参麦注射液对气阴两虚型血瘀证脓毒症患者凝血功能障碍的影响

Effect of Shenmai injection on coagulopathy in septic patients with deficiency of both Qi and Yin type blood stasis syndrome

目的观察参麦注射液对脓毒症气阴两虚型血瘀证患者凝血功能障碍的影响，为中药治疗脓毒症凝血功能障碍提供思路与方法。方法采用前瞻性、随机对照研究方法，选择2014年3月至2015年2月广东省中医院本部重症医学科收治的脓毒症凝血功能障碍患者50例，按简单随机方法分为参麦组和对照组，每组25例。所有患者均采用脓毒症综合治疗方案，参麦组在此基础上加用具有益气扶正养阴功效的参麦注射液50mL，每日2次，两组疗程均为7d。将弥散性血管内凝血（DIC）评分〈5分的30例脓毒症非显性DIC期患者按是否使用参麦注射液治疗分为观察Ⅰ组（16例）和对照Ⅰ组（14例），而DIC评分≥5分的20例脓毒症显性DIC期患者按是否使用参麦注射液治疗分为观察Ⅱ组（9例）和对照Ⅱ组（11例）。检测患者治疗前后活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）、凝血酶原活动度（AT）、国际标准化比值（INR）、血浆纤维蛋白原（Fib）、D-二聚体、血小板计数（PLT）、血常规水平等，比较两组急性生理学与慢性健康状况评分系统Ⅱ（APACHEII）、院内出血风险评分（CRUSADE）、DIC评分及28d病死率。结果参麦组治疗后APTT、PT、INR、D-二聚体和CRUSADE、APACHEⅡ、DIC评分均明显低于对照组[APTT（S）：41．42±10．74比62．96±39．74，PT（S）：15．96±1．96比19．69±4．19，INR：1．29±0．21比1．65±0．48，D-二聚体（μg/L）：3753．20±2319．04比5254．40±2642．75，CRUSADE（分）：44．96±17．69比53．56±13．61，APACHEⅡ评分（分）：12．72±6．67比19．72±8．94，DIC评分（分）：3．32±1．60比4．40±1．68，均P〈0．05]，而AT、Fib、PLT、血红蛋白（Hb）均明显高于对照组[AT（s）：72．84±14．77比55．28±17．46，Fib（g／L）：4．49±1．77比3．38±1．80，PLT（×10^9）：194．51±140．61比115．24±86．20，Hb（g/L）：103．48±24．10比91．16±16．69，均P〈0．05]。观察Ⅰ组治疗后APTT、PT、INR、D-二聚体较对照Ⅰ组明显降低[APTT（s）：38．94±3．35比63．13±41．36，PT（s）：15．30±1．38比19．28±3．78，INR：1．22±0．16比1．58±0．41，D-二聚体（μg／L）：3441．25±2286．14比4663．57±2746．66j．而AT、Fib、PLT较对照Ⅰ组明显升高（AT（s）：77．44±13．92比58．14±19．96，Fib（g／L）：5．01±1．80比3．93±1．87，PLT（×10^9）：229．56±149．80比144．21±98．99，均P〈0．05]。参麦组28d病死率明显低于对照组[20．0％（5／25）比56．0l％（14／25），均P〈0．05]。观察Ⅰ组28d病死率明显低于对照Ⅰ组[12．5％（2／16）比57．1％（8／14），P〈0．05]；而观察Ⅱ组28d病死率低于对照Ⅱ组，但差异无统计学意义[44．4％（4／9）比54．5％（6／11），P〉0．05]。结论益气养阴中药对脓毒症凝血功能障碍患者的凝血指标及病死率有积极的改善作用，特别是对DIC评分〈5分的非显性DIC患者干预效果更为明显，显示参麦注射液对脓毒症凝血功能障碍的早期患者有一定积极治疗作用。

