Closure of the ductus arteriosus with indomethacin in ventilated neonates with respiratory distress syndrome. Effects of pulmonary compliance and ventilation

The reported effects of indomethacin on pulmonary compliance are variable depending upon the patient population and on the degree to which indomethacin resulted in successful ductal closure. Eleven fluid-restricted, furosemide-treated premature infants being mechanically ventilated for respiratory distress syndrome (RDS) who also had a significant patent ductus arteriosus (PDA) had pulmonary function testing performed before and after successful closure of the PDA. The diagnosis of a significant PDA was made by clinical and echocardiographic criteria. Indomethacin was administered at a dosage of 0.2 mg/kg/dose every 12 to 18 h for 1 to 3 doses. To control for the 48-h time interval to achieve ductal closure, nine premature infants being ventilated for RDS but who did not have a significant PDA also had pulmonary function evaluations performed before and after the 48 h. Also, to control for the independent effect of fluid restriction and diuretic therapy on pulmonary compliance, eight such premature infants with a PDA had pulmonary function evaluations performed at a 48-h interval. Successful closure of the ductus with indomethacin was associated with an improvement in compliance and ventilation parameters in all infants in the indomethacin-treated infants. In the indomethacin-treated group, the mean percent improvements were noted in the following parameters: CLdyn, 59.2%; CLI, 78.3%; CLE, 63.3%; VT, 63.3%; VE, 54.6%. There were no significant changes in the pulmonary functions in the 48-h RDS or the 48-h PDA fluid-restricted, furosemide-treated control groups. In conclusion, successful closure of the ductus with indomethacin causes a significant improvement in compliance and ventilation parameters in infants being mechanically ventilated for RDS.     

极低体重早产儿动脉导管未闭的床旁外科治疗

目的 探讨极极低体重早产儿动脉导管未闭（PDA）床旁外科治疗的临床效果.方法 纳入24例诊断PDA的极低体重早产儿,行床旁开胸PDA结扎术,从术前准备、麻醉管理及手术方法三个方面分析极低体重早产儿床旁PDA手术的特点及临床疗效.结果 24例极低体重早产儿床旁手术均取得成功,平均手术时间为（30.8±12.5） min,出血量平均为（10.5±4.6）ml,呼吸机辅助平均时间为（6.4±2.5）d.术后平均动脉压均有不同程度升高,脉压增大.所有患儿术后顺利拔除气管插管,围术期无意外及明显并发症发生.术后6个月所有患儿均无动脉导管再通和肺炎发作.结论 对于极低体重早产儿,实施床旁PDA手术安全可行.     

Surgical Closure of Patent Ductus Arteriosus in Preterm Low Birth Weight Infants

Background and Aim of the Study. In many preterm low‐birth‐weight infants, ductus arteriosus fails to close spontaneously. This study evaluates the results of surgical ligation of symptomatic patent ductus arteriosus (PDA) in preterm low birth weight infants. Methods. We reviewed the medical records of all infants undergoing surgical closure of PDA from January 1987 to December 2005. Demographic data, age and weight at operation, surgical technique to close PDA and outcome were analyzed. Results. One hundred and forty‐five infants underwent surgical closure of PDA in which either indomethacin treatment had failed or was contraindicated. The mean gestational age was 25.5 ± 2.3 (range 24–36 weeks) and the mean birth weight was 837.7 ± 277.2 g (450–1000 g). The average age and weight at operation were 14.1 (±1.8) days and 881.7 g (±338.1), respectively. PDA was surgically closed by left thoracotomy using either nonabsorbable suture (73%) or hemoclips (27%). Postoperative complications occurred in 10 patients, which included intraoperative bleeding (6), pneumothorax (1), left vocal cord paralysis (1), lymphatic leak (1), and injury to left phrenic nerve (1). There was no mortality related to surgical closure of PDA. Conclusion. We conclude that surgical closure of hemodynamically significant PDA is safe and effective in preterm low birth weight infants when pharmacological treatment is ineffective or contraindicated. The associated morbidity is minimal and no surgery‐related mortality was observed.     

Effects of a clinically detectable PDA on pulmonary mechanics measures in VLBW infants with RDS.

