Paul E. Marik, MD, FCCP, FCCM

Chief, Pulmonary and Critical Care Medicine,
Department of Internal Medicine
Eastern Virginia Medical School, Norfolk, VA

 image of Dr. Paul Marik

Abstract: A large body of experimental data has demonstrated that both corticosteroids and intravenous vitamin C reduce activation of nuclear factor κB (NF-κB) attenuating the release of pro-inflammatory mediators, reduce the endothelial injury characteristic of sepsis thereby reducing endothelial permeability and improving microcirculatory flow, augment the release of endogenous catecholamine’s and enhance vasopressor responsiveness. In animal models these effects have resulted in reduced organ injury and increased survival. Corticosteroids have been evaluated in several clinical trials, with meta-analysis of these trials demonstrating somewhat conflicting outcomes. Low-dose stress corticosteroids have proven to be safe with no increased risk of clinically important complications. While corticosteroids decrease vasopressor dependency the effect on the risk of developing organ failure and survival is less clear. Similarly intravenous Vitamin C has been evaluated in unselected surgical ICU patients, patients with burns those with pancreatitis and in two pilot studies of patients with severe sepsis and septic shock [1]. In general these studies have demonstrated a reduction in the risk of multisystem organ failure (MSOF) although the effect on mortality is less clear. However, IV vitamin C was shown to be extremely safe with no recorded complications.

In vitro data has suggested that vitamin C and hydrocortisone may act synergistically. Barabutis et al. have demonstrated that hydrocortisone together with vitamin C protects the vascular endothelium from damage by endotoxin while neither agent alone had this effect [2]. Based on these clinical and experimental data we initiated a treatment protocol for patients with severe sepsis and septic shock that included intravenous vitamin C, hydrocortisone and thiamine. We have demonstrated that this therapeutic cocktail reverses the organ dysfunction of sepsis with a marked reduction in mortality [3].

References:

1. Fowler AA, Syed AA, Knowlson S et al. Phase 1 safety trial of intravenous ascorbic acid in patientswith severe sepsis. J Transl Med 2014; 12:32.
2. Barabutis N, Khangoora V, Marik PE et al. Hydrocortisone and Ascorbic Acid synergistically protectagainst LPS-induced pulmonary endothelial barrier dysfunction. Chest 2017; In press.
3. Marik PE, Khangoora V, Rivera R et al. Hydrocortisone, Vitamin C and Thiamine for the treatment ofsevere sepsis and septic shock: A retrospective before-after study. Chest 2017; 151:1229-38.