PURPOSE:Methods are needed for detection and treatment of mass casualty cyanide poisoning. Recent studies show that a novel agent, cobinamide, binds cyanide with a much greater affinity than hydroxocobalamin, is more water soluble than hydroxocobalamin, and may be an ideal antidote for mass casualty cyanide treatment. We used a Broadband Diffuse Optical Spectroscopy (DOS) prototype system we developed that combines multi-frequency domain photon migration with near infrared spectroscopy to measure bulk tissue absorption and scattering between 650 and 1000nm wavelengths for monitoring the severity of in vivo cyanide toxicity induced physiological changes during cobinamide treatment in a rabbit model. DOS simultaneously quantified oxy- and deoxy- hemoglobins, tissue oxygen saturation, and redox states of cytochrome C oxidase during the procedure.
METHODS:A New Zealand white rabbit cyanide model was used in this study. A DOS probe was placed over the shaved inner thigh muscle of the right hind leg. A sodium cyanide solution of 10mg in 60cc saline was infused at a rate of 1cc per minute, for 1 hour. This was followed by cyanide treatment with either high dose (241 mg) or low dose (83.5 mg) of cobinamide, administered as a bolus IV dose, a slow infusion, or transpulmonary instillation. DOS measurements and concurrent physiological measurements including arterial and venous blood gases, CO, and oxygen saturation, were obtained throughout the experiment.
RESULTS:Cobinamide caused rapid and complete reversal of cyanide toxicity effects when administered IV or by transpulmonary routes as demonstrated non-invasively by DOS and confirmed by blood sampling.
CONCLUSION:Cobinamide is a novel agent that is capable of rapidly reversing cyanide toxicity, and was assessable non-invasively using DOS. The high potency and solubility of cobinamide make it potentially an ideal agent for treatment of mass casualty CN exposures.
CLINICAL IMPLICATIONS:These results show that cyanide toxicity can be successfully reversed with cobinamide. Additionally, the changes were able to be monitored non-invasively which would lead to more accurate clinical decisions and more effective patient care.
DISCLOSURE:Kelly Kreuter, None.