University Department of Anaesthesia, Queens Medical Centre and City Hospital, Nottingham NG7 2UH, UK*Corresponding author
Accepted for publication: March 9, 2001
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Abstract |
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Br J Anaesth 2001; 87: 1937
Keywords: brain, cerebral autoregulation; blood flow, cerebral; measurement techniques, transcranial Doppler ultrasound; anaesthetics volatile, desflurane
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Introduction |
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To our knowledge, only one study has examined the effects of desflurane on cerebral autoregulation. Strebel and colleagues3 showed that desflurane, at concentrations greater than 0.5 MAC, produced a dose-dependent impairment in both static and dynamic cerebral autoregulation. However, in that study, 70% nitrous oxide was used as the background anaesthetic, on the assumption that it had minimal effects on cerebral autoregulation. We have shown that nitrous oxide can have profound effects on cerebral autoregulation,4 and that its presence can modify the effects of sevoflurane on cerebral autoregulation.5 Therefore, the results of the study by Strebel and colleagues3 could have been confounded by the presence of nitrous oxide.
In the present study, we aimed to evaluate the effects of desflurane, when used as the sole inhalation anaesthetic, on cerebral autoregulation as assessed by the transient hyperaemic response test (Fig. 1).
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Methods |
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Study set-up
All patients were studied in the supine position with the head resting on a pillow. The study was performed in the anaesthetic room before surgery.
A standardized procedure for the measurement of flow velocity in the middle cerebral artery was followed. The left middle cerebral artery was insonated through the temporal window using a 2 MHz transcranial Doppler ultrasound probe (SciMed QVL 120, SciMed, Bristol, UK). The identity of the flow velocity waveform in the middle cerebral artery was confirmed using standard criteria.6 7 The position of the transcranial Doppler probe was fixed using a headband to ensure a constant angle of insonation throughout the study. The flow velocity was recorded continuously on digital audiotape for subsequent analysis using specific software (SciMed, Bristol, UK). I.v. access was secured and monitoring was initiated using an electrocardiogram, non-invasive arterial pressure measurement and pulse oximetry. Mean arterial pressure was measured at 2-min intervals and the partial pressure of end-tidal carbon dioxide (PE'CO2) was measured continuously using a Marquette Tramscope (Marquette Electronics, Milwaukee, USA).
After an initial period of rest of approximately 10 min, each patient was subjected to repeated left common carotid artery compressions of 10 s duration for the baseline measurements at 2-min intervals until a test fulfilling the predetermined criteria (see below) was obtained. Mean arterial pressure and PE'CO2 were recorded immediately before every transient hyperaemic response test.
Following the pre-induction test of cerebral autoregulation, anaesthesia was induced using a target-controlled infusion of propofol set to a target blood concentration of 8 µg ml1. Neuromuscular block was produced by vecuronium 0.1 mg kg1. The trachea was intubated and the lungs were mechanically ventilated with 100% oxygen. Ventilation was controlled to maintain PE'CO2 at the pre-induction (±0.1 kPa) level. The infusion of propofol was stopped after tracheal intubation had been achieved and administration of desflurane was started. Two end-tidal concentrations of desflurane, 7.4% (1 MAC) and 10.8% (1.5 MAC), were studied in random order. The transient hyperaemic response tests were repeated allowing a 15-min equilibration period after achieving a constant end-tidal concentration of desflurane, and after ensuring that the estimated blood concentration of propofol was below 1.5 µg ml1. Phenylephrine was used to maintain mean arterial pressure at the pre-induction (±10%) level throughout the study.
Transcranial Doppler data
The methods of processing the transcranial Doppler data have been described previously.4 5 8 The criteria for accepting a transient hyperaemic response test included:
(i) sudden and maximal decrease in flow velocity at the onset of common carotid artery compression;
(ii) stable heart rate and power of reflected Doppler signal during compression; and
(iii) absent flow transients after release of compression (associated with inertial or volume compliance).9
For analysis, the flow velocity waveform in the middle cerebral artery immediately before the compression (F1), the first waveform immediately following compression (F2), and that immediately after release (F3), were selected (Fig. 1). The time-averaged mean of the outer envelope of the flow velocity was used for analysis. The power of the Doppler signal was recorded as an indicator of any change in the diameter of the middle cerebral artery during the transient hyperaemic response test. The change in power was considered significant if, at any stage, it was outside the range recorded within 10 s of the baseline measurement.
Calculations
Two indices of cerebral autoregulation were derivedthe transient hyperaemic response ratio and the strength of autoregulation, calculated as follows:
transient hyperaemic response ratio10 11 = F3/F1
strength of autoregulation8 12 = (F3.P2)/(MAP.F1), where MAP is the mean arterial pressure.
