Abstract

Background This systematic review and meta-analysis aimed to determine whether the combination of hydrocortisone, vitamin C (ascorbic acid), and thiamine (HAT therapy) diminishes the mortality and is effective in expediting the resolution of sepsis and septic shock or not.Methods The following databases of PubMed, Scopus, ISI Web of Science, and Google Scholar were explored until March 2021 for all existing literature related to this field. An automatic alert for all databases was also activated to update our search. Meta-analysis was performed on clinical trials and cohorts separately as well as on all the pooled populations.Results This study evaluated nine clinical trials (1358 participants) and nine cohorts (339,437 participants) and is the most comprehensive systematic review in this field. The results of our meta-analysis demonstrated a significant difference in the reduction of Sepsis-Related Organ Failure Assessment (SOFA) score changes (Delta-SOFA) over 72 h (Standard Mean Difference (SMD) = -0.429; 95 CI: -0.737, 0.120; p = 0.006), duration of vasopressor (VP) (SMD = -0.373; 95 CI: -0.619, -0.128; p = 0.003), and procalcitonin (PCT) clearance (SMD = 0.496; 95 CI: 0.061, 0.931; p = 0.026). Considering the results of cohorts, HAT therapy was effective in the survival of intensive care units (ICUs) patients (OR = 0.641; 95 CI: 0.423-0.970, p = 0.035). However, no significant difference was observed between the intervention and control groups in hospital mortality (Odds Ratio (OR) = 0.811, 95 CI: 0.544-1.209, p = 0.304), 28- to 30-day mortality (OR = 1.000; 95 CI: 0.782-1.279, p = 0.998), new onset acute kidney injury requiring renal replacement therapy ((OR = 0.856, 95 CI: 0.526, 1.391; p = 0.529), in-hospital length of stay (LOS) (SMD = 0.090; 95 CI: -0.036, 0.216 days; p = 0.162), LOS in ICU (SMD = 0.016, 95 CI: -0.138, 0.170 days; p = 0.838), and mechanical ventilation-free days (SMD = 0.004; 95 CI: -0.154, 0.163 days; p = 0.956).Conclusion Supplementation of septic and septic shock patients with HAT therapy has significant beneficial effects on SOFA score over 72 hours, duration of exogenous vasopressor infusion and procalcitonin clearance. Considering the results of cohort studies, supplementation with HAT is efficacious in reducing ICU mortality.