H Owen-Reece

Delayed ("secondary") cerebral energy failure after acute hypoxia-ischemia in the newborn piglet: continuous 48-hour studies by phosphorus magnetic resonance spectroscopy

ABSTRACT: Phosphorus (31P) spectra from the brains of severely birth-asphyxiated human infants are commonly normal on the first day of life. Later, cerebral energy failure develops, which carries a serious prognosis. The main purpose of this study was to test the hypothesis that this delayed (“secondary”) energy failure could be reproduced in the newborn piglet after a severe acute reversed cerebral hypoxicischemic insult. Twelve piglets were subjected to temporary occlusion of the common carotid arteries and hypoxemia [mean arterial Po2 3.1 (SD 0.6) kPa]. Mean cerebral phosphocreatine concentration [PCr]/inorganic orthophosphate concentration [Pi] decreased from 1.40 (SD 0.29) to 0.01 (SD 0.02), and nucleotide triphosphate concentration [NTP]/exchangeable phosphate pool concentration [EPP] decreased from 0.19 (SD 0.02) to 0.06 (SD 0.04) (p<0.001 for each decrease). On reperfusion and reoxygenation of the brain, mean [PCr]/[Pi] and [NTP]/[EPP] returned to baseline. Observations continuing for the next 48 h showed that [PCr]/[Pi] again decreased, in spite of normal arterial Po2, mean arterial blood pressure, and blood glucose, to 0.62 (SD 0.61) at 24 h (p<0.01) and 0.49 (SD 0.37) at 48 h (p<0.001). [NTP]/[EPP] also decreased, but to a lesser degree. Intracellular pH remained unchanged. These findings appeared identical with those seen in birth-asphyxiated human infants. No changes in cerebral metabolite concentrations took place in six control piglets. The severity of secondary energy failure, as judged by the lowest [PCr]/[Pi] recorded at 24-48 h, was directly related to the extent of acute energy depletion, obtained as the time integral of reduction in [NTP]/[EPP] (p<0.0001). This animal model of secondary energy failure may prove useful for testing cerebroprotective strategies.

Continuous measurement of cerebral oxygenation by near infrared spectroscopy during induction of anesthesia.

UNLABELLED Near infrared spectroscopy (NIRS) measures tissue oxygenation continuously at the bedside. Major disturbances of cerebral oxygenation can be detected by using NIRS, but the ability to observe smaller changes is poorly documented. Although anesthetics generally depress cerebral metabolism and enhance oxygen delivery, the administration of etomidate has been associated with cerebral desaturation. We used this difference to study the ability of NIRS to detect the small changes associated with the onset of anesthesia. Thirty-six healthy patients were randomly allocated to have anesthesia induced with either etomidate, propofol, or thiopental. We found that there was a temporal association between the onset of anesthesia and NIRS-derived indices of cerebral oxygenation. Etomidate was associated with a decrease in cerebral oxygenation, whereas propofol and thiopental were associated with an increase in cerebral oxygenation. We conclude that NIRS is capable of detecting the small changes in cerebral oxygenation associated with the induction of general anesthesia and shows promise as a bedside investigational tool for the noninvasive assessment of cerebral oxygenation. IMPLICATIONS We conclude that near infrared spectroscopy is capable of detecting the small changes in cerebral oxygenation associated with the induction of general anesthesia and shows promise as a bedside investigational tool for the noninvasive assessment of cerebral oxygenation.

Measurement of Adult Cerebral Haemodynamics Using Near Infrared Spectroscopy

Near infrared spectroscopy (NIRS) is a non invasive, portable, safe technique for monitoring cerebral oxygenation and haemodynamics. Since it does not involve the use of ionising radiation it may be used repeatedly to produce serial measurements of CBF and CBV in patients, and continuously to provide trend data about cerebral circulation changes. NIRS allows measurements to be made at the bedside with minimal disturbance to other monitoring and treatment procedures. Although regional information is not yet available, good time resolution allows rapid changes in cerebral haemodynamics to be observed.

Influence of Respiration and Changes in Expiratory Pressure on Cerebral Haemoglobin Concentration Measured by Near Infrared Spectroscopy

Near infrared spectroscopy (NIRS) was used to measure the changes in concentration of cerebral oxy-and deoxygenated haemoglobin ([HbO2] and [Hb]) in six healthy adult volunteers spontaneously breathing against increased expiratory pressures (IEPs) between 0 and 20 cm H20. During expiration, an increase in [HbO2] was recorded, accompanied by a smaller decrease in [Hb], producing a small increase in total cerebral haemoglobin concentration ([Hbsum]). The mean ± SD change in [Hbsum] at the maximum IEP of 20 cm H2O was 1.2 ± 0.7 μmol L−1 (equivalent to 1.4%). Changes in [Hbsum] correlated with IEP level (r = 0.95) and changes in MABP (r = 0.96). The results suggest that homeostatic mechanisms do not maintain cerebral blood volume or flow constant over the period of a single breath in normal adults.

Brain-metabolite transverse relaxation times in magnetic resonance spectroscopy increase as adenosine triphosphate depletes during secondary energy failure following acute hypoxia-ischaemia in the newborn piglet.

