We studied the vasoactive profile of a term infant with congenital diaphragmatic hernia and intractable pulmonary hypertension who was refractory to conventional medical management despite an early stable period. Plasma prostanoid vasoconstrictor thromboxane A2 (TxB2) levels were elevated prior to ECMO at 150pg/mL, rose to 310pg/mL with the first hour of bypass and remained elevated until 72 hours by which time they fell to less than 50pg/mL. This coincided with the decreased extracorporeal circulatory support needed to maintain systemic arterial pO2 between 70 to 90 torr. Pulmonary vasodilator prostacyclin (6-keto-PGF1α) was minimally elevated prior to bypass a 50pg/mL and became undertectable. Catecholamine levels were markedly elevated prior to ECMO at 4,000pg/mL with no demonstrable pulmonary extraction of norepinephrine. Though catecholamine levels remained nonspecifically elevated, pulmonary metabolism of norepinephrine improved with bypass time to 48% at 96 hours and coincided with the overall improvement of the infant's respiratory function. These data suggest pulmonary hypertension associated with congenital diaphragmatic hernia is at least partially precipitated by alterations in prostanoid homeostasis as selective activation of thromboxane synthetase pathways rather than nonspecific activation of the entire archidonate cascade. While ECMO per se may have no lasting effect on prostanoid homeostasis, ECMO can allow a period of cardiopulmonary rest during which more physiologic prostanoid levels are established. Although activation of the sympatho-adrenal axis may contribute to pulmonary hypertension, the role of catecholamines in this infant is not clear. Return of the lungs ability to clear norepinephrine may be an additional marker of biologic lung recovery.
All Science Journal Classification (ASJC) codes
- Pediatrics, Perinatology, and Child Health