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Daniel Black

Daniel Black

Department of Medicine, Austin Hospital, Australia

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

Biography

Biography: Daniel Black

Abstract

Background: Sepsis has high mortality. Remote-ischaemic-conditioning (RIC) lowers sepsis-associated mortality. The complex biology of RIC includes regulation of mitochondrial function and prevention of metabolic collaspe. Vitamin-C and thiamine can mimic aspects of RIC and preserve mitochondrial function. Study-aim was to describe the effect-sizes of vitamin-C and thiamine suppressing mortality amongst patients in critical care with presumed sepsis.

Methods: Controlled-trials investigating the effect of vitamin-C or thiamine on mortality of patients with presumed sepsis were identified. Meta-analysis of the mortality-data was performed using Comprehensive Meta-Analysis software to generate Hedges's g scores. Publication-bias was assessed using the Begg-Mazumdar-rank-correlation-scores (BMRCS). Hedges's g scores were transformed into Numbers-Needed-to-Treat (NNT) with Psychometria software. 

Results: Fourteen-studies compared vitamin-C on 3256 patients in comparison to 3076 control patients. A significant treatment-effect of vitamin-C was observed: Hedges's g=0.268 (95% CI 0.069-0.468), p=0.008, I2=59.475. The risk of publication-bias was considered non-significant: BMRCS =-0.18382, p=0.30310. Conversion of the Hedges's g to NNT=6.653. Eight studies compared thiamine on 389 patients in comparison to 642 control patients. A significant treatment effect of thiamine was observed: Hedges's g=0.452 (95% CI 0.080 to 0.824), p=0.017, I2=58.129. The risk of publication bias was considered non-significant: BMRCS =-0.19444, p=0.4655. Conversion of the Hedges's g to NNT=3.988.

Discussion: Vitamin-C and thiamine were associated with significant treatment effects suppressing mortality amongst patients with presumed sepsis. Within an investigational paradigm both vitamin-C and thiamine are adjunctive treatments for sepsis and prevention of patient deterioration. Understanding how these treatments regulate mitochondrial function may in part explain heterogeneity of patient outcomes.