1Department of Anaesthesia and Intensive Care Medicine and 2Department of Magnetic Resonance Imaging, University of Innsbruck, Austria*Corresponding author: Department of Anaesthesia and Intensive Care Medicine, Leopold Franzens University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
Accepted for publication: July 13, 2001
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Abstract |
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Br J Anaesth 2001; 87: 6918
Keywords: anaesthetics volatile, isoflurane; anaesthetics gases, nitrous oxide; brain, blood volume; brain, blood flow, regional mean transit time; humans
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Introduction |
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The present study used contrast-enhanced magnetic resonance imaging (MRI) perfusion measurements to investigate the influence of nitrous oxide and isoflurane on regional cerebral blood flow (rCBF), rCBV and regional mean transit time (rMTT). rMTT was used to analyse changes in rCBV in relation to changes in rCBF.
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Methods |
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Wearing a closely fitting face-mask, the volunteers breathed to achieve normocarbia [end-tidal carbon dioxide concentration (E'CO2) 40 mm Hg, FIO2 0.5] during the control measurement and administration of isoflurane [fraction of expired isoflurane 0.45 (SD 0.02)%; 0.4 MAC]7 (n=10) or nitrous oxide [fraction of expired nitrous oxide 45 (2)%; 0.4 MAC]8 (n=10). A minimum of 1015 min was allowed for stabilization of the end-tidal concentration of either anaesthetic before contrast-enhanced MRI perfusion measurement.The volunteers had been trained both by verbal instruction and by watching the capnographic trace of the monitor on the day before the MRI session. During the experiment, breathing at a constant E'CO2 (e.g. 40 mm Hg) was supported by voice command when necessary. The fraction of inspired and expired isoflurane, nitrous oxide, oxygen (FIO2, FE'CO2, E'CO2, respiration rate, non-invasive mean arterial blood pressure (MAP) and pulse oximetry haemoglobin saturation (SpO2) were monitored (S/5 MRI-MonitorTM, Datex-Ohmeda, Helsinki, Finland). Quick Cal calibration gas (Ref. 755582; Datex) was used to calibrate the monitor.
MRI measurements were performed with a 1.5-tesla whole-body scanner (Magnetom Vision; Siemens, Erlangen, Germany) using a standard circular polarized head-coil. Single-shot echoplanar imaging (EPI) was performed with a repetition time of 2 s and an echo time of 64 ms. An acquisition matrix of 64x128 (field of view 22x22 cm, in-plane resolution 1.7x3.4 mm) was used. The slice thickness was set to 5 mm (slice gap 1.25 mm) and 15 slices were measured simultaneously. A paramagnetic contrast agent gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA, 0.1 mmol kg1) was injected into an antecubital vein at the rate of 9 ml s1 using an MR-compatible power injector (Spectris; Medrad, Pittsburgh, PA, USA). EPI scans (n=60) were performed at 2-s intervals to cover the entire passage of the contrast agent through the brain. Six scans (6/60 scans) taken before injection were used as the baseline.
rCBV and rCBF were calculated by a blinded investigator in regions of interest. In each subject, regions of interest were outlined freehand bilaterally in white and in grey matter (frontal, parietal, occipital, striatal and thalamic) on CBV maps (Fig. 1). Outlining regions of interest on corresponding anatomical T2-weighted scans is not possible as EPI T2*-weighted contrast-enhanced perfusion scans have a known geometric distortion. In order to check the regions of interest for correct anatomical position, they were copied into the EPI T2*-weighted scans acquired before contrast media application. The definition of regions produced in this way is reliable and reproducible and is not biased to high signal areas on the CBV maps. Furthermore, varying partial volume effects as a result of the inclusion of white and grey matter in regions allocated primarily to one category, which could account for some of the differences between the regions, were minimized. Corresponding regions of interest contained similar numbers of pixels.
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After correction for the density of brain tissue,13 rCBF values are given in ml 100 g1 min1 and rCBV values in ml 100 g1.
MTT, which defines the average time that any particle of tracer, e.g. contrast medium, remains within the region of interest,14 was calculated with the equation:
Values for rMTT are given in seconds.
