Nikolai C Brun

Cerebrovascular responses to carbon dioxide as detected by near-infrared spectrophotometry: comparison of three different measures.

ABSTRACT: Near-infrared spectrophotometry can be used to measure cerebral concentrations of oxyhemoglobin and deoxyhemo-globin. This has been applied to developing methods for quantifying cerebral blood volume (CBV), which is relevant for the investigation of the pathogenesis of brain injury in newborn infants as well as older infants. This study investigates the internal consistency between measurements of CBV using two methods: the oxygen method, which is able to determine absolute values of CBV, and the total Hb method, which can detect changes in CBV only. Cerebral blood flow (CBF) was also measured. Fifteen premature infants were examined. Due to practical problems, in only eight of these was a minimum of two CBF and two CBV values obtained both before and after a change in arterial Pco2 of at least 0.5 kPa. A significant difference between the CBV-CO2 reactivity found by the two methods was demonstrated: 0.89 mL/100 g/kPa (95% confidence interval = 0.63–1.26) for the oxygen method and 0.22 mL/100 g/kPa (95% confidence interval = 0.08–0.36) for the total Hb method. This finding is substantiated by the absolute values of CBV [mean value = 3.7 mL/100 g (SD = 1.1)], CBF [mean value =11.3 mL/100 g/min (SD = 5.9)], and CBF reactivity [59 ± 9% (SEM)]. All the values correspond well with previous findings, although the CBV reactivity determined by the oxygen method has not been reported previously. The reason for the discrepancy between the two methods is unclear, but induced changes in the scattering properties of the brain would give rise to errors influencing the total Hb method rather than the oxygen method.

Cerebral excitatory amino acids and Na+,K+-ATPase activity during resuscitation of severely hypoxic newborn piglets

We tested the hypothesis that early brain recovery in hypoxic newborn piglets is improved by resuscitating with an O2 supply close to the minimum level required by the newborn piglet brain. Severely hypoxic 2‐5‐d‐old anaesthetized piglets were randomly divided into three resuscitation groups: hypoxaemic (n= 8), 21% O2 (n= 8), and 100% O2 groups (n= 8). The hypoxaemic group was mechanically ventilated with 12‐18% O2 adjusted to achieve a cerebral venous O2 saturation of 17‐23% (baseline; 45 ± 1%, mean ± SEM). During the 2h resuscitation period, extracellular aspartate and glutamate concentrations in the cerebral striatum were higher during hypoxaemic resuscitation (p= 0:044 and p= 0:055, respectively) than during resuscitation with 21% O2 or 100% O2, suggesting an unfavourable accumulation of potent excitotoxins during hypoxaemic resuscitation. The cell membrane Na+, K+‐ATPase activity of cerebral cortical tissue after 2h resuscitation was similar in the three groups (p= 0:30). In conclusion, hypoxaemic resuscitation did not normalize early cerebral metabolic recovery as efficiently as resuscitation with 21% O2 or 100% O2. Resuscitation with 21% O2 was as efficient as resuscitation with 100% O2 in this newborn piglet hypoxia model.

Neonatal intensive care: an obvious, yet difficult area for cerebral near-infrared spectroscopy.

The first clinical application of near-infrared spectroscopy (NIRS) 11 years ago was on the head of newborn infants under intensive care. Since then much credible and some important data have been accumulated in this area of research. The best data have been obtained using manipulation of arterial oxygen saturation to obtain single or repeated estimates of cerebral blood flow or cerebral blood volume, or interference with cerebral venous return to obtain measures of venous oxygen saturation. It has been more difficult to take advantage of the continuous and noninvasive nature of NIRS. In particular, the value of the cytochrome signal can still be doubted. A role has not yet developed for NIRS in clinical neonatology.

