Hydroxocobalamin vs. Sodium Nitrite: Cyanide Antidote Smackdown

December 18, 2009, 5:43 pm

★★★½☆

HYDROXOCOBALAMIN AND SODIUM THIOSULFATE VERSUS SODIUM NITRITE AND SODIUM THIOSULFATE IN THE TREATMENT OF ACUTE CYANIDE TOXICITY IN A SWINE (Sus scrofa) MODEL Bebarta VS et al.  Ann Emerg Med 2009 (in press)

Abstract

This is a great example of a interesting paper whose conclusion seems completely at odds with the data.  The authors — from the Wilford Hall Medical Center in San Antonio — poisoned 24 swine with a lethal dose of intravenous cyanide, and then treated them with either hydroxocobalamin plus sodium thiosulfate, or sodium nitrite plus thiosulfate. Their primary outcome measure was change in mean arterial pressure after administration of antidote; they also looked at other outcomes, including mortality. Their conclusion: Although hydroxocobalamin plus thiosulfate led to a faster return to baseline mean arterial pressure, there was no significant difference in mortality.

Excuse me? There were three deaths in this study, one in the hydroxocobalamin group, and two in the sodium nitrite group.  In other words, sodium nitrite was associated with twice the mortality than was hydroxocobalamin.  Maybe the study did not have enough animals to make this difference statistically significant, but until proven otherwise I’m going take this as — potentially — clinically significant. It is important to realize that in contrast to sodium nitrite which decreases blood pressure, hydroxocobalamin increases mean arterial pressure, even above baseline.  This can be crucial in a patient unstable from cyanide exposure.  Note that all the deaths in this study occurred during the administration of antidote.*

For further discussion of hydroxocobalamin, see Part I and Part II of my 2007 column in Emergency Medicine News.

*Correction (3/31/10): In an unfortunate typo that somewhat changed the intended meaning of this sentence, the original post read: “Not that all the deaths in this study occurred during the administration of antidote.”

2 Comments:

  1. Steve Aks Says:

    What I really like about this study is that the authors ask a good question. Let’s compare the old antidote (nitrite + thiosulfate) to hydroxocobalomin + thiosulfate. I’m sold on using hydroxocobalamin over the old kit, but I want to know if we should also give thiosulfate. That’s especially relevant in an intentional overdose. The burden of cyanide will be much greater than in the smoke inhalation situation. I hope we see more studies fleshing this out.

  2. Leon Says:

    I agree. One disadvantage of using sodium thiosulfate as the sole antidote is that, since it works by supplying sulfur to the cyanide detoxification pathway, there is a delay in effect until it can penetrate into the mitochondria. Hydroxocobalamin (HC) acts immediately, detoxifying cyanide in the blood. However, if a patient does not quickly improve with HC, or as you mention if continued absorption and exposure is anticipated, it would make sense to also treat with thiosulfate. Note that HC and sodium thiosulfate are not compatible and should not be given simultaneously through the same IV line. They can be given through separate lines or sequentially after the line has been flushed.