甲磺酸萘莫司他在心脏外科术后应用体外膜肺氧合患者中抗凝的有效性与安全性研究

Efficacy and safety of namostat mesylate for anticoagulation in patients with extracorporeal membrane oxygenation after cardiac surgery

目的探讨甲磺酸萘莫司他在心脏外科术后应用体外膜肺氧合(ECMO)患者中的抗凝有效性与安全性。方法2022年1月至2024年1月,洛阳市中心医院心脏外科术后应用ECMO治疗的患者40例,在建立V-A ECMO后,采用随机数字表法分为实验组和对照组进行抗凝治疗。实验组21例,对照组19例,目标值维持活化部分凝血活酶时间(APTT)值50~70 s,激活全血凝固时间(ACT)值150~200 s。实验组经静脉以0.50~0.75 mg/(kg·h)泵入甲磺酸萘莫司他;对照组经静脉以7.50~20.0 U/(kg·h)泵入肝素。比较两组患者在ECMO置入24 h内8个连续样本点APTT值、ACT值;比较两组患者在ECMO运行期间的APTT值、ACT值、血小板水平、血小板输注量、血红蛋白水平、红细胞输注量、出血事件、血栓事件、过度抗凝发生率,连续变量符合正态分布者采用两独立样本t检验,连续变量不符合正态分布者采用Mann-WhitneyU检验,分类变量采用卡方检验。结果实验组男性例数与对照组比较,差异无统计学意义[14(66.7%)比13(68.4%),P>0.05];实验组年龄与对照组比较,差异无统计学意义[(55.8±15.1)岁比(59.0±7.5)岁,P>0.05];实验组体重与对照组比较,差异无统计学意义[(67.7±16.6)kg比(68.9±18.4)kg,P>0.05];实验组ECMO运行时间与对照组比较,差异无统计学意义[(5.8±2.6)d比(4.5±2.5)d,P>0.05];实验组ECMO前血小板水平与对照组比较,差异无统计学意义[(162.5±65.9)×10^(9)比(145.0±87.9)×10^(9),P>0.05];实验组ECMO前血红蛋白水平与对照组比较,差异无统计学意义[(9.0±1.4)g/L比(9.0±2.5)g/L,P>0.05]。ECMO置入24 h内,实验组APTT值与对照组比较,差异无统计学意义[T1(44.6±13.5)s比(62.7±23.5)s,P>0.05;T2(44.9±8.3)s比(49.7±11.7)s,P>0.05;T3(49.7±11.0)s比(53.1±10.6)s,P>0.05;T4(47.8±11.0)s比(52.4±22.7)s,P>0.05;T5(48.8±21.4)s比(49.0±17.7)s,P>0.05;T6(40.7±17.2)s比(41.9±7.5)s,P>0.05;T7(49.3±9.9)s比(45.5±12.5)s,P>0.05;T8(46.4±10.1)s比(49.4±10.7)s,P>0.05]。ECMO置入24 h内,实验组ACT值与对照组比较,差异无统计学意义[T1(177.9±20.6)s比(202.6±47.2)s,P>0.05;T2(181.2±22.3)s比(196.0±26.4)s,P>0.05;T3(177.9±19.9)s比(185.9±26.3)s,P>0.05;T4(185.0±24.6)s比(190.1±30.3)s,P>0.05;T5(179.6±19.5)s比(181.9±24.6)s,P>0.05;T6(182.1±16.6)s比(180.4±25.8)s,P>0.05;T7(171.3±24.1)s比(174.8±22.4)s,P>0.05;T8(185.5±12.9)s比(178.9±25.3)s,P>0.05]。ECMO运行期间,实验组APTT值与对照组比较,差异无统计学意义[(49.4±11.9)s比(52.1±13.1)s,P>0.05];实验组ACT值与对照组比较,差异无统计学意义[(181.7±11.8)s比(188.4±16.6)s,P>0.05];实验组血小板水平高于对照组[(87.7±22.2)×10^(9)比(59.8±27.3)×10^(9),P<0.05];实验组血小板输注量低于对照组[(1.6±0.5)U比(2.0±0.4)U,P<0.05];实验组血红蛋白水平高于对照组[(8.7±0.9)g/L比(7.8±1.2)g/L,P<0.05];实验组红细胞输注量低于对照组[(7.0±3.4)U比(12.4±9.7)U,P<0.05];实验组出血事件低于对照组[2(12.5%)比7(29.2%),P<0.05];实验组血栓事件与对照组比较,差异无统计学意义[0(0%)比2(12.5%),P>0.05];实验组过度抗凝发生率低于对照组(6.3%比14.7%,P<0.05)。结论甲磺酸萘莫司他可作为V-A ECMO期间抗凝剂,对心脏外科术后应用ECMO的患者安全有效。

