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Pediatrics Nov 2020Postnatal ductal closure is stimulated by rising oxygen tension and withdrawal of vasodilatory mediators (prostaglandins, nitric oxide, adenosine) and by... (Review)
Review
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.
Topics: Algorithms; Ductus Arteriosus, Patent; Humans; Infant, Newborn; Infant, Premature
PubMed: 33093140
DOI: 10.1542/peds.2020-1209 -
Pediatrics and Neonatology Apr 2020The ductus arteriosus is likely to close without treatment in most infants born at gestational age (GA) > 28 weeks (73%), and those with birth weight > 1000 g... (Review)
Review
The ductus arteriosus is likely to close without treatment in most infants born at gestational age (GA) > 28 weeks (73%), and those with birth weight > 1000 g (94%). However, the rates of spontaneous ductal closure among less mature or smaller infants with respiratory distress syndrome are not known. Extremely preterm infants born at GA < 28 weeks are associated with a high risk of severe intraventricular hemorrhage (IVH) or pulmonary hemorrhage, which usually occur within 72 h after birth and affect mortality and long-term neurological development. These serious hemorrhagic complications may be closely related to hemodynamic changes caused by a hemodynamically significant patent ductus arteriosus (hs-PDA). While prophylactic indomethacin has been shown to reduce the rates of PDA, PDA ligation, severe IVH and early pulmonary hemorrhage, the available evidence does not support its prophylactic use in preterm infants. Symptomatic or late treatment is associated with lower success rate, and increased complications of a hs-PDA. The issue of "to treat or not to treat a PDA" is controversial. Considering the relationship between the effectiveness and timing of pharmacological treatment, early targeted treatment may be an alternative approach for the early identification of a hs-PDA in specific high-risk patient population, especially infants <26 weeks GA who are at the highest risk of severe IVH or pulmonary hemorrhage. Serial echocardiographic studies can be used to select patients who are candidates for early targeted medical treatment of hs-PDA. Surgical ligation of PDA, and transcatheter closure if proven to be safe, can be used as back-up therapy for patients who fail medical treatment and continue to have cardiopulmonary compromise.
Topics: Acetaminophen; Ductus Arteriosus, Patent; Echocardiography; Humans; Indomethacin; Infant, Extremely Premature; Infant, Newborn; Ligation
PubMed: 31740267
DOI: 10.1016/j.pedneo.2019.10.002 -
The Journal of Pediatrics Jul 2017Persistent patency of the ductus arteriosus (PDA) has challenged neonatologists for more than 40 years. Surgical ligation of the ductus was first performed in children...
Persistent patency of the ductus arteriosus (PDA) has challenged neonatologists for more than 40 years. Surgical ligation of the ductus was first performed in children nearly 80 years ago and proved that prevention of prolonged exposure to left-to-right shunting through the ductus arteriosus improved pulmonary, cardiac, and systemic outcomes. In the 1970s, the discovery that nonsteroidal anti-inflammatory drugs could induce PDA closure and are effective in infants born preterm provided neonatologists with a pharmacologic alternative to surgery. The clear advantages, however, of having a medical approach have been clouded by conflicting information on the long-term benefits of treatment, disagreement regarding the clinical indicators that warrant treatment for PDA, optimal drug choice, preferred dosing regimens, and indecision regarding the best time to treat a select population of fragile preterm infants.
