A method to calculate arterial and venous saturation from near infrared spectroscopy (NIRS).

For adequate development and functioning of the neonatal brain, sufficient oxygen (O2) should be available. With a fast sampling (f(s) > 50 Hz) continuous wave NIRS device, arterial (SaO2) and venous (SvO2) saturation can be measured using the physiological fluctuations in the oxyhemoglobin (O2Hb) and total hemoglobin (tHb) concentrations due to heart action and respiration. Before using this technique in a neonatal setting, the method was verified on adult volunteers (n=7) by decreasing inspired oxygen down to an arterial saturation of 70% using a pulse oximeter as reference. NIRS optodes were placed on the left forehead; the pulse oximeter sensor was placed on the right forehead. The experiments were repeated with different optode spacings. SaO2 and SvO2 were determined using the ratio between the O2Hb and tHb value in the amplitude spectrum at the heart rate and respiration rate, respectively. A good agreement between calculated SaO2 and reference SaO2 from pulse oximetry was found (bias range -3.5% to 5.2%, SD of the residuals 1.3% to 3.5%). Optode spacing of 15 mm yielded a negative bias compared to optode spacing of 45 mm. It was not always possible to calculate SvO2 because the respiration peak could not always be detected.

Cerebral oxygen supply during hypotension in near-term lambs: a near-infrared spectroscopy study.

Sufficient O(2)-supply to the brain is necessary for an adequate cerebral energy metabolism, function and growth. To elucidate the relation between changes in, respectively, mean arterial blood pressure (MABP) and cerebral O(2)-supply and changes in the oxygenation state of hemoglobin during hypotension in preterm born lambs. Preterm lambs were delivered at 141 days (n=7) or 127 days (n=7) of gestation. Hypotension was induced by stepwise withdrawal of blood. Cerebral arterial blood gases were analyzed at the end of each level to calculate cerebral O(2)-supply. Near-infrared spectroscopy was used to measure changes in the concentration of cerebral oxyhemoglobin (cO(2)Hb), deoxyhemoglobin (cHHb) and cHbD (the difference between cO(2)Hb and cHHb). In the 141 and the 127 d lambs, changes in MABP and cerebral O(2)-supply were positively linearly related with DeltacO(2)Hb, and negatively with DeltacHHb. MABP was positively linearly related with changes in cHbD. During hemorrhagic hypotension, changes in MABP and cerebral O(2)-supply are reflected by changes in the oxygenation state of cerebral hemoglobin in near-term born lambs.

Hemodynamic changes during opening of the bridge in venoarterial extracorporeal membrane oxygenation.

OBJECTIVE: To investigate the cause of the hemodynamic changes occurring during opening of the bridge in venoarterial (VA) extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective intervention study in animals. SETTING: Animal research laboratory of a university medical center. SUBJECTS: Eight anesthetized lambs installed on VA-ECMO. INTERVENTIONS: During VA-ECMO the bridge was randomly opened during 1, 2.5, 5, 7.5, 10, and 15 secs at ECMO flow rates of 500, 400, 300, 200, 100, and 50 mL/min. Flows in the ECMO circuit between venous cannula and bridge and bridge and arterial cannula, mean arterial blood pressure, mean left carotid artery blood flow, central venous pressure, superior sagittal sinus pressure, inline mixed venous oxygen saturation, heart rate, and arterial oxygen saturation were measured continuously. Using near infrared spectrophotometry, changes in concentrations of cerebral oxygenated and deoxygenated hemoglobin and cerebral blood volume were also measured. Values during bridge opening were compared with values before opening. The same variables were determined with a roller pump on the bridge with a flow over the bridge at various flow rates. MEASUREMENTS AND MAIN RESULTS: Bridge opening resulted in a change of flow direction between venous cannula and bridge and bridge and arterial cannula. A biphasic response with initial decrease and secondary increase occurred in mean arterial blood pressure and mean left carotid artery blood flow. Central venous pressure, superior sagittal sinus pressure, deoxygenated hemoglobin, and cerebral blood volume increased, whereas cerebral oxygenated hemoglobin decreased. These effects occurred in each combination of ECMO flow rate and opening time. These effects could be abolished by installing a roller pump on the bridge. CONCLUSIONS: Bridge opening in VA-ECMO resulted in significant cerebral hemodynamic changes caused by an arteriovenous shunt over the bridge. The decreased cerebral perfusion pressure may contribute to the occurrence of cerebral ischemia, and the venous congestion may result in intracranial hemorrhages. These could be prevented by installing a roller pump on the bridge.