We examined the effect of a clinically detectable patent ductus arteriosus (PDA) and its successful treatment with indomethacin on serial measures of pulmonary mechanics in 10 very-low-birthweight (VLBW) intubated infants with respiratory distress syndrome (RDS). Pulmonary mechanics were measured by the passive expiratory flow technique. Total respiratory system compliance (Crs) gradually improved as RDS resolved. However, a significant decrease in mean Crs was associated with the development of a clinically detectable PDA, ranging from 1.51 +/- 0.21 to 0.90 +/- 0.08 mL/cmH2O/m (P less than 0.05). We also noted an increase in mean Crs, from 0.90 +/- 0.08 to 1.49 +/- 0.21 mL/cmH2O/m (P less than 0.05), after successful treatment of a PDA with indomethacin. Total respiratory system resistance (Rrs) did not change. We conclude that a clinically significant PDA is associated with a decreased Crs and that successful treatment of a PDA with indomethacin is associated with an improvement in lung compliance. These findings imply that the development of a clinically detectable PDA and its subsequent treatment complicates the interpretation of pulmonary mechanics data in VLBW infants with RDS.     

Blood L-arginine levels in early respiratory distress syndrome

L-arginine is the precursor of nitric oxide which plays an important role on pulmonary circulation and pulmonary vascular tone. Our aim was to compare the levels of L-arginine between infants with respiratory distress syndrome and infants without respiratory distress syndrome and to determine the relationship between plasma L-arginine concentrations and severity of disease. Thirty premature infants who were admitted to our neonatal intensive care unit were included the study. Seventeen of these infants with respiratory distress syndrome were study group and the other 13 infants without respiratory distress syndrome served as controls. Blood collection was made before any treatment or intervention given to infants and tandem mass spectrometry was used for laboratory testing. In the respiratory distress syndrome group mean L-arginine level was 33.0 (+/- 11.5) mM/l, and in controls it was 79.0 (+/- 23) mM/l. This difference was statistically significant (P < 0.05). There was a reverse relationship between L-arginine levels and oxygenation index (r = 0.732, P = 0.001). If level of L-arginine is low or insufficient in respiratory distress syndrome patients' nitric oxide level would decrease in pulmonary circulation and results increased pulmonary resistance and severity of respiratory distress syndrome. We concluded that L-arginine levels are low in patients with rspiratory distress syndrome and for further investigations, supplementation of respiratory distress syndrome patients with L-arginine may decrease disease severity.     

婴幼儿动脉导管未闭的微创外科治疗研究

目的总结左腋下直小切口对婴幼儿动脉导管未闭(PDA)患儿微创伤治疗的经验.方法采用左腋下腋中线直小切口第4肋间进胸方法,对72例婴幼儿PDA患儿施行动脉导管结扎术.结果所有病例术野显露清楚,术毕不放置胸腔闭式引流,无手术死亡病例,无喉返神经损伤、导管破裂等并发症,住院时间短(平均住院4.2 d).随访2个月至8年,无导管再通和动脉瘤形成.结论左腋下直小切口动脉导管结扎术, 更适用于婴幼儿PDA患儿,手术安全可靠,并发症少,远期效果满意.     

Noninvasive assessment of indomethacin therapy in patent ductus arteriosus in preterm infants

We performed 138 serial two-dimensional (2-D), M-mode, and Doppler echocardiographic studies to assess the efficacy of intravenous indomethacin (INDO) therapy for patent ductus arteriosus (PDA) in 41 preterm infants. Nine infants expired without sufficient echo data to warrant inclusion in the study. Of the remaining 32 infants, 12 (Group 1) required ligation despite INDO therapy, 18 (Group 2) responded to INDO or spontaneously closed their PDAs, and 2 were transferred to other hospitals with their PDAs still open and were lost to follow-up. The presence of PDA was verified by 2-D echo visualization of the ductus (high parasternal short-axis views) and Doppler demonstration of high velocity ductal flow toward the main pulmonary artery. The ratio of PDA lumen to aortic root inner diameter (Ao) was measured as well. Indication for surgical ligation was failure of the PDA to close after 3 or more courses of INDO. In Group 1, the PDA/Ao ratio was 0.45 +/- 0.10 standard error of the mean (SEM) pre-INDO, and 0.40 +/- 0.12 SEM post-INDO (immediately before ligation). In Group 2, the PDA/Ao ratio was 0.42 +/- 0.11 SEM pre-INDO, and 0.19 +/- 0.14 SEM at the end of INDO course (p less than 0.001), with 12 infants showing no ductal flow by Doppler. Follow-up six months after INDO therapy has shown no residual murmurs or other evidence of PDA in any INDO-closed infant. Five of the 18 infants have undergone repeated echocardiographic studies, all of which were negative for PDA patency or flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

