Patent Ductus Arteriosus


Article Author:
Maria Gillam-Krakauer


Article Editor:
Kunal Mahajan


Editors In Chief:
Michelle Miranda


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
1/11/2019 3:35:28 PM

Introduction

The ductus arteriosus is a fetal vessel which allows the oxygenated blood from the placenta to bypass the lungs in utero. At birth, the lungs fill with air with the first breaths, pulmonary vascular resistance drops, and blood flows from the right ventricle to the lungs for oxygenation. The increased arterial oxygen tension and the decreased flow through the ductus arteriosus allow the ductus to constrict. The ductus arteriosus is functionally closed by 12 to 24 hours of age in healthy, full-term newborns. Permanent (anatomic) closure is complete within 2 to 3 weeks. 

In the premature infant, the ductus arteriosus does not close rapidly and may require pharmacologic or surgical closure to treat side effects.[1][2][3]

Etiology

A patent ductus arteriosus (PDA) is rare in healthy term newborns. As gestational age decreases, the incidence of PDA increases. In extremely premature infants, especially those with respiratory distress syndrome, up to 80% may have a PDA at 3 days of age. Some genetic conditions are associated with PDA: Trisomy 13, 18, 21; Char, Holt-Oram, Noonan, CHARGE, TAAD/PDA, DiGeorge, and familial PDA, many forms of congenital heart disease. Maternal conditions and exposures associated with PDA include maternal diabetes, magnesium exposure, cocaine, and calcium channel blockers. Neonatal conditions and exposures associated with PDA include extreme prematurity, respiratory distress syndrome, neonatal sepsis, birth at high altitude, excess fluid administration, loop diuretics, aminoglycosides, cimetidine, and heparin. [4][5]

Epidemiology

The ductus arteriosus will close in virtually all healthy term newborns by 72 hours of age. The incidence of PDA in premature infants is inversely proportional to gestational age. In infants who are > 30 weeks gestation at birth, 90% will have a closed ductus at day 4, and 98% will be closed by the time of discharge. Infants born weighing less than 1000 grams are at highest risk for PDA. In this population, 70% will have a PDA at day 7.[6]

Pathophysiology

A PDA is associated with pulmonary edema and pulmonary hemorrhage, necrotizing enterocolitis, intraventricular hemorrhage, congestive heart failure, renal failure, and bronchopulmonary dysplasia (BPD).  A PDA can result in blood flowing from the descending aorta across the patent ductus arteriosus into the pulmonary circulation ("right-to-left"). This results in pulmonary edema. The "steal" from the aorta during diastole requires increased cardiac output to compensate. Extremely premature infants have limited ability to increase stroke volume and thus use increased heart rate to increase cardiac output. Decreased blood flow to the lower body results in increased risk for necrotizing enterocolitis and renal failure. [7][8][9]

History and Physical

The classic PDA murmur is a continuous, “machinery” murmur below the clavicle, radiating to the back, although it can also manifest as a systolic or holosystolic murmur. The infant will have a prominent precordial impulse, tachycardia, and bounding peripheral pulses due to increased cardiac output. Hypotension is most prominent in infants < 1000g grams. A widened pulse pressure (> 30mmHg) occurs both because of a mild increase in systolic blood pressure to overcome the decrease in distal blood flow due to run-off through the PDA during diastole, in addition to a lower diastolic blood pressure from the run-off. The increase in respiratory distress and hypoxia occur with pulmonary edema. Hepatomegaly can be appreciated when there is congestive heart failure. 

Evaluation

Chest radiography may show increased pulmonary vascular markings and pulmonary edema. Echocardiography shows a patent ductus arteriosus. Left to right flow is indicative of a typical PDA. Right to left flow across the PDA indicates pulmonary hypertension for which the PDA may be a secondary finding. A hemodynamically significant PDA manifests on echo with increased left atrial and left ventricular enlargement. Reversal of diastolic flow in the abdominal aorta at the level of the diaphragm may be seen but is technically challenging, so the absence of a reversal of diastolic flow on echo does not mean it is clinically absent. Increased serum creatinine and decreased urine output indicate the level of renal impairment. [10][11][12]

Treatment / Management

In gestationally more mature infants, conservative management of a PDA may be sufficient to support the infant while awaiting spontaneous closure. Conservative management includes careful fluid restriction (110 to 130ml/kg/d while monitoring urine output) and increasing peak end-expiratory pressure (PEEP) to treat pulmonary edema. Diuretics are controversial due to lack of evidence that they improve outcomes in very premature infants, may prevent PDA closure, and cause electrolyte derangements which can be difficult to manage in the extremely premature infant. [13][14][15]

Pharmacologic treatment with indomethacin, ibuprofen, or acetaminophen/paracetamol should be considered for preterm infants with a symptomatic PDA. Infants who are born weighing greater than 1000 grams are unlikely to require pharmacologic therapy to close the ductus. Although the ductus in a preterm infant > 1000g at birth does not close as quickly as in a healthy term infant (median time for closure is 7 days in infants >1000g), the vast majority close spontaneously prior to hospital discharge and do not require medication.

