated. Two other groups (one for each cyanide dose) were treated within 1 min after poisoning with ISDN oral spray: 3 spray actuations (averaging a total of 3.75 mg) after the lower cyanide dose and 4 spray actuations (averaging a total of 5.0 mg) after the higher dose. The study outcomes were clinical score, time to death, and blood tests including pH, lactate, and methemoglobin levels.
All the animals started to convulse within 20 to 30 sec after KCN poisoning, then became unresponsive and hemodynamically depressed after another 20 to 30 sec. After the KCN 2 mg/kg dose, 3 of 4 control animals survived, while all treated animals survived. Compared with control animals, ISDN-treated animals displayed significantly better clinical scores starting 5 min after KCN poisoning. Acidosis was significantly more pronounced in the untreated animals. After the KCN 4 mg/kg dose, similar survival rates were observed for control and ISDN-treated groups (1/4), but treated animals had longer time to death and better pH and lactate levels.
ISDN oral spray administration following KCN poisoning in this porcine model did not result in statistically significant increased survival. However, based on clinical scores and clinical laboratory values, ISDN may benefit as a bridging countermeasure until currently-available specific cyanide antidotes can be administered. Further research is warranted to better characterize this potential role of ISDN in cyanide poisoning.
在这项概念验证研究中，旨在评估硝酸异山梨酯（ISDN）口腔喷雾在未麻醉氰化物中毒猪中的短期临床疗效。
使用国产猪进行了一项比较研究。动物通过静脉注射氰化钾（KCN），剂量为 2mg/kg 或 4mg/kg。两个对照组（每个氰化物剂量一个）未进一步治疗。另外两个组（每个氰化物剂量一个）在中毒后 1 分钟内用 ISDN 口腔喷雾治疗：较低氰化物剂量后 3 次喷雾（平均总量为 3.75mg），较高剂量后 4 次喷雾（平均总量为 5.0mg）。研究结果为临床评分、死亡时间以及包括 pH 值、乳酸和高铁血红蛋白水平在内的血液检测。
所有动物在 KCN 中毒后 20 至 30 秒内开始抽搐，然后在另外 20 至 30 秒内变得无反应和血液动力学压低。在 KCN 2mg/kg 剂量后，4 只对照动物中有 3 只存活，而所有治疗动物均存活。与对照动物相比，ISDN 治疗动物在 KCN 中毒后 5 分钟时显示出明显更好的临床评分。未治疗动物的酸中毒明显更为明显。在 KCN 4mg/kg 剂量后，对照组和 ISDN 治疗组的存活率相似（1/4），但治疗动物的死亡时间更长，pH 值和乳酸水平更好。
在该猪模型中，KCN 中毒后给予 ISDN 口腔喷雾并未导致统计学上显著增加的存活率。然而，基于临床评分和临床实验室值，ISDN 可能作为一种桥梁对策有益，直到目前可用的特定氰化物解毒剂可以给予。需要进一步研究以更好地描述 ISDN 在氰化物中毒中的潜在作用。