The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: a randomized controlled trial--BARTrial.

BACKGROUND AND OBJECTIVE: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome. METHODS: In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death. RESULTS: Composite motor (100 ± 13 vs. 101 ± 12) and cognitive (101 ± 12 vs. 101 ± 11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤ 1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g. CONCLUSIONS: The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74465643.

Cerebral O2 supply thresholds for the preservation of electrocortical brain activity during hypotension in near-term-born lambs.

The fetal brain develops rapidly during the last trimester of pregnancy. Therefore, the brain of infants who are born preterm is vulnerable to changes in oxygen and nutrient supply in the neonatal period. The objective was to determine the effect of gestational age (GA) on the cerebral O2 supply threshold level for preservation of brain function during hypotension in near-term-born lambs. Lambs were delivered at 141 or 127 d of gestation. Hypotension was induced by stepwise withdrawal of blood. Mean arterial blood pressure (MABP) baseline levels were 63.2 (6.4) in 141-d and 54.4 (15.5) mm Hg in 127-d lambs. The MABP threshold below which MABP and blood flow in the left carotid artery were linearly related was 36.1 (13.1) mm Hg in 141-d lambs. In 127-d lambs, MABP and blood flow in the left carotid artery were linearly related over the whole range of recorded MABP values. Electrocortical brain activity (ECBA) was used as a measure of brain function. Thresholds of MABP for maintenance of ECBA were reached at, respectively, 31.6% (4.9%) of baseline in 141-d and 61.9% (13.0%) of baseline MABP in 127-d lambs. However, thresholds of cerebral O2 supply for maintenance of ECBA were similar in both GA groups. We conclude that thresholds of cerebral O2 supply for maintenance of brain cell function are independent of GA but are reached at higher MABP levels in 127-d than in 141-d lambs and therefore places the sick preterm infant easily at risk for ischemic cerebral injury.

Brain cell function during hypoxemia in near-term lambs: a near-infrared spectroscopy study.

BACKGROUND: Sufficient O2 supply to the brain is necessary for adequate cerebral energy metabolism, function and growth. OBJECTIVES: To elucidate the relation between changes in cerebral arterial O2 content and cerebral O2 supply and changes in the oxygenation state of cerebral hemoglobin, and to determine whether concentration changes in oxyhemoglobin (DeltacO2Hb), deoxyhemoglobin (DeltacHHb), and cerebral arterial oxygenation (DeltacHbD; the difference between DeltacO2Hb and DeltacHHb), and cerebral blood volume (DeltaCBV) can be used to assess the decline in brain cell function during hypoxemia in lambs born near term. METHODS: 17 preterm lambs were delivered at a mean gestational age of 133 days. Decreases in cerebral arterial oxygen content were induced by a stepwise reduction in inspired oxygen concentration. Mean values of all continuous variables were calculated over the last 180 s of each hypoxemic level. Cerebral arterial blood gases were analyzed at the end of each level to calculate cerebral arterial O2 content and cerebral O2 supply. RESULTS: Changes in cerebral arterial O2 content and cerebral O2 supply were positively linearly related with DeltacO2Hb and DeltacHbD, and negatively with DeltacHHb and the concentration changes in total hemoglobin. Electrocortical brain activity remained stable until the cO2Hb and cHbD decreased to >3.0 +/- 0.9 and >8.1 +/- 1.9 (mean +/- SD) micromol/100 g, respectively, and cHHb and CBV increased to >4.3 +/- 1.7 and 1.37 +/- 0.48 ml/100 g, respectively, as compared to baseline. CONCLUSIONS: Changes in cerebral arterial O2 content and cerebral O2 supply are adequately reflected by changes in the oxygenation state of cerebral hemoglobin. Concentration changes in DeltacO2Hb, DeltacHHb, DeltacHbD and DeltaCBV can be used to assess the decline in brain cell function during hypoxemia in lambs born near term.

Oxygenation and hemodynamics in left and right cerebral hemispheres during induction of veno-arterial extracorporeal membrane oxygenation.

