Comparative efficacy of Chinese tonic medicines for treating sepsis or septic shock: A systematic review and Bayesian network meta-analysis of randomized controlled trials

Background: Sepsis or septic shock is a life-threatening medical emergency with a poor prognosis and a high economic burden for both individuals and healthcare resources. Evidence suggests that Chinese tonic medicines (CTMs), as adjuvant treatments, are effective in treating this disease. Nevertheless, the ongoing discourse regarding the optimal CTMs persists. This study was conducted to further explore the comparative effectiveness of CTMs for patients with sepsis or septic shock. Methods: We systematically searched Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang database, VIP database from inception to November 15, 2023. Primary outcomes encompassed the delta Sequential Organ Failure Assessment (zSOFA) score at day 7 after interventions and 28-day mortality. Secondary outcomes included delta serum lactate (zLac) and delta mean arterial pressure (zMAP) levels at day 7 after interventions, as well as the duration of vasoactive drug administration. The safety outcome was adverse drug reactions or adverse drug events (ADRs/ADEs). The risk ratio (RR) and mean difference (MD) with a 95 % confidence interval (95 %CI) were selected as effect measures. The Bayesian network meta-analysis was conducted by R version 4.2.2 software. The surface under the cumulative ranking curve (SUCRA) values were used to rank each treatment. The Cochrane Risk of Bias V.2.0 tool was employed to assess the within-study risk of bias. The CINeMA (Confidence in Network Meta-Analysis) web application was utilized to assess the quality of evidence. This protocol was prospectively registered in PROSPERO (CRD4202348572). Results: A total of 45 randomized controlled trials (RCTs) involving 3433 patients were identified in this study. Seven CTMs including Shenfu injection (SF), Shenmai injection (SM), Sini decoction (SN), Shenfu and Shengmai granules (SF+SGM), Shengmai injection (SGM), Yiqifumai injection (YQFM), and Shenqifuzheng injection (SQFZ) were involved. Regarding the z SOFA score, interventions combining SM with Western medicine (WM) (MD,-2.77; 95 %CI,-3.28 to-2.27), YQFM+WM (MD,-1.76; 95 %CI,-2.73 to-0.79), SGM+WM (MD,-1.11; 95 %CI,-1.88 to-0.34), and SF+WM (MD,-0.98; 95 %CI,-1.17 to-0.78) demonstrated superiority over WM alone. According to the SUCRA values, SM+WM (99.28 %) achieved the highest ranking for the z SOFA score. Concerning 28-day mortality, SM+WM (RR, 0.51; 95 %CI, 0.35 to 0.72) and SF+WM (RR, 0.73; 95 %CI, 0.65 to 0.83) exhibited a superior effect in reducing 28-day mortality. Based on the SUCRA values, SM+WM (82.49 %) secured the top ranking for 28-day mortality. Among the secondary outcomes, SM+WM (MD,-2.50; 95 %CI,-4.15 to-0.83; SUCRA, 94.27 %) emerged as the most favorable in reducing serum lactate levels. SF+WM (MD, 10.78; 95 %CI, 3.11 to 18.71; SCURA, 78.3 %) exhibited superior effectiveness compared to other treatments in improving mean arterial pressure (MAP). The certainty of evidence for these outcomes was assessed as low. Conclusion: CTMs combined with WM led to a significant improvement in Delta SOFA score and MAP, as well as a reduction in 28-day mortality and serum lactate levels. SM+WM emerged as the optimal treatment regimen for enhancing Delta SOFA, reducing 28-day mortality, and lowering serum lactate levels. Additionally, SF+WM exhibited superiority in improving MAP. Nevertheless, there is a need for large-scale, multicenter, and direct comparative RCTs to generate higher-quality evidence.