危重早产儿动脉导管未闭的床旁外科治疗

目的:总结内科药物治疗无效的早产儿动脉导管未闭(patent ductus arteriosus,PDA)床旁外科手术的经验。方法:回顾性分析2009年10月至2011年10月,43例层流病房行床旁动脉导管结扎(或钳夹)术的手术过程及术后转归进行总结。结果:接受床旁动脉导管结扎(或钳夹)术的手术的早产PDA患儿共43例,男性28例、女性15例,胎龄26～34 w,出生体质量0.75～2.31 kg,平均1.44 kg。其中低出生体质量22例、极低出生体质量18例、超低出生体质量3例。手术时患儿年龄为3～30 d,平均7.2 d,体质量和出生体质量无明显差别。43例中有39例使用异丁苯丙酸治疗失败,4例因伴有严重出血倾向未予异丁苯丙酸而直接手术治疗。39例药物治疗的患儿中,治疗前均未发现药物治疗禁忌,但在治疗过程中出现肺出血、颅内出血及坏死性小肠结肠炎等并发症或者无效,而改行外科手术。术前43例中40例使用呼吸机辅助治疗,术前呼吸机治疗时间最长29 d,其中8例病情突然恶化行急诊手术。术后1例出现喉返神经损伤,所有患儿无术中死亡、无术中大出血等并发症。4例(9%)术后不能脱离呼吸机而死亡,其余均痊愈出院。结论:经内科保守治疗无效或内科药物治疗禁忌的早产儿PDA,行床旁动脉导管外科结扎(或钳夹)术是治疗早产儿PDA的相对安全有效的方法。     

极低体重早产儿动脉导管未闭的治疗

目的:探讨极低体重早产儿动脉导管未闭(PDA)的治疗方法。方法:本研究回顾性分析6例经外科手术治疗的PDA的极低体重早产儿的临床特点。结果:4例患者布洛芬治疗失败、2例患者因药物禁忌行动脉导管结扎术,术后由对呼吸机依赖转为3～4d过渡脱机,胃肠内喂养耐受性及体重增加显著改善[(45±41)∶(258±77)g/周,P<0.001],5例存活患者均无手术并发症,1例患者死于早产儿并发症。结论:对于有手术指征的PDA的极低体重早产儿,外科手术结扎是安全而有效的方法。     

A rational approach to ligation of patent ductus arteriosus in the neonate.

During a 23-month period, 25 premature infants underwent ligation of a patent ductus arteriosus performed in the neonatal intensive care unit utilizing a limited posterolateral muscle-retracting incision. This approach afforded adequate exposure with minimal surgical time and trauma. All infants manifested severe respiratory distress and congestive heart failure. Both standard and contrast echocardiographic studies were used for noninvasive preoperative evaluation. Echocardiographic study proved to be a highly reliable and sensitive indicator of ductal patency. Eight infants (32 percent) died at 8 to 225 days of age. The primary cause of death was progressive pulmonary disease with subsequent failure of multiple organ systems. Seventeen (68 percent) of the 25 infants survived to leave the hospital. Advantages of ligation of a patent ductus arteriosus in the neonatal intensive care unit include the elimination of problems of transportation (thermoregulation, ventilation, and loss of lines) and continuity of ongoing care and monitoring. The standard facilities of the neonatal intensive care unit proved completely satisfactory for ligation of a patent ductus arteriosus. Ligation in the neonatal intensive care unit is suggested to minimize potential complications of care in the operating room and transport of these critically ill infants.     

Overview of transcatheter patent ductus arteriosus closure in preterm infants

Clinically significant patent ductus arteriosus (PDA) has been associated with significant morbidity in extremely low birth weight (ELBW) infants. Current management of ELBW infants with hemodynamically significant PDA includes supportive treatment, pharmacological therapy, and surgical ligation. All of these therapeutic options have their advantages and limitations. More recently, transcatheter PDA closure has been described as a viable option in this population. In this paper, we provide a comprehensive review of this emerging procedure.     

Transcatheter closure of the patent ductus arteriosus in adults using the gianturco coil

Background and hypothesis: Although results of surgical ligation of the patent ductus arteriosus (PDA) in the pediatric age group are excellent, surgical management of the adult with a PDA may be more problematic. The PDA that presents in adulthood may be calcified and friable, rendering simple ligation via a thoracotomy difficult, inadequate, and hazardous. Patch closure of the ductus arteriosus from either the aortic or pulmonary artery orifice using cardiopulmonary bypass or transient aortic cross-clamping is necessary but increases surgical risks. Furthermore, older patients with diseases unrelated to their PDA and patients with Down's syndrome may have higher risks with intubation, general anesthesia, and surgery. Early results of percutaneous transcatheter occlusion of the PDA with Gianturco coils performed under sedation and local anesthesia are promising. Methods: Six adults with mean age of 39.1 years (range 23.1–62.0 years) were found to have an isolated PDA with mean minimum diameter of 2.7 mm (range 1.0–5.0 mm) at cardiac catheterization. All underwent percutaneous transcatheter occulsion of the PDA using Gianturco coils. Results: Coil implantation was successful in all patients. There were no complications and all were discharged home within 24 hours. Complete ductal occlusion was seen immediately in 4 of 6 patients (67%) while 2 of 6 (33%) had small residual leaks. However, complete occlusion was achieved in all patients by 6 months following the procedure. Conclusion: Transcatheter occlusion of the PDA using coils is safe and efficacious in adults.     

