Condition: patent ductus arteriosus
Definition: The ductus arteriosus (DA) is a vascular connection between the aorta and the main pulmonary artery that shunts blood away from the lungs and to the body during fetal development. After birth, the ductus usually closes; however, postnatal failure of ductal closure results in a patent ductus arteriosus (PDA).
Incidence: A PDA is more common in premature infants and has been reported in 30% of very low birthweight infants (birthweight less than 1500 g) and in 65% of those born at less than 28 weeks’ gestational age.
Pathophysiology
In utero the DA is approximately the same diameter as the aorta and 85% to 90% of the blood ejected from the right ventricle shunts from the pulmonary circulation to the systemic circulation across the DA.
After birth, lung ventilation and increased pulmonary arterial oxygenation cause a drop in pulmonary vascular resistance. Concomitantly, elimination of the placental circulation increases systemic vascular resistance. The change in the relative resistances causes reversal of the shunt across the PDA from a right-to-left shunt to a left-to-right shunt.
Consequently, the PDA results in increased pulmonary blood flow and diastolic steal from the systemic circulation. These physiologic alterations account for many of the clinical features.
Two factors determine postnatal DA closure.
Increased arterial oxygen concentration typically seen with transition from fetal circulation.
Decreased circulating prostaglandin E2 (PGE2). Circulating PGE2 levels decrease after birth due to a decrease in placental production and increased clearance by the lungs as they receive more blood flow. Neonatal levels of circulating PGE2 are close to maternal levels within hours of birth with the exception of severely ill neonates, especially those with respiratory distress syndrome.
Risk factors
Prematurity: The incidence of PDA increases as the gestational age decreases. This occurs because preterm neonates have a higher circulating level of PGE2 than do full-term neonates.
Genetics: Genes that regulate prostaglandin activity and/or smooth muscle development and contraction have been associated with the PDA. Numerous congenital syndromes have an increased incidence of PDA including trisomy 13, trisomy 18, Char syndrome, Holt-Oram syndrome, DiGeorge syndrome, Noonan syndrome, and others.
Respiratory distress syndrome (RDS): RDS disrupts the normal physiological processes that result in ductal closure, particularly for neonates born prior to 30 weeks’ gestational age.
Surfactant administration: Administration of artificial surfactant within 30 minutes of delivery has been linked to an increase in ductal size and increased left-to-right flow. An increase in the left-to-right shunt can partially be explained with surfactant causing a decrease in pulmonary vascular resistance; however, the apparent vasodilation of the ductus after surfactant administration is not understood.
Asphyxia: Any neonate who has had a perinatal event consistent with asphyxia is at increased risk of having a PDA. In some situations, hypoxia from the event can lead to increased pulmonary resistance, which can cause a persistent right-to-left shunt across the PDA.
High altitude: There is a higher rate of PDAs in infants born at high altitudes compared to those born at low altitudes.
Fluid administration: Fluid intake greater than 170 mL/kg/d in the first few days of life has been linked to an increased risk of PDA.
Clinical presentation
Signs and symptoms
With a patent DA, a murmur is often heard over the precordium that is described as being machine like.
Initially, the murmur may be soft and heard only during systole.
After birth, the pulmonary diastolic pressures decrease and the shunt extends into diastole, resulting in a continuous murmur.
Because the PDA murmur is related to the volume of the shunt, the murmur can be very soft or even silent.
An infant who has pulmonary hypertension might have a relatively small shunt and an inaudible murmur. In this scenario, the presence of a PDA and pulmonary hypertension can be confirmed by a lower extremity saturation that is decreased relative to the upper extremity saturation due to right-to-left ductal shunt.
Other physical examination features of a PDA are prominent left ventricular impulse (also known as a ventricular heave), bounding pulses, and a widened pulse pressure (which is defined as a difference greater than or equal to 35 mm Hg between the systolic and diastolic pressures or a difference between systolic and diastolic pressures that are more than half). These features are due to the increased left ventricular stroke volume and the diastolic runoff through the PDA.
An unrestricted PDA can cause congestive heart failure with symptoms including tachypnea, tachycardia, and hepatomegaly.
Condition variability: The condition of patients with PDAs can vary widely depending on the size of the PDA, degree of shunt, and baseline stability of the patient.
A small, restrictive PDA in a stable patient may not cause any symptoms.
A large PDA in a critically ill neonate can cause hypotension, respiratory compromise, and congestive heart failure.
The signs and symptoms of a PDA in premature infants are particularly challenging to distinguish from underlying respiratory disease (eg, RDS or bronchopulmonary dysplasia [BPD]).
Diagnosis: The diagnosis of a PDA is with echocardiography.
When Doppler color flow is added to a two-dimensional echocardiogram, the PDA can be directly visualized and the direction of flow can be determined.
Echocardiography can be used to estimate the amount of shunt based on the degree of left-sided chamber dilation.
Echo-Doppler can also be used to determine the pressure gradient across the PDA.
