| Summary: | Ever since the discovery of endogenous H<sub>2</sub>S and the identification of its cytoprotective properties, efforts have been made to develop strategies to use H<sub>2</sub>S as a therapeutic agent. The ability of H<sub>2</sub>S to regulate vascular tone, inflammation, oxidative stress, and apoptosis might be particularly useful in the therapeutic management of critical illness. However, neither the inhalation of gaseous H<sub>2</sub>S, nor the administration of inorganic H<sub>2</sub>S-releasing salts or slow-releasing H<sub>2</sub>S-donors are feasible for clinical use. Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub> is a clinically approved compound with a good safety profile and is able to release H<sub>2</sub>S, in particular under hypoxic conditions. Pre-clinical studies show promise for Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub> in the acute management of critical illness. A current clinical trial is investigating the therapeutic potential for Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub> in myocardial infarct. Pre-eclampsia and COVID-19 pneumonia might be relevant targets for future clinical trials.
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