Background and rationale of the study:

·      Sepsis is a life threatening clinical syndrome caused by dysregulated host immune response to infection leading to constellation of physiologic and biochemical abnormalities. Thus, sepsis involves persistent inflammation, immunosuppression and catabolic syndrome.

·      Our observation suggests that there was > 50% mortality witnessed during perioperative management of surgical patients with septic shock. As there is no study comparing the two treatment protocols in perioperative management of surgical patients with septic shock, an intervention to look for the difference and enhance the outcome in surgical patients with septic shock is warranted.

·      From the available literature, there have been no reports of suspected, unexpected, or serious adverse reactions to dose and frequency of intervention drugs to be used in this study.

·      The role of cocktail of Vit-C and hydrocortisone is under investigation. It has been used in cases of medical sepsis.

·      Hypothesis behind use of Vit-C and thiamine in septic shock: The concept that inotrope induced vasoconstriction and lactic acidosis has come under criticism. It is postulated that tissue hypoxia is not the actual cause for excess production of lactic acid, but when excess amount of pyruvate is generated it gets bypassed (from Krebs cycle) to form lactic acid due to lack of vitamins. Secondly, due to infection the receptor (SVCT2) needed for transport of Vit- C is decreased, and the corticosteroids receptor is oxidized by the inflammatory mediators. Therefore, it is observed that giving hydrocortisone increases expression of SVCT2, and Vit-C helps to reverse oxidized corticosteroids receptors.

·      There is no study in the English literature comparing the two treatment protocol [standard treatment plus cocktail of vitamin and hydrocortisone versus standard treatment plus hydrocortisone] in patients with surgical sepsis. However, there are a few articles published in medical journals (Marik PE et al. Chest. 2017 and Fujii T et. Al JAMA. 2020) that involved majority of patients with pulmonary sepsis. [1, 2] In a study published by Marik PE et al. Chest. 2017 it was observed that early administrations of higher doses of vitamin-c and thiamine along with corticosteroids in pulmonary sepsis prevented progression of disease and reduced mortality. On contrary, the vitamins trial (Fujii T et. Al JAMA. 2020) did not reflect similar results that could be due to non-adherence to sepsis protocol. Variations in their outcome could have resulted because of differences in their study design and execution. Hence, there is an on-going debate about role of metabolic resuscitation in medical sepsis.

1. 

     1. Marik PE, Khangoora V, Rivera R, et al. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017; 151(6): 1229-1238.

2. 2.Fujii T, Luethi N, Young PJ, et al. Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial. JAMA. 2020; 323(5): 423-431.