Urinary ET-1, AVP and sodium in premature infants treated with indomethacin and ibuprofen for patent ductus arteriosus.

The relative potency and interrelationship between vasoactive and natriuretic mediators are thought to be important in the transition from fetal to neonatal life. The relationship between urinary vasoactive factors and sodium excretion has not been adequately addressed in premature infants receiving indomethacin and ibuprofen for therapy of patent ductus arteriosus. Excretion rates of AVP, ET-1 and sodium were measured in premature infants with RDS receiving indomethacin or ibuprofen. Forty-four RDS premature infants (<34-week gestation) with PDA received either ibuprofen (n=22) in an initial dose of 10 mg/kg followed by two doses of 5 mg/kg each after 24 and 48 h or 3 doses at 12-h intervals of indomethacin (n=24), 0.2 mg/kg, infused continuously over a period of 15 min. Urinary ET-1, AVP and sodium excretion were measured before and after treatment. Indomethacin treatment caused a significant decrease in urinary ET-1 and AVP excretion (UET-1/Ucr 0.14+/-0.01 vs. 0.10+/-0.05 fenton/mmol; P<0.05; 24.42+/-6.18 vs. 12.63+/-3.06 pg/mmol; P<0.05, respectively), along with a significant reduction in urinary sodium (92.1+/-36.1 vs. 64.8+/-35.6 mmol/l; P<0.01), fractional excretion of sodium (6.8+/-37.1 vs. 4.5+/-37.1%; P<0.01) and urinary osmolality (276.2+/-103.9 vs. 226.4+/-60.3 mOsmol/kg; P<0.05). Ibuprofen treatment caused a significant decrease in urinary AVP (UAVP/Ucr 24.5+/-3.4 vs. 16.3+/-2.04 pg/mmol; P<0.01), along with a significant decrease in urinary sodium (78.0+/-8.4 vs. 57.0+/-8.0 mmol/l; P<0.05) and in fractional excretion of sodium (7.5+/-1.3 vs. 3.9+/-3.0%; P<0.05), while it did not modify urinary ET-1 excretion. The association of renal ET-1 and AVP activity with sodium excretion in premature infants treated with indomethacin and ibuprofen supports the hypothesis that these factors may play a role in the physiologic changes in sodium excretion.