| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
| ||||||||||||||
| ||||||||||||||
|
|
|
|
||||||||||||
|
||||||||||||||
*Department of Dental Anesthesiology, Nihon University School of Dentistry, Department of Hygiene and Space Medicine and Department of Anesthesiology, Nihon University School of Medicine, Tokyo, Japan
Address correspondence and reprint requests to Ken-ichi Iwasaki, MD, PhD, Associate Professor, Department of Hygiene and Space Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. Address e-mail to kiwasaki{at}med.nihon-u.ac.jp.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Sevoflurane depresses the autonomic nervous system (6,7) and may change impedance properties of the cerebral vascular bed. Therefore, we hypothesized that sevoflurane influences dynamic cerebral autoregulation especially in the very-low-frequency range. To test this hypothesis, we studied dynamic cerebral autoregulation during the administration of sevoflurane by using spectral and transfer function analysis between arterial blood pressure variability and CBF velocity variability.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
All subjects were advised to fast for at least 5 h before the study. Subjects were placed in the supine position in an environmentally controlled experimental room with an ambient temperature of 23°C–25°C. ECG, sphygmomanometer, pulse oximeter, end-tidal carbon dioxide pressure (ETco2), volatile anesthetic concentration, and bispectral index (BIS) (model A-1050; Aspect Medical Systems, Natick, MA) monitors were applied. Continuous blood pressure was measured in the radial artery with a noninvasive arterial blood pressure monitor (JENTOW 7700; COLIN, Komaki, Japan). The accuracy of this device during anesthesia and during hypotension was confirmed by comparisons with tonometric and intraarterial pressure monitors (8,9). CBF velocity in the MCA was measured continuously by TCD ultrasonography (WAKI; Atys Medical, St. Genislaval, France). A 2-MHz probe was placed over the subject’s temporal window and fixed at a constant angle with a probe holder custom made to fit each subject’s facial bone structure (10). ECG, continuous arterial blood pressure, and CBF velocity were recorded on a personal computer at 1 kHz with commercial software (Notocord-hem 3.3; Notocord, Paris, France).
The subjects breathed air (4.5 L/min) and oxygen (1.5 L/min) via a facemask (fraction of inspired oxygen = approximately 40%). Data obtained over 5 min, after an adequate period of rest (minimum of 15 min), were used as the control data (Fig. 1). The sevoflurane vaporizer was set to deliver 0.5% sevoflurane. After stabilization of the end-tidal sevoflurane concentration to ensure anesthetic equilibration, data collected over 5 min with inhalation of 0.5% sevoflurane were obtained as 0.5% sevoflurane data. The measurements were continued in a similar manner with the vaporizer setting adjusted to incrementally deliver 1.0% and 1.5% sevoflurane (Fig. 1). The subjects’ airways were secured with chin lift as necessary and spontaneous respiration was maintained. To measure the state of consciousness objectively without any interference to the subjects, a BIS monitor was used. Arterial oxygen saturation (Spo2), respiratory rate, respiratory minute volume, ETco2, end-tidal sevoflurane concentration, and BIS were recorded every 1 min.
|
Beat-to-beat mean arterial blood pressure and CBF velocity were obtained by integrating signals within each cardiac cycle by Notocord-hem 3.3. The beat-to-beat data of arterial blood pressure and CBF velocity were then linearly interpolated and re-sampled at 2 Hz for spectral analysis. The transfer function between changes in mean arterial blood pressure and CBF velocity was calculated to assess dynamic CBF autoregulation (Fig. 2) (1,2,4,5). Estimates of transfer function gain were used to quantify the ability of the cerebral vascular bed to buffer changes in CBF velocity induced by transient changes in arterial blood pressure, at different frequencies. Phase was used to estimate the temporal relationship between these two variables. Furthermore, coherence function was calculated to assess the linear relationship between these two variables and the reliability of the transfer function gain (1,2,5). Previous studies (2) confirmed that these estimates are stable over 2 h in the supine resting condition.
|
Spectral power of arterial blood pressure, CBF velocity, mean value of transfer function gain, phase, and coherence function were calculated in the very-low- (0.02–0.07 Hz), low- (0.07–0.20 Hz), and high- (0.20–0.30 Hz) frequency ranges. These ranges were specifically chosen to reflect different patterns of the dynamic pressure-flow relationship, as previously identified by transfer function analysis (1,2,4,5). Transfer function analysis was performed with the cross spectral analysis (the Welch method) between changes in mean arterial blood pressure and CBF velocity. In addition, the low-frequency component (0.04–0.15 Hz) of systolic blood pressure was also calculated separately for estimation of peripheral vasomotor sympathetic activity (11,12). Finally, values for steady-state arterial blood pressure, heart rate, CBF velocity, respiratory rate, tidal volume, respiratory minute volume, ETco2, and BIS were obtained by averaging the 5-min data segments for each subject; they were then group-averaged for statistical analysis.
