| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
| ||||||||||||||
| ||||||||||||||
|
|
|
|
||||||||||||
|
||||||||||||||
Department of Anesthesiology, Emory University School of Medicine, Grady Memorial Hospital, Atlanta, Georgia
Address correspondence and reprint requests to Jay W. Johansen, MD, PhD, Department of Anesthesiology, Emory University School of Medicine, Grady Memorial Hospital, Atlanta, GA 30303. Address e-mail to jay_johansen{at}emoryhealthcare.org.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Gan et al. (8) found, in a multicenter trial, that gender was a highly significant, independent predictor for recovery time using a propofol/alfentanil/nitrous oxide anesthetic. Women required more propofol to maintain equivalent bispectral index (BIS) levels than men under general anesthesia. No significant difference was noted in total propofol/alfentanil doses or in maintenance or preemergent BIS values. Women awoke significantly faster, as measured by eye opening and by response to verbal command (MACawake) after discontinuation of the propofol infusion. Gan et al. (8) suggested that a combination of pharmacokinetic and pharmacodynamic factors were responsible for the gender difference.
Gan et al. (8) reported reanalysis of an earlier study (9), finding that women had significantly larger propofol plasma concentrations at the point of loss of consciousness (LOC; loss of response to voice command) and that women had consistently higher BIS values at similar propofol plasma concentrations than men. Because BIS measures the pharmacodynamic response of hypnotic medications, they suggested that women may have a different sensitivity to propofol. Ward et al. (10) found that women had a smaller volume of distribution for propofol and a larger clearance resulting in a larger initial peak and smaller final concentration during similar continuous infusions. They confirmed faster emergence times for women compared with men at equivalent BIS values using propofol anesthesia. They concluded that pharmacokinetic differences were predominately responsible for this effect.
Emergence from anesthesia is a complex, nonsteady-state process that can be influenced by the multiple drugs given during anesthesia, stimuli from airway instrumentation, and type and length of surgery (11). Plasma drug levels and end-tidal gas measurements are not in equilibrium with, and lag behind, brain concentrations, making it difficult to control intra- and interindividual variables. Steady-state conditions can be approximated by maintaining drug delivery for 3 distribution half-lives (t1/2
) for a given medication and delivery route. Exogenous stimuli can be minimized by studying patients before surgery and by maintaining spontaneous ventilation without airway instrumentation.
The goal of this study was to examine the role of gender on anesthetic requirements for loss of arousal response to light touch or mild shaking using either an IV (propofol) or volatile (sevoflurane) anesthetic under conditions approximating steady-state.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patients were recruited during preoperative preparation before surgery. Men and women were separately randomized to either propofol or sevoflurane anesthesia. No preoperative sedation or analgesics were administered. Once in the operating room, standard anesthesia monitors were placed, including electrocardiogram, pulse oximetry, noninvasive blood pressure cuff, BIS of the electroencephalogram (EEG), and end-tidal gas monitors. The BIS A2000 monitor (version 3.2; Aspect Medical Systems, Inc, Natick, MA) uses three adhesive electrodes to the forehead (single channel: Fp1-Fpz). BIS, raw EEG, hemodynamic variables, and end-tidal gas measurements were automatically recorded to a computer at 5-s intervals during the course of the experiment. BIS and other EEG-based variables reported here are an average of recordings taken for 1 min before the administration of the sedation scale.
Either sevoflurane (tightly sealed mask via semiclosed circuit) or propofol (IV) were administered to achieve predetermined end-tidal or effect-site concentrations for each patient. Propofol was administered via a target-controlled infusion (TCI) device (Duke University, Durham, NC), which used a three-compartment population pharmacokinetic model targeting drug effect-site concentration (12). This technology is able to rapidly achieve and maintain stable serum and effective brain concentrations of propofol. The initial target effect-site concentrations were 2.5 µg/mL of propofol or an end-tidal sevoflurane concentration of 0.6%. After 10 min at the target concentration, the modified observer’s assessment of awareness and sedation (OAA/S) was administered (9,13). LOC was defined as an OAA/S of <2 (loss of responsiveness to light tapping on left shoulder or mild shaking with voice command to open eyes). An arousal response and opening the eyes was considered positive, whereas nonspecific motor responses were considered negative. After OAA/S assessment, the study was concluded, and anesthesia was continued at the discretion of the anesthesiologist.
Propofol and sevoflurane target concentration for a given patient were determined by the response of the previous patient. Target concentrations were increased by 10% if the previous patient’s OAA/S score was 
2 and decreased by 10% if <2. The concentrations at which LOC was in 50% of patients (LOC50) were determined by the Dixon method (14). LOC50 was defined as the mean of independent crossover pairs within each group. A crossover represents a unique pair of sequential patients in which the first patient lost consciousness and the next patient did not or vice versa. The investigator administering the OAA/S was not blinded to the sevoflurane or propofol dose.
