HYDROCORTISONE COMBINED WITH VITAMIN C AND THIAMINE IN THE TREATMENT OF SEPSIS/SEPTIC SHOCK: A SYSTEMATIC REVIEW WITH META-ANALYSIS AND TRIAL SEQUENTIAL ANALYSIS

Background: This study explored the efficacy of hydrocortisone combined with vitamin C and thiamine (HVT) in the treatment of sepsis/septic shock. Methods: PubMed, EMBASE and Web of Science were searched (establishment of the database to October 31, 2022). The meta-analysis included randomized controlled trials (RCTs); comparing the efficacy of HVT regimen and placebo in the treatment of sepsis/septic shock. The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias. The Review Manager 5.4 software was used for meta-analysis, and the relative risk (RR), mean difference (MD) and 95% confidence intervals (CI) were then determined. Trial sequential analysis (TSA) was then conducted. Results: Eight RCTs with 1,572 patients were identified. Meta-analysis showed that HVT regimen did not reduce all-cause (RR=0.96, 95% CI: 0.83 - 1.11, P=0.60), hospital (RR=1.03, 95% CI: 0.83 - 1.27, P=0.80) or intensive care unit (ICU) mortalities (RR=1.05, 95% CI: 0.86 - 1.28, P=0.65). Furthermore, there was no significant difference in the change of sequential organ failure assessment score, length of ICU stay, length of hospital stay, duration of the use of vasopressors, incidence of acute kidney injury and ventilator-free days between HVT and control groups. TSA showed that more trials are needed to confirm the results. Conclusions: HVT regimen did not reduce the mortality of patients with sepsis/septic shock and was not associated with a significant improvement in outcomes. The TSA result showed that more RCTs with high quality and large sample sizes are needed to further confirm the results.