Variables were compared using one-way repeated-measures analysis of variance with stage (control, during 0.5%, 1.0%, and 1.5% sevoflurane) as the repeated measure in conjunction with the Dunnett post hoc test for comparisons with a control value. A P value of <0.05 was considered statistically significant. The analysis was performed using PC-based software (ABstat; Anderson Bell, Arvada, CO). Data are presented as mean ± sd.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
|
Respiratory rate increased significantly with 1.0% and 1.5% sevoflurane, whereas tidal volume decreased significantly. Respiratory minute volume, however, did not change. ETco2 decreased significantly with inhalation of 1.0% and 1.5% sevoflurane (Table 1). Spo2 and end-tidal oxygen remained constant. All subjects continued to maintain spontaneous respiration, but 3 of the 11 subjects required chin lift to secure a patent airway during inhalation of 1.5% sevoflurane.
Heart rate and mean arterial blood pressure decreased significantly with 1.0% and 1.5% sevoflurane. The amplitude of the fluctuation in blood pressure did not change significantly. CBF velocity remained relatively constant (Table 1).
The very-low-frequency component of mean arterial blood pressure variability did not change with 0.5% sevoflurane but decreased significantly with 1.0% and 1.5% sevoflurane (Fig. 3A). However, the very-low-frequency component of CBF velocity variability increased significantly with 0.5% sevoflurane (Fig. 3B). Coherence in the very-low-frequency range, which indicates the correlation between blood pressure and CBF velocity variability, increased above 0.5 with 0.5% and 1.0% sevoflurane (Fig. 3C). Transfer function gain in the very-low-frequency range, which indicates the relative amplitude of the response of CBF velocity to oscillations in blood pressure, increased significantly with 0.5% and 1.0% sevoflurane (Fig. 3D). Phase in the very-low-frequency range, which indicates the temporal relationship between blood pressure and CBF velocity, decreased significantly with 1.5% sevoflurane (Table 2).
|
|
The low-frequency component of mean arterial blood pressure variability (0.07–0.2 Hz) decreased significantly with 1.0% and 1.5% sevoflurane. Simultaneously, the low-frequency component of CBF velocity variability decreased significantly with 1.0% and 1.5% sevoflurane. The high-frequency component of mean blood pressure variability and CBF velocity variability increased significantly with 1.0% and 1.5% sevoflurane. Coherence in the low- and high-frequency ranges remained above 0.5 under all conditions. Transfer function gain in the low- and high-frequency ranges did not change (Table 2).
The low-frequency component of systolic blood pressure variability (0.04–0.15 Hz), as an indicator of peripheral vasomotor sympathetic modulation, decreased significantly with 1.0% and 1.5% sevoflurane (Fig. 4).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In the traditional concept of cerebral autoregulation, steady-state CBF remains relatively constant despite large changes in arterial blood pressure (13). Changes in perfusion pressure produce marked changes in cerebrovascular resistance, thereby maintaining CBF relatively constant. In fact, 5-minute averages in CBF velocity remained unchanged, whereas mean blood pressure significantly decreased in the present study. In addition, the 10–20 mm Hg range of blood pressure fluctuation reported during spontaneous respiration in Table 1 is comparable to the approximately 20 mm Hg variation induced by steady-state phenylephrine infusion in some studies (14). Although the present study was not designed to assess static cerebral autoregulation, our results correspond with the current consensus that static cerebral autoregulation is maintained during the administration of sevoflurane (14,15).
