Outcomes of Septic Shock Patients Treated With a Metabolic Resuscitation Bundle Consisting of Intravenous Hydrocortisone, Ascorbic Acid and Thiamine.
Condition: Septic Shock; Ascorbic Acid Deficiency
MeSH terms: Shock, Septic; Ascorbic Acid Deficiency; Shock
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Intravenous Ascorbic Acid
Intervention type(s): Drug
Intervention description(s): 1.5 grams IV ascorbic acid q6h, 50 mg IV hydrocortisone q 6 hours, and 200mg IV thiamine BID administered (as documented in medical record)
Other intervention name(s): Metabolic Resuscitation; HAT therapy
Intervention MeSH terms: Ascorbic Acid
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Patients admitted to the ICU to the medical critical care service with a diagnosis of
        septic shock
      
Keywords: ascorbic acid; septic shock; severe sepsis