Background The objective of this study was to evaluate the clinical efficacy of thiamine and vitamin C with or without hydrocortisone coadministration on the treatment of sepsis and septic shock. Methods MEDLINE, EMBASE and CENTRAL databases were searched for randomized controlled trials (RCTs) that made a comparative study between the combination therapy of vitamin C and thiamine with or without hydrocortisone and the administration of placebo in patients with sepsis or septic shock. Two reviewers independently performed study selection, data extraction and quality assessment. Both short-term mortality and change in the sequential organ failure assessment (SOFA) score from baseline (delta SOFA) were set as the primary outcomes. Secondary endpoints included intensive care unit (ICU) mortality, new onset of acute kidney injury, total adverse events, ICU and hospital length of stay, duration of vasopressor usage and ventilator-free days. Meanwhile, trial sequential analysis was conducted for primary outcomes. Results Eight RCTs with 1428 patients were included in the current study. The results showed no significant reduction of short-term mortality in sepsis and septic shock patients who received combination therapy of vitamin C and thiamine with or without hydrocortisone compared to those with placebo {risk ratio (RR), 1.02 [95% confidence interval (CI), 0.87 to 1.20], p = 0.81, I2 = 0%; risk difference (RD), 0 [95% CI, −0.04 to 0.05]}. Nevertheless, the combination therapy was associated with significant reduction in SOFA score [mean difference (MD), −0.63, (95% CI, −0.96 to −0.29, p < 0.001, I2 = 0%] and vasopressors duration (MD, −22.11 [95% CI, −30.46 to −13.77], p < 0.001, I2 = 6%). Additionally, there were no statistical differences in the pooled estimate for other outcomes. Conclusions In the current meta-analysis, the combination therapy of vitamin C and thiamine, with or without hydrocortisone had no impact on short-term mortality when compared with placebo, but was associated with significant reduction in SOFA score among patients with sepsis and septic shock.

中文翻译：

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硫胺素、维生素 C 和氢化可的松联合治疗脓毒症和感染性休克患者：一项荟萃分析和试验序贯分析

背景 本研究的目的是评估硫胺素和维生素 C 联合或不联合氢化可的松治疗脓毒症和感染性休克的临床疗效。方法检索 MEDLINE、EMBASE 和 CENTRAL 数据库中的随机对照试验 (RCT)，这些试验在败血症或感染性休克患者中对维生素 C 和硫胺素联合或不联合氢化可的松与安慰剂给药进行了比较研究。两名评价员独立进行研究选择、数据提取和质量评估。短期死亡率和序贯器官衰竭评估（SOFA）评分相对于基线（delta SOFA）的变化被设定为主要结果。次要终点包括重症监护病房 (ICU) 死亡率、新发急性肾损伤、总不良事件、ICU 和住院时间、血管加压药使用时间和无呼吸机天数。同时，对主要结局进行了试验序贯分析。结果 本研究纳入了 8 项 RCT，共 1428 名患者。结果显示，与安慰剂组相比，接受维生素 C 和硫胺素联合或不联合氢化可的松治疗的败血症和感染性休克患者的短期死亡率没有显着降低{风险比 (RR)，1.02 [95% 置信区间 (CI) ), 0.87 至 1.20], p = 0.81, I2 = 0%; 风险差 (RD)，0 [95% CI，-0.04 至 0.05]}。然而，联合治疗与 SOFA 评分 [平均差 (MD), -0.63, (95% CI, -0.96 to -0.29, p < 0.001, I2 = 0%] 和血管加压药持续时间 (MD, -22.11 [95% CI，-30.46 至 -13.77]，p < 0.001，I2 = 6%）。此外，其他结果的汇总估计值没有统计学差异。结论 在目前的荟萃分析中，与安慰剂相比，维生素 C 和硫胺素联合治疗（加或不加氢化可的松）对短期死亡率没有影响，但与脓毒症和感染性休克患者的 SOFA 评分显着降低有关.