Effect of Combined Hydrocortisone, Ascorbic Acid and Thiamine for Patients with Sepsis and Septic Shock: A Systematic Review and Meta-Analysis

Objective: This study aims to assess the effect of HAT therapy on patients with sepsis and septic shock. Methods: We searched PubMed, Embase, and Cochrane Library for studies on HAT therapy published up to November 11, 2020. The primary outcome was the duration of vasopressor use. Secondary outcomes were change of Sequential Organ Failure Assessment (SOFA) score within 72 h; death within intensive care unit (ICU), hospital, and 28 or 30 days; length of stay in ICU and hospital; rate of procalcitonin (PCT) clearance and incidence of adverse events. We also used trial sequential analysis (TSA) to assess the reliability of the available evidence. Results: Six randomized controlled trials (RCTs) and seven observational studies enrolling 1,559 patients were included (762 were treated with HAT, and 797 were treated with hydrocortisone alone, standard care or placebo). HAT therapy was associated with significant reductions in duration of vasopressor use (mean differences [MD], -14.68, [95% CI, -24.28 to -5.08], P = 0.003) in RCTs, but not in observational studies (MD, 11.21 [95% CI, -44.93 to 67.35], P = 0.70). HAT therapy was associated with less organ dysfunction at 72 h both in RCTs (MD, -0.86 [95% CI, -1.32 to -0.40], P < 0.001) and observational studies (MD, -2.65 [95% CI, -5.29 to -0.01], P = 0.05). HAT therapy was associated with lower hospital mortality and higher PCT clearance in observational studies. Similar results for the primary outcome were found in the sensitivity analysis. TSA results suggested more trials to reach the required information size. Conclusion: Among patients with sepsis and septic shock, a combination therapy of hydrocortisone, ascorbic acid, and thiamine, compared with placebo, could reduce the duration of vasopressor use and SOFA scores during the first 72 h.