早产儿动脉导管开放的处理

动脉导管开放(PDA)是早产儿常见病症,导致早产儿血流动力学不稳定,严重者可危及生命,应积极处理.药物关闭PDA仍是最有效、方便和经济的治疗方法,吲哚美辛一直是内科保守治疗的主要用药,PDA关闭率为46%～89%,但吲哚美辛有效血药浓度安全范围较窄,且可导致肾功能障碍、颅内出血、坏死性小肠结肠炎和肠穿孔等不良反应.近年国外采用布洛芬治疗早产儿PDA,取得较好疗效,关闭率为73.0%～95.5%,且对肾脏、脑及消化道血流动力学影响显著减少.药物治疗无效且严重影响心肺功能者可选择手术治疗.     

早产儿肺透明膜病伴动脉导管开放的早期诊断

２７例早产儿肺透明膜病（ＨＭＤ）伴呼吸衰竭需要呼吸机治疗者，在２．６９±１．１６天出现动脉导管开放（ＰＤＡ），导管开放时，均有心前区抬举搏动、心音亢强、周围脉搏增强、心脏有杂音、心率增快、脉区差增大，口服消炎痛后，导管关闭。关闭后，心率和脉压差显著下降，ＰａＯ２升高，ＰａＣＯ２下降，与开放时比较均有非常显著差异（Ｐ＜０．００１），提出在ＨＭＤ急性期出现心前区抬举搏动、心音亢强、心率加快、脉压差加大、ＰａＣＯ２升高等，可作为早期诊断动脉导管开放的临床依据。     

血小板聚集功能预测早产儿动脉导管持续开放的价值

目的探讨血小板聚集功能预测早产儿动脉导管持续开放的价值。方法前瞻性选择徐州中心医院新生儿重症监护病房2017年8月至2019年10月收治的出生胎龄<32周早产儿72例进行巢氏病例对照研究。生后第4~5天完成超声心动图检查,将符合有血流动力学意义的动脉导管未闭(hsPDA)诊断标准的早产儿纳入hsPDA组,按照1∶2匹配非hsPDA早产儿作为对照组。记录早产儿基本特征,检测血常规和血小板聚集功能。选用独立样本t检验和χ2检验进行数据的组间比较,二元Logistic回归分析和受试者工作特征曲线分析危险因素和预测价值。结果最终纳入hsPDA组24例(男16例),匹配对照组48例(男30例)。hsPDA组≥Ⅱ级新生儿呼吸窘迫综合征的比例高于对照组[67%(16/24)比27%(13/48),χ²=10.422,P=0.001]。hsPDA组血小板压积和二磷酸腺苷诱导血小板聚集率均低于对照组(0.0021±0.0009比0.0028±0.0009、0.21±0.10比0.32±0.07,t=-3.043、-5.093,P=0.004、<0.01),血小板平均体积大于对照组[(10.3±2.4)比(9.2±2.0)fl,t=2.713,P=0.033]。其他血小板参数(血小板计数、血小板分布宽度和大血小板比率)及诱导剂(胶原、肾上腺素和花生四烯酸)诱导血小板聚集率两组差异均无统计学意义(均P>0.05)。二磷酸腺苷诱导血小板聚集率低和血小板压积低是早产儿发生hsPDA的独立危险因素(OR=4.525、3.994,95%CI:1.305~15.689、1.143~13.958)。二磷酸腺苷诱导血小板聚集率具有预测早产儿发生hsPDA的中等价值(受试者工作特征曲线下面积为0.809,最佳预测界值为0.245,敏感度为0.67,特异度为0.86)。结论血小板聚集功能差和血小板压积低是出生胎龄<32周早产儿发生hsPDA的独立危险因素。血小板聚集功能预测早产儿动脉导管持续开放的价值中等。     

早产儿肺透明膜病伴动脉导管开放的早期诊断

２７例早产儿肺透明膜病（ＨＭＤ）伴呼吸衰竭需要呼吸机治疗者，在２．６９±１．１６天出现动脉导管开放（ＰＤＡ），导管开放时，均有心前区抬举搏动，心音亢强，周围脉搏增强，心脏有杂音，心率增快，脉压差增大，口服消炎痛后，导管关闭，关闭后，心率和脉压差显著下降，ＰａＯ２升高，ＰａＣＯ２下降，与开放时比较均有非常显著差异（Ｐ〈０．００１），提出在ＨＭＤ急性期出现心前区抬举搏动，心音亢强，心率加快，脉压差加大     

