hydroxocobalamin and cobalt-ethylenediamine-tetraacetic-acid-chelate

The importance of cyanide toxicity as a component of inhalational injury in patients with burns is increasingly being recognised, and its prompt recognition and management is vital for optimising burns survival. The evidence base for the use of cyanide antidotes is limited by a lack of randomised controlled trials in humans, and in addition consideration must be given to the concomitant pathophysiological processes in patients with burns when interpreting the literature. We present a literature review of the evidence base for cyanide antidotes with interpretation in the context of patients with burns. We conclude that hydroxycobalamin should be utilised as the first-line antidote of choice in patients with burns with inhalational injury where features consistent with cyanide toxicity are present.

Topics: Adenosine; Amyl Nitrite; Burns; Chelating Agents; Cyanides; Edetic Acid; Humans; Hydroxocobalamin; Hyperbaric Oxygenation; Oxygen Inhalation Therapy; Poisoning; Pteridines; Smoke Inhalation Injury; Sodium Nitrite; Thiosulfates

Topics: Acute Disease; Amyl Nitrite; Cyanides; Edetic Acid; Humans; Hydroxocobalamin; Nitrates; Thiosulfates

The antidotal potency of a cobalt salt (acetate), of dicobalt edetate, of hydroxocobalamin and of cobinamide against hydrocyanic acid was examined mainly on mice and rabbits. All the compounds were active antidotes for up to twice the LD50; under some conditions for larger doses. The most successful was cobalt acetate for rabbits (5xLD50), which was effective at a molar cyanide/cobalt (CN/Co) ratio of 5, but had as a side-effect intense purgation. Hydroxocobalamin was irregular in action, but on the whole was most effective for mice (4.5xLD50 at a molar ratio of 1), and had no apparent side effects. Dicobalt edetate, at molar ratios of up to 2, was more effective for rabbits (3xLD50) than for mice (2xLD50), but had fewer side effects than cobalt acetate. The effect of thiosulphate was to augment the efficacy of dicobalt edetate and, in mice, that of hydroxocobalamin; but, apparently, in rabbits, to reduce that of hydroxocobalamin. Cobinamide, at a molar ratio of 1, was slightly more effective than hydroxocobalamin on rabbits and also less irregular in its action. Cobalt acetate by mouth was effective against orally administered hydrocyanic acid. The oxygen uptake of the body, reduced by cyanide, is rapidly reinstated when one of the cobalt antidotes has been successfully administered.

Topics: Acetates; Animals; Antidotes; Cobalt; Cyanides; Edetic Acid; Hydrogen Cyanide; Hydroxocobalamin; Lagomorpha; Metabolism; Mice; Pharmacology; Poisoning; Rabbits; Research; Salts; Thiosulfates; Toxicology