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    Patent Ductus Arteriosus of the Preterm Infant. Hamrick Shannon E G,Sallmon Hannes,Rose Allison T,Porras Diego,Shelton Elaine L,Reese Jeff,Hansmann Georg Pediatrics Postnatal ductal closure is stimulated by rising oxygen tension and withdrawal of vasodilatory mediators (prostaglandins, nitric oxide, adenosine) and by vasoconstrictors (endothelin-1, catecholamines, contractile prostanoids), ion channels, calcium flux, platelets, morphologic maturity, and a favorable genetic predisposition. A persistently patent ductus arteriosus (PDA) in preterm infants can have clinical consequences. Decreasing pulmonary vascular resistance, especially in extremely low gestational age newborns, increases left-to-right shunting through the ductus and increases pulmonary blood flow further, leading to interstitial pulmonary edema and volume load to the left heart. Potential consequences of left-to-right shunting via a hemodynamically significant patent ductus arteriosus (hsPDA) include increased risk for prolonged ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis or focal intestinal perforation, intraventricular hemorrhage, and death. In the last decade, there has been a trend toward less aggressive treatment of PDA in preterm infants. However, there is a subgroup of infants who will likely benefit from intervention, be it pharmacologic, interventional, or surgical: (1) prophylactic intravenous indomethacin in highly selected extremely low gestational age newborns with PDA (<26 + 0/7 weeks' gestation, <750 g birth weight), (2) early targeted therapy of PDA in selected preterm infants at particular high risk for PDA-associated complications, and (3) PDA ligation, catheter intervention, or oral paracetamol may be considered as rescue options for hsPDA closure. The impact of catheter-based closure of hsPDA on clinical outcomes should be determined in future prospective studies. Finally, we provide a novel treatment algorithm for PDA in preterm infants that integrates the several treatment modalities in a staged approach. 10.1542/peds.2020-1209
    Acute changes in myocardial systolic function in preterm infants undergoing patent ductus arteriosus ligation: a tissue Doppler and myocardial deformation study. El-Khuffash Afif F,Jain Amish,Dragulescu Andreea,McNamara Patrick J,Mertens Luc Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography BACKGROUND:Ligation of a patent ductus arteriosus (PDA) in preterm infants causes profound hemodynamic changes that can result in low cardiac output syndrome and hypotension. The effect of PDA ligation on left ventricular myocardial function has not been studied using tissue Doppler and myocardial deformation imaging, mainly because of the limited validation of these methods in preterm infants. The primary objective of the present study was to determine the feasibility and reliability (intraobserver and interobserver variability) of tissue Doppler and myocardial deformation imaging for evaluating myocardial function in preterm infants undergoing surgical PDA ligation. Additionally, we sought to study the immediate effect of surgical ligation on the left ventricular tissue Doppler and strain measurements in the first 24 hours after surgery. METHODS:Echocardiography was performed in 19 preterm infants before, 1 hour after, and 18 hours after PDA ligation born at 24-29 weeks of gestation. The tissue Doppler velocities of the lateral tricuspid and lateral and septal mitral valve annuli were obtained. The global and regional longitudinal peak systolic strain values were determined using two-dimensional speckle tracking echocardiography. The results of the three measurement points were compared using repeated measures analysis of variance. The intra- and interobserver variability was assessed using the intraclass correlation coefficient and Bland-Altman analysis. RESULTS:The median gestational age was 25.0 weeks (interquartile range 24.9-25.9) and the birth weight was 750 g (interquartile range 600-810). For the global longitudinal strain, the intraobserver intraclass correlation coefficient was 0.92 (95% CI, 0.78-0.97, P < .001), and the interobserver intraclass correlation coefficient was 0.93 (95% CI, 0.66-0.98, P < .001). Bland-Altman analysis showed no significant bias between the two observers, with good agreement. The systolic and diastolic tissue Doppler velocities of the mitral valve