PDA Management in the First Month in High-Risk Preterm Neonate Clinical Pathway – N/IICU and Inpatient
PDA Management in the First Month in High-Risk Preterm Neonate Clinical Pathway – N/IICU and Inpatient
PDA General Information
- A persistently patent ductus arteriosus occurs commonly in VLBW infants, with approximately 2/3rds of infants < 1000 grams BW having persistence of the PDA beyond 4 days
- The PDA usually becomes symptomatic when pulmonary vascular resistance drops several days after birth in the preterm neonate and blood begins to shunt from left to right through the ductus, with the potential for pulmonary over circulation and systemic hypoperfusion. This “ductal steal” can impact cerebral, mesenteric and renal blood flow.
- There have been associations of higher rates of BPD, IVH and NEC in infants < 1500 grams with a PDA, hence the desire to achieve closure in a persistently patent and hemodynamically significant ductus in the high risk infant.
- Echocardiography is the gold standard for diagnosing the presence of a PDA, but the clinical impact of patency of the ductus (“clinical assessment”) should dictate treatment.
- PDA closure can be achieved through pharmacologic means via 2 approved cyclooxygenase inhibitors, Indomethacin and Ibuprofen, both given intravenously. Paracetamol is also being used in some centers but is not yet FDA approved for this use in neonates. A proposed randomized controlled trial is to compare the efficacy and the safety of standard PDA treatment (ibuprofen) versus experimental (paracetamol) treatment is posted on clinicaltrials.gov
- Both approved medications have side effects, some of which can be severe and are associated with reduction in cerebral, renal and mesenteric blood flow with their use. The most serious side effects are NEC and spontaneous intestinal perforation (particularly seen with the combination of indomethacin and corticosteroids). Other side effects that are usually transient include decreased renal function as well decreased platelet function with increased risk for bleeding. There is some evidence suggesting that NEC is more common with Indomethacin vs Ibuprofen use (Cochrane Review 2015).
- Decisions around timing of pharmacologic treatment are challenging because the PDA may close spontaneously in some low birth weight infants, especially those who are more mature and small for gestational age; however medical therapy effectiveness is greatest in the first few weeks of postnatal life. Spontaneous closure is less common in the most preterm infants who also are at highest risk of severe complications from a persistent ductus.
- In infants who do not respond to pharmacologic closure or who have a contraindication to these medications, surgical ligation may be utilized.
- In addition to the usual complications of surgery in the very preterm infant, including the frequent postsurgical inflammatory response often causing worsened pulmonary status and hypotension, other potential complications of PDA ligation include pneumothorax, chylothorax, vocal cord paralysis and scoliosis. Only one randomized trial of ligation vs conservative management was performed in the 1980’s, without long-term follow-up (Cassady et al).
- Ligation has become less common over the past decade due to concerns of an association of higher rates of CLD as well as neurosensory impairment in infants who underwent surgical ligation for a PDA in the large TIPP trial. However, for VLBW infants requiring respiratory support with a hemodynamically significant PDA non-responsive to medical therapy, ligation is often indicated
- Closure of the PDA by the coil method via cardiac catheterization is available for larger infants at CHOP, but has not been utilized in the < 1500 grams group.
- Prophylactic Indomethacin for prevention of the ductus is not recommended routinely for all VLBW infants but may be indicated for some infants at high risk for IVH (not addressed in this pathway).