早产儿动脉导管持续开放相关并发症及预后分析

目的探讨动脉导管持续开放对早产儿的影响和危害。方法采用回顾性调查研究,选择2007—2010年我院新生儿科住院治疗的动脉导管未闭(PDA)早产儿,根据出院时或死亡前动脉导管关闭情况分为动脉导管关闭组和动脉导管持续开放组。比较两组早产儿相关并发症的发生情况、氧疗情况、预后及住院费用等多方面的差异。结果动脉导管持续开放组(59例)发生充血性心力衰竭、喂养不耐受和Ⅲ～Ⅳ级脑室内出血的比例、需要呼吸支持的比例及用氧时间均高于动脉导管关闭组(112例),差异有统计学意义[50.8%比32.1%,33.9%比17.9%,8.5%比0.9%,66.4%比32.1%,7.0天(3.0,13.0)比6.0天(0,9.8),P均<0.05];两组发生NEC、Ⅰ～Ⅱ级脑室内出血、支气管肺发育不良和早产儿视网膜病的比例差异无统计学意义(P>0.05)。导管持续开放组住院时间和住院费用均多于动脉导管关闭组[(26.3±14.9)天比(20.0±12.9)天,(21079±13166)元比(17761±10849)元,P均<0.05]。结论动脉导管持续开放可使早产儿相关并发症增加,对呼吸支持的要求增多,也增加了住院时间和费用。     

口服布洛芬治疗早产儿动脉导管未闭的疗效

目的观察口服布洛芬治疗早产儿动脉导管未闭(PDA)的疗效及安全性。方法发生症状性PDA的早产儿22例,出生体质量(1426.59±355.74)g,胎龄(29.95±2.53)周。用口服布洛芬混悬滴剂治疗,布洛芬10 mg/kg,共3次,间隔24 h。用药期间监测心率、血压、氧饱和度、血糖、尿量、胆红素、电解质。治疗结束后复查肾功能、血常规、超声心动图、头颅B超。结果经治疗14例(63.63%)PDA关闭,疗效与出生体质量有关,出生体质量≥1500 g疗效好于出生体质量<1500 g(P<0.05)。3例(13.64%)在PDA关闭后发生再开放。13例(59.10%)患儿用药后出现一过性少尿[尿量<1 mL/(kg.h)],均发生于第1次给药后;治疗前肌酐和尿素水平与治疗后比较无显著性差异(P>0.05)。血小板治疗前后比较无显著性差异(P>0.05)。10例(45.56%)发生喂养不耐受,经减少喂养量或暂停喂养后均好转。结论口服布洛芬治疗早产儿PDA有一定疗效,且安全,使用方便,但尚需进行早产儿药代动力学研究及临床对照研究以明确其疗效,制定有效治疗方案。     

早产儿动脉导管未闭高危因素分析

目的探讨早产儿动脉导管未闭(PDA)的危险因素。方法对2010年7月至2011年7月在我院新生儿监护病房住院的早产儿进行回顾性研究。其中出生48h后进行超声检查诊断PDA的患儿为病例组,按2.5∶1的比例从动脉导管关闭的早产儿中随机抽取对照组。将两组早产儿的产科合并症、宫内情况、早产儿相关疾病、生后干预及相关检验指标进行对照研究。单因素分析中有统计学意义的因素进行Logistic回归分析。结果共纳入病例组96例,对照组250例。单因素分析显示胎龄、出生体重、母亲产前用药情况、早产儿相关疾病及生后干预与PDA相关。趋势卡方检验等级效应分析显示,胎龄越小,出生体重越低,PDA发生率越高,Logistic回归分析提示感染和暂时性甲状腺功能低下是PDA的独立危险因素,胎龄为独立保护因素(OR值分别为2.183、2.935和0.806),P均<0.05。结论本研究中,早产儿PDA与小胎龄、低出生体重、合并感染及暂时性甲状腺功能低下密切相关。     