Chest radiography findings are nonspecific and may include cardiomegaly and/or increased pulmonary interstitial fluid.
Management: All patients with a hemodynamically significant PDA should receive supportive therapy.
Respiratory support
The use of positive end-expiratory pressure improves gas exchange and decreases the left-to-right shunt through the PDA.
Fluid restriction and/or diuretics
This helps decrease potential pulmonary edema and decreases the risk of potentiating ductus patency.
Beyond these conservative measures, management of a PDA in premature infants in the intensive care setting is more controversial.
Many clinicians refrain from treating an open ductus unless there is evidence of harm such as intractable hypotension or congestive heart failure.
Reasons cited for opting not to treat significant PDAs are the lack of evidence supporting treatment from randomized controlled trials, failure of treatment to improve developmental outcomes, the potential side effects of treatment, and the high rate of spontaneous closure.
Medical
Currently, there are two FDA-approved drugs used to close PDAs: indomethacin and ibuprofen. These cyclooxygenase (COX) inhibitors act to decrease circulating PGE2 and thus facilitate ductal closure. Both intravenous indomethacin and ibuprofen are equally effective in closing a PDA.
Indomethacin has been linked to higher rates of necrotizing enterocolitis (NEC) and transient renal insufficiency.
Ibuprofen (intravenous) has been linked to a higher rate of chronic lung disease (CLD)/BPD.
Contraindications to the use of indomethacin or ibuprofen include untreated infection, active bleeding, thrombocytopenia, coagulation defects, NEC, or significant renal impairment.
Surgical
Surgical ligation of a PDA is reserved for infants who fail to respond to medical treatment and still have significant symptoms or those who have contraindications to medical therapy.
Surgical ligation has been linked to greater risks of BPD, retinopathy of prematurity, and neurosensory impairment.
Surgical ligation has several other risks including hypotension, pneumothorax, chylothorax, infection, and vocal cord paralysis due to recurrent laryngeal nerve injury during the procedure.
Scoliosis is another long-term risk factor that has been linked to prior surgical repair of a PDA.
Two surgical approaches are employed to close the PDA.
Open thoracotomy.
Video-assisted thorascopic (VAT) procedure. The VAT procedure is less invasive and has been linked to fewer side effects and shorter healing than the open procedure.
Early developmental/therapeutic interventions: Some clinicians in the past have used prophylactic indomethacin therapy in all extremely low birthweight infants (less than or equal to 1000 g), as this group is at increased risk of developing a PDA. However, this practice has not been shown to be effective in decreasing long-term morbidity.
Prognosis
Early predictors: Currently, there are no biological markers that readily predict PDA outcomes. Initial enthusiasm for biomarkers such as N-terminal pro-B-type natriuretic peptide has been tempered as levels do not appear to correlate with therapeutic responsiveness of a PDA to treatment.
Outcomes: The outcomes of patients with PDAs can vary significantly. Many infants with small- to moderate-sized PDAs experience spontaneously closure. However, a large PDA may significantly worsen the clinical course of a sick premature infant.
Condition: persistent patent ductus arteriosus
Definition: above
Incidence: The incidence of a persistent PDA after neonatal intensive care varies depending on weight, gestational age, inhospital treatment, and comorbidities.
Approximately 24% of infants born less than 28 weeks have spontaneous closure of their DA.
Another study looking at infants less than 1500 g showed a spontaneous closure rate of 47% before discharge and 86% after discharge.
Approximately 94% of DA closes spontaneously in infants more than 1000 g.
Thus, only a small percentage of very preterm infants have a PDA that remains open through NICU discharge.
Pathophysiology: A PDA has been associated with several comorbidities of prematurity, including exacerbation of RDS and increased risk of BPD or CLD, NEC, intraventricular hemorrhage (IVH), and cerebral palsy.
PDA and CLD
Many clinicians have noted the relationship between a PDA and RDS and potentially CLD.
Increased pulmonary blood flow decreases lung compliance and increases airway resistance, which can lead to higher oxygen requirements and need for increased ventilator pressures. All of these factors are associated with lung injury. However, the cause/effect relationship between PDA and CLD is debated.
The use of prophylactic indomethacin decreases incidence of PDA but does not significantly decrease incidence of BPD. Investigators have theorized that this may be because COX inhibitors decrease urine output, which increases lung water and the risk of developing lung disease, and/or because indomethacin exposure is associated with an increased fraction of inspired oxygen in premature infants without a PDA.
PDA and NEC
A PDA has been recognized as a risk factor for developing NEC. This is likely due to the “diastolic steal” phenomenon, which describes intestinal hypoperfusion due to runoff through the PDA to the lungs during diastole. PDA-mediated hypoxia may also contribute to bowel ischemia.
PDA and renal dysfunction
Diastolic steal can also affect renal perfusion and may contribute to renal dysfunction.
Unfortunately, treatment of a PDA with COX inhibitors can also adversely affect renal function. Therefore, COX inhibitor use should be approached with caution in a patient with baseline decreased renal function.