Topics: Bronchopulmonary Dysplasia; Humans; Indomethacin; Infant; Infant, Extremely Premature; Infant, Newborn; Risk
PubMed: 28396028
DOI: 10.1016/j.jpeds.2017.03.036 -
Seminars in Perinatology Mar 2023Platelet plug formation is critically involved in murine ductus arteriosus closure and thrombocytopenia in preterm infants seems to negatively affect spontaneous and... (Randomized Controlled Trial)
Randomized Controlled Trial
Platelet plug formation is critically involved in murine ductus arteriosus closure and thrombocytopenia in preterm infants seems to negatively affect spontaneous and pharmacologically induced ductal closure. Furthermore, platelet dysfunction may contribute to ductal patency, especially in extremely immature infants. Neonatal platelets likely have multifaceted roles during ductal closure, such as secretion of several signaling molecules and facilitation of specific cell-cell interactions. The only available randomized-controlled trial on platelet transfusions in preterm infants with patent ductus arteriosus demonstrated that a liberal transfusion regimen did not promote ductal closure, but was associated with an increased rate of intraventricular hemorrhage. Herein, we discuss the available mechanistic evidence on the role of platelets in ductus arteriosus closure and their potential clinical implications in preterm infants. We further briefly outline future research directions aimed at a better understanding of platelet-endothelial interactions in neonatal health and disease.
Topics: Infant; Infant, Newborn; Humans; Animals; Mice; Indomethacin; Cyclooxygenase Inhibitors; Ibuprofen; Ductus Arteriosus; Ductus Arteriosus, Patent; Infant, Extremely Premature
PubMed: 36925318
DOI: 10.1016/j.semperi.2023.151719 -
International Journal of Pediatrics &... Mar 2020Management of persistent patent ductus arteriosus (PDA) continues to be a challenging issue. The attitude toward PDA has shifted in the opposite direction during the...
Management of persistent patent ductus arteriosus (PDA) continues to be a challenging issue. The attitude toward PDA has shifted in the opposite direction during the last 20 years, from advocating an aggressive and early closure toward a call for watchful observation. While persistent PDA may cause challenges in the medical management of preterm neonates secondary to volume overload, pulmonary edema or hemorrhage, hypotension, and impaired tissue perfusion, its contribution toward long-term neonatal morbidities including bronchopulmonary dysplasia (BPD), ROP, NEC, and NDI has not been substantiated. By advocating conservative management, it is clear now that the majority of the PDA cases show spontaneous closure and do not require treatment. However, there has not been agreement regarding what constitutes a hemodynamically significant PDA and when, if any, it should be targeted for treatment. With increasing concern regarding possible associated complications with PDA ligation, a new trend for transcatheter approach to PDA closure is expanding. In this review, we summarize current understanding of the pathophysiology, diagnosis, and management of PDA in preterm infants, and we make some recommendations regarding evidence-based approach.
PubMed: 32373696
DOI: 10.1016/j.ijpam.2019.12.001 -
Archives of Disease in Childhood Jan 1990The records of all children who had a tracheostomy performed over a 10 year period from January 1979 were reviewed. Altogether 142 patients aged 1 day to 24.8 years...
The records of all children who had a tracheostomy performed over a 10 year period from January 1979 were reviewed. Altogether 142 patients aged 1 day to 24.8 years received a tracheostomy, 70 in the first year of life. The conditions necessitating tracheostomy were trauma (n = 21), acquired subglottic stenosis (n = 21), subglottic haemangioma (n = 16), Guillain-Barré syndrome (n = 14), Pierre Robin syndrome (n = 9), craniofacial disorders (n = 9), micrognathia (n = 5), and others in 47. In patients successfully decannulated the median period of tracheostomy was 104 days (range 3 days to 9.0 years) and in 25 patients the tracheostomy is still in situ. Eighty four patients (60%) were discharged from hospital with their tracheostomy in situ and no patient was kept in hospital because of a tracheostomy beyond four weeks. There were two tracheostomy related deaths in hospital. Both patients had severe acquired subglottic stenosis secondary to ventilation for lung disease of prematurity. There were no tracheostomy related deaths at home; complications included tracheal granulomas and polyps (n = 19). After removal of the tracheostomy 13 children had a fistula requiring surgical closure and four required revision of the tracheostomy scar. Tracheostomy is well tolerated in small children, with few complications and can be managed safely in the home by the family.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Home Nursing; Humans; Infant; Infant, Newborn; Length of Stay; Male; Postoperative Complications; Postoperative Period; Retrospective Studies; Tracheostomy
PubMed: 2301974
DOI: 10.1136/adc.65.1.123 -
Clinics in Perinatology Mar 2022Percutaneous-based patent ductus arteriosus closure is technically feasible among infants less than 1.5 kg. However, marked heterogeneity in the type and nature of... (Review)
Review
Percutaneous-based patent ductus arteriosus closure is technically feasible among infants less than 1.5 kg. However, marked heterogeneity in the type and nature of adverse events obscures current safety profile assessments. Although data on the risks of postdevice closure syndrome remain promising, a lack of comparative trials of surgical ductal ligation and inconsistent surveillance across published studies obscure confidence in present estimates of safety and efficacy. To minimize risk and yield the greatest benefits, clinical studies of patent ductus arteriosus treatment should consider incorporating more robust assessments to ensure that infants at greatest risk for adverse ductal consequences are included.
