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NEUROSURGICAL ANESTHESIA

The Effect of Desflurane and Sevoflurane on Cerebral Oximetry Under Steady-State Conditions

Department of Anesthesiology, Aretaieion Hospital, Athens, Greece

Address correspondence and reprint requests to Argyro Fassoulaki MD, PhD, DEAA, 57-59 Raftopoulou Street, 11744 Athens, Greece. Address e-mail to afassou1{at}otenet.gr or fassoula{at}aretaieio.uoa.gr.

	Abstract

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We studied the effect of sevoflurane and desflurane on regional cerebral oxygenation (rSO₂). Twenty-two patients undergoing abdominal hysterectomy received sevoflurane and desflurane for 15 min each and 30 min apart under steady-state conditions in a randomized, crossover manner to maintain a bispectral index (BIS) of 40–50. In another 22 patients undergoing the same anesthesia and surgery BIS was maintained at 20–30. During the 15-min administration of each anesthetic at steady-state conditions rSO₂, BIS, inspired and end-tidal anesthetic concentrations, end-tidal CO₂, Spo₂, systolic and diastolic blood pressures, and heart rate were recorded every 3 min. The rSO₂ did not differ between sevoflurane and desflurane when BIS values were maintained between 40–50 or 20–30. The MAC_BIS values required to maintain BIS at 40–50 and at 20–30 were 1.0 versus 1.2 (P = 0.004) and 1.6 versus 1.8 (P < 0.001) for desflurane and sevoflurane respectively. Higher rSO₂ values were obtained by 1.6 MAC (71 ± 13) than by 1 MAC of desflurane (66 ± 10; P < 0.001) and by 1.8 MAC (72 ± 11) than by 1.2 MAC of sevoflurane (66 ± 13; P < 0.001). In conclusion, equipotent concentrations of desflurane or sevoflurane in terms of BIS are associated with similar rSO₂ values, but larger anesthetic concentrations of both anesthetics increased the rSO₂ values.

	Introduction

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The effect of different concentrations of sevoflurane and desflurane on intraoperative cerebral oxygenation might be clinically important. In dog experiments 3% end-expired isoflurane depressed cortical electrical activity and decreased cerebral metabolic rate of oxygen consumption (CMRO₂) (1). Also in dogs 1.5 and 2.0 MAC of desflurane produced changes in the electroencephalograph pattern along with a significant decrease in the CMRO₂ (2).

Near-infrared spectroscopy (NIRS) monitors changes in parenchymal and microcirculatory oxygenation of the frontal cerebral cortex, which may reflect tissue oxygen use (3). The method has been used to detect different causes of cerebral hypoxia during carotid endarterectomy where cerebral hypoxia due to hypotension, slippage of the tracheal tube into the right main bronchus, or arterial occlusion were identified (4,5). NIRS has also been used to monitor disturbances of cerebral perfusion during orthotopic liver transplantation (6).

Our hypothesis is that regional cerebral oxygenation (rSO₂) will not differ at equipotent steady anesthetic concentrations of sevoflurane and desflurane. The present study was designed to compare the rSO₂ during desflurane and sevoflurane anesthesia when maintaining bispectral index (BIS) values between 40 and 50, as well as between 20 and 30. The second aim of the study was to compare the MAC_BIS values of the two anesthetics required to produce the same BIS values, high and low, as predetermined by the study protocol. The reason we compared the MAC_BIS values of the two anesthetics producing the same BIS values is that BIS values represent cortex suppression whereas MAC (the response to a noxious stimulus) is mediated through the spinal cord.

We designed two studies, one for the higher BIS value and one for the lower BIS value produced by the two anesthetics. To measure rSO₂ we used NIRS, which assesses rSO₂ from the mixed venous capillary and arterial blood pool and provides continuous and noninvasive monitoring of intracerebral oxygen saturation (7).