PDA and IVH
A large PDA with a left-to-right shunt has been associated with IVH.
Proposed mechanisms include decreased cerebral circulation with PDA diastolic steal as well as higher levels of circulating prostaglandins that have been found in neonates with both IVH and PDAs.
While there is an association between PDA and IVH, treatment with indomethacin has been shown to increase the risk of IVH.
PDA and CP
A hemodynamically significant PDA has been linked to later development of cerebral palsy in infants less than 34 weeks’ gestational age. Again, causality has not been established and studies have not shown that treatment of a PDA decreases cerebral palsy risk.
Risk factors
Prematurity: The risk of having a PDA is inversely related to gestational age; however, the very youngest preterm infants are more likely to have their patent ductus more aggressively managed early in their NICU course and may be less likely to have a PDA by the time of discharge.
Congenital syndromes: Several genetic conditions are associated with a PDA that may persist through discharge.
Congenital heart disease: A PDA is associated with several congenital heart conditions and may be clinically beneficial or have negative effects.
Sepsis: A sepsis evaluation must be considered in the convalescing infant who suddenly becomes symptomatic of their PDA.
Clinical presentation
As above, a heart murmur is the most common sign of a ductus that has remained patent.
Heart failure: Tachypnea and crackles from pulmonary edema. Other signs of heart failure may include fever, tachycardia, hepatomegaly, and poor growth.
Feeding intolerance: A PDA may result in decreased mesenteric blood flow and increase the risk of feeding intolerance and NEC.
Diagnosis
Radiologic studies: A chest film may reveal increased pulmonary vasculature and interstitial fluid as evidence of pulmonary edema from the left-to-right shunt. Cardiomegaly may be a concerning sign in an infant with a persistent PDA.
Echocardiography: A two-dimensional echo with Doppler continues to be the best diagnostic study, as well the study of choice in determining the long-term impact of the patent ductus. Left atrial or ventricular enlargement, or evidence of pulmonary arterial hypertension, would warrant more aggressive means of closure.
Management
Management of an infant with a PDA and the above mentioned comorbidities is more complex. The treating physician must weigh the risks and benefits of the treatment choice, ie, COX inhibitors or surgical ligation, with the clinical status of the patient. For example, NEC is a contraindication to COX inhibitor use, so one must weigh the clinical or hemodynamic significance of the PDA with the risks associated with surgical ligation.
Pulmonary edema
A persistent, untreated PDA may lead to pulmonary edema, or even full-blown heart failure, from the left-to-right shunt. The use of loop diuretics, such as furosemide, may significantly improve the respiratory status of the infant.
Nutrition
Infants with a persistent PDA may have increased metabolic demands and, thus, may have high caloric needs in order to maintain steady growth. The aggressive fluid restriction required early with a PDA is less important when the child is tolerating full enteral feeds; however, working up to full feeds should be gradual given the increased risk of feeding intolerance and necrotizing enterocolitis with a PDA.
Anemia
Maintaining a hematocrit greater than 40% will decrease the left-to-right shunt and may improve a symptomatic PDA.
Status post-ligation
Infants who have previously undergone surgical closure of their PDA warrant close observation for a paralyzed left vocal cord (hoarse or absent cry, stridor, feeding difficulties), from left recurrent nerve injury as a complication of the procedure.
As many as 40% of ELBW infants undergoing ligation may develop unilateral vocal cord paresis.
A significant number of these infants will have feeding difficulties due to aspiration from an inability to protect their airway while swallowing. Thickening their feeds may help but, ultimately, many require a gastrostomy tube.
Also, likely due to chronic microaspiration, many of these infants develop reactive airway disease and will benefit from regular aerosol treatment (bronchodilators and/or inhaled steroids)
Any infant suspected of a paralyzed vocal cord s/p PDA ligation should have a skilled otolaryngologist perform a direct laryngoscopy to visualize movement of the vocal folds.
Discharge
Stable cardiorespiratory status
A persistent large PDA in an older infant can cause left-sided volume overload and heart failure.
Teaching
Parents should be instructed on signs and symptoms that would be suggestive of pulmonary edema or congestive heart failure.
Tachypnea
Increased work of breathing
Poor feeding
Poor growth
All caregivers should be instructed in infant CPR.
Monitoring
Unless otherwise indicated, home monitoring is not necessary.
Safety
An emergency plan should be established, instructing the parents on what to do (give diuretic, bring to PCP, call cardiologist, call 911, etc) and what medical facility to bring the child to if he/she shows symptoms suggestive of CHF.
Concern for dehydration should be discussed with the parents when an infant is discharged home on diuretics so that they can monitor for symptoms in the event of an acute febrile or GI illness, especially if the child is on highly concentrated formula.
Steady growth
Due to high metabolic demands in infants with hemodynamically significant PDAs, steady growth must be established prior to considering discharge. This may require feeds to include fortified breast milk and high calorie formulas.
Cardiology follow-up
Close follow-up with a pediatric cardiologist should be arranged prior to discharge.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
