Propofol is widely used for maintenance of sedation during local and regional anesthesia [1-3]. In order to facilitate the clinical evaluation of depth of sedation, Chernik et al.  developed the observer's assessment of alertness/sedation (OAA/S) scale. However, monitoring the patient using the OAA/S scale requires frequent stimulation during the operation, a practice which can be disturbing to both the patient and the surgeon. Liu et al.  have recently demonstrated that the bispectral (BIS) index, and to a lesser degree the 95% spectral edge frequency (95% SEF), are useful adjuncts for monitoring the depth of midazolam-induced sedation.
Recent studies have also suggested that the BIS index, which measures interfrequency phase relationships in the electroencephalogram (EEG), predict responses to noxious stimulation during propofol anesthesia [6,7]. However, a major concern during intravenous (IV) anesthesia and sedation relates to recall of intraoperative events [8,9]. During propofol-induced sedation, an excessive depth of sedation may be associated with clinically significant cardiovascular and respiratory depression, whereas less intense levels of sedation may be associated with intraoperative recall [2,3]. This study was designed to study the effectiveness of the BIS index and 95% SEF as a potential monitor for determining the level of sedation and degree of amnesia during propofol-induced sedation.
Ten healthy (ASA physical status I and II) consenting adult males scheduled for elective surgery involving the lower extremities under regional anesthesia were studied according to a protocol approved by the local institutional review board. Patients with known neurologic disorders, as well as those with significant cardiovascular, respiratory, and hepatic diseases, were excluded from the study. The patients ranged in age from 29 to 72 yr (50 +/- 15 yr; mean +/- SD) and in weight from 60 to 100 kg (81 +/- 12 kg). All the patients fasted for at least 6 h prior to surgery and received no premedication. For EEG monitoring of the BIS index and 95% SEF, gold cup electrodes (Grass Instruments, Quincy, MA) were placed on the scalp in the following configuration: Fp1-Cz and Fp2-Cz (International 10-20 System of electrode placement). A ground electrode was placed behind the right ear lobe and all the electrodes were secured with collodion. Conductive gel was applied inside the electrodes to reduce the impedance of each electrode to less than 5K Omega.
After performing successful regional anesthesia (e.g., spinal subarachnoid or epidural blockade), patients were shown a picture of an animal (cat) prior to administration of a loading dose of propofol, 40 mg IV. Thereafter, propofol was administered in increments of 10-20 mg IV at 5- to 10-min intervals in an attempt to achieve OAA/S scores of 4, 3, 2, and 1 (Appendix Table 4) . The total doses of propofol administered ranged from 220 to 560 mg, with a mean dose (+/- SD) of 396 +/- 139 mg. After achieving an OAA/S score of 1, the administration of propofol was discontinued and recovery from propofol-induced sedation was observed until the OAA/S score returned to 4. To minimize interobserver variability, all OAA/S assessments were performed by one investigator (JL). At the time of the OAA/S assessments, patients who were arousable and able to correctly identify a picture were shown one of five different pictures during both the onset and recovery phases. After arrival in the postanesthesia care unit, five groups of five pictures each (containing animals, clothings, furniture, transportation vehicles, and weapons) were shown to the patients, and they were asked to identify the picture they saw during the operation in each of the five groups. During the surgical procedure, all the patients received supplemental oxygen, 3-4 L/min, via nasal cannula to maintain a SpO2 value greater than 95%. The duration of time in the operating room varied from 60 to 230 min, with a mean value (+/- SD) of 132 +/- 51 min.
In order to minimize artifacts during the EEG recording intervals immediately prior to assessments of the OAA/S levels, patients were asked to close their eyes, and not to speak or move during these brief assessment periods. The BIS index and 95% SEF values were calculated at 4-s epochs and recorded at 15-s intervals at a frequency of 128 Hz using the EEG monitor (Model B500; Aspect Medical Systems, Natick, MA). In this study, the BIS index and 95% SEF values reported are the average of real time BIS indices obtained from channels 1 and 2 (Fp1-Cz and Fp2-Cz), respectively. The BIS index and 95% SEF values at each OAA/S score were calculated by averaging the values during the 45-s interval immediately prior to the OAA/S assessment.