On the other hand, continuous measurements of CBF by techniques that provide a high temporal resolution, such as the TCD technique used in a large cerebral vessel, have revealed prominent beat-to-beat fluctuations, similar to those observed in arterial blood pressure (1). Thus, in dynamic situations, it has been found that beat-to-beat CBF velocity fluctuates spontaneously in response to dynamic changes in arterial blood pressure (1,2,4,5,16), CBF responds briskly to transient changes in arterial blood pressure (17). The cerebral vascular bed buffers this change in CBF velocity induced by transient changes in arterial blood pressure. We used cross-spectral methods for transfer function analysis to quantify this ability of the cerebral vascular bed to buffer changes in CBF velocity by measuring CBF velocity in the MCA with TCD ultrasonography (1,18). Because TCD ultrasonography provides a continuous measurement of cerebral autoregulatory responses (19), it permits an estimation of beat-to-beat flow velocity in large intracranial vessels. If MCA diameter remains relatively constant, as has been shown by many studies (20,21), changes in CBF velocity reflect changes in CBF. Thus, estimation of the transfer function between CBF velocity variability and blood pressure variability would reflect dynamic cerebral autoregulation. Moreover, previous studies, using transfer function analysis between these two variables, have revealed frequency-dependent properties of dynamic cerebral autoregulation (1,2). Short-term fluctuations (>0.20 Hz, high frequency) in CBF velocity closely match those observed in arterial blood pressure and likely reflect changes in CBF velocity in simple mechanical responses to changes in arterial blood pressure without effective buffering. In contrast, slower fluctuations (<0.07 Hz, very low frequency) in CBF velocity are more independent of changes in arterial pressure. Thus, the buffering action of the cerebrovascular bed on oscillations in CBF velocity in response to changes in arterial blood pressure as perfusion pressure, is more effective in the very-low-frequency ranges. Furthermore, estimates of coherence function, which evaluate the linear relationship between these two variables, are generally under 0.5 in the very low-frequency range (1,2,5,16), signifying little correlation between these two variables or little dependence of CBF on arterial blood pressure. The buffering capacity is sufficient in the very-low-frequency range under normal conditions (1,2,5,16). Thus, the frequency-dependent nature of dynamic autoregulation is like a high path filter. Cerebral autoregulation is better able to buffer slower changes in arterial pressure (low coherence in lower frequency ranges) than more rapid changes (high coherence and high gain in higher frequency ranges).
In the present study, the very-low-frequency component of CBF velocity variability increased significantly while blood pressure variability remained unchanged during administration of 0.5% sevoflurane. In addition, coherence in the very-low-frequency range increased above 0.5 during administration of 0.5% and 1.0% sevoflurane, suggesting that blood pressure variability strongly influences CBF velocity variability. Transfer function gain in the very-low-frequency range, which reflects the relative amplitude of the relationship between the changes in blood pressure and CBF velocity, also increased significantly with 0.5% and 1.0% sevoflurane, suggesting relatively larger changes in CBF velocity induced by comparatively smaller changes in arterial blood pressure. Coherence and transfer function gain, however, remained unchanged at higher frequencies during the administration of sevoflurane, cerebral autoregulation indexes being similar in lower and higher frequency ranges (high coherence and high gain over all frequency ranges). This suggests that cerebral autoregulation loses its frequency-dependent nature during the administration of sevoflurane. Furthermore, our results documented for the first time that sevoflurane alters the beat-to-beat pressure-flow velocity relationship. Further studies using this analysis method may be able to reveal whether any other anesthetics are better or worse than sevoflurane in this aspect.
Several other studies have shown that sevoflurane has very little effect on dynamic cerebral autoregulation as estimated by the thigh cuff deflation method (22) or the transient hyperemic response test (23,24). The thigh cuff method and the hyperemic response test calculate the autoregulation indexes from approximately 5 seconds after restoration of CBF. The time scale of the estimates for dynamic cerebral autoregulation in these other studies is similar to that of transfer function indexes in the low- and high-frequency ranges in our study. All things considered, our results of unchanged dynamic cerebral autoregulation in these frequency ranges are consistent with previous results (22–24).
It is reported that estimates of phase decrease under clinical conditions of cerebral subarachnoid hemorrhage or hypercapnia (4,25,26), suggesting impaired dynamic cerebral autoregulation. However, phase in the very-low-frequency range in the present study decreased significantly only with 1.5% sevoflurane. We considered the fact that decreases in phase did not accompany increases of transfer function gain during inhalation of 0.5% and 1.0% sevoflurane to be attributable to the possibility that phase changes were antagonized by the slight hypocapnia, as indicated by ETco2, or that the number of subjects was too small, relative to the large variability of phase estimates, to show significant changes.
To evaluate the depressive effect of sevoflurane on sympathetic nerve activity, we calculated the low-frequency component of systolic blood pressure variability in the range of 0.04–0.15 Hz as being separate from the low-frequency range of 0.07–0.2 Hz. The low-frequency component (0.04–0.15 Hz) of systolic blood pressure variability is considered to be an index of vasomotor sympathetic activity (11,12). In the present study, the low-frequency component of systolic blood pressure variability decreased significantly with 1.0% and 1.5% sevoflurane, suggesting that sevoflurane markedly reduces both sympathetic nerve modulation of peripheral vessels and sympathetic nerve activity in a concentration-dependent manner. These reductions in sympathetic nerve activity may be one of the possible mechanisms for impaired cerebral autoregulation. Cerebral circulation is also regulated by metabolic, myogenic, and endothelial processes (1,5,13). It is possible that changes in these processes by sevoflurane induce impairment of dynamic cerebral autoregulation.