34 EFFECT OF INCREASED BLOOD OXYGEN CONTENT ON CEREBRAL BLOOD VOLUME AS DETECTED BY NEAR-INFRARED SPECTROFOTOMETRY IN NEWBORNS

The cerebral vascular system in newborn infants is known to react to marked hyper- or hypoxaemia. Near-infrared spectrophotometry (NIRS) uses oxyhaemoglobin as a tracer for investigation of both cerebral blood flow(CBF) (a brief large oxygen transient) and cerebral blood volume(CBV) (a longer lasting smaller transient). This analysis investigates the cerebrovascular reactivity to increased blood oxygen content in the physiological range.Material and methods: Twenty-two mechanically ventilated infants (25-42 weeks GA, mean postnatal age (PNA)=10 days) were exposed to a 0.1-0.15 increase in FiO2 lasting 2-5 minutes in 77 measurements of CBV and exposed to a FiO2 of 1.0 lasting 10-20 seconds in 142 measurements of CBF. The change in total cerebral haemoglobin concentration during the oxygen transients was recorded by NIRS and from this the change in cerebral blood volume was derived.Results: The longer, small increase in FiO2 increased mean arterial saturation (SaO2) from 92.6% by 4.0%(SD=2.2) and CBV fell by 0.0045mL/100g/pct change in SaO2(SE=0.0016). The size of the change was characteristic for each infant(p=0.003) but was not related to GA, PNA, initial SaO2, arterio/alveolar-ratio, or initial CBV. The larger, but brief oxygen transient changed mean SaO2 more (p<0.0001) from 92.0% by 7.0%(SD=2.9), but did not alter CBV significantly.Conclusion: An increase in blood oxygen content within the physiological range lasting a few minutes produced a decrease in CBV, probably due to cerebral vasoconstriction. A larger but briefer transient did not produce this response. Apart from their physiological interest, these findings are directly relevant for the interpretation of the currently used methods to determine CBF and CBV using NIRS.

RESUSCITATION WITH LOW OXYGEN CONCENTRATIONS IN NEWBORN PIGLETS DOES NOT IMPROVE CEREBRAL METABOLIC RECOVERY OR EEG RECOVERY |[dagger]| 871

We investigated whether resuscitation with lower O2 concentrations than 21% reduces reoxygenation injury and thereby improves cerebral metabolic recovery and EEG recovery. Methods: Hypoxia was induced by ventilating 24 anesthetized and instrumented newborn piglets with 6% O2 in N2. CO2 was added to the inspiratory gas to achieve PaCO2 between 52 and 60 mm Hg. When EEG became isoelectric, and either mean arterial blood pressure fell below 25 mmHg or base excess (BE) was lower than -25 mmol/L, a 2 hour resuscitation period was started. The piglets were randomly divided into three groups: Hypoxemic (n=8), 21% O2 (n=8), and 100% O2 group (n=8). The hypoxemic group was ventilated with 12 to 18% O2 to achieve a cerebral venous O2 saturation of 17 to 23%(baseline; 42-46%), levels which in a previous study was shown not to give any changes of EEG or hypoxanthine (Hx) in cerebral cortex in healthy piglets. PaCO2 was kept in normal range during resuscitation. Extracellular Hx was sampled by in vivo microdialysis from cerebral cortex and striatum. EEG and Oxygenation Index (Near Infrared Spectrophotometry, NIRS) were continuously recorded. Results: Arterial oxygen tensions at 30 mins of resuscitation were (mean±SEM) 45±2, 74±4, and 431±20 mmHg in the hypoxemic, 21% O2 and 100% O2 groups. There were no significant differences between the groups in recovery of EEG(p=0.22) or Hx concentrations in cerebral cortex, striatum, and plasma. Mean BE was -20 to -23 mmol/L at the end of hypoxia (p=0.67) and rose during resuscitation to -13±2, -5±2, and -5±1 mmol/L in the hypoxemic, 21% O2 and 100% O2 groups(p<0.05, hypoxemic vs. 21% O2 and 100% O2 groups). Resuscitation with 21% O2 and 100% O2 reestablished the O2 support to the brain measured by NIRS within the first mins of resuscitation. Conclusion: Hypoxemic resuscitation of newborn piglets does not improve cerebral metabolic recovery or EEG recovery, and delays the correction of the metabolic acidosis.

