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

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Abstract

Introduction

Hydrogen sulfide (H2S) is found in various settings. Reports of chemical suicide, where individuals have combined readily available household chemicals to produce lethal concentrations of H2S, have demonstrated that H2S is easily produced. Governmental agencies have warned of potential threats of use of H2S for a chemical attack, but currently there are no FDA-approved antidotes for H2S. 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 H2S toxicity.

Discussion

In vivo, H2S undergoes an incomplete oxidation after an exposure. The remaining non-oxidized H2S is found in dissolved and combined forms. Dissolved forms such as H2S 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 H2S. 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

H2S exists in two main pools in vivo after exposure. While several countermeasures are being studied for H2S 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.

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Funding

M. Brenner, SB Mahon, GR Boss, P Haouzi, VS Bebarta, TB Hendry‐Hofer, AE Witcoff are supported in part by NIH 5U01NS087964‐04.

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Authors and Affiliations

  1. Denver Health and Hospital Authority, Rocky Mountain Poison and Drug Center, Denver, CO, USA

    Patrick C. Ng & Vikhyat S. Bebarta

  2. Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Patrick C. Ng, Tara B. Hendry-Hofer, Alyssa E. Witeof & Vikhyat S. Bebarta

  3. Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA

    Matthew Brenner & Sari B. Mahon

  4. Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, USA

    Matthew Brenner

  5. Department of Medicine, University of California, San Diego, CA, USA

    Gerry R. Boss

  6. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, USA

    Philippe Haouzi

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  1. Patrick C. Ng
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  2. Tara B. Hendry-Hofer
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Correspondence to Patrick C. Ng.

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Ng, P.C., Hendry-Hofer, T.B., Witeof, A.E. et al. Hydrogen Sulfide Toxicity: Mechanism of Action, Clinical Presentation, and Countermeasure Development. J. Med. Toxicol. 15, 287–294 (2019). https://doi.org/10.1007/s13181-019-00710-5

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