Patent ductus arteriousus in the premature neonate: current concepts in pharmacological management.
In utero, the ductus arteriosus shunts deoxygenated blood away from the pulmonary artery and towards the placental circulation where foetal gas exchange occurs. As a result of an intricately intertwined network of both physiological and biochemical changes, this vessel constricts rapidly after birth. Deoxygenated blood is diverted away from the placenta and through the lungs now vital for gas exchange. Premature closure of the ductus in utero can cause pulmonary hypertension and even death. Conversely, failure to close after birth can exacerbate respiratory distress, precipitate congestive heart failure and increase the risk of subsequent intestinal ischaemia leading to necrotising enterocolitis, bronchopulmonary dysplasia, renal hypoperfusion and/or cerebral ischaemia. In this review we summarise current knowledge of the delicately orchestrated control of the ductus arteriosus, focusing on the role of cyclo-oxygenase isoforms on prostaglandin production, on the interaction between prostaglandins and oxygen, and on the effects of these on ductal patency. We also seek to describe some of the standard and nonstandard therapeutic approaches available to the clinician when natural closure fails, reviewing alternative protocols for indomethacin administration and comparing indomethacin treatment with newer approaches such as ibuprofen. In summary, we will follow the course of this unique blood vessel as it is transformed over several hours from an organ absolutely vital to survival into programmed obsolescence.
Hammerman
C
C
Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel. cathy@cc.huji.ac.il
Kaplan
M
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D011448:Prostaglandin Antagonists / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011448:Prostaglandin Antagonists; D007213:Indomethacin