UC Irvine

Background: Hydrogen sulfide (H2S) is a potent, toxic gas, frequently inhaled accidentally from natural or industrial (petroleum, metallurgy, agriculture) sources. Moreover, it can potentially be weaponized for malicious use, for civilian terrorism or against military personnel. Unfortunately, currently no effective antidote exists to neutralize the fatal effects of H2S; this is a major public health concern. Preliminary studies have demonstrated that cobinamide (a precursor of cobalamin, vitamin B12) can inhibit H2S toxicity. We developed a novel inhalation model, simulating realistic toxic exposure to investigate the efficacy of cobinamide.

Method: Twenty New Zealand White rabbits (10 in each, cobinamide and control groups) were anesthetized, intubated and placed in a respiratory inhalation circuit, delivering an anesthetic (isoflurane) and H2S mixture, using a compressed air flow-by model. Rabbits’ vital signs (heart rate, blood pressure, respiratory rate and oxygen saturation) and gas levels within the hood were continuously monitored. After any change in respiratory pattern, 1cc cobinamide or normal saline was administered intramuscularly. The primary endpoint was mean survival time.

Result: Cobinamide-treated rabbits had an average 7-minute increase in survival time (12.6±3.37 min versus 19.5±7.26 min). Kaplan Meier survival curves showed significant difference. Log rank analysis of the two groups’ survival curves was statistically different (p<0.007).

Conclusion: We have demonstrated the first utilization of cobinamide as an intramuscular antidote to H2S in a rabbit inhalation model, successfully prolonging survival more than 50%. Further investigations are required to address the serious public health concern for hydrogen sulfide mass casualty.