Efficacy and safety of Xuebijing injection (a Chinese patent) for sepsis: A meta-analysis of randomized controlled trials.

J Ethnopharmacol. 2018 Oct 5;224:512-521. doi: 10.1016/j.jep.2018.05.043. Epub 2018 Jun 1. Li C1, Wang P2, Zhang L3, Li M4, Lei X5, Liu S6, Feng Z7, Yao Y8, Chang B9, Liu B10, Shang H11. Author information 1 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing 100700, China. Electronic address: lichengyu@bucm.edu.cn. 2 Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China. Electronic address: 714235528@qq.com. 3 Clinical Pharmacology Department, Second Affiliated Hospital of Tianjin University of TCM, 816 Zhenli Road, Hebei District, Tianjin 300150, China. Electronic address: 280495132@qq.com. 4 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Haiyuncang Lane, Dongcheng District, Beijing 100700, China. Electronic address: limin9030@163.com. 5 Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China. Electronic address: lei_xiang@foxmail.com. 6 Tianjin Chase Sun Pharmaceutical Co. LTD, 20 Quanfa Road, Tianjin Wuqing Development Area, Tianjin 300170, China. Electronic address: liusi002@163.com. 7 Tianjin Chase Sun Pharmaceutical Co. LTD, 20 Quanfa Road, Tianjin Wuqing Development Area, Tianjin 300170, China. Electronic address: janefzq@126.com. 8 The First Hospital Affiliated to the PLA General Hospital, 51 Bucheng Road, Haidian District, Beijing 100048, China. Electronic address: c_ff@sina.com. 9 Metabolic Diseases Hospital, Tianjin Medical University, 66 Tongan Road, Heping District, Tianjin 300070, China. Electronic address: changbai1972@126.com. 10 The General Hospital, Tianjin Medical University, Anshan Road, Heping District, Tianjin 300070, China. Electronic address: 910894750@qq.com. 11 Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China. Electronic address: shanghongcai@foxmail.com. Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Xuebijing injection (XBJ), a Chinese patent medicine that was approved for treating sepsis in China in 2004, consists of Carthamus tinctorius L. (Carthami Flos, hong hua), Paeonia lactiflora Pall. (Paeoniae Radix Rubra, chi shao), Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma, chuan xiong), Salvia miltiorrhiza Bge. (Salviae Miltiorrhizae Radix Et Rhizoma, dan shen) and Angelica sinensis (Oliv.) Diels (Angelicae Sinensis Radix, dang gui). AIM OF THE STUDY: This study aimed to assess the efficacy and safety of XBJ combined with routine treatment (RT) for treating sepsis through systematic review and meta-analysis. MATERIALS AND METHODS: Databases including Embase, PubMed, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP) and the Wanfang database were searched from inception to June 6, 2017 to collect relevant RCTs comparing XBJ combined with RT and RT alone for sepsis. The primary clinical outcomes were 28-day mortality and mortality during treatment. The secondary outcomes of our study included APACHE Ⅱ scores, WBC counts, body temperature, and adverse events or reactions. We excluded low-quality studies (Jadad score < 3) and calculated risk ratios (RR) for primary outcomes with fixed effects models. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. RESULTS: We identified 1602 records, and 16 RCTs (1144 patients) were included. Moderate-quality evidence suggested that combined therapy reduced 28-day mortality (934/1144, RR 0.62, 95% CI 0.51-0.76 P < 0.000 01, I2 = 0%), APACHE Ⅱ scores (792/1144, MD -3.53, 95% CI -4.49 to -2.54; P < 0.000 01, I2 = 59%) and body temperature (362/1144, MD -0.43, 95% CI -0.55 to -0.31; P < 0.000 01, I2 = 0%). Very low-quality evidence showed that WBC count improved with combined medication at high dosages (one study included, 40/1144, MD -8.00, 95% CI -10.18 to -5.82), but there was no reduction at moderate dosages (230/1144, MD -2.38, 95% CI -5.01 to 0.25; P = 0.08, I2 = 70%). However, moderate-quality evidence indicated positive results with low dosages (142/1144, MD -2.88, 95% CI -3.79 to -1.96; P < 0.000 01, I2 = 0%). Nevertheless, due to the insufficient number of studies and the poor quality of the current evidence, more studies of dose-effect relationships and safety concerns of XBJ are needed. Low-quality evidence showed no risk difference for mortality during treatment (210/1144, RR 0.65, 95% CI 0.36-1.17; P = 0.15, I2 = 0%). CONCLUSIONS: This study suggested that supplementation with XBJ in addition to regular treatment may improve the 28-day mortality rate, APACHE Ⅱ scores, WBC count and body temperature of sepsis patients without serious adverse events, but it may not reduce mortality during treatment, revealing a specific, remote effect of traditional Chinese medicine. However, given the high risk of bias and the low quality of the included trials, we may be unable to draw any conclusions about its routine use. Rigorously designed, multicentre, large-scale, methodologically sound trials are warranted. Copyright © 2018 Elsevier B.V. All rights reserved. KEYWORDS: Efficacy; Meta-analysis; Safety; Sepsis; Systematic review; Traditional Chinese medicine; Xuebijing injection PMID: 29860133 DOI: 10.1016/j.jep.2018.05.043 [Indexed for MEDLINE]