Intravenous Cobinamide, a Novel Cyanide Antidote, versus Hydroxocobalamin in the Treatment of Acute Cyanide Toxicity and Apnea in a Swine (Sus scrofa) Model

Compare time to breathing between 3 groups of swine 11group with cyanideCN induced apnea treated with intravenousIV hydroxocobalaminHOC, IV cobinamideCOB, or IV normal salineNS control. Method33 swine45-55kg intubated, anesthetized instrumented MAP and cardiac output. Isoflurane low to allow breathing room air0.21FiO2. CN infused until apnea. Given HOC65mgkg, COB12.5mgkg or NS20ml monitored 60min. ResultsWeight, time to apnea, CN dose similar p0.10. At treatment, blood CN, lactate levels, decrease in MAP similar p0.10. 211 swine in NS group survivedp0.001, compared to 1011 in HOC 1011 in COB group. Time to breaths post treatment similarHOC 148min, COB 149min. Blood CN levels undetectable post HOC or COB infusion. No statistically significant differences were detected between groups for CO, MAP, RR, or min vent at 60min. Lactate, pH, and PCO2 at 60 min were similar p0.10. Conclusion IV COB led to similar time to breathing as IV HOC for CN induced apnea and severe toxicity. Cobinamide was 5 times as potent as hydroxocobalamin.