早产儿动脉导管未闭危险因素临床分析

目的 探讨早产儿动脉导管未闭(PDA)发生的有关危险因素.方法 对2008年1～12月在我院新生儿科住院751例早产儿进行回顾性分析,其中133例行超声心动图检查,48例诊断PDA为病例组,85例非PDA为对照组,对两组临床资料进行对照研究,应用Logistic回归模型分析.结果 单因素分析显示,胎龄、出生体重、母亲产前用激素、胎儿宫内窘迫、吸氧、出生窒息、呼吸衰竭、肺透明膜病、败血症、液体摄入、超声心动图检查时机与早产儿PDA的发生有关联,其OR值分别为2.636、2.755、0.311、12、0.431、3.692、3.038、7.085、2.282、2.581、1.026、0.474;Lo-gistic回归分析表明小胎龄、低出生体重、出生窒息、败血症是主要危险因素,其OR值分别是2.517、2.957、13.770、3.493,而母亲产前用激素、吸氧是主要保护因素,其OR值是0.208和0.127.结论 早产儿发生PDA与围生期多种因素有关,有针对性开展围生期保健是降低早产儿PDA的有效措施.     

布洛芬口服治疗动脉导管未闭早产儿的疗效及安全性

目的观察布洛芬治疗动脉导管未闭(PDA)早产儿的疗效及安全性。方法早产儿PDA 43例,根据有无并其他心脏畸形,分为单纯PDA组及复合型PDA组,单纯PDA组根据出生体质量分为≥1500 g及<1500 g组。均予以布洛芬口服治疗,观察布洛芬的疗效及其不良反应。结果单纯组PDA关闭率为80.78%,复合组关闭率为47.06%,两组有显著差异(χ2=5.981 P<0.01);体质量≥1500 g组关闭率为80.0%,<1500 g组关闭率为81.81%,两组无显著差异(χ2=0.38 P>0.05)。43例仅1例出现胃潴留,未观察到其他不良反应。结论布洛芬口服治疗早产儿单纯PDA疗效好,对复合型PDA也有一定效果。     

布洛芬治疗早产儿动脉导管未闭效果及影响因素

目的探讨口服布洛芬治疗早产儿动脉导管未闭（PDA）的疗效及其相关因素对治疗效果影响。方法选取发生症状性PDA早产儿42例,予口服或鼻饲布洛芬混悬滴剂,共3次,首剂10mg/kg,于24、48h后各予5mg/kg。观察内容包括每一疗程布洛芬治疗的效果和总布洛芬治疗的最终效果。记录相关因素包括性别、体质量、日龄、婴儿的宫内发育状况、治疗前动脉导管内径、首剂布洛芬应用时的日龄（h）及不良反应等。结果本组早产儿经布洛芬1个疗程治疗,PDA的关闭率为78.5%。经过2个疗程治疗后,最终关闭PDA的总有效率为85.7%。患儿出生体质量和首次布洛芬应用时间对PDA的关闭效果有显著影响（P〈0.05）。而孕周、婴儿性别、应用布洛芬前PDA内径和胎儿的宫内发育状况,对布洛芬的使用效果无影响（P〉0.05）。结论布洛芬对关闭早产儿PDA有良好效果,且较安全,其效果随着早产儿出生体质量增加而增强,首剂布洛芬应用时间越早,其PDA关闭率越高。     

Prophylactic ibuprofen therapy of patent ductus arteriosus in preterm infants

This study was aimed at evaluating the efficacy of ibuprofen in the prophylaxis of patent ductus arteriosus (PDA) in very preterm neonates and at detecting eventual side-effects. A total of 46 preterm neonates with gestational age under 31 weeks were randomly assigned at 2 h of life: 23 to the prophylaxis group and 23 to the control group. The prophylaxis group received intravenous treatment with ibuprofen lysine (10 mg/kg), followed by 5 mg/kg after 24 h and 48 h. No placebo was given to the control group. No PDA was demonstrated at 72 h of life in 20 of the 23 babies in the ibuprofen group (87%) nor in 7 of the 23 control neonates (30.4%). All neonates with PDA received treatment with indomethacin. One neonate in the prophylaxis group and three in the control group underwent surgical ligation. Prophylaxis with ibuprofen was not associated with any significant side-effect except for food intolerance. Conclusion Ibuprofen prophylaxis seems to be efficient in closing patent ductus arteriosus and in reducing indomethacin treatment. No significant early side-effects were found due to ibuprofen. Received: 1 April 1999 / Accepted: 30 November 1999     