decreased significantly immediately after ligation and remained significantly lower than the preoperative levels at 18 hours. Also, the global longitudinal strain values significantly decreased 1 hour after the procedure (global longitudinal strain before -19.7% ± -3.8% vs -11.5% ± -3.5%; P = .001) but had significantly improved 18 hours after the procedure (-15.1% ± -2.9%, P = .01). CONCLUSIONS:The present study has shown the feasibility and reliability of using tissue Doppler and strain imaging in premature infants with a hemodynamically significant PDA. Significant changes in myocardial function were observed immediately after PDA ligation, suggesting important changes in myocardial performance immediately after ductal ligation. 10.1016/j.echo.2012.07.016
    Predictors of Respiratory Improvement 1 Week after Ligation of Patent Ductus Arteriosus in Preterm Infants. Hsu Kai-Hsiang,Wong Pierre,Ram Kumar S,Evans Julie,Noori Shahab The Journal of pediatrics OBJECTIVE:To characterize preterm infants that demonstrates respiratory improvement 7 days after ligation of a patent ductus arteriosus (PDA). STUDY DESIGN:We performed a 2-phase study of preterm infants (birthweight <1500 g between 2010 and 2016). We first did a retrospective analysis using regression modeling of ligation population. We then performed a case-control study comparing a ligation group with infants matched by gestational age, postnatal age, and preligation respiratory condition (ventilator mode, mean airway pressure [MAP], and fraction of inspired oxygen [FiO]). Respiratory improvement was defined as either extubation, downgrading of ventilatory mode, reduction in MAP >25%, or decrease in FiO >25%. RESULTS:Forty-five (42%) of 107 preterm infants (gestational age 25.5 ± 1.7 weeks) with ligation showed respiratory improvement at 7 days. Infants on high frequency ventilation (HFV) were more likely to have respiratory improvement (aOR 5.03, 95% CI [1.14-22.18]). In matched-control analysis of 89 pairs, there was no difference in respiratory improvement. Among infants on HFV, the ligation group had an increase in MAP during 3 days prior to ligation. For infants on conventional ventilation, the ligation group had higher MAP and FiO than the control group during the first 2-3 postoperative days. CONCLUSIONS:Among infants undergoing PDA ligation, those on HFV were more likely to have respiratory improvement in the first week, possibly because of the prevention of further respiratory deterioration. For infants on conventional ventilation, ligation was associated with higher respiratory support in the immediate postligation period without respiratory benefits at 7 days. As HFV was used as a rescue mode, our findings suggest that those with worse lung disease may achieve greater short term benefit from PDA ligation. 10.1016/j.jpeds.2018.09.061
    Predictors of Early Extubation after Patent Ductus Arteriosus Ligation among Infants Born Extremely Preterm Dependent on Mechanical Ventilation. Krishnappa Srinath,Shah Prakesh S,Jain Amish,Resende Maura H F,McNamara Patrick J,Weisz Dany E The Journal of pediatrics We conducted a retrospective study of 166 ventilator-dependent neonates born extremely preterm in whom patent ductus arteriosus was surgically ligated and evaluated the association of preoperative characteristics and time-to-successful postoperative extubation. Larger patent ductus arteriosus diameter ([>2.5 mm], adjusted hazard ratio 0.51, 95% CI 0.36-0.72) and left-ventricular dilatation (z score ≥2, adjusted hazard ratio 0.61, 95% CI 0.42-0.87) were associated with earlier extubation. 10.1016/j.jpeds.2019.06.027
    Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis. Mitra Souvik,Florez Ivan D,Tamayo Maria E,Mbuagbaw Lawrence,Vanniyasingam Thuva,Veroniki Areti Angeliki,Zea Adriana M,Zhang Yuan,Sadeghirad Behnam,Thabane Lehana JAMA Importance:Despite increasing emphasis on conservative management of patent ductus arteriosus (PDA) in preterm infants, different pharmacotherapeutic interventions are used to treat those developing a hemodynamically significant PDA. Objectives:To estimate the relative likelihood of hemodynamically significant PDA closure with common pharmacotherapeutic interventions and to compare adverse event rates. Data Sources and Study Selection:The databases of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until August 15, 2015, and updated on December 31, 2017, along with