Title: Hydroxocobalamin versus Thiosulfate for Cyanide Poisoning
Abstract: We read with great interest the review by Hall et al, comparing thiosulfate and hydroxocobalamin as cyanide antidotes.1Hall A.H. Dart R. Bogdan G. Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning?.Ann Emerg Med. 2007; 49: 806-813Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar While we agree with the authors that available evidence to compare the 2 antidotes is incomplete, several elements of this review concern us. The authors state,“No animal study compared hydroxocobalamin and thiosulfate by using the same experimental protocol.” We respectfully disagree. In some cases, thiosulfate demonstrated greater effect. In rabbits with nitroprusside-induced cyanide toxicity, thiosulfate blunted acidemia and provided 100% survival at 4 and 24 hours.2Hobel M. Engeser P. Nemeth L. et al.The antidote effect of thiosulphate and hydroxocobalamin in formation of nitroprusside intoxication of rabbits.Archives of Toxicology. 1980; 46: 207-213Crossref PubMed Scopus (10) Google Scholar All rabbits receiving hydroxocobalamin survived 4 hours, but only 70% survived 24 hours. In a study where guinea pigs received simultaneous cyanide and antidote, thiosulfate doubled the time to toxicity compared to hydroxocobalamin.3Mengel K. Kramer W. Isert B. et al.Thiosulphate and hydroxocobalamin prophylaxis in progressive cyanide poisoning in guinea pigs.Toxicology. 1989; 54: 335-342Crossref PubMed Scopus (9) Google Scholar The reviewers state, “the onset of antidotal action of thiosulfate may be too slow for it to be the only cyanide antidote for emergency use.” This critical assertion is referenced with a review article and demands further exploration. Some evidence demonstrates rapid effect following thiosulfate. Cats and guinea pigs showed a decrease in exhaled cyanide within minutes of either aquocobalamin or thiosulfate.4Friedberg K.D. Shukla U.R. The efficiency of aquocobalamine as an antidote in cyanide poisoning when given alone or combined with sodium thiosulfate.Archives of Toxicology. 1975; 33: 103-113Crossref PubMed Scopus (22) Google Scholar Although exhaled cyanide initially declined faster with aquocobalamin, thiosulfate provided more lasting effect. Within 10 minutes after aquocobalamin, exhaled cyanide levels increased, whereas they remained negligible after thiosulfate. Any discussion of time to effect of these antidotes should also consider that, in the clinical setting, thiosulfate can be administered rapidly, over several minutes, while hydroxocobalamin requires reconstitution and then administration over 15 minutes. This slow administration rate likely negates any advantage of hydroxocobalamin’s more rapid action and greatly complicates antidote delivery in the mass casualty event in which victims outnumber rescuers. The authors assert that thiosulfate offers “only a preventive action and not a curative action.” We agree that rescue data is more complete for hydroxocobalamin, but thiosulfate rescue studies do exist. In guinea pigs and cats, thiosulfate reversed acidemia within minutes and demonstrated prolonged effect compared to aquocobalamin.4Friedberg K.D. Shukla U.R. The efficiency of aquocobalamine as an antidote in cyanide poisoning when given alone or combined with sodium thiosulfate.Archives of Toxicology. 1975; 33: 103-113Crossref PubMed Scopus (22) Google Scholar We are surprised that the review did not consider combined hydroxocobalamin-thiosulfate therapy. Indeed, the subject of the review–which monotherapy is best–is almost moot. Dual therapy offers advantages, including possible synergy of complementary mechanisms. Animal studies4Friedberg K.D. Shukla U.R. The efficiency of aquocobalamine as an antidote in cyanide poisoning when given alone or combined with sodium thiosulfate.Archives of Toxicology. 1975; 33: 103-113Crossref PubMed Scopus (22) Google Scholar and human cases5Hall A.H. Rumack B.H. Hydroxocobalamin/sodium thiosulfate as a cyanide antidote.Journal of Emergency Medicine. 1987; 5: 115-121Abstract Full Text PDF PubMed Scopus (89) Google Scholar support dual therapy. As long as the antidotes are not infused simultaneously through the same IV, there are no significant drawbacks other than hydroxocobalamin cost. The FDA approved hydroxocobalamin via the animal rule, which allows antidote approval based on a combination of human safety and animal efficacy studies. It does not require direct comparison between a candidate drug and previously FDA-approved therapy. Unfortunately, there are no data to directly demonstrate which combination of hydroxocobalamin, thiosulfate, and nitrite represents the ideal cyanide treatment strategy. A modern animal study directly comparing rescue with all 3 drugs administered individually and together is urgently needed. While we celebrate hydroxocobalamin as another cyanide treatment option, we advise caution. Neither a hospital nor a nation should abandon a treatment strategy established by robust animal research and 74 years of human experience until data shows that replacement strategy is at least as effective as its predecessor. Until a comparison study is available, we recommend that hospitals keep nitrite and thiosulfate available for cyanide poisoning.
Publication Year: 2008
Publication Date: 2008-03-01
Language: en
Type: letter
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 9
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