Patent ductus arteriosus in preterm neonates

Failure of the ductus arteriosus to close within 48–96 hours of postnatal age results in a left to right shunt across the ductus and overloading of the pulmonary circulation. This is more likely to happen in premature neonates with respiratory distress syndrome. Deterioration in the respiratory status on day 3–4 in a ventilated neonate and unexplained metabolic acidosis may be the earliest indicators of a patent ductus arteriosus (PDA). Indomethacin is the main stay of medical management of PDA in preterm neonates. Guidelines for administration of indomethacin have been described in the protocol. Restricted fluid therapy may be beneficial in the prevention of PDA in preterm neonates. Presence of PDA in a term neonate should be investigated to rule out an underlying congenital heart disease.     

氨基末端脑钠肽前体预测早产儿症状性动脉导管未闭的价值

目的 探讨氨基末端脑钠肽前体(NT-proBNP)预测早产儿症状性动脉导管未闭(sPDA)的价值。方法 选择2014年6月至2015年4月出生、胎龄≤32周、48 h内超声心动图确定存在动脉导管的早产儿为研究对象,监测其临床表现,于生后3 d及5 d检测血清NT-proBNP水平并行超声心动图检查,根据患儿临床表现、超声心动图结果分为sPDA组及非症状性动脉导管未闭(asPDA)组,分析血清NT-proBNP水平与超声指标的关系,比较两组间相同日龄血清NT-proBNP水平,ROC曲线确定血清NT-proBNP水平预测sPDA的敏感性、特异性。结果 共69例早产儿纳入研究,其中sPDA组13例,asPDA组56例。血清NT-proBNP水平与动脉导管管径、左房内径与主动脉根部内径比值(LA/AO)呈正相关关系(分别r=0.856、0.713,均 PPCI:0.892~1.000,PCI:0.848~1.000,P结论 NT-proBNP可能是动脉导管分流量的量化指标;生后3 d 及5 d血清NT-proBNP水平的检测均有助于早期预测sPDA。     

Precordial contrast echocardiographic detection of patent ductus arteriosus in small preterm infants

Summary Clinical detection of patent ductus arterious (PDA) remains an important and challenging problem in the small preterm infant with respiratory distress. In this study, PDA was diagnosed in 28 small preterms using an improved contrast echocardiographic method. In these infants, the injection of saline into the aorta generated echoes which were imaged at the pulmonary valve. This was accomplished using a conventional M-mode ultrasound transducer applied at the usual precordial position. Contrast echo studies were compared with the degree of ductal patency shown by single film aortography. Ductal patency was detected by contrast echo in 29 of 31 instances of aortographically proven PDA. Indirect echo indices commonly used for detection of PDA (cardiac chamber enlargement) may be limited since factors other than left-to-right shunt can cause cardiac enlargement in distressed small preterms. This direct contrast echo technique is an easily performed, sensitive, qualitative method for confirmation of the diagnosis of PDA in small preterm infants. This work was supported in part by grant 5507 RR05551-17 from U.S. Public Health Service, Bethesda, Maryland Presented to members of the Cardiology Section at the 20th Annual Meeting of the Society for Pediatric Research, April 29–May 2, 1980, San Antonio, Texas     

