Vitamin-C and thiamine have powerful experimental treatment effects suppressing mortality in critical care: implications for preventing patient deterioration in sepsis

Dr Simon Black1, Dr Daniel Black2,3
1Emergency Department,  Sunshine Hospital, Western Health, St Albans, Australia, 2The Northern Hospital, Northern Health, Epping, Australia, 3Austin Hospital, Heidelberg, Australia

Introduction: Patient deterioration associated with sepsis remains a major burden, with mortality of 25%. Sepsis biology includes an initial hypermetabolic state followed by a hypometabolic collapse. Recently remote ischemic conditioning (RIC) was demonstrated to prevent sepsis-associated mortality. The biology of conditioning includes regulating mitochondrial function and preventing metabolic collapse. Vitamin-C and thiamine can mimic RIC and prevent mitochondrial failure.
Aim: The purpose of this study was to describe the effect sizes of vitamin-C and thiamine suppressing mortality amongst patients in critical care with presumed sepsis.
Method: A systematic-like review was undertaken to identify controlled trials investigating the effect of vitamin-C or thiamine on mortality in critical care. Results: Fourteen studies with 17 comparisons  were identified that investigated the impact of vitamin-C on 3256 patients in comparison to 3076 control patients with presumed sepsis. A significant treatment effect of vitamin-C was observed: Hedge’s g=0.268 (95% CI 0.069-0.468), z = 2.640, p=0.008, I²=59.475. The risk of publication bias was considered non-significant according to the Begg and Mazumdar rank correlation score of -0.18382, z = 1.02982, p = 0.30310. Eight studies with nine comparisons of the effect of thiamine on 389 septic patients compared with 642 control patients with potential for sepsis were identified.  A significant treatment effect of thiamine was observed: Hedge’s g = 0.452 (95% CI 0.080-0.824), z = 2.379, p=0.017, I² = 58.129. The risk of publication bias was considered non-significant according to the Begg and Mazumdar rank correlation score of -0.19444, z = 0.72980, p = 0.4655.
Discussion: The treatment effects of vitamin-C and thiamine for suppressing sepsis-related mortality were relatively homogeneous and clinically-significant. Numbers Need to Treat (NNT) translated from the treatment effects was 6.653 for Vitamin-C and 3.988 for thiamine. Vitamin-C and thiamine should be considered a potential adjunctive treatment for sepsis and prevention of patient deterioration.

Simon is a Registered Nurse with many years of experience in Neonatal Intensive (RWH, RBWH) and Adult-Paediatric Emergency Care (Footscray, THN, Sunshine Hospital). His formal qualifications include Dip App Sci (Nursing) (Deakin), Neonatal Nursing Certificate (La Trobe), and Dip Advance Nursing (Emergency) (University of Melbourne), BSc (Hons) (La Trobe) and PhD (Monash). His science-based studies in Australia and Germany involved understanding the mechanisms of cellular memory (gene duplication and deletion), cellular and tissue responses to metabolic perturbations with an in vitro human placental explant model, and how the conditioning mechanism influences cellular and tissue resilience. Simon has translated his perspective of conditioning-mediated influences into clinical science through meta-analytical methods investigating of the impact of tight-glycaemic control, remote-ischaemic conditioning and pharmacologic induction of conditioning on patient outcomes, and is engaging a contemporary working hypothesis that promoting conditioning is key for preventing patient deterioration.