Effect of Indomethacin Infused over 30 Minutes on Cerebral Fractional Tissue Oxygen Extraction in Preterm Newborns with a Patent Ductus Arteriosus

Abstract

Background: A significant patent ductus arteriosus (PDA) is a common finding in the first days of life and, if persistent, is associated with an increased morbidity and mortality in the preterm newborn. Objectives: Our aim was to investigate, using near-infrared spectroscopy, the effect of indomethacin on the fractional tissue (cerebral) oxygen extraction (FT_cOE) in a group of preterm newborns undergoing medical treatment for a PDA. Methods: This is a prospective, observational study. A cohort of 18 preterm newborns (<32 weeks) undergoing treatment for a PDA with indomethacin were monitored continuously for mean arterial blood pressure, arterial oxygen saturation (SpO₂) and regional cerebral oxygen saturation (r_cSO₂). Measurements were started 1 h before and continued for 4 h after the first indomethacin dose. A final measurement (1 h) was made within 24 h of completing the full course. FT_cOE = [SpO₂ – r_cSO₂]/SpO₂ was then calculated. To analyze the data, we chose to average the measurements over 1-hour periods. Results: There was a significant increase in the FT_cOE (0.06, 95% CI 0.04–0.09, p < 0.001) noticeable within the 1st hour after the start of indomethacin administration, which peaked in the 2nd hour (FT_cOE increased by 0.08, 95% CI 0.04–0.11, p < 0.001) and lasted for the full 4-hour period measured. Conclusion: Indomethacin, infused over 30 min, significantly increased the FT_cOE in the preterm newborn, the effect lasting at least 4 h. This may represent a protective response to the indomethacin-induced reduction in cerebral blood flow demonstrated by others and warrants further investigation.

Prophylactic indomethacin infusion increases fractional cerebral oxygen extraction in ELBW neonates

“…Furthermore, our subgroup analysis indicates that responses to indomethacin may differ among racial groups. Our findings in neonates in the first day of life complement those of Keating et al 11 who reported a similar magnitude increase in fractional cerebral oxygen extraction in neonates being treated for a clinically significant ductus arteriosus at 2 to 11 days old.…”

Brain oxygenation monitoring during neonatal resuscitation of very low birth weight infants

“…Applications in preterm infants included cerebral monitoring during the first days of life 7,14,20 or during therapy of a patent ductus arteriosus. 11,13 We tested, if monitoring of cerebral StO 2 is feasible in VLBW infants during neonatal resuscitation during the first minutes after delivery. In our study, at the age of 1 minute the range of cerebral StO 2 was 31 to 49% and increased to a steady state of 61 to 84% B7 min after birth.…”

“…It has been used in preterm infants for various healthcare conditions such as respiratory distress syndrome, 7 red blood cell transfusion, 8 desaturations, 9 indomethacin therapy 10,11 or ligation of a patent ductus arteriosus 12,13 and during the critical first days of life. [14][15][16][17] Major determinants of the regional tissue oxygen saturation are changes in SpO 2 , regional perfusion, regional blood volume and metabolic rate of oxygen utilization.…”

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.…”