Effects of desflurane on cerebral autoregulation

N. M. Bedforth, K. J. Girling, H. J. Skinner and R. P. Mahajan

University Department of Anaesthesia, Queen’s Medical Centre and City Hospital, Nottingham NG7 2UH, UK*Corresponding author

Accepted for publication: March 9, 2001


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The aim of this study was to determine the effects of desflurane, at 1 and 1.5 MAC, on cerebral autoregulation. Data were analysed from eight patients undergoing non-neurosurgical procedure. The blood flow velocity in the middle cerebral artery was measured by transcranial Doppler ultrasound and cerebral autoregulation was assessed by the transient hyperaemic response test. Partial pressure of the end-tidal carbon dioxide (PE'CO2) and mean arterial pressure were measured throughout the study. Anaesthesia was induced with propofol and was maintained with desflurane at end-tidal concentrations of 7.4% (1 MAC) or 10.8% (1.5 MAC). The order of administration of the desflurane concentrations was determined randomly and a period of 15 min was allowed for equilibration at each concentration. The transient hyperaemic response tests were performed before induction of anaesthesia and after equilibration with each concentration of desflurane. An infusion of phenylephrine was used to maintain pre-induction mean arterial pressure and ventilation was adjusted to maintain the pre-induction value of PE'CO2 throughout the study. Two indices derived from the transient hyperaemic response test (the transient hyperaemic response ratio and the strength of autoregulation) were used to assess cerebral autoregulation. Desflurane resulted in a marked and significant impairment in cerebral autoregulation; at concentrations of 1.5 MAC, autoregulation was almost abolished.

Br J Anaesth 2001; 87: 193–7

Keywords: brain, cerebral autoregulation; blood flow, cerebral; measurement techniques, transcranial Doppler ultrasound; anaesthetics volatile, desflurane


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Desflurane is a relatively new volatile anaesthetic agent with a low blood:gas solubility coefficient, a physical property that allows rapid alterations in depth of anaesthesia. It has been shown to cause a dose-dependent decrease in cerebral vascular resistance.1 2

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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Fig 1 Middle cerebral artery flow velocity during a typical transient hyperaemic response test. The flow velocity decreases suddenly at the onset of compression of ipsilateral common carotid artery and, if the autoregulation is intact, shows hyperaemic response at the release of compression. The pulse wave form immediately before the onset of compression (F1), immediately after the onset of compression (F2) and that immediately after the release of compression (F3) are taken for calculating the transient hyperaemic response ratio and strength of autoregulation.

 

    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
After obtaining approval from the Hospital Ethics Committee and written, informed consent, eight patients, ASA 1 or 2, aged between 18 and 40 yr and undergoing elective non-neurosurgical procedures, were recruited. Patients were excluded if they were overweight, had any evidence of cerebrovascular or neurological disease or if they were taking any vasoactive medications.

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 ml–1. Neuromuscular block was produced by vecuronium 0.1 mg kg–1. 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 ml–1. 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 derived—the 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 (%) = (F1–F2)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 {alpha}<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.


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Four male and four female patients were recruited. The mean (SD) age was 29 (5) yr and weight was 73.5 (7.5) kg. At each stage, up to three tests were performed to obtain one test that fulfilled all the criteria described in the Methods section.

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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Table 1 Mean (SD) values of compression ratio (CR), middle cerebral artery (MCA) flow velocity (FV), transient hyperaemic response ratio (THRR) and strength of autoregulation (SA) before induction of anaesthesia, and after equilibration with end-tidal concentrations of desflurane of 7.4 and 10.8%
 


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Fig 2 Middle cerebral artery (MCA) flow velocity (FV) for the eight patients before induction of anaesthesia and during anaesthesia maintained with desflurane at end-tidal concentrations of 7.4 and 10.8%. The thin lines show changes for each individual and the thick line shows mean changes. The changes were insignificant.

 


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Fig 4 The strength of autoregulation (SA) for the eight patients before induction of anaesthesia and during anaesthesia maintained with desflurane at end-tidal concentrations of 7.4 and 10.8%. The thin lines show changes for each individual and the thick line shows mean changes. The changes were significant (P<0.001).

 

    Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
In this study, desflurane significantly impaired cerebral autoregulation. Based on studies of changes in this transient hyperaemic response ratio and strength of autoregulation induced by carbon dioxide,8 or the transient hyperaemic response ratio and rate of regulation assessed by the thigh-cuff method,10 it can be inferred that a change of 0.2 (>2 SD) in transient hyperaemic response ratio or of 0.16 (>2 SD) in strength of autoregulation would indicate a significant effect on autoregulation. The mean changes induced by 10.8% desflurane in our study were well above these values. At an end-tidal concentration of 10.8% of desflurane, the mean (SD) transient hyperaemic response ratio was 1.04 (0.04) and the mean (SD) strength of autoregulation was 0.76 (0.09). These values suggest that at 1.5 MAC of desflurane most patients had poor or abolished autoregulation. It has been shown that transient hyperaemic response ratio of less than 1.09 indicates absent autoregulation.14 Seven out of eight patients in this study had a transient hyperaemic response ratio <1.09 at 10.8% desflurane.

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 ml–1. 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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Fig 3 The transient hyperaemic response ratio (THRR) for the eight patients before induction of anaesthesia and during anaesthesia maintained with desflurane at end-tidal concentrations of 7.4 and 10.8%. The thin lines show changes for each individual and the thick line shows mean changes. The changes were significant (P<0.001).

 

    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
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2 Ornstein E, Young WL, Ostapkovich N, Prohovnik I, Stein BM. Comparative effects of desflurane and isoflurane on cerebral blood flow. Anesthesiology 1991; 75: A209

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