For those infants who are symptomatic despite conservative management (increasing PEEP and restricting fluid), there are three choices for pharmacologic treatment: indomethacin, ibuprofen, and acetaminophen/paracetamol. Indomethacin typically is given in 3 doses, 12 hours apart. A fourth dose can be given 24 hours after the third to ensure closure. Ibuprofen typically is given in 3 doses, 24 hours apart. Indomethacin and ibuprofen have a fairly equivalent efficacy (around 66% to 70%). In resistant cases, a second course of medication may be considered, but cumulative effects on renal function should be evaluated before embarking on a second course. The side effects of indomethacin and ibuprofen are similar, but indomethacin has been associated with more concerns for gut perfusion and necrotizing enterocolitis. However, in a large multi-center randomized controlled trial, no increase in necrotizing enterocolitis in infants fed small (15ml/kg/d) amounts of milk during treatment with indomethacin when compared with infants who were fasted.

Acetaminophen/paracetamol shows promise for treating a patent ductus arterious. Multiple small studies show close equivalence to indomethacin and ibuprofen, although it may be less effective in infants previously treated with indomethacin or ibuprofen or in the smallest infants. It is administered intravenously 15mg/kg/dose every 6 hours for 3 to 8 days, and most studies were 3 days, continuing to 6 days if closure was not achieved. Liver enzymes should be monitored for toxicity.  

If the PDA is hemodynamically significant despite pharmacologic therapy and results in increased respiratory support, renal impairment, or if there are contraindications to use of pharmacologic therapy, surgical ligation can be performed. 

Differential Diagnosis

  • Coronary artery fistula
  • Sinus of valsalva aneurysm
  • Aortopulmonary defect
  • Persistent truncus arteriosus
  • Pulmonary arteriovenous fistula
  • Total anomalous pulmonary venous return

Complications

Postoperative and Rehabilitation Care

Endocarditis prophylaxis is required for the first 6 months after closure

Consultations

  • Cardiac surgeon
  • Interventional radiology
  • Cardiologist
  • Pediatrician

Enhancing Healthcare Team Outcomes

PDA is not an uncommon finding in neonates. The majority of patients with a PDA are young children and the care of this congenital anomaly has changed over the years. Since most infants are managed in the NICU, a healthcare team is usually involved in the care. A pediatrician, intensivist, cardiac surgeon and interventional radiologist are usually consulted on the best treatment approach. Initially, premature infants are managed with ibuprofen, and if that fails, surgery is an option. Today endovascular procedures are also available to close the ductus. However, the care of an infant with a PDA is always done by a nurse. These patients need close monitoring because often they have other comorbidities. The pharmacist should be fully aware of the dose of ibuprofen and other drug options available to close the ductus. Only through a systemic approach to congenital heart disorders can the morbidity and mortality be lowered. [16][17][18] (Level V)

Outcomes

The outcome for the majority of patients in whom the PDA is ligated or medically treated is good. However, in most of these infants, it is the presence of other disorders that dictate the prognosis. Spontaneous closure of the ductus is very rare after the first three months of birth. Further, even in infants treated medically with ibuprofen, sometimes the ductus may reopen and require surgical closure. In all adults, the presence of a ductus requires surgical closure. In fact, before the ductus is closed in the adult population, the status of the pulmonary vasculature must be determined. Thus with mild pulmonary hypertension have a normal life expectancy. The surgical mortality for ductus varies from 2-20% depending on the infant age and other co-existing comorbidities. If left untreated, the mortality rate increases with age. [19][20][21](Level V)


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Patent Ductus Arteriosus - Questions

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What structure typically is found inferior to the patent ductus arteriosus?



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Which of the following conditions have a continuous machinery murmur?



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What maintains the patency of the ductus arteriosus?



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Which of the following does not maintain the patency of the ductus arteriosus?



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Which of the following is not used to close a patent ductus arteriosus?



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An infant is being treated with indomethacin for a patent ductus arteriosus. Which finding is of greatest concern?



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Which of the following is responsible for the functional closure of the patent ductus arteriosus at birth?



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What does the ductus arteriosus become?



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What drug is used to close a patent ductus arteriosus?



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For which of the following congenital heart lesions is alprostadil indicated at birth?



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Which substance/factor is associated with closure of patent ductus arteriosus?



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Which of the following medications promotes the functional closure of a patent ductus arteriosus?



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A 2-week-old infant, born at 24 weeks gestational age, has an ostomy because of spontaneous intestinal perforation. You now notice a continuous machine type murmur and a blood pressure of 40/17 mmHg and decreased urine output. What medication would be the best choice to treat this infant?



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Which of the following drugs can close a patent ductus arteriosus?



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A 3-week-old infant presents with tachypnea, diaphoresis, difficulty with feeding, and weight loss. Patent ductus arteriosus is suspected. What is the appropriate treatment?



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A ventilator dependent neonate born at 29 weeks and 950 g now one-month-old has hypotension, a low diastolic blood pressure, and requires dopamine to maintain blood pressure. There is a large patent ductus arteriosus (PDA) that has not closed after 3 trials of indomethacin. Select appropriate treatment.



