The Safety And Effectiveness Of Vitamin C On Sepsis And Septic Shock:A Systematic Review And Meta-analysis Including Animal And Human

Objective: Sepsis is a disordered inflammatory response caused by the body against infection.Disordered inflammatory response leads to oxidative damage,resulting in life-threatening tissue damage and organ dysfunction.Previous studies suggested that vitamin C(a co-factor and antioxidant)supplement could attenuate inflammation and oxidative damage,and improve the prognosis of sepsis animals/patients.The objective of this meta-analysis was to investigate the safety and effectiveness of parenteral supplement with isolated vitamin C on sepsis and septic shock.Methods: We searched PUBMED,EMbase,CBM,and the Cochrane Central Register of Controlled Trials for RCTs that compared the effect of vitamin C with placebo/blank on outcomes of sepsis and septic shock.The primary outcome was mortality(without time limit).Secondary outcomes were the length of ICU stay,duration of vasopressor support,free days of mechanical ventilation and functional parameters(mean arterial pressure,serum lactate level,liver function and so on).Results: A total of 3 human trials and 13 animal studies were included in this meta-analysis.For human trials,compared with controls,parenteral supplement with vitamin C alone was associated with a decreased need for vasopressor support(SMD,-0.89 days;95% CI,-1.48--0.30,P=0.003),GRADE assessment was moderate quality of evidence;but no difference was found in mortality(RR,0.68;95%CI,0.26-1.78,P=0.43),GRADE assessment showed low quality of evidence;and no effect on length of ICU stay(MD,-1.66days;95% CI,-5.78-2.46,P=0.43),GRADE assessment was moderate quality of evidence.No adverse effects were reported.For animal studies,parenteral supplement with isolated vitamin C was associated with a significant reduction in mortality,including 24 h,48h and 72 h mortality(RR,0.49;95% CI,0.39-0.61,P<0.00001);significant improvement in liver function,including AST(SMD,-1.39;95% CI,-2.7--0.07,P=0.04)and ALT(SMD,-0.82;95% CI,-1.47--0.17,P=0.01).The associated mechanisms of vitamin C in improving outcomes of sepsis includes reduction on epithelial and endothelial damage and enhancement of the endothelial barrier function,improvement of micro-vascular and macro-vascular function,inhibition of oxidative stress,attenuation of the inflammatory response and immunosuppression.Conclusions: The parenteral supplement with isolated vitamin C reduced the duration of vasopressor support in patients with sepsis and septic shock,but had no effect on mortality and length of ICU stay.Despite the lack of clinical evidence,the dramatic reduction of mortality by vitamin C in animal studies indicated a bright future of vitamin C in sepsis and septic shock,so that more randomized controlled trials with high quality are urgent to clarify the clinical value of vitamin C in the future.