Metabolic Resuscitation Using Hydrocortisone, Ascorbic Acid, and Thiamine: Do Individual Components Influence Reversal of Shock Independently?

Aims and objective: To study the effects of various components of"metabolic resuscitation" on the shock reversal among patients with septic shock Introduction: Sepsis is characterized by dysregulated host response to infection. Mitochondrial dysfunction which occurs early in sepsis is associated with multiorgan dysfunction. Therapies such as adequate resuscitation, early administration of antibiotics, and aggressive monitoring reduced mortality substantially but it still remains high for those with septic shock. Combination of vitamin C, hydrocortisone, and thiamine improved outcome in a retrospective study, but how effective is this therapy in isolation compared to combination has to be known before implementation. Materials and methods: This study is single-center, prospective, randomized nonblinded trial done in septic shock patients admitted to the medical intensive care unit. Subjects were randomized to three groups of hydrocortisone (H), hydrocortisone, ascorbic acid (HA), hydrocortisone, ascorbic acid, thiamine (HAT). Following randomization, they received hydrocortisone 200 mg over 24 hours as infusion, intravenous ascorbic acid 1.5 g every 6 hours, thiamine 200 mg twice daily as allotted and continued till shock reversal or death. Primary outcome is time to shock reversal and secondary outcome is time to vasopressor dose reduction from hemodynamic SOFA score 4-3. Results: Twenty seven subjects were randomized into 3 groups of 9 each, of which 17 (63%) patients met primary outcome and secondary outcome has been studied in 16 (59%) patients. Eight patients (29.5%) died and did not meet either outcome and two patients (7.5%) met secondary outcome but not primary outcome because of discharge to other hospital. There is no difference in time to shock reversal [mean, SD in H (7422, 8348), HA (2528, 3086), HAT (1860, 749), p value 0.17]. There is no difference in time to shock reversal from hemodynamic SOFA 4-3 [mean, SD in H (4935, 6406), HA (2310, 2515), HAT (1800, 1282), p value 0.35]. Conclusion: In patients with septic shock, there is no difference in time to shock reversal comparing individual components of metabolic resuscitation.