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"Machinery murmur" is characteristic of which of the following?



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What is the most likely cause of a systolic ejection-type murmur in a newborn which is best heard at the upper left sternal border and which progresses to a continuous murmur?



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Which of the following statements is not true of patent ductus arteriosus after birth?



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Which of the following is the correct management of a small patent ductus arteriosus in a 2-week old premature infant born weighing 1200 grams on no ventilatory support with no associated cardiac pathology and no evidence of pulmonary congestion or heart failure?



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Which of the following is not a treatment to close a patent ductus arteriosus prior to 1 year of age?



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Bounding pulses are classically associated with a hemodynamically significant patent ductus arteriosus. What is the etiology of the bounding pulses?



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A child presents with slight breathlessness on exertion. On examination you note the absence of cyanosis, hypertrophy of the right ventricle, and on cardiac catheterization you note that the pressure in the pulmonary artery is the same as the in the aorta. You suspect:



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How long after birth does the ductus arteriosus take to functionally close in a healthy term infant?



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Which is true of the murmur of patent ductus arteriosus?



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A 1-month old infant born at 26 weeks' gestation undergoes ligation of the patent ductus arteriosus. The surgery is uneventful but the infant is noted to have a hoarse cry. When he is old enough to nipple feed, he is noted to have desaturation events during oral feedings. What is the underlying cause of this infant's problems?



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A premature infant in the neonatal unit has a symptomatic patent ductus arteriosus. If the goal is to close the ductus, which drug would be indicated?



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Which of the following substances can be used to maintain patency of the ductus arteriosus?



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A newborn infant delivered at term is being examined following delivery. The mother reports an uncomplicated pregnancy. On physical exam, auscultation reveals a continuous, machine-like murmur heard best at the left infraclavicular area. No evidence of any other cardiac defect is found. What is the most appropriate treatment for this infant?



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Patent Ductus Arteriosus - References

References

Fink D,Nitzan I,Bin-Nun A,Mimouni F,Hammerman C, Ductus arteriosus outcome with focus on the initially patent but hemodynamically insignificant ductus in preterm neonates. Journal of perinatology : official journal of the California Perinatal Association. 2018 Aug 17     [PubMed]
Clyman RI, Patent ductus arteriosus, its treatments, and the risks of pulmonary morbidity. Seminars in perinatology. 2018 Jun     [PubMed]
Jasani B,Weisz DE,McNamara PJ, Evidence-based use of acetaminophen for hemodynamically significant ductus arteriosus in preterm infants. Seminars in perinatology. 2018 Jun     [PubMed]
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Reese J,Scott TA,Patrick SW, Changing patterns of patent ductus arteriosus surgical ligation in the United States. Seminars in perinatology. 2018 Jun     [PubMed]
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de Freitas Martins F,Ibarra Rios D,F Resende MH,Javed H,Weisz D,Jain A,de Andrade Lopes JM,McNamara PJ, Relationship of Patent Ductus Arteriosus Size to Echocardiographic Markers of Shunt Volume. The Journal of pediatrics. 2018 Aug 13     [PubMed]
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Halil H,Buyuktiryaki M,Atay FY,Yekta Oncel M,Uras N, Reopening of the ductus arteriosus in preterm infants; Clinical aspects and subsequent consequences. Journal of neonatal-perinatal medicine. 2018 Aug 21     [PubMed]
Hundscheid T,Onland W,van Overmeire B,Dijk P,van Kaam AHLC,Dijkman KP,Kooi EMW,Villamor E,Kroon AA,Visser R,Vijlbrief DC,de Tollenaer SM,Cools F,van Laere D,Johansson AB,Hocq C,Zecic A,Adang E,Donders R,de Vries W,van Heijst AFJ,de Boode WP, Early treatment versus expectative management of patent ductus arteriosus in preterm infants: a multicentre, randomised, non-inferiority trial in Europe (BeNeDuctus trial). BMC pediatrics. 2018 Aug 4     [PubMed]
Corcoran S,Briggs K,O' Connor H,Mullers S,Monteith C,Donnelly J,Dicker P,Franklin O,Malone FD,Breathnach FM, Prenatal detection of major congenital heart disease - optimising resources to improve outcomes. European journal of obstetrics, gynecology, and reproductive biology. 2016 Aug     [PubMed]
Luca AC,Holoc AS,Iordache C, CONGENITAL HEART MALFORMATIONS IN NEWBORN BABIES WITH LOW BIRTH WEIGHT. Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi. 2015 Apr-Jun     [PubMed]
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Aygün A,Poryo M,Wagenpfeil G,Wissing A,Ebrahimi-Fakhari D,Zemlin M,Gortner L,Meyer S, Birth weight, Apgar scores and gentamicin were associated with acute kidney injuries in VLBW neonates requiring treatment for patent ductus arteriosus. Acta paediatrica (Oslo, Norway : 1992). 2018 Sep 3     [PubMed]
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StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Nurse-Maternal Newborn RN, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Nurse-Maternal Newborn RN, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Nurse-Maternal Newborn RN. When it is time for the Nurse-Maternal Newborn RN board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Nurse-Maternal Newborn RN.