摘要
目的了解布洛芬或扑热息痛初始治疗和高剂量布洛芬营救治疗早产儿血流动力显著异常动脉导管未闭(hsPDA)的疗效及安全性。方法选择2016年10月至2019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hsPDA早产儿。初始治疗随机分为布洛芬组(口服布洛芬10 mg/kg,24 h及48 h后5 mg/kg)、扑热息痛组(口服扑热息痛15 mg/kg,每8小时1次,共3d)和保守管理组(口服注射用水1 ml/kg,24 h及48 h后0.5 ml/kg)。治疗失败者给予高剂量布洛芬营救治疗(口服布洛芬20 mg/kg,24 h及48 h后10 mg/kg)。治疗前后均查超声心动图、血肌酐、胱抑素C、谷丙转氨酶、总胆红素、大便潜血、头颅彩超、留取尿液2 ml备查前列腺素E_(2),记录尿量及并发症等。结果共计纳入110例患儿,其中布洛芬组38例、扑热息痛组37例、保守管理组35例。布洛芬组[71.1%(27/38)]和扑热息痛组[70.3%(26/37)]初始治疗成功率均高于保守管理组[40.0%(14/35)],差异有统计学意义(P=0.008、0.010)。给予高剂量布洛芬营救治疗31例,成功率58.1%(18/31)。初始治疗期间3组患儿少尿、上消化道出血、大便隐血阳性、Ⅲ~Ⅳ级脑室内出血和≥Ⅱ期坏死性小肠结肠炎等发生率相似(均P>0.05);营救治疗期间上述并发症发生率与初始治疗期间比较差异无统计学意义[6.5%(2/31)比6.4%(7/110)、3.2%(1/31)比4.5%(5/110)、12.9%(4/31)比6.4%(7/110)、0比4.5%(5/110)、3.2%(1/31)比1.8%(2/110),均P>0.05]。各组治疗前后血肌酐和谷丙转氨酶水平差异均无统计学意义(P>0.05)。血清胱抑素C在布洛芬组[(0.44±0.17)μmol/L]和扑热息痛组[(0.18±0.09)μmol/L]治疗后均升高(t=-15.70、-14.64;均P<0.001),且布洛芬组升高幅度更大(P<0.001)。尿前列腺素E_(2)在布洛芬组[(-11.63±3.70)ng/L]和扑热息痛组[(-4.89±1.91)ng/L]治疗后均下降(t=15.57、7.03;均P<0.001),且布洛芬组下降幅度更大(P<0.001)。高剂量布洛芬营救治疗后,血清胱抑素C略升高,前后差异无统计学意义[(1.67±0.17)mg/L比(1.71±0.21)mg/L;t=-1.12,P=0.273]。结论布洛芬或扑热息痛初始治疗、高剂量布洛芬营救治疗均能有效地促进早产儿hsPDA关闭,治疗成功率相似,均高于保守管理,均未明显增加并发症发生率,但应注意监测尿量和血清胱抑素C等肾功能指标。高剂量布洛芬相对安全,可作为营救治疗措施之一。
Objective To investigate the efficacy and safety of initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen in preterm infants with haemodynamically significant patent ductus arteriosus(hsPDA).Methods The preterm infants(gestational age≤32 weeks)with hsPDA who were admitted to neonatal intensive care unit(NICU)of Xuzhou Central Hospital from October 2016 to November 2019 were enrolled in the study.A total of 110 eligible cases were included and randomly divided into three groups for initial treatment:38 cases received oral ibuprofen 10 mg/kg,and 5 mg/kg after 24 h and 48 h(ibuprofen group),37 cases received oral paracetamol 15 mg/kg,q.8.h for 3 d(paracetamol group)and 35 cases received oral injection water 1 ml/kg,and 0.5 ml/kg after 24 h and 48 h(conservative management group).The preterm infants who failed in the initial treatment were given high-dose ibuprofen for rescue treatment(oral ibuprofen 20mg/kg,and 10 mg/kg after 24 h and 48 h).Serum creatinine,cystatin C,glutamic-pyruvic transaminase(GPT),total bilirubin,fecal occult blood and urinary prostaglandin E_(2) were measured;echocardiography and brain color Doppler ultrasonography examinations were performed before and after treatment.Urine output and complications were recorded.The data were analyzed by ANOVA,t-test,non-parametric test,chi-square test and Pearson correlation coefficient with SPSS 20.0 statistical software.Results During initial treatment,the success rates of ibuprofen group and paracetamol group were higher than that of conservative management group[71.1%(27/38)and 70.3%(26/37)vs.40.0%(14/35),P=0.008 and 0.010].Thirty one patients,who failed in initial treatment,received rescue treatment(8,7,16 cases from ibuprofen,paracetamol and conservative groups,respectively).The success rate of rescue treatment with high-dose ibuprofen was 58.1%(18/31).During initial treatment,there were no significant differences in the incidence of oliguria,upper gastrointestinal bleeding,positive fecal occult blood tests,Ⅲ-Ⅳ grade intraventricular hemorrhage,and≥Ⅱ stage necrotizing enterocolitis among the three groups(all P>0.05).There were no significant differences in the incidence of above complications between rescue treatment and initial treatment[6.5%(2/31)vs.6.4%(7/110),3.2%(1/31)vs.4.5%(5/110),12.9%(4/31)vs.6.4%(7/110),0 vs.4.5%(5/110),3.2%(1/31)vs.1.8%(2/110),all P>0.05].The changes of serum creatinine and GPT before and after treatment were not significant in all groups(P>0.05).Serum cystatin C were increased in both ibuprofen group[(0.44±0.17)μmol/L]and paracetamol group[(0.18±0.09)μmol/L]after treatment(t=-15.70,-14.64;P<0.001),and the increase in ibuprofen group was greater than that in paracetamol group(P<0.001).Urinary prostaglandin E_(2) were decreased in both ibuprofen group[(-11.63±3.70)ng/L]and paracetamol group[(-4.89±1.91)ng/L]after treatment(t=15.57,7.03;P<0.001),and the decrease in ibuprofen group was greater than that in paracetamol group(P<0.001).Serum cystatin C was not significantly increased after high dose ibuprofen rescue treatment[(1.67±0.17)mg/L vs.(1.71±0.21)mg/L;t=-1.12,P=0.273].Conclusion Both initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen can effectively promote hsPDA closure in preterm infants without increase of complications.However,renal function indexes such as urine output and serum cystatin C should be monitored.The high-dose ibuprofen is relatively safe,and can be used as one of rescue treatment.
作者
李敏
王乐瑶
赵丹丹
杨波
雷红林
任漪
黄迪
高翔羽
Li Min;Wang Leyao;Zhao Dandan;Yang Bo;Lei Honglin;Ren Yi;Huang Di;Gao Xiangyu(Department of Neonatology,Xuzhou Central Hospital(The Xuzhou Clinical College of Xuzhou Medical University),Xuzhou 221009,China)
出处
《中华全科医师杂志》
2022年第3期250-257,共8页
Chinese Journal of General Practitioners
基金
徐州市科技局科研项目(KC16SH051)
江苏省妇幼保健协会科研项目(FYX201902)
江苏省妇幼健康科研项目(F202063)
徐州市科技局重点研发计划(KC20069)。
关键词
动脉导管未闭
婴儿
早产
布洛芬
醋氨酚
Ductus arteriosus,patent
Infant,premature
Ibuprofen
Acetaminophen