Therapeutic review: Do diethyldithiocarbamate and disulfiram have a role in acute nickel carbonyl poisoning?

Introduction: Sodium diethyldithiocarbamate and disulfiram have been propos ed as effective nickel chelators, This paper examines the value of these co mpounds in the treatment of acute nickel carbonyl poisoning by reviewing pu blished experimental and clinical data. Review: In 2 studies, parenteral ad ministration of diethyldithiocarbamate 50-100 mg/kg to rats immediately fol lowing nickel carbonyl exposure ensured the survival of all animals: Mortal ity fell from 73% to 8% when diethyldithiocarbamate was administered at 10 minutes in a third study. In the same study, there was no protection when d iethyldithiocarbamate was administered at 6 hours, and the mortality was gr eater, though not significantly different, when diethyldithiocarbamate was administered at 24 hours. In another study in mice, total protection was af forded by diethyldithiocarbamate given at 8 hours but this protection was l imited when diethyldithiocarbamate was administered at 24 hours, with dieth yldithiocarbamate 100 mg/kg apparently being less protective than diethyldi thiocarbamate 50 mg/kg, In 3 studies, oral diethyldithiocarbamate administr ation was less effective than parenteral administration. There are no adequ ately controlled clinical studies of the use of diethyldithiocarbamate in a cute nickel carbonyl poisoning despite claims that this therapy has been ef fective in the treatment of several hundred such patients. Disulfiram, a me tabolite of diethyldithiocarbamate, offered complete protection against nic kel carbonyl-induced toxicity when administered in a dose of 1000 mg/kg to rats immediately following nickel carbonyl exposure. In contrast, disulfira m 500 mg/kg offered no protection and disulfiram 1500 mg/kg appeared to enh ance mortality, possibly by increasing brain nickel accumulation. Conclusio n: Animal studies demonstrate that diethyldithiocarbamate is an effective a ntidote in acute nickel carbonyl poisoning when it is administered parenter ally soon after exposure. However, as no adequately controlled clinical stu dies have been performed, further clinical data are required before diethyl dithiocarbamate can be recommended routinely in acute nickel carbonyl poiso ning, If diethyldithiocarbamate Is to be employed, it should be administere d parenterally soon after exposure as delay in administration may increase nickel carbonyl toxicity. There are currently insufficient data to recommen d disulfiram as an alternative to diethyldithiocarbamate even when diethyld ithiocarbamate is not available.