"Agenesis" of ductus arteriosus associated with the syndrome of tetralogy of Fallot and absent pulmonary valve.

Four infants with the severe form of the syndrome of tetralogy of Fallot and absent pulmonary valve are described. All had severe respiratory distress due to bronchial compression from massively dilated pulmonary arteries. The clinical diagnosis was confirmed by cardiac catheterization and angiocardiography. The infants died at age 3, 5, 30 and 90 days, respectively. Autopsy revealed, in addition to the usual components of the syndrome, absence of the ductus arteriosus or its remnants. The possible relation of "agenesis" of the ductus arteriosus to the pathogenesis of the severe form of this syndrome is discussed and pertinent studies are reviewed.     

Congenital tuberculosis in a premature infant

Congenital tuberculosis was first suspected in a premature infant with patent ductus arteriosus (PDA), progressive respiratory distress and septic shock, when an enlarged mediastinal lymph node was noted intraoperatively at the time of PDA ligature. Culture revealed Mycobacterium tuberculosis. The asymptomatic mother was subsequently diagnosed with urogenital tuberculosis.     

Echocardiographic Assessment of Ductal Anatomy in Premature Infants—Lessons for Device Design

Objective: Echocardiographic analysis of patent ductus arteriosus (PDA), proximal left main pulmonary artery (LPA) and descending thoracic aorta (Ao) dimensions in preterm infants who undergo surgical ligation of the PDA. A discussion for percutaneous ductal occlusion in preterm infants. Methods: Echocardiographic analysis of the LPA diameter, PDA diameter, PDA length, and descending thoracic aorta diameter in 55 preterm infants who underwent surgical ligation of the PDA from 2004 to 2008. Patients were stratified by weight into four groups: those less than 750 g, 751–1,000 g, 1,001–1,250 g, and those greater than 1,250 g. Mean and standard deviation for each structure dimension was calculated in each weight group. Structural dimensions were compared between groups using ANOVA for multiple comparisions. Results: The mean patient weight was 1,018 g (560–2,400 g). The mean ductal length was 4.1 mm (2.5–5.3 mm). The mean ductal diameter was 2.2 mm (1.5–3.6 mm). The mean LPA diameter was 3 mm (1.5–4.5 mm). The mean aortic diameter was 4.3 mm (2.7–7.8 mm). The alpha value for between weight groups for PDA length was 0.21, PDA diameter 0.16, LPA diameter 0.39, and aortic diameter 0.1. Discussion: No statistical significance was seen when comparing structure dimension by weight. This suggests uniform structural dimensions across a broad weight distribution in this patient population. To date, there has been no attempt to standardize dimensions of these vascular structures. The information gathered in this study may be useful in developing an implantable device for ductal occlusion in preterm infants. (ECHOCARDIOGRAPHY 2010;27:575‐579)     

Anomalous Left Coronary Artery from the Pulmonary Artery in a Preterm Infant: Presentation after Ligation of Ductus Arteriosus

Surgical or medical closure of a patent ductus arteriosus (PDA) is a very common practice in premature infants in the neonatal intensive care unit, but often the coronary arteries are not delineated prior to closure. In this report, a 32‐week gestational age premature infant who underwent surgical ligation of a PDA developed new‐onset left ventricular systolic dysfunction. A repeat echocardiogram noted an anomalous left coronary artery from the pulmonary artery. Successful left coronary artery reimplantation with rapid normalization of left ventricular systolic function occurred. As previously not reported, ligation of a PDA in a premature infant can unmask anomalous left coronary artery from the pulmonary artery. Surgical left coronary artery reimplantation is the mainstay of therapy and should be performed to establish normal coronary blood flow, even in a premature, low birth weight infant.     

Exosurf treatment investigational new drug phase: effect of an individualized third dose in infants with respiratory distress syndrome.