Regional cerebral blood volume (CBV) is overestimated by Near-infrared spectrophotometry (NIRS) validation against Single Photon Emission Computerized Tomography (SPECT) in newborn piglets. 29

Regional cerebral blood volume (CBV) is overestimated by Near-infrared spectrophotometry (NIRS) validation against Single Photon Emission Computerized Tomography (SPECT) in newborn piglets. 29

Controlled Hypoxemic Resuscitation Does Not Improve Early Cerebral Metabolic or Electrophysiological Recovery in Piglets

Background: We tested the hypothesis that controlled hypoxemic resuscitation of hypoxic newborn piglets improves early cerebral metabolic and electrophysiological recovery. Subjects: Twenty-four 2-5 days old piglets. Interventions: Hypoxia was induced by ventilating the piglets with 6% O2 in N2. When EEG became isoelectric, and either mean arterial blood pressure fell below 25 mm Hg or base excess (BE) was lower than -25 mmol/L, a 2 h resuscitation period was started. The piglets were randomly divided into three resuscitation groups: Hypoxemic (n=8), 21% O2 (n=8), and 100% O2 group (n=8). The hypoxemic group was ventilated with 12-18% O2 to achieve a cerebral venous oxygen saturation of 17-23% (baseline; 44±6%). Results: BE reached-22±6 mmol/L (mean±SE) at the end of hypoxia. PaO2 at 30 min of resuscitation were 6.0±0.4, 9.9±0.5, and 57.5±2.7 kPa in the hypoxemic, 21% O2, and 100% O2 group. No significant differences in time to recovery of EEG (p=0.17), quality of EEG at recovery (p=0.22), or extracellular hypoxanthine concentrations in cerebral cortex and striatum were found between the groups. Brain cell membrane Na+,K+-ATPase activity at the end of resuscitation was not different between the groups (p=0.30). BE and plasma hypoxanthine, however, normalized during hypoxemic resuscitation significantly slower than during resuscitation with 21% or 100% O2.Conclusion: Controlled hypoxemic resuscitation did not improve early brain recovery compared with resuscitation with 21% and 100% O2, and showed a delayed metabolic correction of the total body hypoxia. In contrast, resuscitation with 21% O2 was as efficient as resuscitation with 100% O2 in this newborn piglet hypoxia model.

Oximetry with phase modulation NIR spectroscopy based on phase measurement only

Near infrared spectroscopy, based on frequency domain methods, has been successfully applied to study turbid media, using amplitude and phase measurements. Oximetry based on phase measurements only may prove advantageous over amplitude phase measurements due to relative simplicity of use and calibration of systems with phase output only. Suggestions for hemoglobin saturation calculation, based on the diffusion approximation and phase information only, have been proposed in the past. There exist many factors though that may introduce inaccuracies in the data analysis and in the measurements, besides the inherent inability of such systems to account for absorption of water and chromophores besides oxy- and deoxy- hemoglobin. Such factors, as theoretical approximations, voltage to phase conversion and initial phase calibration, have to be carefully considered in order to produce consistent and reliable calculations. In the present work, simulation models, based on the solution of the diffusion equation in the frequency domain, have been developed, to study the performance of different approximations used for the calculation of hemoglobin saturation. A new approach for data analysis is presented and investigated. Methods for instrument calibration are discussed and an example, based on experimental measurements, is demonstrated.

Cytochrome aa3 -signal changes in newborn piglets during hypoxia. 38

Background: The aim was to study changes in cerebral oxidized cytochrome aa3 (cytaa3) with near-infrared spectrophotometry (NIRS) during stepwise hypoxia.

Experimental hypoxia in newborn piglets - a methodological study. 112

AIM: To study the effect of postnatal age, weight, sex, and chronological order on time to acidosis or fall in blood pressure, and isoelectric EEG in hypoxic piglets. SUBJECTS: Twentyseven piglets, aged 2-5 days, in general anesthesia with halothane, fentanyl, and pancuronium. Two piglets were studied each day. INTERVENTION: Hypoxia (FiO2 6%) and inhaled CO2 (paCO2 7-8 kPa). Time to BE lower than -25 mmol/L or a drop in mean arterial blood pressure <25 mm Hg (hypoxia time) and time to isoelectric EEG (isoEEG). RESULTS: There was an inverse linear relation between age and hypoxia time (p= 0.007). Piglets in the afternoon had longer time to isoEEG (afternoon 30,4±7,9 min vs. morning 17,2± 12,3 min., p=0,003). No other differences were found. CONCLUSIONS: This study demonstrates the effect of postnatal age on hypoxic resistance in piglets. The increased durability of EEG in piglets studied in the afternoon was surprising.