Topics: Ductus Arteriosus, Patent; Humans; Infant; Infant, Newborn; Infant, Premature; Ligation; Treatment Outcome
PubMed: 35209997
DOI: 10.1016/j.clp.2021.11.009 -
Journal of Cardiovascular Development... Sep 2023Transcatheter device closure of patent ductus arteriosus (PDA) in preterm infants has been proven to be a feasible and safe technique with promising results when... (Review)
Review
Transcatheter device closure of patent ductus arteriosus (PDA) in preterm infants has been proven to be a feasible and safe technique with promising results when compared to surgical ligation. However, managing transport and anaesthesia in extremely premature infants with haemodynamically significant PDA and limited reserves presents unique challenges. This review article focuses on the key considerations throughout the clinical pathway for the PDA device closure, including referral hospital consultation, patient selection, intra- and inter-hospital transport, and anaesthesia management. The key elements encompass comprehensive patient assessment, meticulous airway management, optimised ventilation strategies, precise thermoregulation, patient-tailored sedation protocols, vigilant haemodynamic monitoring, and safe transport measures throughout the pre-operative, intra-operative, and post-operative phases. A multidisciplinary approach enhances the chances of procedure success, improves patient outcomes, and minimises the risk of complications.
PubMed: 37754806
DOI: 10.3390/jcdd10090377 -
The Cochrane Database of Systematic... Feb 2020Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective as indomethacin with fewer adverse effects.
OBJECTIVES
To determine the effectiveness and safety of ibuprofen compared with indomethacin, other cyclo-oxygenase inhibitor(s), placebo, or no intervention for closing a patent ductus arteriosus in preterm, low-birth-weight, or preterm and low-birth-weight infants.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 10), MEDLINE via PubMed (1966 to 30 November 2017), Embase (1980 to 30 November 2017), and CINAHL (1982 to 30 November 2017). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials of ibuprofen for the treatment of a PDA in preterm, low birth weight, or both preterm and low-birth-weight newborn infants.
DATA COLLECTION AND ANALYSIS
Data collection and analysis conformed to the methods of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence.