Objective To observe the effect of Shenmai injection on coagulation dysfunction in patients with sepsis accompanied by deficiency of both Qi and Yin type blood stasis syndrome to provide traditional Chinese medicine （TCM） ideas and methods for treatment of septic coagulopathy. Methods A prospective randomized controlled study was conducted; 50 sepsis patients with coagulation dysfunction met the inclusion criteria and admitted to Deparlment of Critical Care Medicine in Second Affiliated Hospital, Guangzhou University of TCM from March 2014 to February 2015 were enrolled, and they were randomly divided into a Shenmai group and a control group, 25 cases in each group. The patients in both groups were treated with sepsis comprehensive treatment program, additionally, Shenmai injection 50 mL having the effects of supporting the healthy energy, reinforcing qi and nourishing yin was given to the patients in Shenmai group, twice a day, and the treatment course of the two groups was 7 days. Fifty patients with sepsis were included in the study, 30 were assigned in a group of patients with DIC score 〈 5 as non-overt dispersion of intravascular coagulation （DIC） group, and according to whether using Shenmai injection or not in the treatment, the cases were subdivided into an observation group I （16 cases） and a control group I （14 cases）. And another 20 septic cases with DIC score ≥ 5 were arranged in another group as overt DIC-patient group, and according to whether applying Shenmai injection or not in treatment, they were subdivided into an observation group Ⅱ （9 cases） and a control group Ⅱ （11 cases）. Before and after treatment, the levels of activated partial thromboplastin time （APTT）, prothrombin time （PT）, prothrombin time activity （AT）, international normalized ratio （INR）, plasma fibrinogen （Fib）, D-dimer, platelet count （PLT） and so on were detected, and the acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ ） score, evaluation score of hemorrhagic risk in the hospital （CRUSADE）, DIC score and 28-day mortality were compared between the two groups. Results After treatment, the levels of APTT, PT, INR, D-direct, CRUSADE score, APACHE Ⅱscore, D/C score were significantly lower in Shenmai group than those in the control group [APTT （s）： 41.42 ± 10.74 vs. 62.96 ± 39.74, PT （s）： 15.96± 1.96 vs. 19.69 ± 4.19, INR： 1.29 ± 0.21 vs. 1.65 ± 0.48, D-Dimer （μg/L）： 3 753.20± 2 319.04 vs. 5 254.40± 2642.75, CRUSADE score： 44.96± 17.69 vs. 53.56 ± 13.61, APACHE Ⅱ score： 12.72± 6.67 vs. 19.72± 8.94 and DIC score： 3.32 ± 1.60 vs. 4.40± 1.68, all P 〈 0.05]; while the levels of AT, Fib, PLT and hemoglobin （Hb） were all obviously higher than those in the control group [AT （s）： 72.84 ± 14.77 vs. 55.28± 17.46, Fib （g/L）： 4.49±1.77 vs. 3.38±1.80, PLT （x 109）： 194.51±140.61 vs. 115.24±86.20, Hb （g/L）： 103.48 ± 24.10 vs. 91.16 ± 16.69, all P 〈 0.05]. After treatment, the levels of AFFT, PT, INR, D-dimer were significantly lower in the observation group I than those in the control group I [APTT （s）： 38.94±3.35 vs. 63.13±41.36, PT （s）： 15.30± 1.38 vs. 19.28±3.78, INR： 1.22±0.16 vs. 1.58±0.41, D-Dimer （μg/L）： 3 441.25±2 286.14 vs. 4 663.57 ± 2 746.66]; while the levels of AT, Fib, PLT were significantly higher than those in the control group I [AT （s）： 77.44 ± 13.92 vs. 58.14 ± 19.96, Fib （g/L）： 5.01 ± 1.80 vs. 3.93± 1,87, PLT （ × 10^9）： 229.56 ± 149.80 vs. 144.21± 98.99, all P 〈 0.05]. Shenmai group 28-day mortality rate was significantly lower than that of the control group [20.0% （5/25） vs. 56.01% （14/25）, P 〈 0.05]. 28-day mortality rate in the observation group I was significantly lower than that in the control group I [12.5% （2/16） vs. 57.1% （8/14）, P 〈 0.05]. The 28-day mortality rate in the observation group Ⅱ was lower than that in the control group U [44.4% （4/9） vs. 54.5% （6/11）], but the difference was not statistically significant （P 〉 0.05）. Conclusions The research confirms that TCM of Supplementing Qi and nourishing Yin has a positive role in improving coagulation dysfunction and mortality in sepsis patients, especially in non-overt DIC patients with DIC score 〈 5, showing that the injection has certain energetic therapeutic effects on early coagulation dysfunction in septic patients.