长疗程消炎痛治疗早产儿动脉导管未闭疗效和血浆6-酮-前列腺素F_1α变化的研究

Prolonged course of indomethacin for treatment of patent ductus arteriosus in preterm infants and 6-keto PGF_1α plasma level

目的探讨长疗程和常规疗程(短疗程)消炎痛关闭早产儿动脉导管的疗效、安全性及治疗前后前列腺素水平的变化。方法设计前瞻性双盲随机对照试验。体重≥1250g的动脉导管未闭(PDA)早产儿随机分为短疗程组(对照组)[0.2mg/(kg.次),确诊后即刻、12、36h各用1次]和长疗程组(试验组)[0.15mg/(kg.次),确诊后即刻、12、36、48h各用1次]。在治疗前后监测血浆6-酮-前列腺素F1α水平,评估临床症状和心脏彩超改变,主要观察指标为动脉导管的关闭情况及不良反应。结果一个疗程消炎痛治疗后试验组动脉导管关闭率高于对照组(75.0%比64.3%,RR1.17,95%CI0.823～1.654),少尿发生率低于对照组(7.1%比32.0%,RR0.22,95%CI0.053～0.938)。两组患儿血浆6-酮-前列腺素F1α在消炎痛治疗后较治疗前明显降低(280ng/L比295ng/L,P<0.001),但两组差异无统计学意义。结论长疗程消炎痛治疗早产儿PDA的疗效与短疗程相当,且降低了少尿的发生率,并未增加坏死性小肠结肠炎发生率。血浆6-酮-前列腺素F1α在应用消炎痛后降低。

Objective To determine the effectiveness and safety of prolonged versus short course of indomethacin for the treatment of patent ductus arteriosus（PDA）in preterm infants and the plasma 6-Keto PGF1α levels,pre-and post treatment.Methods Totally 56 infants of gestational ages 27 to 36 weeks were randomized to either short course regime group（0.2 mg/kg/dose in 36 hours）or prolonged low-dose indomethacin regime group（0.15 mg/kg/dose in 48 hours）.Echocardiography was done 24 to 72 hours after the last dose of the drug.Plasma 6-Keto PGF1α levels were tested before and after treatment.The primary outcome measure was ductal closure rate,and other outcomes,as well as side effects.Results Primary PDA closure occurred more in the prolonged course group（75% vs 64%,RR：1.17,95%CI：0.823-1.654）.The incidence of transient oliguria was higher in the short course dose group,32% vs 7%,RR：0.22,95% CI：0.053-0.938.6-Keto PGF1α plasma level）had statistical difference before and after treatment,but had no difference between the 2 dosing regiments.ConclusionsThere was no difference in efficacy between the 2 dosing regimens.The prolonged course indomethecin group had a lower rate of oliguria,with the similar rate of necrotizing enterocolitis and the other short-term morbidities and outcome.The prolonged course indomethecin may be as effective as the short course,with fewer side effects.Plasma level 6-KetoPGF1α dimished after the treatment.