conference proceedings up to December 2017. Randomized clinical trials that enrolled preterm infants with a gestational age younger than 37 weeks treated with intravenous or oral indomethacin, ibuprofen, or acetaminophen vs each other, placebo, or no treatment for a clinically or echocardiographically diagnosed hemodynamically significant PDA. Data Extraction and Synthesis:Data were independently extracted in pairs by 6 reviewers and synthesized with Bayesian random-effects network meta-analyses. Main Outcomes and Measures:Primary outcome: hemodynamically significant PDA closure; secondary: included surgical closure, mortality, necrotizing enterocolitis, and intraventricular hemorrhage. Results:In 68 randomized clinical trials of 4802 infants, 14 different variations of indomethacin, ibuprofen, or acetaminophen were used as treatment modalities. The overall PDA closure rate was 67.4% (2867 of 4256 infants). A high dose of oral ibuprofen was associated with a significantly higher odds of PDA closure vs a standard dose of intravenous ibuprofen (odds ratio [OR], 3.59; 95% credible interval [CrI], 1.64-8.17; absolute risk difference, 199 [95% CrI, 95-258] more per 1000 infants) and a standard dose of intravenous indomethacin (OR, 2.35 [95% CrI, 1.08-5.31]; absolute risk difference, 124 [95% CrI, 14-188] more per 1000 infants). Based on the ranking statistics, a high dose of oral ibuprofen ranked as the best pharmacotherapeutic option for PDA closure (mean surface under the cumulative ranking [SUCRA] curve, 0.89 [SD, 0.12]) and to prevent surgical PDA ligation (mean SUCRA, 0.98 [SD, 0.08]). There was no significant difference in the odds of mortality, necrotizing enterocolitis, or intraventricular hemorrhage with use of placebo or no treatment compared with any of the other treatment modalities. Conclusions and Relevance:A high dose of oral ibuprofen was associated with a higher likelihood of hemodynamically significant PDA closure vs standard doses of intravenous ibuprofen or intravenous indomethacin; placebo or no treatment did not significantly change the likelihood of mortality, necrotizing enterocolitis, or intraventricular hemorrhage. Trial Registration:PROSPERO Identifier: CRD42015015797. 10.1001/jama.2018.1896
    Transcatheter occlusion of the patent ductus arteriosus in premature infants weighing less than 1200 g. Morville Patrice,Douchin Stephanie,Bouvaist Helene,Dauphin Claire Archives of disease in childhood. Fetal and neonatal edition OBJECTIVES:Over the last few decades different strategies have been proposed to treat persistent ductal patency in premature infants. The advent of the Amplatzer Duct Occluder II Additional Size (ADOIIAS) provided the potential to close the patent ductus arteriosus (PDA). Opinions differ on the significance and treatment of PDA in premature neonates. Because surgical ligation and medical therapy both have their drawbacks, interventional catheterisation can be considered as an alternative means of closing the ductus arteriosus. Our aim was to analyse the feasibility, safety and efficacy of this device in premature infants weighing <1200 g at procedure. METHODS:Eighteen premature infants underwent transcatheter closure. The procedure was performed in the catheterisation laboratory by venous cannulation without angiography. The position of the occluder was directed by X-ray and ultrasound. We looked at procedural details, device size selection, complications and short-term and mid-term outcomes. RESULTS:Eighteen infants born at gestational ages ranging between 23.6 and 29+6 weeks (mean±SD 25+6±3 weeks) underwent transcatheter PDA closure. Their mean age and weight at the time of the procedure was 20 days (range 8-44 days) and 980 g (range 680-1200 g), respectively. The mean PDA and device waist diameters were 3.2±0.6 mm (range 2.2-4 mm) and 4.5±0.6 mm, respectively, and the mean PDA and device lengths were 4.3±1.2 mm (range 2-10 mm) and 2.5±0.9 mm, respectively. Complete closure was achieved in all but one patient. There was no device migration. One patient developed a left pulmonary artery obstruction. Three infants died. Two deaths were related to complications of prematurity and one to the procedure. CONCLUSIONS:Transcatheter closure of a PDA is feasible in very low weight infants with ADOIIAS and is an alternative to surgery. Success requires perfect selection and placement of the occluder. 10.1136/archdischild-2016-312582