Day :
Keynote Forum
Daniel Black
Department of Medicine, Austin Hospital, Australia
Keynote: Vitamin-C and thiamine have powerful experimental treatment effects suppressing mortality in critical care: Implications for preventing patient deterioration in sepsis
Time : 11:30AM
Biography:
Daniel Black completed his MBBS in 2012 from Queensland University and his Basic Physican Training in 2017 at Western Health, Melbourne, Australia. Daniel has an interest in understanding the basic mechanisms of patient deterioration. Daniel also has a focus on identifying sustainable and cost effective approaches to monitoring for and preventing patient deterioration. While well aware of the power of the RCT, Daniel is concerned that delays in implementing safe and effective therapies because of the lack of RCT data may be counter productive; and that the scope of clinical research may be constrained by the focus on the RCT.
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.