The adenosine triphosphate (ATP)-dependent sodium/potassium pump extrudes intracellular sodium in exchange for extracellular potassium. Low ATP causes pump dysfunction increasing both intracellular sodium and water thereby enhancing metabolite mobility. This should be detectable by proton magnetic resonance spectroscopy (MRS) as increased metabolite transverse relaxation times (T2s). During secondary cerebral energy failure in the newborn piglet, proton and phosphorus MRS showed large increases in the T2s of choline, creatine, N-acetylaspartate, and lactate that correlated with ATP depletion. These results provide insight into factors affecting metabolite T2s and show that T2s may be useful for studying cellular oedema.

Measurement of changes in cerebral haemodynamics during inspiration and expiration using near infrared spectroscopy

Near infrared spectroscopy (NIRS) has been employed over the last decade to monitor the changes in tissue oxygenation of intact organs (Jobsis 1977, Brazy et al. 1985, 1986, Ferrari et al. 1986a, 1986b, Hampson et al. 1988, Reynolds et al. 1988). Quantification of cerebral blood flow (CBF) and cerebral blood volume (CBV) using this technique has been described in both neonates and adults (Edwards et al. 1988, Wyatt et al. 1990, Elwell et al. 1992). An NIRS instrument is now commercially available (NIRO 500, Hamamatsu, Japan) which is capable of measuring the changes in the concentration of cerebral oxy - and deoxyhaemoglobin ([HbO2] and [Hb]) at a rate of 2 Hz. This has allowed the detailed investigation of the haemodynamic effects of respiratory and cardiac manoeuvres over the period of one breath.

An Automated System for the Measurement of the Response of Cerebral Blood Volume and Cerebral Blood Flow to Changes in Arterial Carbon Dioxide Tension Using Near Infrared Spectroscopy

Since it was first described by Jobsis in 1977, near infrared spectroscopy (NIRS) has become widely used as a non invasive technique for monitoring the blood and tissue oxygenation of intact organs and to date has been primarily applied to measurements of cerebral oxygenation and haemodynamics (Brazy et al., 1985, 1986, Ferrari et al., 1986, Hampson et al., 1990). Methods have been developed to make discrete absolute measurements of cerebral blood volume (CBV) (Wyatt et al., 1990) and cerebral blood flow (CBF) (Edwards et al., 1988) by inducing a small change in cerebral oxyhaemoglobin concentration and have largely been applied to neonates (Edwards et al., 1990, Skov et al., 1991). More recently these methods of quantifying cerebral haemodynamics have been applied to adults (Elwell et al., 1992).

Investigation of the Effects of Hypocapnia upon Cerebral Haemodynamics in Normal Volunteers and Anaesthetised Subjects by near Infrared Spectroscopy (NIRS)

The effect of alterations in arterial carbon dioxide tension (PaCO2) upon the cerebral blood vessels was first described in 1930 by Wolff and Lennox and quantified in 1948 by Kety and Schmidt. Since then many studies have investigated this relationship in terms of cerebral blood flow (CBF) (Novack et al 1953, Severinghaus et al 1967, Grubb et al 1974.) and volume (CBV)(Greenberg et al 1978, Artru 1984). CBV has not been as closely studied as CBF because of the paucity of measurement techniques. Since arterial PCO2 is frequently maintained at an artificially low level during anaesthesia for neurosurgery, to reduce intracranial pressure, it is of interest to measure the changes in cerebral haemodynamics as well as to describe the time course. 133Xenon washout and positron emission tomography (PET) are relatively invasive and can only provide measurements intermittently. Near infrared spectroscopy (NIRS) has been used to quantify the response of CBV to altered PaCO2 (CBVR) in newborn infants and is capable of measuring changes in CBV at 0.5 second intervals. The purpose of this study was to quantify both the extent and the duration of the haemodynamic response to an alteration in PaCO2 in anaesthetised patients and healthy volunteers.

Predicting Oscillation in Arterial Saturation from Cardiorespiratory Variables

The potential of near infrared spectroscopy (NIRS) as a non invasive tissue oxygenation monitor was first outlined by J6bsis (J6bsis, 1977). Extension of the basic technique to measure tissue blood flow using a Fick technique was developed by Edwards and Reynolds (Edwards et aI., 1988; Edwards et aI., 1993). This uses a rapid change in arterial oxyhaemoglobin concentration to act as an intravascular tracer, avoiding the problem of recirculation of indicator.

Continuous Measurement of Cerebral Oxygenation by Nirs During Induction of Anaesthesia

Continuous intraoperative monitoring of cerebral oxygenation is not routine because existing techniques are either invasive, require a prolonged period of equilibration or involve the use of ionizing radiation. The potential of near infrared spectroscopy (NIRS) as a non invasive tissue oxygenation monitor was first outlined by Jobsis (Jobsis, 1977). NIRS enables the continuous measurement of oxyhaemoglobin (HbO2) and deoxyhaemoglobin (Hb). To date most of the studies that have used NIRS during anaesthesia have considered either the effects on cerebral dynamics of extreme manoeuvres, such as clamping of a carotid artery and induction of ventricular fibrillation (Kirkpatrick et al., 1995; Mason et al., 1994; Williams et al., 1995; Levy et al., 1995), or have been confined to measuring cerebral blood flow (CBF) or cerebral blood volume (CBV) (Owen-Reece et al., 1994; Owen-Reece et al., 1996).