Influence of indomethacin on renal function in conscious newborn lambs

Transient renal dysfunction has been observed in some premature infants who received indomethacin to constrict patent ductus arteriosi, and it has been suggested that this complication may be dose related. Accordingly, the present study was designed to investigate the influence of high (7.5 mg/kg) and low (0.2 mg/kg) doses of indomethacin on effective renal blood flow, glomerular filtration rate, urine flow, sodium and potassium excretion and plasma levels of indomethacin in conscious newborn lambs studied continously over a 24-hour period. When compared to control lambs, both indomethacin doses reduced effective renal blood flow significantly at 2--4 h, but only high doses significantly reduced renal blood flow at 22--24 h (6.5 +/- 0.9 vs. 13.4 +/- 1.4 ml/min/kg, respectively; p less than 0.001). At 8-16 and 16-24 h after drug administration, urine flow was significantly lower than in the control group only in high-dose lambs (p less than 0.05). During the 16 to 24-hour period, urine flow for control, low- and high-dose animals was 0.15 +/- 0.01, 0.14 +/- 0.01, and 0.08 +/- 0.02 ml/min/kg, respectively. Glomerular filtration rate and sodium and potassium excretion rates were not affected by either indomethacin dose.