Medication Summary

Medication use in patent ductus arteriosus (PDA) is based upon the clinical status of the patient.

In the presence of symptoms of pulmonary overcirculation or pulmonary hypertension related to a patent ductus arteriosus (PDA), closing the lesion is usually most prudent; therefore, anticongestive therapy is not discussed.

Prostaglandins are utilized to maintain the patency of the ductus arteriosus until surgical ligation is performed. When surgical ligation is not indicated, prostaglandin inhibitors (eg, nonsteroid antiinflammatory drugs [NSAIDs]) are used to close the ductus arteriosus.

Intravenous (IV) indomethacin or IV ibuprofen is used to treat patent ductus arteriosus (PDA) in the neonate and in premature infants. The dose used for ibuprofen is 10 mg/kg bolus followed by 5 mg/kg/d for 2 additional days. (IV ibuprofen became available in the United States on June 2009.)

Ibuprofen was initially thought to have less adverse effects, such as a decreased incidence of oliguria, gastrointestinal (GI) toxicity, and cerebral hypoperfusion. The use of ibuprofen has been shown to increase the incidence of pulmonary hypertension and chronic lung disease.

A Cochrane database review showed no statistically significant difference in closure between ibuprofen and indomethacin.^[8]A decision to use one drug versus another should be based upon the infant's presentation and comorbidities.

A similar Cochrane database article that looked at the initial treatment of symptomatic patent ductus arteriosus (PDA) in preterm infants showed no difference in risks or benefits of surgery versus the use of cyclooxygenase inhibitors.^[30]

In a prospective, randomized, controlled trial, Attridge et al found that patients administered b-type natriuretic peptide (BNP) received fewer primary indomethacin doses compared with those who were not guided by BNP concentrations.^[6]Renal toxicity is associated with indomethacin, and dose reduction guided by BNP may reduce this risk.^[6]

Class Summary

Prostaglandins promote vasodilatation by direct effect on the vasculature and smooth muscle of the ductus arteriosus.

Alprostadil (Prostin VR Pediatric)

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Alprostadil is used to maintain the patency of the ductus arteriosus when a cyanotic lesion or interrupted aortic arch presents in a newborn. Prostaglandin E1 (PGE1) is most effective in premature infants.

Class Summary

In the neonate, ductal patency appears to be related to continued production of prostaglandin. This is particularly true in the premature infant; therefore, prostaglandin inhibition can affect ductal closure. NSAIDs inhibit the production of prostaglandins by decreasing the activity of cyclooxygenase. The result is a functional closure of the patent ductus arteriosus (PDA) in 80% of patients.

Ibuprofen lysine injection (NeoProfen)

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The mechanism of action of ibuprofen lysine injection that results in patent ductus arteriosus (PDA) closure in neonates is not known; however, ibuprofen is an inhibitor of prostaglandin synthesis. This agent is indicated to close a clinically significant PDA in premature infants who weigh between 500-1500 g at ≤ 32 weeks' gestational age when the usual medical management (eg, fluid restriction, diuretics, respiratory support) is ineffective.

Indomethacin (Indocin)

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Indomethacin is indicated for patent ductus arteriosus (PDA) closure, as it promotes closure of the PDA and generally has an onset of action within minutes. Prostaglandins, especially E-type prostaglandins, maintain the patency of the ductus. Thus, inhibition of prostaglandin synthesis by indomethacin results in constriction of the ductus arteriosus.

Questions

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Media Gallery

Schematic diagram of a left-to-right shunt of blood flow from the descending aorta via the patent ductus arteriosus (PDA) to the main pulmonary artery.
Diagram illustrating the patent ductus arteriosus.
Diagram illustrating ligation of the patent ductus arteriosus.
Diagram illustrating division and oversewing of the patent ductus arteriosus.
Diagram illustrating patch closure of the patent ductus arteriosus.

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Author

Luke K Kim, MD Assistant Professor of Medicine, Department of Internal Medicine, Division of Cardiology, New York Presbyterian Hospital, Weill Cornell Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Jeffrey C Milliken, MD Former Chief, Division of Cardiothoracic Surgery, University of California at Irvine Medical Center; Clinical Professor, Department of Surgery, University of California, Irvine, School of Medicine; Current Professor Emeritus, University of California

Jeffrey C Milliken, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Thoracic Surgery, American College of Cardiology, American College of Chest Physicians, American College of Surgeons, American Heart Association, American Society for Artificial Internal Organs, California Medical Association, International Society for Heart and Lung Transplantation, Phi Beta Kappa, Society of Thoracic Surgeons, SWOG, Western Surgical Association

Disclosure: Nothing to disclose.

Chief Editor

Stuart Berger, MD Executive Director of The Heart Center, Interim Division Chief of Pediatric Cardiology, Lurie Childrens Hospital; Professor, Department of Pediatrics, Northwestern University, The Feinberg School of Medicine

Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American College of Chest Physicians, American Heart Association, Society for Cardiovascular Angiography and Interventions

Disclosure: Nothing to disclose.

Acknowledgements

Hugh D Allen, MD Professor, Department of Pediatrics, Division of Pediatric Cardiology and Department of Internal Medicine, Ohio State University College of Medicine

Hugh D Allen, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, American Pediatric Society, American Society of Echocardiography, Society for Pediatric Research, Society of Pediatric Echocardiography, and Western Society for Pediatric Research