Administration of E-type prostaglandins in ductus-dependent congenital heart disease.

Abstract

In 1938 yon Eu/er first demonslrated the remarkable sensitivity of placental vessels to a crude extract from the prostate gland [25]. Nearly 30 years were to elapse before prostaglandins were identified in the human umbilical cord [14]. Subsequently the F-type prostaglandins were shown to cause profound vasoconstriction of isolated umbilical vessels, while the E-series caused vasodilatation [13]. These findings were to have important implications because, in common with the umbilical vessels, the ductus arteriosus is a fetal vessel. Both in vin-o [3] and in vivo [22] experiments confirmed that the E-type prostaglandins (PGE) caused relaxation of ductus arteriosus muscle. In the clinical studies that followed it soon became apparent that infusions of PGE~ or PGE2 were consistently effective in relieving hypoxemia and acidemia in neonates Whose pulmonary blood flow was dependent on patency of the ductus arteriosus [2, 5, 11, 16-19]. A major clinical trial of PGE~ infusion is in progress in the United States and in Europe, several hundreds of neonates having been treated. The indications for treatment have expanded to include not only those with a severe decrease in pulmonary blood flow, but also those who depend on the dUctus arteriosus for a major part of the systemic blood flow, e.g. interrupted aortic arch, juxtaductal COarctation of the aorta and hypoplastic left heart Syndrome [6, 12, 16, 21]. Neonates with complete transposition of the great arteries have also been shown to benefit from PGEI infusions [18, 20]. The increased flow through Address reprint requests ta: Eric D. Silove, MD, FRCP, FRCPE, The Children's Hospital, Ladywood Middleway, Birrningham, BI6 SET, England the ductus fl'om aorta to pulmonary artery with consequent increase in pulmonary blood flow results in an increased puhnonary venous return to the left atrium. Thus, left atrial pressure may rise, encouraging the flow of oxygenated blood across the interatrial communication and thence into the systemic circulation. The earlier clinical reports suggested that PGE should be used as an emergency measure in neonates with pulmonary atresia in order to relieve hypoxemia and acidemia and so improve the prospects of early palliative surgery. It was suggested that the preferred route of administration was via an umbilical artery catheter placed just proximal to the aortic end of the ductus arteriosus [11, 20] and that PGEI might be more effective than PGE2. These choices were influenced by two important considerations: (l) infusion near the origin of the ductus might not only achieve higher concentrations of PGE in that region, but cerebral side effects might be fewer if the infusion was distal to the origins of the cerebral vessels; (2) PGEI is a more powerful pulmonary vasodilator than PGE2 and might therefore promote a greater increase in pulmonary blood flow. However, no clinical evidence has been presented to show that PGE~ is any less effective than PGEI in improving oxygenation in right ventricular outflow obstruction. Similarly, infusion by either the intravenous or the intra-aortic route appears to be equally effective. Both routes of administration have practical difficulties and a significant incidence of side effects [15, 16, 19, 20]. It is likely that these limitations have discouraged prolonged infusions, reports of which have been few [16]. For some years an oral preparation of PGE: has