Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic? - PubMed (original) (raw)
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Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic?
Heitor Pons Leite et al. J Thorac Dis. 2016 Jul.
Abstract
Despite the advances made in monitoring and treatment of sepsis and septic shock, many septic patients ultimately develop multiple organ dysfunction (MODS) and die, suggesting that other players are involved in the pathophysiology of this syndrome. Mitochondrial dysfunction occurs early in sepsis and has a central role in MODS development. MODS severity and recovery of mitochondrial function have been associated with survival. In recent clinical and experimental investigations, mitochondrion-target therapy for sepsis and septic shock has been suggested to reduce MODS severity and mortality. This intervention, which might be named "metabolic resuscitation", would lead to improved mitochondrial activity afforded by pharmacological and nutritional agents. Of particular interest in this therapeutic strategy is thiamine, a water-soluble vitamin that plays an essential role in cellular energy metabolism. Critical illness associated with hypermetabolic states may predispose susceptible individuals to the development of thiamine deficiency, which is not usually identified by clinicians as a source of lactic acidosis. The protective effects of thiamine on mitochondrial function may justify supplementation in septic patients at risk of deficiency. Perspectives of supplementation with other micronutrients (ascorbic acid, tocopherol, selenium and zinc) and potential metabolic resuscitators [coenzyme Q10 (CoQ10), cytochrome oxidase (CytOx), L-carnitine, melatonin] to target sepsis-induced mitochondrial dysfunction are also emerging. Metabolic resuscitation may probably be a safe and effective strategy in the treatment of septic shock in the future. However, until then, preliminary investigations should be replicated in further researches for confirmation. Better identification of groups of patients presumed to benefit clinically by a certain intervention directed to "mitochondrial resuscitation" are expected to increase driven by genomics and metabolomics.
Keywords: Mitochondria; multiple organ failure; oxidative stress; selenium; sepsis; thiamine.
Conflict of interest statement
Conflicts of Interest: The authors have no conflicts of interest to declare.
Comment on
- Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study.
Donnino MW, Andersen LW, Chase M, Berg KM, Tidswell M, Giberson T, Wolfe R, Moskowitz A, Smithline H, Ngo L, Cocchi MN; Center for Resuscitation Science Research Group. Donnino MW, et al. Crit Care Med. 2016 Feb;44(2):360-7. doi: 10.1097/CCM.0000000000001572. Crit Care Med. 2016. PMID: 26771781 Free PMC article. Clinical Trial.
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