	Methods

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Study I
After obtaining approval from the Hospital Ethics Committee and informed written patient consent, 22 patients aged between 25 and 49 yr, physical status ASA I–II and scheduled for abdominal hysterectomy under general anesthesia were entered into the study. Patients receiving preoperative sedatives, tranquilizers, analgesics, or other drugs that could affect cerebral blood flow (CBF) or brain metabolism were excluded. Respiratory, cardiovascular, metabolic, or central nervous system disease were also criteria for exclusion from the study.

Each patient intraoperatively received two volatile anesthetics, sevoflurane and desflurane, in a crossover manner. The order of administration was determined using sealed envelopes containing 11 even (sevoflurane administration first) or 11 odd (for desflurane administration first) numbers from a computer-generated table. The allocation sequence and participant assignment were generated by the first author. The interventions and the recordings of measurements were open to all the authors.

Before induction of anesthesia each patient was attached to standard monitors (electrocardiogram, heart rate, noninvasive systolic blood pressure, diastolic blood pressure, Spo₂). A BIS^TM sensor was attached to each patient in conjunction with the BIS XP monitor (BIS^TM Monitor, Model A-2000^TM, Aspect Medical Systems, Inc, Newton, MA). An adult sensor (Somasensor®; Somanetics, Troy, MI) connected to an INVOS 3100 cerebral oximeter (Somanetics) was attached to the skin over the left temporal lobe. This device performs transcranial cerebral oximetry. The BIS and rSO₂ baseline values were recorded after a 5-min period to allow equilibration. Intraoperatively the capnogram and the inspired and end-tidal concentrations of the inspired gases and volatile anesthetics were also monitored.

Patients were not premedicated. On their arrival to the operating room a 16-gauge catheter was inserted in a peripheral vein via which metoclopramide (10 mg) and ranitidine (50 mg) were administered IV. All patients were administered oxygen for 3 min. Anesthesia was induced with fentanyl 3 µg/kg and thiopental 5 mg/kg IV. Cisatracurium 0.15 mg/kg was administered to facilitate tracheal intubation and provide muscle relaxation for the surgical procedure. To maintain anesthesia, sevoflurane and desflurane were administered interchangeably in a 1:1 nitrous oxide:oxygen mixture. The inspired concentration of the volatile anesthetic was adjusted to obtain BIS values between 40 and 50. Ventilation was adjusted to obtain an end-tidal CO₂ partial pressure (Petco₂) between 31 and 36 mm Hg.

After anesthesia induction either sevoflurane or desflurane was administered first according to the randomization procedure. Equilibrium between the inspired and end-tidal concentration of the anesthetic and for BIS values between 40 and 50 was obtained. rSO₂, BIS, inspired and end-tidal anesthetic concentrations, Petco₂, Spo₂, systolic, diastolic blood pressure, and heart rate were recorded every 3-min for a 15-min period. At the end of this period the volatile anesthetic was discontinued and replaced by the second volatile anesthetic. The fresh gas flow was then increased to 6 L/min and the first inhaled anesthetic was changed to the second one. After a 30-min period allowing for equilibration of the second anesthetic the same variables were recorded again every 3 min for a 15-min period. After this data collection was completed. During the 15-min periods of measurements no surgical stimulus was applied. To calculate MAC_BIS values the end-tidal concentration of each anesthetic recorded at each time point was divided by its conventional MAC value, 2% for sevoflurane and 6% for desflurane.

Study II
The study was repeated with 22 patients undergoing the same surgical procedure under the same anesthetic technique, using the same volatile anesthetics in a crossover manner. In study II the target BIS values ranged between 20 and 30 instead of 40 to 50.

Mean rSO₂ was calculated for the first 14 patients (7 patients who received desflurane first and 7 patients who received sevoflurane first in Study I). For desflurane, the average rSO₂ was 72.7 with a standard deviation of 16.4. The average rSO₂ for sevoflurane was 71.6 with a standard deviation of 9.02. The difference between the two drugs was approximately 1.1%. To detect a difference of 15% between the 2 drugs with a 5% level of significance and 80% power, 22 patients were needed.