The P2 is the estimated pressure in the middle cerebral artery at the onset of compression and is derived using the formula: P2 = MAP.F2/F1 or the value of 60 mm Hg (the assumed lower limit of autoregulation), whichever is the greater.8 12
The magnitude of decrease in the flow velocity during compression, the compression ratio, was calculated from the formula:10 11
Compression ratio (%) = (F1F2)x100/F1
Statistics
Pooled data from subjects involved in studies in our department indicate that the mean (SD) value for transient hyperaemic response ratio is 1.33 (0.09) and for the strength of autoregulation is 0.96 (0.07) under normal physiological condition.4 5 8 11 13 A change of >2 SD in the value of strength of autoregulation was considered significant. We calculated that eight subjects would be required to reject our null hypothesis for <0.05 and that for ß>0.95
Analysis of variance (ANOVA) for repeated measurements was used to compare the values of flow velocity, compression ratio, transient hyperaemic response ratio, and strength of autoregulation after each intervention. Significance was assumed at P values <0.05.
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Results |
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Changes in compression ratio and flow velocity were not significant (Table 1). Figures 24 show the changes in flow velocity, transient hyperaemic response ratio, and strength of autoregulation for the eight subjects. Both transient hyperaemic response ratio and strength of autoregulation were decreased significantly under desflurane anaesthesia.
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Discussion |
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The details of the modelling of cerebral autoregulation using the transient hyperaemic response test have been published previously.8 1012 14 15 The decrease in the perfusion pressure in the middle cerebral artery at the onset of carotid artery compression provokes the autoregulatory vasodilatation in the territory of the middle cerebral artery. Release of compression allows the perfusion pressure to return to baseline but because of the reduced vascular resistance the flow velocity overshoots the baseline value (the hyperaemic response). In theory the hyperaemic response can be affected by the changes in both the gradient and the limits of the autoregulatory plateau.8 12 15 In practice, however, it is not possible to differentiate between the two effects. In the past, the transient hyperaemic response test has been used to assess the effects of carbon dioxide, nitrous oxide, sevoflurane and propofol on cerebral autoregulation.4 5 8 13
According to theoretical modelling, as an index of autoregulation, the transient hyperaemic response ratio is likely to be affected by changes in mean arterial pressure or compression ratio; strength of autoregulation is unlikely to be affected by these experimental factors.11 12 15 However, when the mean arterial pressure and compression ratio remain unchanged on repeated measurements, as in this study, there is likely to be little difference between the findings of the two indices.
Strebel and colleagues,3 using static and thigh-cuff methods, examined the effects of desflurane on cerebral autoregulation with nitrous oxide in the background; in this study, desflurane impaired cerebral autoregulation in a dose-dependent fashion. At 0.5 MAC, the autoregulation was delayed but preserved; at 1 and 1.5 MAC it was significantly impaired. After having shown that nitrous oxide per se can impair cerebral autoregulation,4 and also that it can influence the effect of sevoflurane on cerebral autoregulation,5 we felt it necessary to study desflurane in the absence of any possible confounding effects of nitrous oxide. However, the results of the present study using 1 and 1.5 MAC of desflurane are similar to those of Strebel and colleagues3 suggesting that desflurane in these concentrations is detrimental to cerebral autoregulation whether it is used with or without nitrous oxide.
In the present study, propofol was used for induction of anaesthesia but the measurements for cerebral autoregulation were made only after its predicted blood concentration was below 1.5 mg ml1. In previous studies, infusion of anaesthetic doses of propofol did not impair cerebral autoregulation.3 13. Therefore, it is unlikely that any small quantities of propofol remaining in the blood during equilibration with desflurane would have had a significant effect on the results of this study.
We found that the mean flow velocity in the middle cerebral artery tended to increase during inhalation of desflurane, but this increase failed to reach statistical significance. We noted a large between-subject variability of these measurements. Previous studies suggest that desflurane can increase cerebral blood flow by dilating the cerebral blood vessels.1 2 It is well known that reduced cerebrovascular resistance, including that caused by hypercapnia, causes a significant shortening of the autoregulatory plateau with a higher lower limit and a lower upper limit.16 This may partly explain why both transient hyperaemic response ratio and strength of autoregulation were significantly affected in our study, indicating impaired cerebral autoregulation secondary to vasodilatation caused by desflurane. However, as discussed earlier,8 12 the transient hyperaemic response test cannot determine whether the primary effect of an agent (desflurane in this study) is on the width or the gradient of the autoregulatory plateau.
The present study has a number of limitations. Changes in flow velocity measured using transcranial Doppler reflect changes in blood flow only if the diameter of the insonated vessel remains constant. Matta and Lam17 presented data that suggest that desflurane has a minimal effect on the diameter of the middle cerebral artery. In addition, modest changes in arterial pressure and carbon dioxide partial pressure have been shown to have minimal effects on the middle cerebral artery diameter.18 In the present study, the reflected power of the Doppler signal remained unchanged during the transient hyperaemic response tests, suggesting that the changes in the diameter of the middle cerebral artery, if any, were insignificant.19
The present study was conducted in patients with no intracranial pathology, who were maintained normocapnic and normotensive. Therefore, the clinical conditions were different from those of patients undergoing neurosurgical procedures. Further studies are required to determine the interactions between desflurane and other techniques, such as hyperventilation, which influence cerebral blood flow and autoregulation, in order to define the clinical conditions during which desflurane may adversely affect cerebral haemodynamics.
In conclusion, we have shown that desflurane, at concentrations of 1 MAC or above, causes a significant impairment in cerebral autoregulation.
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References |
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