极早产儿动脉导管未闭营救治疗疗效与安全性的前瞻性研究

Oral acetaminophen or high-dose ibuprofen as rescue treatment for very preterm infants with patent ductus arteriosus

目的:探讨有血流动力学意义的动脉导管未闭(haemodynamically significant patent ductus arteriosus,hsPDA)极早产儿早期保守管理失败后口服对乙酰氨基酚或高剂量布洛芬营救治疗hsPDA的疗效及安全性。方法:选择2020年5月至2022年11月徐州市中心医院新生儿重症监护病房收治的胎龄<32周、生后4~6 d诊断hsPDA的极早产儿进行前瞻性研究。若保守管理3~4 d后仍存在hsPDA,则给予营救治疗。随机分为对乙酰氨基酚组(口服15 mg/kg,每6 h 1次,共3 d)和高剂量布洛芬组(口服首剂20 mg/kg,24 h、48 h后各10 mg/kg)。治疗前后均进行超声心动图、血常规、血生化、B型尿钠肽、粪便隐血、颅脑彩超检查,记录尿量及并发症。应用SPSS 20.0统计软件进行数据分析。结果:共纳入对乙酰氨基酚组36例,高剂量布洛芬组37例,两组营救治疗成功率差异无统计学意义[80.6%(29/36)比78.4%(29/37),P>0.05]。营救治疗期间,两组上消化道出血、粪便隐血阳性、少尿、Ⅱ~Ⅲ期坏死性小肠结肠炎和Ⅲ~Ⅳ级脑室内出血发生率差异均无统计学意义(P>0.05)。营救治疗后,高剂量布洛芬组血清胱抑素C高于对乙酰氨基酚组[(1.72±0.29)mg/L比(1.58±0.26)mg/L]、24 h尿量低于对乙酰氨基酚组[(3.1±1.0)ml/(kg·h)比(3.7±0.7)ml/(kg·h)],差异均有统计学意义(P<0.05);两组血清肌酐、血小板计数、B型尿钠肽、谷丙转氨酶、血清总胆红素等差异均无统计学意义(P>0.05)。结论:hsPDA极早产儿早期保守管理失败后,生后7~10 d开始口服对乙酰氨基酚或高剂量布洛芬营救治疗,成功率均为80%左右,均较安全。口服高剂量布洛芬对肾功能的影响可能大于对乙酰氨基酚。

Objective To study the efficacy and safety of oral acetaminophen or high-dose ibuprofen as rescue treatment after failure of conservative management in very preterm infants(VPIs)with haemodynamically significant patent ductus arteriosus(hsPDA).Methods From May 2020 to November 2022,VPIs with hsPDA(gestational age<32 weeks and age 4~6 d)admitted to NICU of our hospital were prospectively enrolled.The rescue treatment was initiated if hsPDA still exist after 3~4 d of conservative management.The infants were randomly assigned into acetaminophen group(oral acetaminophen 15 mg/kg,once every 6 h for 3 d)and high-dose ibuprofen group(oral ibuprofen 20 mg/kg for the first dose,10 mg/kg each dose after 24 h and 48 h).Before and after rescue treatment,the following were recorded:echocardiography,complete blood count,biochemistry,B-type natriuretic peptide(BNP),fecal occult blood test(FOBT)and transcranial Doppler ultrasound.Urine output and complications were also examined.SPSS 20.0 was used for statistical analysis.Results A total of 36 cases were in the acetaminophen group and 37 in the high-dose ibuprofen group.The two groups showed similar efficacy as rescue treatment[80.6%(29/36)vs.78.4%(29/37),P>0.05].No significant differences existed in the incidences of upper gastrointestinal bleeding,positive FOBT,oliguria,stageⅡ-Ⅲnecrotizing enterocolitis and stageⅢ-Ⅳintraventricular hemorrhage between the two groups(P>0.05).After rescue treatment,the serum cystatin C in high-dose ibuprofen group was higher[(1.72±0.29)mg/L vs.(1.58±0.26)mg/L]and 24-hours urine output was lower[(3.1±1.0)ml/(kg·h)vs.(3.7±0.7)ml/(kg·h)]than the acetaminophen group(all P<0.05).No significant differences existed in serum creatinine,platelet count,BNP,alanine aminotransferase and total serum bilirubin between the two groups(P>0.05).Conclusions After failure of early conservative management in VPIs with hsPDA,when initiated within 7-10 d after birth,rescue treatment with oral acetaminophen or high-dose ibuprofen has a similar efficacy of 80%,and both drugs are safe.Oral high-dose ibuprofen may have a greater effect on renal function than acetaminophen.