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

Abstract

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).

Measurement of Cerebral Oxidative Metabolism with Near-Infrared Spectroscopy: A Validation Study

“…By combining CBF and absolute Hb concentration measurements, our group has developed an NIRS method for measuring the CMRO 2 that is based on the Fick Principle (Siesjo, 1978). The feasibility of this technique was first shown by measuring the effects of indomethacin on CBF and CMRO 2 in a piglet model (Brown et al, 2003). In agreement with previous studies (Armstead et al, 1988;Coyle et al, 1995), it was shown that indomethacin reduced CBF (by 18%) but had no effect on CMRO 2 .…”

“…If this variation is real, then it could limit the use of the NIRS technique clinically. However, Brown et al (2003) found only a 15% error in the CMRO 2 when there was a 10% error in the relative contributions of arterial and venous blood.…”

Response

“…With regard to the first point, Coyle et al (3) observed in newborn piglets that while CMRO 2 was reduced following administration of a large dose (5.0 mg/kg) of indomethacin, CMRO 2 was not affected by a lower, more clinically relevant dose (0.3 mg/ kg). In a recent study using a novel near-infrared spectroscopy technique to measure CMRO 2 , a dose of 0.2 mg/kg (which is the same dose used in our study) was found to have no effect on CMRO 2 in newborn piglets, although it did reduce CBF and increase oxygen extraction (4). With regard to the second point, prostaglandins are believed to contribute to the regulation of CBF and CMRO 2 in the developing brain, but not in the mature brain (5).…”

Cerebral metabolic rate of oxygen and amplitude-integrated electroencephalography during early reperfusion after hypoxia-ischemia in piglets

“…The method used to calculate CMRO 2 with NIRS has been discussed in detail previously (3). Measurements of CMRO2 were based on the Fick principle:…”

“…By combining these measurements, our group has developed a bedside NIRS system capable of rapidly measuring the CMRO 2 that was validated in healthy piglets over a range of metabolic states (3,38). Furthermore, our group observed early, persistent reductions in the CMRO 2 of piglets subjected to transient hypoxia-ischemia (37).…”