Can isosorbide dinitrate oral spray serve as an immediate bridging therapy for a mass cyanide poisoning?

Abstract

Objective 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. Methods 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. Results 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. Conclusion 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.