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Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic?
Heitor Pons Leite1, Lúcio Flávio Peixoto de Lima2
1Discipline of Nutrition and Metabolism, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil.
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.
Insights
Metabolic resuscitation targeting mitochondrial dysfunction may improve outcomes for sepsis and septic shock patients. Thiamine supplementation shows promise for preventing organ dysfunction and death in critically ill individuals.
Area of Science:
- Biochemistry
- Critical Care Medicine
- Pathophysiology
Background:
- Sepsis and septic shock often lead to multiple organ dysfunction syndrome (MODS) and death, despite advances in treatment.
- Mitochondrial dysfunction is an early and central factor in MODS development and is linked to patient survival.
- Current treatments do not fully address the underlying pathophysiology, indicating a need for novel therapeutic strategies.
Discussion:
- Mitochondrion-targeted therapy, termed "metabolic resuscitation," aims to enhance mitochondrial activity through pharmacological and nutritional agents.
- Thiamine (vitamin B1) is crucial for cellular energy metabolism and may prevent thiamine deficiency-induced lactic acidosis in critically ill patients.
- Supplementation with thiamine could protect mitochondrial function and reduce MODS severity and mortality in septic patients.
Key Insights:
- Thiamine's protective effects on mitochondria suggest its utility in sepsis management, particularly for patients at risk of deficiency.
- Other micronutrients (ascorbic acid, tocopherol, selenium, zinc) and metabolic resuscitators (CoQ10, CytOx, L-carnitine, melatonin) are being explored for sepsis-induced mitochondrial dysfunction.
- Metabolic resuscitation presents a potential future strategy for treating septic shock, pending further research.
Outlook:
- Further clinical and experimental research is required to confirm the safety and efficacy of metabolic resuscitation.
- Genomics and metabolomics may help identify patient subgroups who would benefit most from mitochondrial resuscitation interventions.
- Metabolic resuscitation holds promise as a future therapeutic approach to reduce MODS and mortality in sepsis and septic shock.
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