新型国产体外膜肺氧合器主机效果与安全性的评价

Efficacy and safety evaluation of a novel domestic extracorporeal membrane oxygenation mainframe

目的利用大动物评价新型国产体外膜肺氧合器(extracorporeal membrane oxygenation,ECMO)主机的运行效果及安全性,为进一步的临床应用提供依据。方法选择国产健康雄性白猪5头,体质量(51±4)kg,应用新型国产ECMO主机配合进口膜氧合器与管路建立ECMO系统,持续运行72 h。ECMO设定参数为:静脉-动脉ECMO模式,离心泵转速3000~3500 r/min,持续输注肝素维持活化凝血时间(activate clotting time,ACT)在140~200 s。实时监测转速、流量、泵前压力、泵后压力、膜后压力等设备参数情况,并进行设备性能评分。动态监测动物血流动力学、乳酸、血常规等指标的变化。组内不同时间点比较,采用重复测量方差分析。于实验终点,观察泵头和氧合器内的血栓形成情况,处死动物获取主要器官的组织标本,进行大体肉眼观察及病理损伤评估。结果所有动物均成功运行ECMO系统72 h。(1)离心泵转速维持在3029~3483 r/min,流量维持在2.24~2.60 L/min,泵前压力-107.57~-31.86 mmHg,泵后压力197.50~282.43 mmHg,膜后压力178.71~261.5 mmHg,均处于合理范围,不同时间点比较差异无统计学意义(均P>0.05)。主机性能评分均在4分及以上,满足使用要求。(2)动物心率为50~80次/min,平均动脉压为85~115 mmHg,乳酸0.996~2.25 mmol/L,均处于正常范围,不同时间点比较差异无统计学意义(均P>0.05);游离血红蛋白为8.98~16.39 mg/L,血红蛋白为6.58~7.52 g/L,均处于合理范围,不同时间点比较差异无统计学意义(均P>0.05);血小板为69.6~231.6×10^(9)/L,且呈持续下降趋势(P<0.05)。ACT维持在135~169 s,位于目标范围内,不同时间点比较差异无统计学意义(P>0.05)。(3)实验终点观察泵头和氧合器未见明显血栓,心、脑、肝、肺、肾大体肉眼观未见明显血栓和梗死病灶、显微镜下未见明显出血和坏死等表现。结论新型国产ECMO主机联合进口膜氧合器和管路建立的ECMO顺利运行72 h,达到目标的效果和安全性。

Objective To evaluate the safety and efficacy of a novel domestic extracorporeal membrane oxygenation(ECMO)mainframe in a porcine model,and to provide the basis for further clinical application.Methods Five domestic healthy male white pigs,weighing(51±4)kg,were selected.The ECMO system was established by using a novel ECMO mainframe with imported membrane oxygenator and pipeline,and continued to run for 72 hours.ECMO parameters are as follows:veno-arterial ECMO,centrifugal pump speed 3000-3500 r/min,continuous infusion of heparin anticoagulation to maintain the activate clotting time(ACT)of 140-200 s.Real-time monitoring of speed,flow,pressure before pump,pressure after pump,pressure after membrane and other equipment parameters,and the equipment performance was scored.The changes of hemodynamics,blood lactic acid and blood routine were monitored dynamically.Repeated measures analysis of variance was used to compare different time points within the group.At the end of the experiment,the thrombosis in the pump head and oxygenator was observed.The animals were sacrificed to obtain the tissue samples of the main organs for gross observation and pathological injury evaluation.Results All animals successfully ran the ECMO system for 72 hours.(1)The centrifugal pump speed should be maintained at 3029-3483 r/min,the flow rate was maintained at 2.24-2.60 L/min,The pressure before the pump between minus 107.57 and minus 31.86 mmHg,the pressure after the pump was 197.50-282.43 mmHg,and the pressure after the membrane was 178.71-261.5 mmHg,all were in the normal range,and there was no significant difference between different time points(all P>0.05).The performance scores of the mainframe were all 4 points or above,indicating that the use requirements were met.(2)The heart rate of the animals was 50-80 beats/min,the mean arterial pressure was 85-115 mmHg,and the lactic acid was 0.996-2.25 mmol/L,all within the normal range,and there was no significant difference between different time points(all P>0.05).The free hemoglobin was 8.98-16.39 mg/L,and the hemoglobin was 6.58-7.52 g/L,both within a reasonable range,and there was no significant difference between different time points(all P>0.05).The platelet count was 69.6-231.6x10/L,and showed a continuous downward trend(P<0.05).ACT was maintained at 135-169 s,which was within the target range,and there was no significant difference between different time points(P<0.05).(3)At the end of the experiment,there was no obvious thrombosis in the pump head and oxygenator,no obvious thrombosis or infarction in the heart,brain,liver,lung and kidney,and no obvious hemorrhage or necrosis under the microscope.Conclusions The ECMO established by the novel domestic ECMO mainframe combined with imported membrane oxygenator and pipeline ran smoothly for 72 hours,achieving the target of effect and safety.