Bench-to-bedside review: Hydrogen sulfide – the third gaseous transmitter: applications for critical care

Hydrogen sulfide (H₂S), a gas with the characteristic odor of rotten eggs, is known for its toxicity and as an environmental hazard, inhibition of mitochondrial respiration resulting from blockade of cytochrome c oxidase being the main toxic mechanism. Recently, however, H₂S has been recognized as a signaling molecule of the cardiovascular, inflammatory and nervous systems, and therefore, alongside nitric oxide and carbon monoxide, is referred to as the third endogenous gaseous transmitter. Inhalation of gaseous H₂S as well as administration of inhibitors of its endogenous production and compounds that donate H₂S have been studied in various models of shock. Based on the concept that multiorgan failure secondary to shock, inflammation and sepsis may represent an adaptive hypometabolic reponse to preserve ATP homoeostasis, particular interest has focused on the induction of a hibernation-like suspended animation with H₂S. It must be underscored that currently only a limited number of data are available from clinically relevant large animal models. Moreover, several crucial issues warrant further investigation before the clinical application of this concept. First, the impact of hypothermia for any H₂S-related organ protection remains a matter of debate. Second, similar to the friend and foe character of nitric oxide, no definitive conclusions can be made as to whether H₂S exerts proinflammatory or anti-inflammatory properties. Finally, in addition to the question of dosing and timing (for example, bolus administration versus continuous intravenous infusion), the preferred route of H₂S administration remains to be settled – that is, inhaling gaseous H₂S versus intra-venous administration of injectable H₂S preparations or H₂S donors. To date, therefore, while H₂S-induced suspended animation in humans may still be referred to as science fiction, there is ample promising preclinical data that this approach is a fascinating new therapeutic perspective for the management of shock states that merits further investigation.