The mean and standard deviation for rSO₂, end-tidal CO₂, BIS, MAC, systolic and diastolic arterial blood pressures, heart rate, and Spo₂ for each anesthetic were calculated. To assess differences a linear mixed-effects model was used. This model has fixed effects for anesthetic, order, and time and a random effect for subject, i.e., patient, to consider that observations are taken repeatedly on the same individual. Before fitting the mixed-effects model, the distribution of each parameter of interest was assessed. This was done by plotting cell variances against cell means and cell standard deviations against cell means. In both plots, the variance should be constant, i.e., independent of the mean. If this held and moreover the distributions were symmetric, then we assumed that the data were normally distributed and no transformation was needed when fitting the model. Moreover, the inclusion or not of an interaction term (time by order or time by anesthetic or order by anesthetic or time by order by anesthetic) was assessed by using the likelihood ratio test.

We repeated this procedure separately for each study and for each anesthetic. The fixed effects were time, BIS, and order the anesthetic was given. Since the outcomes of interest (rSO₂, Petco₂, BIS, MAC, systolic and diastolic arterial blood pressures, heart rate, and Spo₂) are all independent from each other, no Bonferroni correction was applied to adjust for a common level of significance. Statistical analysis was performed with Stata version 6.0 (Stat Corp., College Station, TX).

	Results

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Patients recruited for studies I and II did not differ in age, body weight, height, or preoperative hemoglobin levels (Table 1).

Study I (BIS 40–50)
The rSO₂, Petco₂, BIS, and MAC values are shown in Table 2. The rSO₂ values did not differ between the 2 anesthetics (overall anesthetic effect = –0.10. 95% CI –0.51, 0.30; P = 0.61) irrespective of the order and time effect. The difference between the 2 anesthetics was constant over time (P = 0.16 for time by anesthetic interaction).

The Petco₂ values were statistically different between the two anesthetics (overall anesthetic effect = –0.34, 95% confidence interval [CI] –0.68, –0.002; P = 0.05) but this difference was constant over time (P = 0.59 for the anesthetic by time interaction). The overall BIS values differed between the 2 anesthetics (overall anesthetic effect = –0.55, 95% CI –1.0, –10; P = 0.015). However, there was not a significant anesthetic by time interaction (P = 0.28), indicating that anesthetic differences were constant over time.

The MAC values required to maintain BIS values between 40 and 50 differed between the 2 anesthetics (overall anesthetic effect = 0.08, 95% CI 0.03, 0.15; P = 0.004). The difference was constant over time (P = 0.80 for time by anesthetic interaction). The Spo₂ values did not differ between the 2 anesthetics (overall anesthetic effect = 0.08, 95% CI –0.01, 0.18; P = 0.08). The above variables did not differ regarding the order of anesthetic administration.

Study II (BIS 20–30)
The rSO₂, Petco₂, BIS, and MAC values for BIS 20–30 are shown in Table 3. The rSO₂, Petco₂, and BIS values did not differ between the 2 anesthetics administered to 22 patients to maintain BIS between 20 and 30. The overall anesthetic effect was 0.26, 95% CI; –0.24. 0.77; P = 0.30 for rSO₂; –0.14, 95% CI –0.46, 0.18; P = 0.39 for BIS and –0.15, 95% CI –0.24, 0.54; P = 0.44 for Petco₂.

The MAC_BIS values of sevoflurane required to maintain BIS between 20 and 30 were significantly higher than those of desflurane (overall anesthetic effect = 0.12, 95% CI 0.07, 0.17; P < 0.001). This difference remained constant over time (P = 0.75 for time by anesthetic interaction). The Spo₂ values did not differ between the 2 anesthetics (overall anesthetic effect = 0.07, 95% CI –0.08, 0.22; P = 0.36). The order of anesthetic administration had no effect on the above measures.

