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Published on: October 11, 2011
Age-dependent cerebral hemodynamic effects of indomethacin in the newborn piglet
Derek W Brown1, David Lee, Vazhkudai S Kumaran
1Imaging Research Labs, Robarts Research Inst., 100 Perth Dr., London, Ontario, Canada N6A 5K8.
Insights
Early indomethacin administration impacts cerebral hemodynamics in newborns. Piglets under 13 hours old showed delayed increases in cerebral blood flow and volume after indomethacin, suggesting age-dependent effects.
Area of Science:
- Neonatal physiology
- Pharmacology
- Cerebrovascular research
Background:
- Intraventricular hemorrhage is a concern in newborns, with prophylactic indomethacin use under discussion.
- Cerebral circulation undergoes significant postnatal adaptive changes.
- Understanding indomethacin's cerebral hemodynamic effects in neonates is crucial.
Purpose of the Study:
- To investigate if postnatal adaptive changes influence the cerebral hemodynamic response to indomethacin in an age-dependent manner.
- To assess the impact of early, low-dose indomethacin on cerebral hemodynamics in newborn piglets.
Main Methods:
- Near-infrared spectroscopy with indocyanine green was used to measure cerebral hemodynamics, cerebral metabolic rate of oxygen, and cerebral oxygen extraction fraction.
- 39 newborn piglets were grouped by age (<13 h vs. >13 h) and received indomethacin or saline.
- Doppler flow ultrasound monitored patent ductus arteriosus in a subgroup.
Main Results:
- Age was a significant factor in the cerebral hemodynamic response to indomethacin.
- Piglets younger than 13 hours exhibited delayed increases in cerebral blood flow and cerebral blood volume at 150 minutes post-infusion.
- Indomethacin's effects on cerebral hemodynamics were age-dependent.
Conclusions:
- Postnatal adaptive changes influence the cerebral hemodynamic response to indomethacin.
- The timing of indomethacin administration is critical for its effects on neonatal cerebral circulation.
- Further research is needed to optimize prophylactic indomethacin use in neonates.
Abstract:
With recent discussions in the literature regarding prophylactic use of early (within the first 12 h after birth), low-dose indomethacin to reduce the incidence and severity of intraventricular hemorrhage, knowledge pertaining to the cerebral hemodynamic effects of indomethacin in this age group is of significant interest. The cerebral circulation is known to undergo significant changes during the first few days of postnatal life. In the present study, we have investigated the hypothesis that postnatal adaptive changes influence the cerebral hemodynamic response to indomethacin in an age-dependent manner. Near-infrared spectroscopy with indocyanine green was used to measure cerebral hemodynamics, cerebral metabolic rate of oxygen, and cerebral oxygen extraction fraction in 39 newborn piglets. Piglets were grouped by age and received either 0.2 mg/kg indomethacin (14 were <13 h of age and 12 were >13 h of age) or saline (8 were <13 h of age and 5 were >13 h of age) infusions. In a subgroup of indomethacin-treated piglets (9 less than and 7 greater than 13 h of age), Doppler flow ultrasound was used to diagnose and monitor the presence and persistence of patent ductus arteriosus. Age was a significant factor in the cerebral hemodynamic response to indomethacin with piglets <13 h of age exhibiting delayed increases in cerebral blood flow and cerebral blood volume at 150 min post-indomethacin infusion.
