The Outcome of IV Vitamin C Therapy in Patients with Sepsis or Septic Shock: A Meta-Analysis of Randomized Controlled Trials

Abstract

Background: To update a meta-analysis of randomized controlled trials (RCTs) and further explore the outcome of IV vitamin C (IVVC) administration in sepsis or septic shock patients. Methods: This study is a meta-analysis of RCTs. The RCTs of vitamin C therapy in sepsis were searched in PubMed, EMBASE and Clinical Trials.gov since August 16, 2022. We registered the protocol with PROSPERO (CRD42022354875). The primary outcome was mortality included 28-day, 30-day, or in hospital mortality. Two reviewers independently assessed RCTs according to eligibility criteria: 1) Study type: RCT; 2) patient population: patients ≥18 years with sepsis or septic shock; 3) intervention: IVVC at any doses as monotherapy or combined with thiamine or and hydrocortisone compared with standard of care, no intervention, or placebo (defined as control group) ; 4) the RCT described primary outcome. Then, two authors independently extracted related information from RCTs. Results: Eighteen RCTs (n=2980 patients) were identified in this meta-analysis. Treatment with IVVC was not shown to improve mortality (odds ratio,0.87; 95% CI, 0.75–1.02; p=0.09; I2=44%) regardless of different dose or type of therapy, whereas there was significant effects in duration of vasopressor use (MD, –15.31; 95% CI, –21.92 to –8.69; p<0.00001; I2 =59%) and change in the Sequential Organ Failure Assessment (SOFA) score from baseline to 72–96 hours (MD, –0.64; 95% CI, –1.15 to –0.13; p=0.01; I2=65%), and was relatively safe in sepsis or septic shock patients (OR, 1.22; 95% CI, 0.98–1.51; p=0.08; I2=40%). Conclusion: In this meta-analysis, IVVC in sepsis or septic shock patients was relatively safe and significantly shorten the duration of vasopressor use and improved the change of SOFA score, whereas it was not associated with reduction in mortality.