Critical Care |

Cobinamide: A Future Treatment of Hydrogen Sulfide Toxicity in Mass Casualty Instances FREE TO VIEW

Sebastian Benavides, MD; Matthew Brenner, MD; Sari Mahoon, PhD; David Mukai, BS; David Yoon, BS; Tanya Burney, BS; Charlotte Alexander, BS; Gerry Boss, MD; Jingjign Jaing, MD; Jangwoen Lee, PhD
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University of California Irvine, Orange, CA

Chest. 2013;144(4_MeetingAbstracts):369A. doi:10.1378/chest.1704684
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SESSION TITLE: Critical Care Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 30, 2013 at 01:30 PM - 02:30 PM

PURPOSE: Background and Purpose: Hydrogen sulfide, a highly toxic naturally occurring gas, can be easily produced and used as a chemical weapon. It binds to cytochrome c oxidase, causing cellular asphyxiation and anoxia. Cobalamin has been used to treat hydrogen sulfide in anecdotal cases, binding H2S to the cobalt moiety. Cobinamide is the penultimate precursor in cobalamin biosynthesis, can be injected intramuscularly, and also binds hydrogen sulfide. We investigated cobinamide as a possible treatment of H2S toxicity.

METHODS: Methods: Twelve New Zealand white rabbits were anesthetized, intubated, ventilated, and had central lines placed. Sodium hydrosulfide (NaHS), was injected intravenously, blood gasses were sampled, and deoxygenated and oxygenated hemoglobin were continuously measured in the CNS and muscle by diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS). Six of the animals received cobinamide.

RESULTS: Results: CWNIRS of the CNS showed an initial decrease in oxyhemoglobin and concomitant increase in deoxyhemoglobin followed by a reversal of the changes and increase in total hemoglobin as poisoning progressed. The initial change correlated with a decrease in blood pressure, leading to decreased tissue perfusion, which was partially compensated by an increase in heart rate. Cobinamide reversed the H2S effects and stabilized total hemoglobin levels compared to placebo, with early results indicating improved survival.

CONCLUSIONS: Conclusions: Hydrogen sulfide is a highly toxic gas causing cellular asphyxiation and death. It has clear physiologic effects, including changes in blood pressure and tissue perfusion resulting in changes in tissue oxygenation as measured by DOS and CWNIRS. Cobinamide reversed most of the H2S-induced changes and prolonged life compared to placebo.

CLINICAL IMPLICATIONS: Such a trial may lead to the production of a rapid acting antidote in hydrogen sulfide mass casualty toxicity.

DISCLOSURE: The following authors have nothing to disclose: Sebastian Benavides, Matthew Brenner, Sari Mahoon, David Mukai, David Yoon, Tanya Burney, Charlotte Alexander, Gerry Boss, Jingjign Jaing, Jangwoen Lee

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