Influence of Indomethacin on Renal Function in Conscious Newborn Lambs

Abstract

Transient renal dysfunction has bee 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 continuously 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 < 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 < 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.

Fractional excretion tests: a critical review of methods and applications in domestic animals

“…Furosemide and hydrochlorothiazide administered to normal cows and cows with udder edema at parturition increased FE Na , FE K , and FE Cl , whereas acetazolamide increased only FE Na , and a 50% glucose solution increased both FE Cl and FE K 58 . No change in GFR or in sodium and potassium excretion was induced by indomethacin in newborn lambs 127 …”

Effects of indomethacin on systemic and renal haemodynamics in conscious lambs

“…For example, Herin & Aperia (1982) showed in anaesthetized, paralysed lambs that indomethacin (2.5 mg kg −1 bolus plus 1.0 mg kg −1 h −1 ) had no effect on RBF measured using radiolabelled microspheres. In conscious lambs, Winther et al (1980) reported a decrease in effective RBF, calculated from the clearance of radiolabelled hippurate, at 2–4 h after administration of low‐dose (0.2 mg kg −1 ) as well as high‐dose indomethacin (7.5 mg kg −1 ). They also showed a further decrease in effective RBF at 12–14 h and again at 22–24 h after administration of high‐ but not low‐dose indomethacin.…”

Cyclooxygenase (COX) Inhibitors and the Newborn Kidney

“…This variability may reflect differences in experimental design, state of the animal, method of measurement of renal haemodynamics, species, choice of drug, and dose: For example, Herin & Aperia [67] showed in anaesthetised, paralysed lambs that indomethacin (2.5 mg/kg bolus plus 1.0 mg/h/kg) had no effect on renal blood flow measured using radio-labelled microspheres. In conscious lambs, Winther et al [68] reported a decrease in effective renal blood flow, and calculated from the clearance of radio-labelled hippurate at two to four hours after administration of low dose (0.2 mg/kg) as well as high dose (7.5 mg/kg) indomethacin. They also showed a further decrease at 12–14 h and again at 22–24 h after administration of high but not low dose indomethacin.…”