Acute effects of indomethacin on cerebral hemodynamics and oxygenation

Although an indomethacin-induced decrease of brain perfusion in preterm infants has been well established, the acute effects of this vasoactive drug on cerebral hemodynamics and oxygenation are not well documented. Using near infrared spectroscopy we monitored in 6 very preterm infants changes in cerebral blood volume (ΔCBV) and cytochrome oxidase concentration (ΔCytaa₃), used as relative measures of changes in brain perfusion and as an indicator for cellular oxygenation of brain tissue, during and up to 1 h after indomethacin infusion. ΔCBV showed a quick blood-pressure-related increase as compared to baseline (preindomethacin values) during indomethacin infusion (averaged maximal increase 13%), followed by a sharp decrease below baseline values (averaged maximal decrease 24%). There was a sustained recovery to baseline during the registration period. ΔCytaa₃ showed a small, early increase in 4 of 6 babies, followed by a substantial decrease below baseline in 5 babies. ΔCytaa₃ showed only a partial recovery in those 5 babies during the study period. We conclude that a therapeutic dose of indomethacin may cause substantial swings in brain perfusion and a marked and rather longstanding decrease in Cytaa₃, suggesting a decrease in cellular oxygenation of brain tissue. Awareness of these effects may be important in sick preterm babies during periods of pulmonary and cardiac instability.