MAIN RESULTS
We included 39 studies enrolling 2843 infants. Ibuprofen (IV) versus placebo: IV Ibuprofen (3 doses) reduced the failure to close a PDA compared with placebo (typical relative risk (RR); 0.62 (95% CI 0.44 to 0.86); typical risk difference (RD); -0.18 (95% CI -0.30 to -0.06); NNTB 6 (95% CI 3 to 17); I = 65% for RR and I = 0% for RD; 2 studies, 206 infants; moderate-quality the evidence). One study reported decreased failure to close a PDA after single or three doses of oral ibuprofen compared with placebo (64 infants; RR 0.26, 95% CI 0.11 to 0.62; RD -0.44, 95% CI -0.65 to -0.23; NNTB 2, 95% CI 2 to 4; I test not applicable). Ibuprofen (IV or oral) compared with indomethacin (IV or oral): Twenty-four studies (1590 infants) comparing ibuprofen (IV or oral) with indomethacin (IV or oral) found no significant differences in failure rates for PDA closure (typical RR 1.07, 95% CI 0.92 to 1.24; typical RD 0.02, 95% CI -0.02 to 0.06; I = 0% for both RR and RD; moderate-quality evidence). A reduction in NEC (necrotising enterocolitis) was noted in the ibuprofen (IV or oral) group (18 studies, 1292 infants; typical RR 0.68, 95% CI 0.49 to 0.94; typical RD -0.04, 95% CI -0.07 to -0.01; NNTB 25, 95% CI 14 to 100; I = 0% for both RR and RD; moderate-quality evidence). There was a statistically significant reduction in the proportion of infants with oliguria in the ibuprofen group (6 studies, 576 infants; typical RR 0.28, 95% CI 0.14 to 0.54; typical RD -0.09, 95% CI -0.14 to -0.05; NNTB 11, 95% CI 7 to 20; I = 24% for RR and I = 69% for RD; moderate-quality evidence). The serum/plasma creatinine levels 72 hours after initiation of treatment were statistically significantly lower in the ibuprofen group (11 studies, 918 infants; MD -8.12 µmol/L, 95% CI -10.81 to -5.43). For this comparison, there was high between-study heterogeneity (I = 83%) and low-quality evidence. Ibuprofen (oral) compared with indomethacin (IV or oral): Eight studies (272 infants) reported on failure rates for PDA closure in a subgroup of the above studies comparing oral ibuprofen with indomethacin (IV or oral). There was no significant difference between the groups (typical RR 0.96, 95% CI 0.73 to 1.27; typical RD -0.01, 95% CI -0.12 to 0.09; I = 0% for both RR and RD). The risk of NEC was reduced with oral ibuprofen compared with indomethacin (IV or oral) (7 studies, 249 infants; typical RR 0.41, 95% CI 0.23 to 0.73; typical RD -0.13, 95% CI -0.22 to -0.05; NNTB 8, 95% CI 5 to 20; I = 0% for both RR and RD). There was low-quality evidence for these two outcomes. There was a decreased risk of failure to close a PDA with oral ibuprofen compared with IV ibuprofen (5 studies, 406 infants; typical RR 0.38, 95% CI 0.26 to 0.56; typical RD -0.22, 95% CI -0.31 to -0.14; NNTB 5, 95% CI 3 to 7; moderate-quality evidence). There was a decreased risk of failure to close a PDA with high-dose versus standard-dose of IV ibuprofen (3 studies 190 infants; typical RR 0.37, 95% CI 0.22 to 0.61; typical RD - 0.26, 95% CI -0.38 to -0.15; NNTB 4, 95% CI 3 to 7); I = 4% for RR and 0% for RD); moderate-quality evidence). Early versus expectant administration of IV ibuprofen, echocardiographically-guided IV ibuprofen treatment versus standard IV ibuprofen treatment, continuous infusion of ibuprofen versus intermittent boluses of ibuprofen, and rectal ibuprofen versus oral ibuprofen were studied in too few trials to allow for precise estimates of any clinical outcomes.
AUTHORS' CONCLUSIONS
Ibuprofen is as effective as indomethacin in closing a PDA. Ibuprofen reduces the risk of NEC and transient renal insufficiency. Therefore, of these two drugs, ibuprofen appears to be the drug of choice. The effectiveness of ibuprofen versus paracetamol is assessed in a separate review. Oro-gastric administration of ibuprofen appears as effective as IV administration. To make further recommendations, studies are needed to assess the effectiveness of high-dose versus standard-dose ibuprofen, early versus expectant administration of ibuprofen, echocardiographically-guided versus standard IV ibuprofen, and continuous infusion versus intermittent boluses of ibuprofen. Studies are lacking evaluating the effect of ibuprofen on longer-term outcomes in infants with PDA.
Topics: Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Enzyme Inhibitors; Humans; Ibuprofen; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Randomized Controlled Trials as Topic
PubMed: 32045960
DOI: 10.1002/14651858.CD003481.pub8