ObjectiveTo investigate the anticoagulant efficacy and safety of namostat mesylate in patients with extracorporeal membrane oxygenation(ECMO)after cardiac surgery.MethodsFrom January 2022 to January 2024,40 patients treated with ECMO after cardiac surgery in Luoyang Central Hospital were divided into experimental group(n=21)and control group(n=19)for anticoagulation therapy by a random number table method.The target value of activated partial thromboplastin time(APTT)was 50-70 s.The activated clotting time(ACT)was 150-200 s.The experimental group was injected intravenously with 0.50-0.75 mg/(kg·h)naphthalmostat mesylate.The control group was intravenously injected with heparin at 7.50-20.0 U/(kg·h).APTT and ACT values of 8 consecutive sample points were compared between the two groups within 24 h after ECMO implantation.APTT value,ACT value,platelet level,platelet transfusion volume,hemoglobin level,red blood cell transfusion volume,bleeding event,thrombotic event and incidence of excessive anticoagulation were compared between the two groups during ECMO operation.SPSS 26.0 software was used for statistical analysis.T test of two independent samples was used for continuous variables conforming to normal distribution,Mann-Whitney U test was used for continuous variables not conforming to normal distribution,and Chi-square test was used for categorical variables.ResultsThere were no significant differences in number of males[14(66.7%)vs.13(68.4%),P>0.05],age[(55.8±15.1)years vs.(59.0±7.5)years,P>0.05],body weight[(67.7±16.6)kg vs.(68.9±18.4)kg,P>0.05],and ECMO running time[(5.8±2.6)d vs.(4.5±2.5)d,P>0.05]between the experimental group and the control group.There was no significant difference in platelet count[(162.5±65.9)×10^(9) vs.(145.0±87.9)×10^(9),P>0.05]and hemoglobin level[(9.0±1.4)g/L vs.(9.0±2.5)g/L,P>0.05]before ECMO between the experimental group and the control group.Within 24 h after ECMO implantation,there was no significant difference between the experimental group and the control group in APTT value[T1(44.6±13.5)s vs.(62.7±23.5)s,P>0.05;T2(44.9±8.3)s vs.(49.7±11.7)s,P>0.05;T3(49.7±11.0)s vs.(53.1±10.6)s,T4(47.8±11.0)s vs.(52.4±22.7)s,P>0.05;T5(48.8±21.4)s vs.(49.0±17.7)s,P>0.05;T6(40.7±17.2)s vs.(41.9±7.5)s,P>0.05;T7(49.3±9.9)s vs.(45.5±12.5)s,P>0.05;T8(46.4±10.1)s vs.(49.4±10.7)s,P>0.05].Within 24 h of ECMO implantation,there was no significant difference in ACT values between the experimental group and the control group[T1(177.9±20.6)s vs.(202.6±47.2)s,P>0.05;T2(181.2±22.3)s vs.(196.0±26.4)s,P>0.05;T3(177.9±19.9)s vs.(185.9±26.3)s;T4(185.0±24.6)s vs.(190.1±30.3)s,P>0.05;T5(179.6±19.5)s vs.(181.9±24.6)s,P>0.05;T6(182.1±16.6)s vs.(180.4±25.8)s,P>0.05;T7(171.3±24.1)s vs.(174.8±22.4)s,P>0.05;T8(185.5±12.9)s vs.(178.9±25.3)s,P>0.05].During ECMO operation,there was no significant difference between the experimental group and the control group in APTT value[(49.4±11.9)s vs.(52.1±13.1)s,P>0.05]and ACT[(181.7±11.8)s vs.(188.4±16.6)s,P>0.05].The platelet count in the experimental group was greater than that in the control group[(87.7±22.2)×10^(9) vs.(59.8±27.3)×10^(9),P<0.05].The platelet transfusion volume in the experimental group was lower than that in the control group[(1.6±0.5)U vs.(2.0±0.4)U,P<0.05].The hemoglobin level in the experimental group was higher than that in the control group[(8.7±0.9)g/L vs.(7.8±1.2)g/L,P<0.05].The red blood cell transfusion volume in the experimental group was lower than that in the control group[(7.0±3.4)U vs.(12.4±9.7)U,P<0.05].The incidence of bleeding events in the experimental group was lower than that in the control group[2(12.5%)vs.7(29.2%),P<0.05].There was no significant difference in thrombotic events between the experimental group and the control group[0(0%)vs.2(12.5%),P>0.05].The incidence of excessive anticoagulation in the experimental group was lower than that in the control group(6.3%vs.14.7%,P<0.05).ConclusionNathomostat mesylate can be used as an anticoagulant during V-A ECMO and is safe and effective in patients who receive ECMO after cardiac surgery.