Author:
Deng Jiawen,Zuo Qi Kang,Venugopal Kaden,Hung Jay,Zubair Areeba,Blais Sara,Porter Victoria,Moskalyk Myron,Heybati Kiyan
Abstract
<b><i>Introduction:</i></b> This systematic review aimed to assess the efficacy and safety of hydrocortisone, ascorbic acid, and thiamine (HAT) combination therapy in patients with sepsis and septic shock. <b><i>Methods:</i></b> We conducted a database search in MEDLINE, Embase, CENTRAL, Web of Science, and CNKI for randomised controlled trials (RCTs) comparing HAT against placebo/standard of care or against hydrocortisone in sepsis/septic shock patients. Outcomes included mortality, ICU/hospital length of stay (LOS), vasopressor durations, mechanical ventilation durations, change in SOFA at 72 h, and adverse events. RCT results were pooled in random-effects meta-analyses. Quality of evidence was assessed using GRADE. <b><i>Results:</i></b> Fifteen RCTs (<i>N</i> = 2,594) were included. At 72 h, HAT reduced SOFA scores from baseline (mean difference [MD] −1.16, 95% confidence interval [CI]: −1.58 to −0.74, <i>I</i><sup>2</sup> = 0%) compared to placebo/SoC, based on moderate quality of evidence. HAT also reduced the duration of vasopressor use (MD −18.80 h, 95% CI: −23.67 to −13.93, <i>I</i><sup>2</sup> = 64%) compared to placebo/SoC, based on moderate quality of evidence. HAT increased hospital LOS (MD 2.05 days, 95% CI: 0.15–3.95, <i>I</i><sup>2</sup> = 57%) compared to placebo/SoC, based on very low quality of evidence. HAT did not increase incidence of adverse events compared to placebo/SoC. <b><i>Conclusions:</i></b> HAT appears beneficial in reducing vasopressor use and improving organ function in sepsis/septic shock patients. However, its advantages over hydrocortisone alone remain unclear. Future research should use hydrocortisone comparators and distinguish between sepsis-specific and comorbidity- or care-withdrawal-related mortality.