口服消炎痛和布洛芬治疗早产儿动脉导管未闭的比较

目的：静脉注射消炎痛是早产儿动脉导管未闭的常规治疗方法,但治疗过程中常出现一些副作用,如少尿、消化道出血、脑血流灌注减少。近年来,静脉注射布洛芬已用于治疗早产儿动脉导管未闭。布洛芬治疗不会减少脑血流灌注,也不会影响胃肠道和肾脏的血流动力学。伊朗目前尚无消炎痛和布洛芬的静脉制剂供应。该研究旨在比较这两种药的口服制剂治疗早产儿动脉导管未闭的疗效和安全性。方法：36例胎龄小于34周经超声心动图确诊患有动脉导管未闭的早产儿被随机分为两组,每组18人。一组给予消炎痛口服,每次0.2 mg/kg,24 h给药 1 次,共3次。另一组给予布洛芬口服,共 3 次,间隔时间为24 h,首剂为 10 mg/kg,随后两次各 5 mg/kg。用药后观察导管闭合率、副作用、并发症及临床过程。结果：用药后布洛芬组18例患儿动脉导管都闭合（100％）,而消炎痛组18例中有15例患儿动脉导管闭合（83.3%）（P＞0.05）。两组疗效差异统计学无显著性意义。治疗前后两组的血清尿素氮和肌酐含量差异也无显著性意义。消炎痛组发生了3例（16.6%）坏死性小肠结肠炎,布洛芬组则无,差异有显著性意义 (P＜0.05)。治疗1个月后两组成活率均为 94%（17／18）。消炎痛组1例死于坏死性小肠结肠炎,布洛芬组1例死于败血症。结论：口服布洛芬治疗早产儿动脉导管未闭和口服消炎痛治疗一样有效,而且坏死性小肠结肠炎的发生率较口服消炎痛治疗低。［中国当代儿科杂志,2007,9（5）：399-403］     

早期早产儿动脉导管未闭发生的危险因素的病例对照研究

目的 探讨早期早产儿动脉导管未闭(PDA)发生的危险因素,为进一步减少早产儿PDA 的发生提供临床依据。方法 将2013 年1 月至2014 年12 月住院治疗的136 例诊断为有血流动力学意义的PDA(hs-PDA)的早期早产儿(胎龄≤ 32 周)设为病例组,按1:1 的比例从同期住院的早期早产儿中按匹配病例对照原则抽取136 例无hs-PDA 的早产儿作为对照组,两组匹配因素包括性别及胎龄。收集可能与PDA 发生有关的新生儿基本情况、母亲孕期及围产期情况等资料,应用多因素条件logistic 回归分析筛选PDA 发生的危险因素。结果 单因素分析结果显示:新生儿感染性疾病、新生儿呼吸窘迫综合征(RDS)、生后24 h 内血小板计数减低及低出生体重与hs-PDA 的发生相关(P<0.05)。多因素条件logistic 回归分析显示新生儿感染性疾病(OR=2.368)及生后24 h 内血小板计数减低(OR=0.996)是hs-PDA 发生的独立危险因素。结论 新生儿感染性疾病及生后24 h 内血小板计数减低会增加早期早产儿hs-PDA 的发生风险。     

Management of the patent ductus arteriosus in preterm infants

Management of the patent ductus arteriosus (PDA) is one of the most contentious topics in the care of preterm infants. PDA management can be broadly divided into prophylactic and symptomatic therapy. Prophylaxis with intravenous indomethacin in extremely low birth weight infants may reduce severe intraventricular hemorrhage. Echocardiography should be routinely used to confirm the presence of a PDA before considering symptomatic therapy. A symptomatic PDA can be managed conservatively, using pharmacotherapy or with procedural closure. Ibuprofen should be considered as the pharmacotherapy of choice for a symptomatic PDA. High-dose ibuprofen may be preferable, especially for preterm infants beyond the first 3 to 5 days of age. If pharmacotherapy fails (after two courses) or is contraindicated, procedural closure may be considered for infants with a persistent PDA with significant clinical symptoms in addition to echocardiographic signs of a large PDA shunt volume and pulmonary over-circulation.     

The use of non-steroidal anti-inflammatory drugs for patent ductus arteriosus closure in preterm infants

Over the last four decades, non-steroidal anti-inflammatory drugs have been widely used to induce closure of the patent ductus arteriosus (PDA) in preterm infants. Evidence to support this practice is lacking, despite performance of >50 randomized trials. The credibility of those trials may have been compromised by high rates of open treatment in controls, era of study prior to advent of modern practices, or inclusion of insufficient numbers of very immature infants. Meta-analyses show little impact of those factors on main conclusions. Essentially all trials reporting important long-term outcomes (other than mortality) initiated treatment within five days after birth, so no evidence regarding later treatment is available. Accruing clinical experience suggests that long-term outcomes are not compromised, and may be improved, with non-interventional management strategies. Future studies to identify preterm infants at greatest risk of potential harm from a persistent PDA, particularly after the second postnatal week, are urgently needed.