The rSO₂, and Petco₂ values for desflurane and sevoflurane concentrations required to maintain BIS between 40 and 50 or between 20 and 30 are shown in Table 4.

The rSO₂ values obtained at 1.6 MAC of desflurane were significantly higher compared with rSO₂ values obtained with 1 MAC of this anesthetic (overall concentration effect = 3.03, 95% CI 1.71, 4.35; P < 0.001). This difference was constant over time (P = 0.29 for time by concentration interaction). Similarly, the rSO₂ values obtained during anesthesia with 1.8 MAC of sevoflurane were significantly higher than those obtained with 1.2 MAC sevoflurane anesthesia (overall concentration effect –3.4, 95% CI 2.23, 4.56; P < 0.001). This difference remained constant (P = 0.75 for time by concentration interaction).

The Petco₂ values did not differ between the 2 desflurane concentrations (overall concentration effect = –0.11, 95% CI –0.33, 0.10; P = 0.31) at any time (P = 0.07 for time by concentration interaction). MAC 1.8 sevoflurane was associated with higher Petco₂ values than was 1.2 MAC of sevoflurane (overall concentration effect = 0.50, 95% CI 0.28, 072; P < 0.001). This difference remained constant over time (P = 0.09, for time by concentration interaction).

The Spo₂ values did not differ between the 2 different concentrations of desflurane or of sevoflurane (overall concentration effect = 0.14, 95% CI –0.02, 0.29; P = 0.08 and 0.15, 95% CI –0.04, 0.35; P = 0.12, respectively).

Table 5 shows the arterial blood pressure and heart rate of the patients who received larger or smaller concentrations of desflurane and sevoflurane. MAC 1.6 desflurane was associated with lower values of systolic and diastolic blood pressure (overall concentration effect –12.3. 95% CI –14.3, –10.4; P < 0.001 and –10.39, 95% CI –11.7, –9.1; P < 0.001 respectively) and increased heart rates (overall concentration effect = 3.35, 95% CI 2.31, 4.41; P < 0.001) when compared with 1 MAC desflurane (Table 5). Systolic and diastolic blood pressures were lower for 1.8 MAC versus 1.2 MAC sevoflurane (overall concentration effect = –10.03, 95% CI –11.6, –8.49; P < 0.001 and –8.41, 95% CI –9.6, –7.2; P < 0.001 respectively). Heart rates were more rapid at 1.8 MAC versus 1.2 MAC sevoflurane anesthesia (overall concentration effect = 2.69. 95% CI 1.46, 3.92; P < 0.001) (Table 5).

	Discussion

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Our results show that at steady-state conditions desflurane and sevoflurane administered in concentrations required to produce the same BIS values are associated with similar rSO₂ values. This applies to both higher and lower BIS values.

In humans sevoflurane and propofol produce similar decreases in rCMRO₂ but propofol decreases rCBF more than does sevoflurane (8,9). Schlunzen et al. (10) found a significant decrease in relative rCBF in the thalamus at sevoflurane concentrations of 0.7% and 2.0%.

We used NIRS. There are several limitations regarding this method. Germon et al. (11) reported rSO₂ decreases from 57% to 41% when Spo₂ values were decreased from 98 to 66%. However, in our study we did not observe significant decreases in Spo₂; in fact the Spo₂ values in all cases were approximately 98%–99%. Hemoglobin concentration is one of the most potent determinants of rSO₂ values (3). None of our patients was anemic or needed blood transfusion perioperatively. Also, hemoglobin concentrations did not differ between patients of study I and study II. A decrease in rSO₂ does not always indicate cerebral ischemia and the monitor has a false-positive rate of 67%. If rSO₂ values are high, cerebral ischemia is unlikely and the false-negative rate is low, approximately 2.6% (12).

