Saghafi Fatemeh, Moghadam Zahra Boostani, Salehi-Abargouei Amin, Beigrezaei Sara, Sohrevardi Seyed Mojtaba, Jamialahmadi Tannaz, Sahebnasagh Adeleh, Sahebkar Amirhossein
Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Pharmaceutical Sciences Research Center, School of Pharmacy, Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Curr Med Chem. 2025;32(16):3258-3282. doi: 10.2174/0109298673245464231121094448.
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.
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.
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 (Δ-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).
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.
本系统评价和荟萃分析旨在确定氢化可的松、维生素C（抗坏血酸）和硫胺素联合治疗（HAT疗法）是否能降低死亡率，以及是否能有效加速脓毒症和脓毒性休克的缓解。
检索了PubMed、Scopus、ISI Web of Science和谷歌学术等数据库，直至2021年3月，以查找该领域的所有现有文献。还启动了所有数据库的自动提醒功能，以更新我们的搜索。分别对临床试验和队列进行荟萃分析，以及对所有汇总人群进行荟萃分析。
本研究评估了9项临床试验（1358名参与者）和9个队列（339437名参与者），是该领域最全面的系统评价。我们的荟萃分析结果显示，在72小时内，脓毒症相关器官功能衰竭评估（SOFA）评分变化（Δ-SOFA）的降低存在显著差异（标准均数差（SMD）=-0.429；95%可信区间：-0.737，0.120；p=0.006），血管活性药物（VP）使用时间（SMD=-0.373；95%可信区间：-0.619，-0.128；p=0.003），以及降钙素原（PCT）清除率（SMD=0.496；95%可信区间：0.061，0.931%；p=0.026）。考虑到队列研究结果，HAT疗法对重症监护病房（ICU）患者的生存有效（比值比（OR）=0.641；95%可信区间：0.423-0.970，p=0.035）。然而，干预组和对照组在医院死亡率（比值比（OR）=0.811，95%可信区间：0.544-1.209，p=0.304）、28至30天死亡率（OR=1.000；95%可信区间：0.782-1.279，p=0.998）、需要肾脏替代治疗的新发急性肾损伤（（OR=0.856，95%可信区间：0.526，1.391；p=0.529）、住院时间（LOS）（SMD=0.090；95%可信区间：-0.036，0.216天；p=0.162）、ICU住院时间（SMD=0.016，95%可信区间：-0.138，0.170天；p=0.838）和无机械通气天数（SMD=0.004；95%可信区间：-0.154，0.163天；p=0.956）方面未观察到显著差异。
对脓毒症和脓毒性休克患者补充HAT疗法对72小时内的SOFA评分、外源性血管活性药物输注时间和降钙素原清除率有显著有益影响。考虑到队列研究结果，补充HAT可有效降低ICU死亡率。