Of 95 infants treated with the synthetic surfactant, Exosurf, under a Treatment Investigational New Drug protocol, 17 received one dose, 40 received two, and 38 received three doses. Seventy-six (80%) of the infants were treated by rescue protocol. We retrospectively reviewed the clinical course of the 67 surviving rescue infants. We found that, compared to one- and two-dose infants, those treated with three doses of Exosurf were more premature, smaller, required a longer ventilator course, and had more frequent complications, including patent ductus arteriosus (PDA), intraventricular hemorrhage, nosocomial pneumonia, and apnea. They required higher oxygen concentrations starting 8 hr after their first dose and higher mean airway pressure (MAP) from the time of their second dose. These trends continued during all subsequent time points, as compared to infants treated with two doses. The third dose was administered an average of 17 hr after the second, resulting in little change of MAP, but some reduction in oxygen requirements. By 24 hr after the last dose, only 4% of three-dose infants were extubated compared with 30% of the two-dose and 71% of one-dose infants. In conclusion, repeated administration of Exosurf is not equally effective in every treated infant with respiratory distress syndrome (RDS) and complications of prematurity may affect or accompany poor response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Real-time Doppler color flow mapping for detection of patent ductus arteriosus

In this study, ultrasound Doppler color flow mapping systems were utilized to examine flow in the pulmonary artery in 31 premature and term infants (aged 4 hours to 9 months) with patent ductus arteriosus accompanying respiratory distress syndrome, as an isolated lesion, or with patent ductus in association with other cyanotic or acyanotic congenital heart disorders. The flow mapping patterns were compared with those of a control population of 15 infants who did not have patent ductus arteriosus. In unconstricted ductus arteriosus, the flow from the aorta into the pulmonary artery was detected in late systole and early diastole and was distributed along the superior leftward lateral wall of the main pulmonary artery from the origin of the left pulmonary artery back in a proximal direction toward the pulmonary valve. In constricted patent ductus arteriosus, or especially in a ductus in association with cyanotic heart disease, the position of the ductal shunt in the pulmonary artery was more variable, often directed centrally or medially. Waveform spectral Doppler sampling could be performed in specific positions guided by the Doppler flow map to verify the phasic characteristics of the ductal shunt on spectral and audio outputs. Shunts through a very small patent ductus arteriosus were routinely detected in this group of infants, and right to left ductal shunts could also be verified by the Doppler flow mapping technique. This study suggests substantial promise for real-time two-dimensional Doppler echocardiographic flow mapping for evaluation of patent ductus arteriosus in infants.     

Compliance measurement in respiratory distress syndrome: the prediction of outcome

Dynamic compliance (Cdyn) measurements within the first three days of life predicted survival in 60 preterm infants suffering from respiratory distress syndrome. Cdyn was measured in 47 survivors at 2.3 +/- 1.4 days of life and in 13 nonsurvivors on 2.7 +/- 1.7 days. All nonsurvivors died from respiratory failure within the first two weeks of life. Mean Cdyn of the survivors was 0.83 +/- 0.33 ml/cm H2O and of the nonsurvivors 0.35 +/- 0.19 ml/cm H2O (p less than 0.001). Cdyn values below 0.45 ml/cm H2O predicted 11 of 13 deaths in infants, and Cdyn measurements above this value predicted 45 of 47 survivals, with a specificity of 81% and a sensitivity of 89%. Eleven of the survivors, who subsequently developed bronchopulmonary dysplasia (BPD), had a mean Cdyn of 0.56 +/- 0.23 ml/cm H2O. When these infants were matched with infants of comparable weight without evidence of BPD, the BPD group had a significantly lower Cdyn (p less than 0.05). Cdyn measurements during the first three days of life are useful in predicting outcome of respiratory failure secondary to respiratory distress syndrome.     

The timing of spontaneous closure of the ductus arteriosus in infants with respiratory distress syndrome

Previous studies evaluating the incidence of patent ductus arteriosus have not made a distinction between physiologic ductal patency and abnormally persistent ductus arteriosus. However, it has recently been shown that healthy premature infants without respiratory distress syndrome (RDS) undergo spontaneous closure of the ductus arteriosus in the first 4 days of life at times comparable to full-term infants. Thus, ductal patency within this time frame would appear to be physiologic. Although sick premature infants are well recognized to be at risk for ductal shunting, the purpose of this investigation was to evaluate systematically the actual impact that RDS has on duration of ductal shunting by assessing the timing of spontaneous functional closure. The presence of ductal shunting was evaluated using echocardiographic color flow Doppler techniques. Thirty-six premature infants (30 to 37 weeks gestational age) were evaluated. By the fourth day of life, only 4 of 36 (11.1%) of the infants continued to have evidence of ductal patency. The remainder of the infants underwent spontaneous functional closure of the ductus arteriosus at times comparable to healthy infants without RDS. For most infants greater than or equal to 30 weeks gestation, uncomplicated RDS does not alter the usual timing of functional ductal closure.