Other issues regarding NIRS reliability are changes in arterial oxygenation and extracranial blood volume (11). During the study we maintained stable oxygenation and hemodynamics. The statistically significant difference observed in the Petco₂ values when sevoflurane and desflurane concentrations were administered to produce BIS values between 40 and 50 was not clinically relevant, as those differences were small. During anesthesia with MAC values less than 2, autoregulation of CBF and thus oxygenation is maintained between mean arterial blood pressure values of 60–160 mm Hg (13). These conditions were met in both studies I and II. Also, the percentage change of SO₂ might be more reliable than absolute values of SO₂.

Despite the limitations of the monitoring we used we demonstrated in humans under the conditions of the study in a simple and noninvasive way the effect of desflurane and sevoflurane on rSO₂ in humans.

An interesting finding of the study was that the MAC_BIS values differed significantly by 0.2%, being 1 MAC_BIS for desflurane and 1.2 MAC_BIS for sevoflurane when BIS was maintained between 40–50. The difference was consistent throughout the study.

This difference was also present for MAC_BIS values required to maintain BIS values between 20 and 30 (Study II), where the calculated MAC_BIS values were approximately 1.6 for desflurane and 1.8 for sevoflurane.

Smaller sevoflurane than desflurane concentrations are required to suppress the response to a noxious stimulus (lower MAC_BIS values) compared with concentrations required to suppress BIS to the same degree. During anesthesia BIS values represent suppression of the cortex while conventional MAC values represent suppression of the response to a noxious stimulus (MAC), mediated through the spinal cord (14,15). These responses between the two anesthetics may not be proportionally different, particularly if one of the anesthetics exerts some analgesic effect.

Schwab et al. (16) reported that during controlled ventilation, BIS values were 34 and 56 for sevoflurane and halothane, respectively. The MAC_BIS concept is introduced in the present study. One MAC_BIS was defined to be the minimum alveolar concentration required to decrease BIS to a predetermined value in 50% of subjects in the absence of a noxious stimulus. The MAC_BIS value when compared with conventional MAC appears to be higher for the more soluble anesthetics as has been reported for halothane versus sevoflurane (16) and with sevoflurane versus desflurane in our studies.

The larger concentrations of desflurane and sevoflurane in Study II patients (1.6 and 1.8 MAC, respectively) are associated with higher rSO₂ values than the smaller concentrations (1.0 and 1.2 MAC, respectively) administered to Study I patients. Because all measurements were done under steady-state conditions, the higher rSO₂ may reflect decreased CMRO₂ and therefore reduced oxygen requirements.

In dog experiments 3% end-expired isoflurane depresses cortical electrical activity and decreases CMRO₂ (1). Also in dogs, 1.5 and 2.0 MAC of desflurane produced changes in the electroencephalogram pattern along with a significant decrease in the CMRO₂ (2). Alkire et al. (17), using positron emission tomography scans during halothane and isoflurane anesthesia in 11 healthy volunteers, reported specific regional reduction of brain glucose metabolism.

We conclude that rSO₂ values during desflurane and sevoflurane anesthesia and under the conditions defined by the study protocol are similar for both anesthetics in larger and in smaller anesthetic concentrations. Deeper anesthesia levels by both anesthetics are associated with higher rSO₂ values and probably reflected reduced CMRO₂. Also the anesthetic concentrations (in terms of MAC values) producing the predetermined BIS values in both studies were consistently higher for sevoflurane than for desflurane.

We thank the statisticians Mrs. Katerina Dimitriou BSc and Mr. Vasili Nikolaou MSc, for their invaluable help in the statistical analysis of the data.

	Footnotes

 
Accepted for publication January 9, 2006.

Supported, in part, by Abbott Laboratories, Hellas and Baxter, Hellas

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fassoulaki, A. Articles by Tsaroucha, A. Search for Related Content PubMed PubMed Citation Articles by Fassoulaki, A. Articles by Tsaroucha, A. Related Collections Neuroanesthesia Monitoring (Non-cardiac) Pharmacology