Efficacy and safety of Shenfu injection for septic shock: A systematic review and meta-analysis of randomized controlled trials.

Objective: To evaluate the efficacy and safety of Shenfu injection (SFI) combined with standard therapy versus standard therapy for septic shock, three groups of patients with septic shock were analyzed based on the level of mean arterial lactate. They were mean arterial lactate level < 4.5 mmol/L, 4.5 mmol/L ≤ mean arterial lactate level < 7 mmol/L and mean arterial lactate level ≥ 7 mmol/L.

Methods: Randomized controlled trials (RCT) from PubMed, Cochrane library, Embase, CENTRAL, SinoMed, Wanfang, CNKI, and Weipu (VIP) databases from the inception to September 2018 were searched. Relative risks (RR), weighted mean difference (WMD), along with 95% confidence interval (95%CI) were used to analyze the main outcomes. Statistical analysis was performed using Rev.Man 5.3. The qualities of the involved studies were accessed by the ROB according to the Cochrane handbook.

Results: 19 randomized controlled trials with 1505 participants were included. Compared with standard therapy, SFI plus standard therapy cannot decrease the 28-day mortality for all of the three groups. Compared with the other two subgroups (mean arterial lactate level < 4.5 mmol/L and mean arterial lactate level ≥ 7 mmol/L), the 4.5 mmol/L ≤ mean arterial lactate level < 7 mmol/L group has a trend to decrease 28-day mortality (RR: 0.67; 95% CI: 0.38-1.19; P = 0.17). In addition, adding SFI could have further increased mean arterial pressure (MAP) at 6-hours (RR: 7.05; 95% CI: 4.14-9.97) and further normalized heart rate (HR) when compared with standard therapy (RR: -17.48; 95% CI: [-19.39-(-15.57)].

Conclusion: For septic shock patients with 4.5 mmol/L ≤ mean arterial lactate level < 7 mmol/L, when the Traditional Chinese Medicine syndrome meet Yang-Qi deficiency, clinicians could choose SFI as a supplementary drug. But further high-quality and large-scale RCT should be performed to verify it.

Prospero Registration Number: CRD42018090320.