参附注射液联合治疗减轻脓毒症凝血病：一项随机对照研究

Shenfu injection combined therapy alleviates sepsis‐induced coagulopathy: A randomized controlled study

摘要

目的：观察参附注射液干预脓毒症性凝血病（SIC）患者后，不同时间点凝血功能及相关指标的变化，评估其临床疗效。方法：选取2021年1月至2025年8月武汉大学人民医院重症监护病房（ICU）收治的118例SIC患者，按治疗方式随机分为参附组（59例）与对照组（59例）。对照组采用脓毒症标准治疗，参附组在标准治疗基础上联合参附注射液100 mL（每日2次，疗程7 d）。收集两组患者治疗前1 d（T0）、治疗后第1、2、3、5、7天（T1、T2、T3、T5、T7）的凝血功能指标,包括血小板计数（PLT）、凝血酶原时间（PT）、国际标准化比值（PT-INR）、纤维蛋白原（FIB）及D-二聚体，以及炎症指标、器官功能指标（肝、肾功能）及病情危重程度评分。结果：治疗第7天（T7），参附组PT（Z=-2.120，P=0.034）、PT-INR（Z=-2.133，P=0.033）显著低于对照组，D-二聚体水平显著下降（Z=-2.207，P=0.027），PLT较治疗前下降（Z=-2.145，P=0.032），尿素显著降低（Z=-2.297，P=0.022）。参附组28天死亡率显著低于对照组（χ²=4.222，P=0.04）。结论：在标准治疗基础上联合参附注射液，可改善ICU脓毒症患者的凝血功能、减轻炎症反应、保护器官功能，可为临床治疗提供参考。

Abstract

Objective: To observe changes in coagulation function and related indicators at various time points in ICU patients with sepsis-induced coagulopathy (SIC) treated with Shenfu Injection, and to evaluate its clinical efficacy. Methods: A total of 118 patients with sepsis-induced coagulopathy (SIC) admitted to the ICU of Renmin Hospital of Wuhan University between January 2021 and August 2024 were enrolled and randomly divided into a treatment group (Shenfu group,n=59) and a control group (n=59) according to therapeutic protocols. The control group received standard sepsis treatment, while the Shenfu group received additional Shenfu Injection (100 mL intravenous drip, twice daily for 7 days). Coagulation function parameters (PLT, PT, INR, FIB, and D-dimer), inflammatory markers, organ function indices (liver and renal function), and severity scores were collected in both groups at baseline (one day before treatment, T0) and on days 1, 2, 3, 5, and 7 after treatment (T1-T7). Results: At T7, the levels of PT (Z=-2.120,P=0.034) and PT-INR (Z=-2.133,P=0.033) in the Shenfu group were significantly lower than those in control group, and the D-dimer level decreased significantly (Z=-2.207, P=0.027). Both PLT and urea levels were significnatly decreased in Shenfu group as compared with baseline (T0) (Z=-2.145, P=0.032; Z=-2.297, P=0.022). The 28-day mortality rate of Shenfu group was significantly lower than that of control group (χ²=4.222, P=0.04). Conclusion: Shenfu Injection combined with standard therapy can improve coagulation function, alleviate inflammatory response, and protect organ function in ICU patients with SIC, providing a reference for clinical treatment.

关键词

脓毒症 / 脓毒症性凝血病 / 预后 / 参附注射液 / 凝血功能

Key words

Sepsis / Sepsis-Induced Coagulopathy / Prognosis / Shenfu Injection / Coagulation Function

参考文献

[1] SINGER M, DEUTSCHMAN C S, SEYMOUR C W, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3) [J]. JAMA, 2016, 315(8): 801-810.

[2] WILLIAMS B, ZOU L, PITTET J F, et al. Sepsis-induced coagulopathy: A comprehensive narrative review of pathophysiology, clinical presentation, diagnosis, and management strategies[J]. Anesth Analg, 2024, 138(4): 696-711.

[3] IBA T, HELMS J, LEVY J H. Sepsis-induced coagulopathy (SIC) in the management of sepsis[J]. Ann Intensive Care, 2024, 14(1): 148.

[4] LYONS P G, MICEK S T, HAMPTON N, et al. Sepsis-associated coagulopathy severity predicts hospital mortality[J]. Crit Care Med, 2018, 46(5): 736-742.

[5] IBA T, LEVI M, THACHIL J, et al. Communication from the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis on sepsis-induced coagulopathy in the management of sepsis [J]. J Thromb Haemost, 2023, 21(1): 145-153.

[6] WELTY-WOLF K E, CARRAWAY M S, MILLER D L, et al. Coagulation blockade prevents sepsis-induced respiratory and renal failure in baboons[J]. Am J Respir Crit Care Med, 2001, 164(10 Pt 1): 1988-1996.

[7] IBA T, HELMS J, NEAL M D, et al. Mechanisms and management of the coagulopathy of trauma and sepsis: Trauma-induced coagulopathy, sepsis-induced coagulopathy, and disseminated intravascular coagulation[J]. J Thromb Haemost, 2023, 21(12): 3360-3370.

[8] IBA T, LEVY J H, WARKENTIN T E, et al. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation[J]. J Thromb Haemost, 2019, 17(11): 1989-1994.

[9] XU F F, XIE X F, HU H Y, et al. Shenfu injection: A review of pharmacological effects on cardiovascular diseases[J]. Front Pharmacol, 2024, 15: 1279584.

[10] CHEN J, DING W C, ZHANG Z, et al. Shenfu injection targets the PI3K-AKT pathway to regulate autophagy and apoptosis in acute respiratory distress syndrome caused by sepsis[J]. Phytomedicine, 2024, 129: 155627.

