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Dear Editor, Previous studies demonstrated that a combination of hydrocortisone, vitamin C, and thiamine (HVT) is a promising adjuvant treatment for sepsis and septic shock, with decreased mortality and improved resolution of disease [1]. However, recently published prospective, randomized controlled trials (RCTs) did not support this finding [2]. Therefore, we performed a meta-analysis to evaluate the efficacy of HVT treatment for patients with sepsis or septic shock. This meta-analysis was performed strictly following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement [3]. The primary outcomes were mortality, decrease of sequential organ failure assessment score from baseline (Delt SOFA), and time of vasopressors use. Relative risk (RR) with 95% confidence intervals (CIs) and weighted mean differences (WMDs) with 95% CIs were used. Meta-analyses were performed using a random-effects model by RevMan version 5.1. Four RCTs with 528 patients and five cohorts involving 412 patients were included, as described in Table 1. As shown in Fig. 1, pooled results from RCTs showed that HVT has no benefit on mortality (RR 0.92, 95%CI 0.69 to 1.24, p = 0.59; I = 0%, PH = 0.69), while it was associated with a significant decrease of SOFA (Delt SOFA: WMD − 1.02, 95%CI − 1.31 to − 0.73, p < 0.001; I = 0%, PH = 0.80) and reduction in time of vasopressors use (WMD − 21.77 h, 95%CI − 29.26 to − 14.29, p < 0.001; I = 0%, PH = 0.4). Overall results from cohorts revealed that HVT could significantly reduce mortality (RR0.46, 95%CI 0.25 to 0.86, p = 0.01; I = 75%, PH = 0.001) and SOFA score (Delt SOFA: WMD − 2.21, 95%CI − 4.22 to − 0.20, p = 0.03; I = 81%, PH = 0.005), but not the duration of vasopressors use (WMD 1.11 h, 95%CI − 59.60 to 61.82, p = 0.97; I = 98%, PH < 0.001). No differences in intensive care unit (ICU) length of stay and hospital length of stay between the HVT and the control group were observed. Our study suggested that HVT has potential beneficial effects. A significant reduction in SOFA score was observed, although no benefit of mortality in the pooled effect of RCTs. Since it is a valuable end-point reflecting the disease process and also a surrogate marker for mortality, our meta-analysis of the four small RCTs might be inadequate to detect a mortality benefit. Additionally, the improved resolution of shock from RCTs also supports HVT use. A generally recognized concept is that the HVT could synergistically restore the dysregulated immune system, oxidative mitochondrial function, and energy production [4]. However, current clinical practice regarding the HVT strategy is still debating. Besides the potential synergistic beneficial effects, the arguments supporting the use of HVT include low risk, low cost, and easy availability. Minor clinical side effects, such as hyperglycemia, hypertension, and hypernatremia induced by hydrocortisone [5], might occur but are insignificant and easily managed in ICU.

Benefit of hydrocortisone, thiamine, and vitamin C for patients with sepsis or septic shock? Too early to draw conclusions