Hydrocortisone,vitamin C,and thiamine may not improve the outcome of patients with sepsis or septic shock:a systematic review and meta-analysis

Background:This study aimed to conduct a systematic review and meta-analysis of the efficacy of hydrocortisone,vitamin C,and thiamine（HVT） in patients with sepsis or septic shock.Methods:A literature search was performed in PubMed,Embase,Cochrane Library,and Web of Science from their inception to April2021.Search terms included hydrocortisone,thiamine,vitamin C,sepsis,and septic shock.Only randomized controlled trials on HVT in treating sepsis and septic shock were analyzed.Risk ratio（RR） was generated using Review Manager 5.3 to evaluate binary variants,whereas mean ± standard deviation（MD） was generated to assess continuous variants.Results:A total of 7 randomized controlled trials,with 1233 patients,were included in this meta-analysis.There was no significant difference in long-term mortality（35.3% vs 33.2 %;RR:1.07;95% confidence interval [95 % CI]:0.90-1.27;P=0.45;I2=0%）,intensive care unit（ICU） mortality（17.4% vs 17.5%;RR:0.99;95% CI:0.75-1.30;P=0.95;I2=0%）,in-hospital mortality（27.4% vs 25.8%;RR:1.06;95% CI:0.84-1.34;P=0.63;I2=0%）,and acute kidney injury morbidity（RR:1.04;95% CI:0.91-1.18;P=0.60;I2=0%） between HVT and control groups.For continuous variables,there was no significant effect of HVT therapy on delta Sequential Organ Failure Assessment（△SOFA） score（MD:-0.44;95% CI:-1.00 to 0.12;P=0.12;I2=49%）,length of ICU stay（MD:0.43;95% CI:-0.27 to 1.14;P=0.23;I2=0%）,and length of hospital stay（MD:0.80;95% CI:-0.38 to 1.97;P=0.18;I2=0%）.Only vasopressor duration was significantly reduced in the HVT group（MD:-17.75;95% CI:-25.56 to-9.94;P <0.00001;I2=38%）.Vasopressor duration refers to the time to shock reversal.Alternatively,it is the amount of time（in hours） required for patients to withdraw all vasoactive medication support.Neither HVT nor control △SOFA reached statistical significance.Conclusion:Hydrocortisone,vitamin C,and thiamine use was not associated with improved mortality,lower acute kidney injury incidence,lower △SOFA,and shorter ICU and in-hospital stays among patients with sepsis and septic shock.However,the use of vasopressors decreased significantly.Further direct head-to-head studies are needed.