Cerebral Blood Flow Responses to Indomethacin in Awake Newborn Pigs

Pourcyrous, Massroor; Leffler, Charles W.; Bada, Henrietta S.; Korones, Sheldon B.; Busija, David W.

doi:10.1203/00006450-199405000-00007

Cited by 29 publications

(18 citation statements)

References 14 publications

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“…CMRO 2 values reported in the current study are in agreement with those observed in previous newborn piglet studies (2, 29 -31 (2) found an average baseline CMRO 2 of 3.57 mL O 2 · min Ϫ1 · 100 g Ϫ1 in awake 3-to 5-d-old piglets using microsphere CBF determination and venous (sagittal sinus) blood samples. Although this value is higher than our reported baseline value, it is to be expected that awake piglets should have a higher CMRO 2 than those receiving anesthetics.…”

Section: Discussionsupporting

confidence: 92%

“…Although this value is higher than our reported baseline value, it is to be expected that awake piglets should have a higher CMRO 2 than those receiving anesthetics. Using microsphere-measured CBF and with arterial and venous (sagittal sinus) blood sampling, Ichord et al (30) 2 values reported in the last study and those reported in the current study are likely due to differences in breed (mixed German domestic breed) and anesthetics used (nitrous oxide with isoflurane).…”

Section: Discussionmentioning

confidence: 53%

“…Because reductions in CBF compromise O 2 delivery, concern has been raised as to whether indomethacin administration may also alter CMRO 2 . Several studies previously reported in the literature have investigated the effect of indomethacin on CMRO 2 in newborn human and animal models with varying results (2,(5)(6)(7), likely attributable to different indomethacin doses used and to differences in techniques used for CMRO 2 measurement.…”

mentioning

confidence: 99%

“…Several studies previously reported in the literature have investigated the effect of indomethacin on CMRO 2 in newborn human and animal models with varying results (2,(5)(6)(7), likely attributable to different indomethacin doses used and to differences in techniques used for CMRO 2 measurement. Benders et al (5), inferring CMRO 2 from cytochrome oxidase (Cyt) measurement, and Pourcyrous et al (2), using microsphere-measured CBF and venous (sagittal sinus) blood samples to calculate CMRO 2 , both observed a decrease in CMRO 2 after indomethacin infusion in preterm infants (indomethacin dose of 1 mg/kg) and newborn piglets (3-5 d old; indomethacin dose of 5 mg/kg), respectively, whereas van Bel et al (6) found indomethacin administration (1 mg/kg) had no effect on CMRO 2 in the fetal lamb. Coyle et al (7) found that high-dose (5 mg/kg) indomethacin elicited a decrease in CMRO 2 , whereas lower-dose (3 mg/kg) indomethacin treatment had no effect in newborn piglets 3-5 d old, reporting that increases in OEF during indomethacin-induced reductions in CBF were sufficient to maintain CMRO 2 in the lower dose group.…”

mentioning

confidence: 99%

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Near-Infrared Spectroscopy Measurement of Oxygen Extraction Fraction and Cerebral Metabolic Rate of Oxygen in Newborn Piglets

2003

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Cerebral metabolic rate of oxygen (CMRO 2 ), the rate at which O 2 is consumed in the brain by metabolic processes, is one of the most useful measures of normal brain function. The present study investigated the use of near-infrared spectroscopy (NIRS) in the noninvasive measurement of O 2 extraction fraction (OEF) and CMRO 2 in the newborn piglet. Indomethacin, although used successfully to effect closure of patent ductus arteriosus in the preterm infant, is known to cause transient reductions in cerebral blood flow (CBF) in both infant and adult humans and pigs. As a test of the NIRS method, the present study also examined the effect of indomethacin-induced reductions in CBF on both OEF and CMRO 2 . CBF, OEF, and CMRO 2 were assessed in 20 newborn piglets, 0.2-3.0 d old. Ten piglets received 0.2 mg/kg of indomethacin infused over 30 min; remaining piglets received saline infusion as control. CBF, OEF, and CMRO 2 measurements were performed before infusion and at 30-min intervals for a period of 90 min post-infusion. Saline infusion elicited no response in CBF, OEF, or CMRO 2 . Immediately after indomethacin infusion, CBF decreased 18.1% below (p Ͻ 0.05) and OEF increased 26.2% above (p Ͻ 0.05) preinfusion values, whereas CMRO 2 showed no significant changes throughout the study. Both CBF and OEF returned to baseline within 60 min after infusion of indomethacin. The proficiency of NIRS in the measurement of OEF and CMRO 2 was demonstrated through the observation of transient increases in OEF, which served to maintain CMRO 2 during indomethacin-induced reductions in CBF. Cerebral metabolic rate of oxygen (CMRO 2 ), the rate at which O 2 is consumed in the brain by metabolic processes, is a key indicator of normal brain function. A means of accurately, noninvasively measuring CMRO 2 at the bedside would provide vital information in the clinical assessment of preterm infants. However, difficulties associated with bedside measurement of cerebral blood flow (CBF) and O 2 extraction fraction (OEF) in the brain have prevented the development of clinically viable CMRO 2 measurement techniques and the widespread clinical use of CMRO 2 as an indicator of proper brain function. The near-infrared spectroscopy (NIRS) system used in the present study allows for quantitative measurement of both CBF and OEF at the bedside and thus may provide a clinically useful means of measuring CMRO 2 in the newborn human infant.As a test of the NIRS method, the present study investigated the effect of the nonsteroidal anti-inflammatory drug indomethacin on both OEF and CMRO 2 in the anesthetized newborn piglet. Indomethacin is currently used in the treatment of patent ductus arteriosus (PDA), a common condition among preterm infants that has been shown to increase the risk of intraventricular hemorrhage, bronchopulmonary dysplasia, and death in this group (1). Although useful in the treatment of PDA, administration of indomethacin is known to cause a transient reduction in CBF in both human and animal newborns (2-4).

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 53%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Near-Infrared Spectroscopy Measurement of Oxygen Extraction Fraction and Cerebral Metabolic Rate of Oxygen in Newborn Piglets

2003

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“…5,6 In animal models as well as in human neonates, indomethacin, administered as a bolus, reduces cerebral blood flow. 5,7,8 Using 133-Xenon and Doppler studies, researchers measured a decrease in cerebral blood flow in response to indomethacin administration in preterm neonates. 9,10 If cerebral blood flow decreases consistently with indomethacin administration, one would expect that cerebral oxygenation would fall following indomethacin administration, which potentially risks long-term harm.…”

Section: Introductionmentioning

confidence: 99%

Prophylactic indomethacin infusion increases fractional cerebral oxygen extraction in ELBW neonates

2012

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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.

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