Is pharmacological, H2S-induced 'suspended animation' feasible in the ICU?

By definition, 'suspended animation' is a hypometabolic state characterized by the “the slowing of life processes by external means without termination” [ 1 ]. Various mammalian species are capable of nearly completely shutting down their vital functions in order to survive otherwise lethal environmental conditions, such as prolonged impairment of O 2 supply and/or extreme temperatures. First described and studied in patients as “hibernation artificielle” induced by the so-called “cocktail lytique” during the Indochina war in the early 1950 s, for obvious reasons the concept of inducing such a hypometabolic condition has attracted special interest in intensive care and emergency medicine. Originally, organ-protection, in particular for the central nervous system (CNS), was demonstrated when suspended animation was induced by rapidly cooling experimental animals to core body temperatures of about 10-15 °C using ice-cold infusions and/or cardiopulmonary bypass (CPB). Given the potential undesired adverse effects of hypothermia per se, e. g., metabolic acidosis, coagulopathy, prolonged inflammation, and impaired host defense, any pharmacological measure allowing for a therapeutic on-demand induction of suspended animation would be of particular interest. Moreover, more recently, it was suggested that the reduced visceral organ function present in critically ill patients and/or after overwhelming hyperinflammation could be referred to as an adaptive mechanism to maintain ATP-homeostasis due to reduced energy expenditure rather than to irreversible organ failure [ 2 ]. A landmark paper by Blackstone et al. produced much excitement among researchers in the field of shock and critical illness: These authors demonstrated that mice inhaling hydrogen sulfide (H 2 S) reversibly decreased their energy expenditure, which was associated with a fall in core temperature [ 3 ]. In the meantime, numerous pre-clinical studies have been published on the possible organ-protective effects of H 2 S, the available data being equivocal depending on the model used and the type of shock investigated. In this context in particular, the impact of H 2 S effects on energy metabolism remains a matter of debate. Therefore, the present chapter reviews the available data on H 2 S-induced on-demand hypometabolism, and its relation (directly as well as via a possible consecutive drop in body temperature) to organ-protective properties of H 2 S.