肺表面活性物质不同给药方案治疗早产儿呼吸窘迫综合征的临床研究

Clinical research of different pulmonary surfactant administration techniques on premature infants with respiratory distress syndrome

目的探讨侵入性较小的肺表面活性物质给药(LISA)和气管插管-使用肺表面活性物质-拔管(INSURE)方案,治疗早产儿呼吸窘迫综合征(RDS)的疗效、安全性及其对预后的影响。方法选择2018年1月1日至2019年4月30日,在扬州大学附属医院接受LISA方案治疗的26例RDS早产儿为研究对象,纳入LISA组。同时,选择2016年7月1日至2017年12月31日,在同一家医院接受INSURE方案治疗的36例RDS早产儿,纳入INSURE组。采用成组t检验,对2组患儿胎龄、出生体重、生后Apgar评分等进行统计学比较。对2组患儿入院年龄、经鼻持续气道正压通气(NCPAP)时间、机械通气(MV)时间、总用氧时间、住院时间、住院费用及不同时间点吸入氧气分数(FiO2)等组间比较,采用Mann-Whitney U检验。对2组患儿动脉血pH值、动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)比较,采用重复测量资料的方差分析;组内总体比较,采用单因素方差分析,进一步组内两两比较,则采用最小显著差异(LSD)法。采用Friedman秩和检验对不同时间点FiO2进行组内比较。对2组患儿性别构成比、剖宫产术分娩率、外院转入率及相关不良反应发生率与母亲产前激素使用率等比较,采用χ^2检验、连续性校正χ^2检验或Fisher确切概率法。本研究经病例收集医院医学伦理委员会审核批准(审批文号:2020-YKL05-003),与所有患儿监护人签署知情同意书。结果①2组患儿性别构成比、分娩胎龄、出生体重、剖宫产术分娩率、双胎妊娠率、入院时年龄、生后Apgar评分、外院转入率、母亲产前激素使用率等临床资料比较,差异均无统计学意义(P>0.05)。②2组患儿无一例死亡。LISA组患儿的中位MV时间及总用氧时间分别为0和84 h(45~180 h),均短于INSURE组的0(0~80 h)和137 h(107~235 h),并且差异均有统计学意义(Z=2.877、1.991,P=0.004、0.047)。2组患儿NCPAP时间、生后72 h内MV率、住院时间、住院费用、不同并发症发生率等比较,差异均无统计学意义(P>0.05)。③2组患儿治疗前、后动脉血pH值、PaO2和PaCO2水平比较结果显示,处理措施与测定时间因素间均不存在交互作用(F处理×时间=1.751、P=0.152,F处理×时间=0.338、P=0.852,F处理×时间=0.396,P=0.810)。LISA组与INSURE组患儿接受PS治疗前及治疗后1、8、24、48 h动脉血pH值、PaO2和PaCO2水平分别组内整体比较,差异均有统计学意义(LISA组的动脉血pH值:F=47.318、P<0.001,PaO2:F=30.370、P<0.001,PaCO2:F=27.140、P<0.001;INSURE组的动脉血pH值:F=20.773、P<0.001,PaO2:F=16.976、P<0.001,PaCO2:F=23.016、P<0.001)。2组患儿动脉血pH值、PaO2和PaCO2水平在接受PS治疗前及治疗后1、8、24、48 h这5个时间点分别组间比较,差异均无统计学意义(P>0.05)。④LISA组和INSURE组患儿接受PS治疗前及治疗后0.5、1、6、12、24、48 h的FiO2分别组内整体比较,差异均有统计学意义(χ^2=131.108、P<0.001,χ^2=81.589、P<0.001);而2组患儿治疗后上述各时间点FiO2分别与治疗前比较,差异均有统计学意义(P<0.05)。2组患儿接受PS治疗前及治疗后0.5、1、6 h的FiO2组间比较,差异均无统计学意义(P>0.05);但是LISA组患儿FiO2在接受PS治疗后12、24、48 h均低于INSURE组,并且差异有统计学意义(Z=3.315、4.312、4.280,P=0.001、<0.001、<0.001)。⑤LISA组患儿接受PS治疗后无不良反应者为18例(69.2%),INSURE组为27例(75.0%),2组比较,差异无统计学意义(χ^2=0.252、P=0.615)。此外,2组患儿在PS给药过程中经皮血氧饱和度(TcSO2)<85%、心动过缓等不良反应发生率比较,差异均无统计学意义(P>0.05)。结论对RDS早产儿采取LISA方案治疗,可缩短MV及总用氧时间,而且不增加不良预后。

