Outcomes of Septic Shock Patients Treated With a Metabolic Resuscitation Bundle Consisting of Intravenous Hydrocortisone, Ascorbic Acid and Thiamine.

Overview

This is a retrospective chart review that will measure the impact on outcomes in septic shock patients who were resuscitated with a novel combination of medicines called iHAT (intravenous hydrocortisone -ascorbic acid-thiamine). Septic shock patients treated with this combination of drugs over the past two years will be compared with similar, concurrent septic shock patients who were not treated with this drug given that adoption of this therapy has been variable.

The condition of septic shock and multi-organ failure directly results from the rapid consumption of ascorbic acid stores in humans suffering an infection (research in septic patients have demonstrated near uniform deficiency/depletion of ascorbic acid on presentation to ICU's). This rapidly acquired ascorbic acid deficiency leads to shock and multi-organ failure due to the fact that ascorbic acid is required for humans to produce endogenous vasopressors (hormones that regulate blood pressure) as well as to maintain the function and integrity of the endothelium-the endothelium is the largest organ in the body and is critical in regulating blood pressure and preventing fluid leakage into all organs of the body, a pervasive dysfunction which underlies "multi-organ failure". Oral administration of ascorbic acid, even in high doses, has limited bioavailability (transporter mechanisms in the intestines are limited) and does not lead to appreciable correction of the deficiency, neither in the short term, nor in the critically ill. In contrast, intravenous administration, in high doses, rapidly achieves not only normal levels, but even supranormal levels.This critical need for intravenous supplementation to treat septic shock was first argued for in 2006 by the European Respiratory Society's "Consensus Committee on Intravenous (Parenteral) Vitamin C" a committee comprised of scientists, researchers, and clinicians studying the role ascorbic acid in sepsis/shock models from all over the world. This was followed by two randomized controlled trials in 2014 showing high efficacy of intravenous ascorbic acid in preventing death in septic shock patients. In 2016, a highly publicized historical control trial further demonstrated a large reduction in vasopressor duration, mortality and renal replacement therapy in a cohort of patients after aggressively correcting ascorbic acid deficiency via the intravenous route showing that multi organ failure and death is immediately prevented in almost all patients. More recently, he has published a study demonstrating the synergistic effects of pairing ascorbic acid with hydrocortisone--endothelial barriers are restored to a greater extent than either agent alone. Lastly, two trials in the past two years have shown that intravenous thiamine, when systematically provided to the critically ill, independently leads to reduced mortality. Thus, HAT therapy appears to be of high utility in preventing death and multi-organ failure in septic shock. Beyond the above mentioned small, single center observational and randomized controlled trials, no other outcome studies have been done in septic shock patients.