Hydrogen Sulfide Toxicity: Mechanism of Action, Clinical Presentation, and Countermeasure Development.

INTRODUCTION: Hydrogen sulfide (H2 S) is found in various settings. Reports of chemical suicide, where individuals have combined readily available household chemicals to produce lethal concentrations of H2 S, have demonstrated that H2 S is easily produced. Governmental agencies have warned of potential threats of use of H2 S for a chemical attack, but currently there are no FDA-approved antidotes for H2 S. An ideal antidote would be one that is effective in small volume, readily available, safe, and chemically stable. In this paper we performed a review of the available literature on the mechanism of toxicity, clinical presentation, and development of countermeasures for H2 S toxicity.

DISCUSSION: In vivo, H2 S undergoes an incomplete oxidation after an exposure. The remaining non-oxidized H2 S is found in dissolved and combined forms. Dissolved forms such as H2 S gas and sulfhydryl anion can diffuse between blood and tissue. The combined non-soluble forms are found as acid-labile sulfides and sulfhydrated proteins, which play a role in toxicity. Recent countermeasure development takes into account the toxicokinetics of H2 S. Some countermeasures focus on binding free hydrogen sulfide (hydroxocobalamin, cobinamide); some have direct effects on the mitochondria (methylene blue), while others work by mitigating end organ damage by generating other substances such as nitric oxide (NaNO2).

CONCLUSION: H2 S exists in two main pools in vivo after exposure. While several countermeasures are being studied for H2 S intoxication, a need exists for a small-volume, safe, highly effective antidote with a long shelf life to treat acute toxicity as well as prevent long-term effects of exposure.