Using near-infrared spectroscopy to measure cerebral metabolic rate of oxygen under multiple levels of arterial oxygenation in piglets.

Improving neurological care of neonates has been impeded by the absence of suitable techniques for measuring cerebral hemodynamics and energy metabolism at the bedside. Currently, near-infrared spectroscopy (NIRS) appears to be the technology best suited to fill this gap, and techniques have been proposed to measure both cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2). We have developed a fast and reliable bolus-tracking method of determining CMRO2 that combines measurements of CBF and cerebral venous oxygenation [venous oxygen saturation (CSvO2)]. However, this method has never been validated at different levels of arterial oxygenation [arterial oxygen saturation (SaO2)], which can be highly variable in the clinical setting. In this study, NIRS measurements of CBF, CSvO2, and CMRO2 were obtained over a range of SaO2 in newborn piglets (n=12); CSvO2 values measured directly from sagittal sinus blood samples were collected for validation. Two alternative NIRS methods that measure CSvO2 by manipulating venous oxygenation (i.e., head tilt and partial venous occlusion methods) were also employed for comparison. Statistically significant correlations were found between each NIRS technique and sagittal sinus blood oxygenation (P<0.05). Correlation slopes were 1.03 (r=0.91), 0.73 (r=0.73), and 0.73 (r=0.81) for the bolus-tracking, head tilt, and partial venous occlusion methods, respectively. The bolus-tracking technique displayed the best correlation under hyperoxic (SaO2=99.9±0.03%) and normoxic (SaO2=86.9±6.6%) conditions and was comparable to the other techniques under hypoxic conditions (SaO2=40.7±9.9%). The reduced precision of the bolus-tracking method under hypoxia was attributed to errors in CSvO2 measurement that were magnified at low SaO2 levels. In conclusion, the bolus-tracking technique of measuring CSvO2, and therefore CMRO2, is accurate and robust for an SaO2>50% but provides reduced accuracy under more severe hypoxic levels.

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

The therapeutic window following perinatal hypoxia-ischemia is brief, and early clinical signs of injury can be subtle. Electroencephalography (EEG) represents the most promising early diagnostic of hypoxia-ischemia; however, some studies have questioned the sensitivity and specificity of EEG. The present study investigated the use of both near-infrared spectroscopy (NIRS) measurements of the cerebral metabolic rate of oxygen (CMRO(2)) and amplitude-integrated EEG (aEEG) to detect the severity of hypoxia-ischemia after 1 h of reperfusion in newborn piglets (10 insult, 3 control). The CMRO(2) was measured before and after 1 h of reperfusion from hypoxia-ischemia, the duration of which was varied from piglet to piglet with a range of 3-24 min, under fentanyl/nitrous oxide anesthesia to mimic awake-like levels of cerebral metabolism. EEG data were collected throughout the study. On average, the CMRO(2) and mean aEEG background signals were significantly depressed following the insult (P < 0.05). Mean CMRO(2) and mean aEEG background were 2.61 +/- 0.11 ml O(2).min(-1).100 g(-1) and 20.4 +/- 2.7 microV before the insult and 1.58 +/- 0.09 ml O(2).min(-1).100 g(-1) and 11.8 +/- 2.9 microV after 1 h of reperfusion, respectively. Both CMRO(2) and aEEG displayed statistically significant correlations with duration of ischemia (P < 0.05; r = 0.71 and r = 0.89, respectively); however, only CMRO(2) was sensitive to milder injuries (<5 min). This study highlights the potential for combining NIRS measures of CMRO(2) with EEG in the neonatal intensive care unit to improve early detection of perinatal hypoxia-ischemia.

Assessing the severity of perinatal hypoxia-ischemia in piglets using near-infrared spectroscopy to measure the cerebral metabolic rate of oxygen.

Reduced cerebral function after neonatal hypoxia-ischemia is an early indicator of hypoxic-ischemic encephalopathy. Near-infrared spectroscopy offers a clinically relevant means of detecting impaired cerebral metabolism from the measurement of the cerebral metabolic rate of oxygen (CMRO2). The purpose of this study was to determine the relationship between postinsult CMRO2 and duration of hypoxia-ischemia in piglets. Twelve piglets were subjected to randomly selected durations of hypoxia-ischemia (5-28 min) and five animals served as controls. Measurements of CMRO2 were taken before and for 24 h after hypoxia-ischemia. Histology was carried out in nine piglets (six insults, three controls) to estimate brain injury. In the first 4 h after the insult, average CMRO2 of the insult group was significantly depressed (33 +/- 3% reduction compared with controls) and by 8 h, a significant correlation developed, which persisted for the remainder of the study, between CMRO2 and the duration of ischemia. Histologic staining suggested little brain damage resulted from shorter insult durations and considerable damage from more prolonged insults. This study demonstrated that near-infrared spectroscopy could detect early changes in CMRO2 after hypoxia-ischemia for a range of insult severities and CMRO2 could be used to distinguish insult severity by 8 h after the insult.

Measurement of cerebral oxidative metabolism with near-infrared spectroscopy: a validation study.

Predicting the onset of secondary energy failure after a hypoxic-ischemic insult in newborns is critical for providing effective treatment. Measuring reductions in the cerebral metabolic rate of oxygen (CMRO(2)) may be one method for early detection, as hypoxia-ischemia is believed to impair oxidative metabolism. We have developed a near-infrared spectroscopy (NIRS) technique based on the Fick Principle for measuring CMRO(2). This technique combines cerebral blood flow (CBF) measurements obtained using the tracer indocyanine green with measurements of the cerebral deoxy-hemoglobin (Hb) concentration. In this study, NIRS measurements of CMRO(2) were compared with CMRO(2) determined from the product of CBF and the cerebral arteriovenous difference in oxygen measured from blood samples. The blood samples were collected from a peripheral artery and the sagittal sinus. Eight piglets were subjected to five cerebral metabolic states created by varying the plane of anesthesia. No significant difference was found between CMRO(2) measurements obtained with the two techniques at any anesthetic level (P>0.5). Furthermore, there was a strong correlation when concomitant CMRO(2) values from the two techniques were compared (R(2)=0.88, P<0.001). This work showed that CMRO(2) can be determined accurately by combining NIRS measurements of CBF and Hb. Since NIRS is safe and measurements can be obtained at the bedside, it is believed that this technique could assist in the early diagnosis of cerebral energy dysfunction after hypoxia-ischemia.