Prophylactic indomethacin infusion increases fractional cerebral oxygen extraction in ELBW neonates

Abstract

Objective: Intraventricular hemorrhage (IVH) occurs in up to 25% of very low birth weight (VLBW) preterm neonates. Previous studies found that indomethacin administered in the first 6 h of life reduces the incidence of severe IVH in VLBW neonates and decreases cerebral blood flow, suggesting a decrease in cerebral oxygen delivery. Using near-infrared spectroscopy (NIRS), we monitored cerebral oxygenation before, during and after slow indomethacin infusion in extremely low birth weight (ELBW) neonates to determine whether indomethacin decreases cerebral oxygen saturation and increases cerebral oxygen extraction.Study Design: Twenty-seven ELBW neonates less than 30 weeks gestational age treated with indomethacin for IVH prophylaxis were monitored for arterial oxygen saturation (SaO 2 ) and NIRS-determined regional cerebral oxygen saturation (rSO 2 ). At 30 to 60 s intervals, SaO 2 , rSO 2 and mean arterial pressure (MAP) were recorded using a VitalSync. Average fractional cerebral oxygen extraction was calculated for the hour before indomethacin infusion, during the infusion and 2 h after infusion.Result: Fractional cerebral oxygen extraction increased from baseline after indomethacin administration from 0.23±0.11 to 0.25±0.10 (P ¼ 0.034). Conclusion:Fractional cerebral oxygen extraction increased 9% with indomethacin 0.1 mg kg À1 given over 1 to 2 h. However, the clinical implications of this small increase in extraction, likely representative of decreased cerebral perfusion, are unknown but may be harmful to the developing brain.

Patent Ductus Arteriosus in Preterm Infants: Do We Have the Right Answers?

“…Fowlie et al [34, 104] conducted a meta-analysis on 19 trials of prophylactic indomethacin therapy and found that prophylactic indomethacin has short-term benefits including reduction in symptomatic PDA, the need for duct ligation, and severe IVH with no evidence of either benefit or harm on neurodevelopmental outcome. More recently, prophylactic indomethacin was shown to decrease cerebral perfusion which may be harmful to the developing brain [105] and was found to worsen the short-term respiratory outcomes in ELBW infants [106]. …”

Preservation of the metabolic rate of oxygen in preterm infants during indomethacin therapy for closure of the ductus arteriosus

“…NIRS studies have shown that indomethacin can alter cerebral oxygenation such as the fractional tissue oxygen extraction, although the magnitude of the changes appears to depend on the infusion protocol (5,14,15). Interpreting cerebral oxygenation in terms of energy metabolism is difficult because cerebral blood oxygenation depends on the balance between oxygen delivery and consumption.…”

Tocolytic indomethacin: effects on neonatal haemodynamics and cerebral autoregulation in the preterm newborn

“…Although that effect appears to be less pronounced when indomethacin is administered by slow infusion,35 a small positive effect on blood pressure was recently also seen in a study of early postnatal indomethacin given over 1–2 h to prevent intraventricular haemorrhage, presumably as a result of an increase in cerebrovascular resistance 36. Since we do not have any information about cardiac output or vascular resistance in our patients, we cannot be sure about the exact mechanism of our findings.…”