OBJECTIVE: Oxygenation and hemodynamics in the left and right cerebral hemispheres were measured during induction of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). STUDY DESIGN: Using near infrared spectrophotometry, effects of right common carotid artery (RCCA) and right internal jugular vein (RIJV) ligation and start of VA-ECMO on concentrations of oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume (CBV) were evaluated in 10 newborn infants. Mean cerebral blood flow velocity (CBFV) in the major cerebral arteries was compared before and after the start of VA-ECMO (pulsed Doppler ultrasonography). RESULTS: RCCA ligation caused a decrease in oxyhemoglobin concentration and an increase in deoxyhemoglobin concentration. RIJV ligation caused no changes. Sixty minutes after the start of VA-ECMO, oxyhemoglobin concentration and CBV had increased, and deoxyhemoglobin concentration had decreased. There were no differences between the hemispheres. Mean CBFV had increased in the left internal carotid artery, and it increased equally in both middle cerebral arteries. Flow direction was reversed in the right internal carotid artery. Three patients had asymmetric cerebral lesions, not related to differences in the measurements between the cerebral hemispheres. CONCLUSION: The initiation of VA-ECMO causes changes in cerebral oxygenation and hemodynamics but without a difference in effect on left and right cerebral hemispheres.

Preservation of electrocortical brain activity during hypoxemia in preterm lambs.

Adequate cerebral perfusion is necessary to preserve cerebral O(2) supply in order to maintain brain cell function. Our aim was to assess the influence of gestational age on the response of cerebral hemodynamics to hypoxemia and to determine thresholds of cerebral O(2) supply for preservation of brain cell function in preterm born lambs. Lambs were delivered by hysterotomy at 141 (n=5), 134 (n=5) or 127 (n=7) days of gestation. Decreases in arterial oxygen content (CaO(2)) were induced by stepwise reduction of the fraction of O(2) in inspired air (FiO(2)). Mean arterial blood pressure (MABP), carotid artery blood flow (Qcar), and electrocortical brain activity as a measure of brain cell function, were continuously recorded. Cerebral arterial blood gases were analyzed at the end of each hypoxemic level to calculate CaO(2) and cerebral O(2) supply. In contrast to 141-day lambs, MABP could not be maintained in 134-day and 127-day lambs at levels of severe hypoxemia. Increases in Qcar were observed at levels of moderate hypoxemia in all gestational age-groups. Albeit Qcar increased further at levels of severe hypoxemia in the 141-day lambs, Qcar declined under these conditions in the 134-day and 127-day lambs. The threshold of cerebral O(2) supply for the preservation of brain cell function was however similar in all gestational age-groups (1.7 ml/min). It is concluded that the ability to maintain cerebral function during hypoxemia depends upon the ability to preserve cerebral O(2) supply by means of cerebral hemodynamic compensatory mechanisms, which are not fully matured until 96% of gestation.

Purine and pyrimidine metabolism and electrocortical brain activity during hypoxemia in near-term lambs.

Insufficient cerebral O(2) supply leads to brain cell damage and loss of brain cell function. The relationship between the severity of hypoxemic brain cell damage and the loss of electrocortical brain activity (ECBA), as measure of brain cell function, is not yet fully elucidated in near-term newborns. We hypothesized that there is a strong relationship between cerebral purine and pyrimidine metabolism, as measures of brain cell damage, and brain cell function during hypoxemia. Nine near-term lambs (term, 147 d) were delivered at 131 (range, 120-141) d of gestation. After a stabilization period, prolonged hypoxemia (fraction of inspired oxygen, 0.10; duration, 2.5 h) was induced. Mean values of carotid artery blood flow, as a measure of cerebral blood flow, and ECBA were calculated over the last 3 min of hypoxemia. At the end of the hypoxemic period, cerebral arterial and venous blood gases were determined and CSF was obtained. CSF from 11 normoxemic siblings was used for baseline values. HPLC was used to determine purine and pyrimidine metabolites in CSF, as measures of brain cell damage. Concentrations of purine and pyrimidine metabolites were significantly higher in hypoxemic lambs than in their siblings, whereas ECBA was lower in hypoxemic lambs. Significant negative linear relationships were found between purine and pyrimidine metabolite concentrations and, respectively, cerebral O(2) supply, cerebral O(2) consumption, and ECBA. We conclude that brain cell function is related to concentrations of purine and pyrimidine metabolites in the CSF. Reduction of ECBA indeed reflects the measure of brain damage due to hypoxemia in near-term newborn lambs.