Changes in cerebral, renal and mesenteric blood flow velocity during continuous and bolus infusion of indomethacin

Abstract

Vasoconstriction induced by bolus injection of indomethacin reduces organ perfusion and has been related to the well‐known side effects of indomethacin given for closure of the patent ductus arteriosus (PDA). The aim of the study was to compare the changes in cerebral, renal and mesenteric blood flow velocities after continuous infusion versus bolus injection of indomethacin for closure of the PDA. Thirty‐two preterm infants (range 26–35 wk gestational age) with PDA were randomly assigned to receive the same amount of indomethacin either as three bolus injections (n= 14) or as a continuous infusion (n= 18) over 36 h. Blood flow velocities were measured in the internal carotid, right renal and superior mesenteric arteries at baseline and serially at 10, 30, 60 and 120 min and 12, 24, 36 and 48 h after the start of indomethacin treatment. There were no differences in blood flow velocities between both groups at baseline. During continuous infusion of indomethacin there was no significant change in the cerebral, renal and mesenteric blood flow velocities, whereas the flow velocities in the infants receiving bolus injections decreased significantly during the first 2 h after indomethacin administration in all arteries measured. There was a transient, but significant reduction in urine output after bolus injection of indomethacin. Conclusion: In contrast to bolus injections, decrease of organ blood flow and impairment of urine output do not accompany continuous infusion of indomethacin over 36 h.

Ibuprofen Versus Continuous Indomethacin in Premature Neonates With Patent Ductus Arteriosus: Is the Difference in the Mode of Administration?

“…Furthermore, renal side effects, such as oliguria and elevated serum creatinine, which often accompany bolus indomethacin, did not occur. Christmann et al (14) confirmed and extended these observations, demonstrating that reductions in mesenteric and renal flow velocities associated with bolus indomethacin were also prevented by continuous infusion.…”

“…In preterm human neonates, Cataldi et al (21) have shown that ibuprofen does constitute a risk factor for acute renal failure. In contrast, we and others have shown that continuous indomethacin administration eliminates the changes in cerebral (13), renal and mesenteric (14) blood flow velocity, and in urine output described with bolus indomethacin administration.…”

Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone

“…Current pharmacological treatments for a PDA include indomethacin or ibuprofen, cyclooxygenase inhibitors that suppress PGE 2 (34). However, these treatments are not ideal as they do not specifically target the DA and can result in constriction of other vascular beds (10). Furthermore, despite pharmacological treatment, the DA fails to close in some infants and surgical ligation is required, a procedure accompanied by concerning surgical and anesthetic risks (52).…”

Controversies in Management of Patent Ductus Arterious in the Preterm Infant

“…Indomethacin mediated reduction in systemic blood flow may be ameliorated by slowing the infusion rate to 20-30 minutes [51] or by continuous administration [52]. Rather than following a fixed dosing schedule, an indomethacin treatment strategy based on serial echocardiographic measurements of PDA flow pattern is associated with reduction in total doses of drug while being equally effective [41].…”