Therapeutic Review: Do Diethyldithiocarbamate and Disulfiram Have a Role in Acute Nickel Carbonyl Poisoning?

Abstract

Introduction: Sodium diethyldithiocarbamate and disulfiram have been proposed as effective nickel chelators. This paper examines the value of these compounds in the treatment of acute nickel carbonyl poisoning by reviewing published experimental and clinical data. Review: In 2 studies, parenteral administration of diethyldithiocarbamate 50–100 mg/kg to rats immediately following nickel carbonyl exposure ensured the survival of all animals: Mortality 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 diethyldithiocarbamate was administered at 6 hours, and the mortality was greater, though not significantly different, when diethyldithiocarbamate was administered at 24 hours. In another study in mice, total protection was afforded by diethyldithiocarbamate given at 8 hours but this protection was limited when diethyldithiocarbamate was administered at 24 hours, with diethyldithiocarbamate 100 mg/kg apparently being less protective than diethyldithiocarbamate 50 mg/kg. In 3 studies, oral diethyldithiocarbamate administration was less effective than parenteral administration. There are no adequately controlled clinical studies of the use of diethyldithiocarbamate in acute nickel carbonyl poisoning despite claims that this therapy has been effective in the treatment of several hundred such patients. Disulfiram, a metabolite of diethyldithiocarbamate, offered complete protection against nickel carbonyl-induced toxicity when administered in a dose of 1000 mg/kg to rats immediately following nickel carbonyl exposure. In contrast, disulfiram 500 mg/kg offered no protection and disulfiram 1500 mg/kg appeared to enhance mortality, possibly by increasing brain nickel accumulation. Conclusion: Animal studies demonstrate that diethyldithiocarbamate is an effective antidote in acute nickel carbonyl poisoning when it is administered parenterally soon after exposure. However, as no adequately controlled clinical studies have been performed, further clinical data are required before diethyldithiocarbamate can be recommended routinely in acute nickel carbonyl poisoning. If diethyldithiocarbamate is to be employed, it should be administered parenterally soon after exposure as delay in administration may increase nickel carbonyl toxicity. There are currently insufficient data to recommend disulfiram as an alternative to diethyldithiocarbamate even when diethyldithiocarbamate is not available.