Frequency data (gender) were analyzed with the 
2 test. Kruskal-Wallis test was also used to detect significant differences in ranked categorical variables such as ASA status. Multifactorial analysis of variance with post hoc Bonferroni test was used to determine the LOC50 and average BIS for propofol and sevoflurane and to examine significant cofactors (gender, age, weight, etc.) using a standard statistical software package (SPSS version 11; SPSS Inc, Chicago, IL). P < 0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
|
The sevoflurane dose at LOC50 measured by loss of response to mild prodding or shaking (OAA/S <2) was 0.83% ± 0.13% in men and 0.92% ± 0.09% in women (Fig. 1). No statistical difference was found between genders (92% power to detect a mean difference of 10%). Propofol effect-site target at LOC50 was significantly different between men (2.9 ± 0.2 µg/mL) and women (2.7 ± 0.2 µg/mL). This comparison had a 95% power to detect a significant difference. After equilibration, and 1 min before the administration of the OAA/S administration, BIS at 50% LOC (BIS50) was not significantly different between men and women in either drug group. However, the average BIS at LOC was statistically different between patients receiving sevoflurane (74 ± 9) and those receiving propofol (62 ± 11) (Table 2; Fig. 1). Average signal quality index (SQI) remained more than 80% (SQI <70% indicates BIS calculation may be influenced by artifact) and electromyographic (EMG) less than 50 dB. No difference in EMG activity in the frontalis muscle, the electrode impedance, or overall SQI between gender or hypnotic drug were identified during automated BIS recordings (Table 2).
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Our study used the same pharmacokinetic variables for propofol and TCI software as Glass et al. (9). They concluded that the correlation of BIS value and measured effect was independent of the choice of sedative/hypnotic drug, with no statistically significant differences between IV and volatile anesthetics. However, they defined LOC as loss of response to verbal command (OAA/S <3), which is similar to Zbinden et al.’s (18) definition of MACawake. They reported LOC50 for propofol 2.35 µg/mL with a BIS50 of 63 for OAA/S <3 (loss of response to verbal command). Reexamination of their data for OAA/S <2 found an LOC50 for propofol 2.4 µg/mL with a BIS50 of 56 for OAA/S (J. Sigl, personal communication) similar to our average value for propofol of 2.8 µg/mL at a BIS50 of 62. Gan et al. (8) reported a reanalysis of the Glass et al. (9) data showing that women had consistently higher BIS values at similar plasma propofol concentrations to men. Our data do not support this conclusion. Although sevoflurane was not used in the Glass et al. (9) study, the LOC50 for isoflurane for OAA/S <2 was 0.57% end-tidal at a BIS50 of 63 (J. Sigl, personal communication). Stimulus-response scales, such as the OAA/S, provide only a ranked-ordered set of tests of increasing sedation with significant overlapping definitions. The OAA/S scale does not represent clearly defined increments or units of hypnosis and cannot clearly differentiate between pure cortical and spinally mediated motor responses. The sedative concentrations of propofol and sevoflurane for loss of response to mild prodding or shaking (OAA/S <2) and those reported for loss of response to loud voice command (OAA/S <3 or MACawake) were very similar.
A higher average, prestimulus BIS at LOC50 for the volatile anesthetic sevoflurane was found compared with propofol. BIS was averaged for one minute before the administration of the OAA/S. It is possible that the BIS is higher in patients receiving volatile anesthetics because of increased EMG activity in the frontalis muscle of the forehead, and this may be increased in spontaneously breathing patients. The BIS value can be artifactually increased by high EMG activity (>50 dB), electrocautery, or high frequency signals (SQI <50%) because of the increased noise below the high-pass filter. In our study, an adequate signal quality was maintained throughout the experiment, and there was no difference in EMG between genders or anesthetic. Many studies fail to report these data and consider sources of potential signal contamination. The explanation of this statistically significant difference between propofol and sevoflurane at the transition from OAA/S 2 to 1 is unclear.
In summary, we conclude that there are no clinically significant differences between genders for LOC defined by lack of response to mild prodding for sevoflurane or propofol in spontaneously breathing patients at conditions approximating steady-state. However, at the clinical end-point of loss of response to mild prodding or shaking, sevoflurane and propofol have differing neurophysiologic effects, as determined by BIS.
|
Footnotes |
|---|
Accepted for publication December 13, 2006.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  N. Ohtani, K. Kida, K. Shoji, Y. Yasui, and E. Masaki Recovery Profiles from Dexmedetomidine as a General Anesthetic Adjuvant in Patients Undergoing Lower Abdominal Surgery Anesth. Analg., December 1, 2008; 107(6): 1871 - 1874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A Otto EEG power spectrum analysis for monitoring depth of anaesthesia during experimental surgery Lab Anim, January 1, 2008; 42(1): 45 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Mourisse, J. Lerou, M. Struys, M. Zwarts, and L. Booij Multi-level approach to anaesthetic effects produced by sevoflurane or propofol in humans: 1. BIS and blink reflex Br. J. Anaesth., June 1, 2007; 98(6): 737 - 745. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
