益母草注射液用于阴道分娩后胎膜残留的多中心临床研究

Multi-center clinical study of motherwort injection for retained fetal membrane after vaginal delivery

目的探讨应用益母草注射液治疗阴道分娩后胎膜残留的有效性和安全性。方法采用多中心、开放、随机、对照的前瞻性研究方法,于2017年12月至2018年10月收集符合纳入、排除标准的全国7所三级医院244例足月阴道分娩产妇作为研究对象。随机分为基础治疗组(对照组)和观察组,分别采用全分析集(FAS)和符合方案分析集(PPS)进行统计分析,失访16例(观察组7例,对照组9例)。主要有效性指标分析结果两者相同,故仅详细报告PPS集分析结果。PPS集中纳入对照组109例,于产后第1天开始给予缩宫素20U每天静脉滴注及二代头孢静脉滴注,连续3d;观察组114例,观察组在产后基础治疗组基础上加用益母草注射液2mL/次,2次/d,连续5d。两组患者出院后均给予口服产复康颗粒或产妇安颗粒,连续7d。以产妇恶露情况、子宫体积变化、残留胎膜排出情况等为主要有效性指标;以产妇感染相关因子及感染情况、晚期产后出血发生率、产后体温变化、合并使用其他止血类药物情况等为次要有效性指标;以实验室检查(血常规、心电图)、不良反应/事件为安全性指标,评价益母草注射液治疗阴道分娩后胎膜残留的有效性和安全性。结果 (1)恶露情况:产妇血性恶露持续时间观察组显著短于对照组[(5.12±1.83)d vs.(6.27±2.07)d,P=0.000];血性恶露5d内终止率观察组显著高于对照组(64.91%vs. 35.78%,P=0.000)。(2)子宫体积比较:观察组子宫体积缩小程度明显优于对照组(Z=-2.27,P<0.05)。(3)残留胎膜情况:观察组治疗5d后及产后42～47d残留胎膜排出率明显高于对照组(62.28%vs. 35.78%,100.00%vs.95.41%,P=0.002);观察组因残留胎膜持续存在所致的清宫率显著低于对照组(1.75%vs. 14.68%,P=0.000)。(4)感染相关因子及感染情况:治疗5d后观察组C-反应蛋白(CRP)值显著小于对照组(P<0.01);将CRP>8.0mg/L或降钙素原(PCT)>0.5ng/L定义为感染,治疗5d后观察组感染率显著低于对照组(P<0.01)。(5)两组患者入院后最高体温与体温恢复正常时间差异无统计学意义(P>0.05),两组患者均未合并使用其他止血类药物,亦未发生晚期产后出血。(6)观察组和对照组均未有不良反应报告,均未有异常血常规指标、心电图出现。结论阴道分娩后应用益母草注射液联合基础药物治疗,可明显缩短血性恶露持续时间,促进子宫缩复,提高残留胎膜排出率和降低清宫率。

Objective To evaluate the efficacy and safety of motherwort(herba leonuri)injection in the treatment of fetal membrane retention after vaginal delivery.Methods The prospective study was designed as a multicenter,open,randomized,controlled research from December 2017 to October 2018.A total of 244 women who achieved fullterm vaginal delivery were enrolled from 7 tertiary hospitals in China.Sixteen people were lost to follow-up(7 in the experimental group and 9 in the control group).All cases were randomly divided into group of motherwort(experimental group)and group of basic treatment(control group).Full Analysis Set(FAS)and Per ProtocolSet(PPS)were used for statistical analysis.The results of main validity indicators were the same.Therefore,only the results of PPS set analysis were reported in detail.PPS set included 109 cases in control group and 114 cases in experimental group.Control group were administered by oxytocin 20 U and cephalosporinⅡintravenous injection daily for3 days after birth;experimental group were administered by motherwort 20 mg intramuscular injection per 12 hours for 5 consecutive days on the basis of basic treatment.Both groups of patients were given oral herb medicine Chan-fu-kang or Chan-fu-an Granules after discharge for 7 consecutive days.The following clinical parameters were collected and analyzed for evaluation of the efficacy and safety of motherwort injection in the treatment of retained fetal membrane after vaginal delivery.The main effectiveness indicators were maternal lochia,uterine volume change,and discharge of retained fetal membrane;the secondary effectiveness indicators were the maternal infection-related factors and infections,the incidence of secondary postpartum hemorrhage,postpartum body temperature changes,and the use of other hemostatic drugs.Safety indicators were laboratory tests(blood routine,electrocardiogram),adverse reactions/events,which were used to evaluate the safety and efficacy of motherwort injection in the treatment of retained fetal membrane after vaginal delivery.Results(1)Lochia:the duration of bloody lochia was significantly shorter in the experiment group than in the control group([(5.12±1.83)d]vs.(6.27±2.07)d,P=0.000);rate of termination of bloody lochia within 5 days was significantly higher in the experiment group than in the control group(64.91% vs. 35.78%,P=0.000).(2)Comparison of uterine volume:the reduction of uterus volume in the experiment group was significantly greater than that in the control group(Z=-2.27,P<0.05).(3)Retained fetal membrane:the discharge rate of retained membrane in the experiment group after 5 days of treatment and 42-47 days after delivery was significantly higher than that of the control group(62.28% vs. 35.78%,100.00% vs. 95.41%,P=0.002);the rate of uterine curettage due to persistent residual fetal membrane in the experiment group was significantly lower than that of the control group(1.75%vs. 14.68%,P=0.000).(4)Infection-related factors and infection:the CRP value of the experiment group after 5 days of treatment was significantly smaller than that of the control group(P<0.01);when CRP>8.0 mg/L or PCT>0.5 ng/L was defined as infection,the infection rate of the experiment group after 5 days of treatment was significantly lower than that of the control group(P<0.01).(5)There was no significant difference between the two groups in the highest body temperature and the time required for body temperature to return to normal(P>0.05).No other hemostatic drugs were used in the two groups,and no secondary postpartum hemorrhage occurred.(6)There were no adverse reactions reported in both groups,and no abnormal blood routine indicators or electrocardiogram appeared.Conclusion The application of motherwort injection combined with the basic treatment after the vaginal delivery can significantly shorten the duration of bloody lochia,promote uterine involution,increase the discharge rate of retained fetal membrane,and reduce the rate of uterine curettage.