Objective To investigate the efficacy,safety and prognosis of less invasive pulmonary surfactant administration(LISA)and intubation-surfactant-extubation(INSURE)techniques in the treatment of respiratory distress syndrome(RDS)in premature infants.Methods Twenty-six premature infants with RDS who underwent LISA technique at the Affiliated Hospital of Yangzhou University from January 1,2018 to April 30,2019 were included in LISA group,and 36 premature infants with RDS who underwent INSURE technique at same hospital from July 1,2016 to December 31,2017 were included into INSURE group.The gestational age,birth weight,and postnatal Apgar score of 2 groups were statistically compared by using independent-samples t test.The age at admission,nasal continuous positive airway pressure(NCPAP)duration,mechanical ventilation(MV)duration,total oxygen consumption time,hospital stay,hospitalization costs and fraction of inspiration oxygen(FiO2)at different time points between 2 groups were statistically compared by Mann-Whitney U test.The pH value,partial pressure of oxygen in artery(PaO2),and partial pressure of carbon dioxide(PaCO2)between 2 groups were compared by the variance analysis of repeated measurement data;furthermore,overall comparison within groups were compared by one-way ANOVA,and least significant difference(LSD)method was used for further pairwise comparison within groups.The Friedman rank sum test was used for within-group comparisons of FiO2 at different time points.The gender composition ratio,cesarean section rate,transfe rate from other hospitals,maternal prenatal hormone use rate and incidence of related adverse reactions between 2 groups were compared by chi-square test,continuity correction of chi-square test or Fisher′s exact test.The procedures followed in this study was in accordance with the ethical standards established by the Human Beings Test Committee of Affiliated Hospital of Yangzhou University,and was approved by the committee(Approval No.2020-YKL05-003).Informed consent was obtained from each participate′s parents.Results①There were no statistically significant differences in the gender composition ratio,gestational age,birth weight,modes of delivery,pregnancy rate of twins,age at admission,Apgar score after birth,transfer rate from other hospitals and maternal prenatal hormone use rate between 2 groups(P>0.05).②No death occurred in 2 groups of RDS preterm infants.The median duration of MV(0)and total oxygen consumption time[84 h(45-180 h)]were significantly shorter than those of INSURE group[0 h(0-80 h),137 h(107-235 h)],there were significantly statistical differences(Z=2.877,1.991;P=0.004,0.047).There were no differences between 2 groups in the aspects of NCPAP duration,MV rate within 72 h after birth,hospital stay,costs and incidence of different complications(P>0.05).③The comparison results of pH value,PaO2 and PaCO2 levels before and after the treatment between 2 groups showed that there were no interactions between treatment measures and determination time factors(Ftreatment×time=1.751,P=0.152,Ftreatment×time=0.338,P=0.852,Ftreatment×time=0.396,P=0.810).The pH value,PaO2 and PaCO2 levels of children in LISA group before and at 1,8,24,48 h after treatment were compared with each other in the group as a whole,and the differences were statistically significant(pH value:F=47.318,P<0.001,PaO2:F=30.37,P<0.001,PaCO2:F=27.140,P<0.001).The pH value,PaO2 and PaCO2 levels of children in INSURE group before and at 1,8,24,48 h after treatment were compared with each other in the group as a whole,and the differences were statistically significant(pH value:F=20.773,P<0.001,PaO2:F=16.976,P<0.001,PaCO2:F=23.016,P<0.001).The pH value,PaO2 and PaCO2 levels of 2 groups were compared before PS treatment and at 1,8,24,48 h after PS treatment respectively,and there were no statistically significant differences(P>0.05).④There were significant differences in FiO2 at 0.5,1,6,12,24,and 48 h after PS treatment in 2 groups(LISA group:χ^2=131.108,P<0.001;INSURE group:χ^2=81.589,P<0.001).The FiO2 at 1,6,12,24,and 48 h after treatment were significantly different from those before treatment(P<0.05).Compared with pre-treatment,there were significant differences in FiO2 at 1,6,12,24 and 48 h after treatment in 2 groups,respectively(P<0.05).There were no significant differences between 2 groups of FiO2 before PS treatment and 0.5,1 and 6 h after PS treatment(P>0.05).The FiO2 of LISA group was lower than that in INSURE group at 12,24 and 48 h after PS treatment,and the difference were statistically significant(Z=3.315,4.312,4.280,P=0.001,<0.001,<0.001).⑤There were 18 cases(69.2%)without adverse reactions after treatment in LISA group,and 27 cases(75.0%)in INSURE group.There was no statistically significant difference between 2 groups(χ^2=0.252,P=0.615).In addition,there was no significant difference in the incidence of adverse reactions such as transcutaneous oxygen saturation(TcSO2)<85%and bradycardia between 2 groups during PS administration(P>0.05).Conclusions LISA technique can shorten MV duration and total oxygen consumption time in premature infants with RDS,and does not increase the adverse prognosis.