There are several limitations in the present study. We were not able to conclusively state the influence of 1.5% sevoflurane on dynamic cerebral autoregulation in the very-low-frequency range. In our results, both systolic and mean arterial blood pressure variability decreased significantly with inhalation of more than 1.0% sevoflurane but was preserved with 0.5% sevoflurane. Marked reduction of blood pressure variability would influence assessment of transfer function analysis. A previous study conducted by Zhang et al. (5) showed results similar to our study that marked reduction in blood pressure variability leads to low coherence. Cerebral circulation also includes a nonlinear component (16). Therefore, changes in transfer function gain and coherence might be induced simply by a reduction in blood pressure variability. Optimal techniques for accurate quantification of these nonlinearities, however, have yet to be determined (16). To resolve this problem with transfer function analysis, we should apply oscillatory lower body negative pressure (5) to regenerate very-low-frequency blood pressure variability.
In addition, there is also the possibility that impairment of signal quality on TCD ultrasonography occurred in association with an increase in sevoflurane concentration, especially during inhalation of 1.5% sevoflurane, when chin lift was needed in 3 of the patients that could have had impaired signal quality.
Moreover, as arterial blood pressure decreased after the administration of sevoflurane, hypotension per se may have modulated cerebrovascular tone and thus affected the estimation of the transfer function. However, a previous study that restored the reduced blood pressure, reported that the reduction in blood pressure (-5 mm Hg in mean blood pressure) did not influence the estimate of transfer function (5).
Another limitation of the present study is the possibility of changes associated with increases in arterial CO2. However, ETco2 significantly decreased in the present study, despite unchanged respiratory minute volume (respiratory rate increased and tidal volume decreased). Moreover, because sevoflurane does not impair cerebrovascular CO2 reactivity (27), if unrecognized hypercapnia existed, CBF velocity would have increased. Hence, we believe that Paco2 did not increase. However, these limitations can not be excluded, as Paco2 was not monitored in the present study.
If cerebral metabolic rate and CBF velocity increased, then a false conclusion regarding impaired cerebral autoregulation would be made. However, cerebral metabolic rate is reported to decrease rather than increase during sevoflurane anesthesia (27).
Finally, the previous methods (22–24), such as the thigh cuff deflation method or the transient hyperemic response test, estimate cerebral vasodilation function during decreases in arterial blood pressure (downward function), whereas transfer function analysis estimates both "downward" and "upward" functions together. Therefore, a new analysis method is needed to further analyze and distinguish between "downward" and "upward" functions of dynamic cerebral autoregulation.
We investigated the effects of sevoflurane on dynamic CBF autoregulation by using spectral and transfer function analysis between arterial blood pressure variability and CBF velocity variability. The results of our study suggest that sevoflurane impairs dynamic cerebral autoregulation in the very-low-frequency range (0.02–0.07 Hz, or 14–50 seconds), even with concentrations of 0.5%, despite the absence of changes in the low- and high-frequency ranges (0.07–0.30 Hz, or 3–14 seconds). Therefore, it must be cautioned that during sevoflurane anesthesia, even short-term exposure to small-dose sevoflurane may impair dynamic cerebral autoregulation, especially during and after neurosurgery or surgeries with induction of anesthesia with volatile anesthetics, which induce changes of 0.02–0.07 Hz (14–50 seconds) in arterial blood pressure.
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  Y. Ogawa, K.-i. Iwasaki, K. Aoki, S. Shibata, J. Kato, and S. Ogawa Central Hypervolemia with Hemodilution Impairs Dynamic Cerebral Autoregulation Anesth. Analg., November 1, 2007; 105(5): 1389 - 1396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Howell Carotid endarterectomy Br. J. Anaesth., July 1, 2007; 99(1): 119 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-i. Iwasaki, B. D. Levine, R. Zhang, J. H. Zuckerman, J. A. Pawelczyk, A. Diedrich, A. C. Ertl, J. F. Cox, W. H. Cooke, C. A. Giller, et al. Human cerebral autoregulation before, during and after spaceflight J. Physiol., March 15, 2007; 579(3): 799 - 810. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