Statistical analysis
Data are presented as boxplots [e.g. median (upper, lower quartiles; range)]. Data were tested for normality with the KolmogorovSmirnov test. As the data were not normally distributed, within-group comparison was performed with a stable non-parametric test (e.g. the MannWhitney U-test), which also considered the similar, but not identical, numbers of pixels in comparable regions (e.g. unpaired test). A value of P<0.05 was considered statistically significant. Presentation of percentage changes in rCBF (-rCBF), percentage changes in rCBV (
-rCBV) and percentage changes in rMTT (
-rMTT) are merely descriptive. Differences between the agents in
-rCBF,
-rCBV and
-rMTT were not tested for significance.
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Results |
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Responsiveness to verbal command, which was necessary once or twice in each volunteer in order to maintain normocapnia, was sustained during isoflurane (n=9) and nitrous oxide (n=9) administration. The contrast-enhanced perfusion measurement was commenced only after verbal command had produced stable normocapnia, so that no further verbal stimulation was needed during perfusion measurement.
Haemodynamic (heart rate, MAP) and respiratory (SpO2, E'CO2, respiratory rate) variables were influenced neither by isoflurane nor by nitrous oxide.
rCBF
Isoflurane increased occipital but not frontal or parietal grey matter rCBF (Fig. 2A), whereas nitrous oxide increased rCBF in all of these regions (Fig. 2B). In the basal ganglia, except for the right hemispheric striatum, however, isoflurane increased rCBF more than did nitrous oxide (Fig. 3A and B).
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Discussion |
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Like isoflurane, nitrous oxide increased occipital grey matter rCBF in our volunteers, but no reversal of the anteriorposterior gradient in rCBF was found, as the greatest effect of nitrous oxide on rCBF was found in the frontal and parietal grey matter regions. A similar increase in frontal rCBF has also been reported for nitrous oxide.19
It has been proposed that nitrous oxide causes disinhibition of frontal cortical activity,19 and this may prompt an exaggerated frontal distribution of rCBF, whereas isoflurane typically causes reversal of the anteriorposterior gradient in rCBF. Without psychological tests, however, it is not possible to establish a relationship between a drug-specific pattern of rCBF changes and a drug-specific altered level of consciousness in humans.
In the infratentorial regions, isoflurane increased thalamic and striatal grey matter rCBF more than did nitrous oxide. A similar redistribution of rCBF to subcortical regions during isoflurane administration was reported in humans4 15 and animals.20 Although observed, the increase in rCBF in these regions was clearly less pronounced after nitrous oxide.
Nitrous oxide increased rCBV in frontal and parietal grey matter more but in infratentorial grey matter less than did isoflurane. These heterogeneous increases in rCBV during administration of nitrous oxide and isoflurane demonstrate that these drugs are not simple vasodilators like hypercapnia, which causes a more uniform increase in rCBV.21
To further analyse changes in rCBV and rCBF, we used rMTT. rMTT defines the average time needed by a tracer to transit the region of interest.14 Because rMTT equals the ratio of rCBV to rCBF, any increase in rMTT (e.g. in the present study during nitrous oxide and isoflurane administration) reflects a relatively greater increase in rCBV than in rCBF. Isoflurane increased supratentorial rMTT more than did nitrous oxide, thereby indicating a greater increase in rCBV than in rCBF. In contrast, the infratentorial increase in rMTT was more pronounced under nitrous oxide. The extent to which drug-specific changes in rCBF and rCBV, as seen in the present study, are caused by direct vasodilatation and/or metabolically mediated effects on cerebral haemodynamics awaits further investigation. In this regard, it is a limitation of the present study that, during administration of nitrous oxide and isoflurane, metabolic data (obtained, for example, by means of phosphate spectroscopy), were not obtainable with the whole-body MR scanner we used (Magnetom Vision).
In conclusion, we have shown that nitrous oxide specifically increases rCBF and rCBV in supratentorial grey matter, whereas isoflurane specifically increases rCBF and rCBV in infratentorial grey matter.
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Acknowledgements |
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References |
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