[11] TIAN R, LI R R, CHEN Y, et al. Shenfu injection ameliorates endotoxemia-associated endothelial dysfunction and organ injury via inhibiting PI3K/Akt-mediated glycolysis[J]. J Ethnopharmacol, 2024, 335: 118634.

[12] 孙海燕, 刘杨, 刘茜, 等 . 参附注射液调控TIMP-3/MMP-1/syndecan-1通路改善脓毒症大鼠心肌损伤的机制研究[J]. 时珍国医国药, 2025, 36(15): 2827-2832.

[13] SUN H Y, LIU Y, LIU Q, et al. Study on the mechanism of Shenfu injection regulating TIMP-3/MMP-1/syndecan-1 pathway to improve myocardial injury in rats with sepsis[J]. J Li Shizhen Tradit Chin Med, 2025, 36(15): 2827-2832.

[14] 吴威, 邵碧波 . 参附注射液调控Nrf2信号通路介导的中性粒细胞诱捕网途径对脓毒血症肾损伤的保护作用研究[J]. 时珍国医国药, 2025, 36(17): 3270-3277.

[15] WU W, SHAO B B. Protective effect of Shenfu Injection on sepsis-associated acute kidney injury through regulating the Nrf2 signaling pathway mediated by neutrophil extracellular traps(NETs) formation[J]. J Li Shizhen Tradit Chin Med, 2025, 36(17): 3270-3277.

[16] 唐娅群, 蒋光辉, 毛媛, 等 . 基于标准集束化方案下参附注射液治疗脓毒症休克的临床疗效[J]. 江苏医药, 2025, 51(7): 679-683.

[17] TANG Y Q, JIANG G H, MAO Y, et al. Clinical efficacy of Shenfu injection based on the standardized bundle protocol in the treatment of septic shock[J]. Jiangsu Med J, 2025, 51(7): 679-683.

[18] 王学朝, 刘彦锋 . 参附注射液联合乌司他丁治疗脓毒症休克患者的效果[J]. 中国医学创新, 2025, 22(5): 52-57.

[19] WANG X C, LIU Y F. Effect of Shenfu injection combined with ulinastatin on septic shock patients[J]. Med Innov China, 2025, 22(5): 52-57.

[20] 张焰, 石雨晴 . 参附注射液辅助治疗对脓毒症休克患者炎性因子水平及血气指标的影响[J]. 新疆中医药, 2025, 43(3): 14-16.

[21] ZHANG Y, SHI Y Q. Effect of adjuvant therapy with Shenfu injection on inflammatory factor levels and blood gas indicators in patients with sepsis shock[J]. Xinjiang J Tradit Chin Med, 2025, 43(3): 14-16.

[22] 宋景春, 丁仁彧, 吕奔, 等 . 脓毒症性凝血病诊疗中国专家共识(2024版)[J]. 解放军医学杂志, 2024, 49(11): 1221-1236.

[23] SONG J C, DING R Y, LÜ B, et al. Chinese expert consensus on the diagnosis and treatment of sepsis-induced coagulopathy(2024 edition) [J]. Med J Chin People's Liberation Army, 2024, 49(11): 1221-1236.

[24] 中国研究型医院学会. 脓毒症诊断与治疗规范: T/CRHA 022—2023[S].北京: 中国研究型医院学会, 2023.

[25] Chinese Research Hospital Association. Specification for Diagnosis and Treatment of Sepsis: T/CRHA 022—2023 [S]. Beijing:Chinese Research Hospital Association, 2023.

[26] KNAUS W A, DRAPER E A, WAGNER D P, et al. APACHE Ⅱ: A severity of disease classification system [J]. Crit Care Med, 1985, 13(10): 818-829.

[27] WU J Y, LI C S, YUAN W. Effects of Shenfu injection on macrocirculation and microcirculation during cardiopulmonary resuscitation[J]. J Ethnopharmacol, 2016, 180: 97-103.

[28] RAGHAVENDRAN H R B, SATHYANATH R, SHIN J, et al. Panax ginseng modulates cytokines in bone marrow toxicity and myelopoiesis: Ginsenoside Rg1 partially supports myelopoiesis[J]. PLoS One, 2012, 7(4): e33733.

[29] 涂学云, 万仑, 王丹丹, 等 . 参附注射液对全髋关节置换术患者围术期循环稳定性及下肢深静脉血栓形成的影响[J]. 辽宁中医杂志, 2023, 50(12): 91-94.

[30] TU X Y, WAN L, WANG D D, et al. Effects of Shenfu injectionon perioperative circulation stability and deep venous thrombosis of lower extremity in patients undergoing total hip arthroplasty[J]. Liaoning J Tradit Chin Med, 2023, 50(12): 91-94.

[31] 焦保庭, 檀晓东, 张邵东 . 参附注射液对腹部手术患者术后深静脉血栓发生及凝血功能的影响[J]. 中国处方药, 2020, 18(8): 138-140.

[32] JIAO B T, TAN X D, ZHANG S D. Effect of Shenfu injection on deep venous thrombosis postoperative and coagulation function in patients undergoing abdominal surgery[J]. J China Prescr Drug, 2020, 18(8): 138-140.

[33] HONG F F, HE C S, LIU X J, et al. Protective effect of Shenfu injection on thromboangiitis obliterans model rats [J]. J Ethnopharmacol, 2011, 138(2): 458-462.

[34] LIAO J J, QIN C Y, WANG Z Y, et al. Effect of Shenfu injection in patients with septic shock: A systemic review and meta-analysis for randomized clinical trials[J]. J Ethnopharmacol, 2024, 320: 117431.

基金资助

国家重点研发计划项目(2023YFC2308404)

新发突发与重大传染病防控国家科技重大专项(2025ZD01902600)

湖北省中医药管理局中医药科研项目(ZY2025L276)