曲前列尼尔在治疗支气管肺发育不良合并肺动脉高压中的应用

The clinical effects of treprostinil in the treatment of pulmonary hypertension associated with bronchopulmonary dysplasia in preterm infants

目的探讨曲前列尼尔治疗支气管肺发育不良合并肺动脉高压(pulmonary arterial hypertension associated with bronchopulmonary dysplasia,BPD-PH)的疗效。方法回顾性分析2017年1月至2019年12月静脉输注曲前列尼尔治疗BPD-PH的患儿,收集患儿曲前列尼尔治疗时日龄、最大剂量、治疗持续时间、并发症、临床转归等,比较患儿曲前列尼尔治疗前、治疗1周后、药物达最大剂量后肺动脉收缩压与体循环收缩压之比(systolic pulmonary artery pressure/systolic blood pressure,sPAP/sBP)、氧合指数(oxygenation index,OI)变化,采用多个相关样本的非参数检验对数据进行统计学分析。结果共纳入6例患儿,男5例,女1例,重度PH 5例,中度PH 1例,胎龄(26.0±1.0)周,出生体重(735±170) g。与用药前相比,曲前列尼尔治疗1周后sPAP/sBP较前下降[1.1(0.8,1.2)比1.3(1.1,1.4)],差异有统计学意义(P<0.05),OI较前无明显变化[24.5(23.0,29.3) mmHg比26.0(23.3,27.3) mmHg],差异无统计学意义(P>0.05);曲前列尼尔达最大剂量后 sPAP/sBP较前下降明显[0.4(0.3,0.4)比1.1(0.8,1.2)],差异有统计学意义(P<0.05)。2例发生呕吐,1例腹泻,1例轻度水肿,无低血压、肝肾功能损害等明显药物不良反应。5例患儿存活,1例死于晚发型败血症。结论曲前列尼尔对BPD-PH患儿控制肺动脉压、改善临床预后有一定效果,但仅限于其他治疗效果差的BPD-PH患儿谨慎使用。

Objective To study the effects of treprostinil in the treatment of pulmonary hypertension associated with bronchopulmonary dysplasia(BPD-PH)in preterm infants.Method From January 2017 to December 2019,a retrospective analysis was conducted on preterm infants with BPD-PH receiving intravenous treprostanil therapy.The timing,dosage and duration of treprostanil,the general information,complications and clinical outcomes of the infants were collected.Ratio of pulmonary artery systolic pressure to systemic systolic pressure(sPAP/sBP)and oxygenation index(OI)of the infants were compared among different timepoints(before treprostinil treatment,one week after the treatment and after reaching the maximum dose).Nonparametric tests were used for statistical analysis.Result A total of 6 infants were included,5 males and 1 female,5 with severe PH and 1 with moderate PH.The gestational age was(26.0±1.0)weeks and the birth weight was(735±170)g.sPAP/sBP was significantly decreased after 1 week and after reaching the maximum dose than before treprostinil treatment[1.1(0.8,1.2),0.4(0.3,0.4)vs.1.3(1.1,1.4),P<0.05].No significant changes were found among the three timepoints in OI(P>0.05).2 cases had vomiting,1 case had diarrhea,1 case had mild edema and no severe adverse effects such as hypotension,liver and/or kidney dysfunction occurred during the treatment.5 patients survived and 1 died of late-onset sepsis.Conclusion Treprostinil may improve the clinical prognosis and the survival rate of refractory BPD-PH infants and may be considered when all other treatments show poor effects.