IMPACT OF MITOCHONDRIAL SUPPLEMENTATION ON RESOLUTION OF PEDIATRIC SEPTIC SHOCK: A PROSPECTIVE RANDOMIZED CONTROL TRIAL

Shock in children results from varied causes, hypovolemic and septic shock being the most common causes. Pediatric septic shock results due to inflammatory response to a focus of infection. In sepsis, there is release of various cytokines which results in increased capillary permeability and myocardial dysfunction. The early manifestations of shock in children include tachycardia, cold peripheries, prolonged CFT, narrow pulse pressure and late signs include altered mental status and hypotension. Early recognition of shock and early interventions are associated with favourable outcomes.

Metabolic supplementation refers to a therapeutic strategy aimed at correcting the underlying metabolic derangements that occur during critical illness, particularly in conditions such as sepsis, septic shock, multi-organ dysfunction, and acute kidney injury (AKI). During severe illness, multiple metabolic pathways become dysregulated, including impaired cellular energy production, mitochondrial dysfunction, oxidative stress, hormonal disturbances, and dysregulated immune responses. These disturbances can further perpetuate organ dysfunction, making targeted metabolic support an important adjunct to conventional resuscitation strategies. The cornerstone of metabolic resuscitation involves the administration of key micronutrients and metabolic cofactors that support mitochondrial function, reduce oxidative stress, and modulate inflammation. One of the most studied regimens is the combination of intravenous Vitamin C, hydrocortisone, and thiamine. Vitamin C acts as a potent antioxidant and cofactor for catecholamine synthesis; thiamine supports mitochondrial oxidative metabolism and prevents lactic acidosis; while hydrocortisone helps restore vascular responsiveness and modulate the exaggerated inflammatory response.

Mitochondrial supplementation represents an emerging therapeutic approach aimed at restoring mitochondrial function in critically ill patients, where mitochondrial dysfunction is increasingly recognized as a central contributor to multi-organ failure. Mitochondria play a pivotal role in energy production, regulation of oxidative stress, calcium homeostasis, and apoptosis. In conditions such as sepsis, ischemia-reperfusion injury, acute kidney injury, cardiac arrest, and neurodegenerative disorders, mitochondrial injury leads to impaired oxidative phosphorylation, excessive generation of reactive oxygen species (ROS), mitochondrial membrane permeability transition pore (mPTP) opening, calcium dysregulation, and activation of intrinsic apoptotic pathways. These processes collectively result in bioenergetic failure, cellular dysfunction, and organ injury. Therapeutic strategies for mitochondrial supplementation include the administration of systemic and mitochondria-targeted antioxidants and metabolic cofactors (e.g., Coenzyme Q10, L-carnitine) and agents that stimulate mitochondrial biogenesis. Given the central role of impaired perfusion, systemic inflammation, and metabolic dysregulation in pediatric shock and AKI, there is a growing interest in adjunctive therapies targeting mitochondrial health and cellular energetics. This trial aims to explore its role in pediatric septic shock as an adjunct to standard of care.