Mean values and SD of the BIS index and 95% SEF were calculated at each OAA/S score during the onset and recovery phases of sedation. Kruskal-Wallis analysis of variance was used to determine significant changes in the BIS index and 95% SEF values at different OAA/S scores. Nonparametric Spearman's correlation analysis was used to evaluate the relationship between the BIS index or 95% SEF and the OAA/S scores. The changes in the number/percentage of patients correctly recalling pictures at different levels of sedation were analyzed for statistical significance using McNemar's chi squared test.
With an increasing "depth" of sedation (from an OAA/S score of 5 to 1), the BIS index decreased progressively from 94.5 +/- 2.9 to 75.6 +/- 7.5 during the onset phase (Table 1). During recovery from propofol-induced sedation, the BIS index increased from 75.6 +/- 7.5 to 93.8 +/- 0.8 as the OAA/S score increased from 1 to 4 (Table 2). The relationship between OAA/S scores and BIS index for individual patients are displayed in Figure 1. The BIS index correlated with the OAA/S scores during both the onset of (Spearman's rho = 0.744) and recovery from (Spearman's rho = 0.705) propofol-induced sedation. The 95% SEF did not change significantly during the onset phase (Table 1). However, the 95% SEF increased from 16.4 +/- 5.0 (at an OAA/S score of 1) to 19.3 +/- 5.6 (at an OAA/S score of 4) during recovery from propofol-induced sedation (Table 2) Figure 2.
With an increased depth of sedation from an OAA/S score of 5 to 2, the percentage of pictures recalled decreased from 100% to 0% (Table 3). However, the success or failure of picture recall at individual BIS values and OAA/S scores displayed considerable interpatient variability. When the BIS value was in the range of 90-100 and 80-90, 78% and 45% of the pictures shown were recalled, respectively. Only 8% of the pictures shown during the intraoperative period were recalled when the BIS index was less than 80.
Analogous to our previous findings when midazolam was used for sedation during regional anesthesia , this study demonstrates a significant correlation between the BIS index and OAA/S scores during both the onset of and recovery from propofol-induced sedation. An increasing depth of sedation was associated with a predictable decrease in the BIS index, whereas a decreasing level of sedation was associated with increasing BIS index. Similar to our findings, Leslie et al.  did not observe any significant changes in the 95% SEF during onset of or recovery from propofol-induced sedation. These investigators suggested that the BIS index may indirectly reflect serum propofol concentrations since the BIS index decreased linearly with increasing propofol concentrations . However, Glass et al.  and Kearse et al.  have reported that the BIS index correlates significantly better with the sedation scores than measured propofol concentrations.
Veselis et al.  found that a small-dose propofol infusion produced significant changes in both memory and EEG variables. Their data suggested that the EEG power spectrum may be useful for monitoring recall during conscious sedation with propofol. Our study demonstrated that impairment of intraoperative recall and changes in the BIS index depended upon the level of sedation. An increasing depth of sedation was associated with a progressive decrease in the BIS value and in the percentage of patients correctly recalling pictures during the operation. None of the patients were able to recall the pictures shown during the operation at an OAA/S score of 2, with a corresponding BIS value of 80.8 +/- 8.3 (mean +/- SD). Recently, Glass et al.  also reported that memory function remained intact at higher BIS values of 93 +/- 5 (mean +/- SD), while recall was absent at lower BIS values of 70 +/- 18 (mean +/- SD). Kearse et al.  found that no patient had intraoperative recall when the BIS index was below 79 during midazolam-, isoflurane-, or propofol-induced sedation. Our findings are consistent with the above studies with respect to the relationship between the BIS index and the percentage of patients recalling pictures during propofol-induced sedation. The BIS index may, therefore, prove to be a useful index for monitoring amnesia during propofol-induced sedation and anesthesia. However, different modalities of stimulation are associated with variable efficacy in creating memory traces. Failure to recall a picture stimulus during regional anesthesia may not correlate with inability to recall more potent stimuli (e.g., painful surgical intervention during general anesthesia). Given the variability which exists among individual patients (Figure 1), further studies are needed to assess the correlation between the BIS index and intraoperative recall in the presence of different stimuli and under differing anesthetic conditions.
When using propofol during a monitored anesthesia care technique, the anesthesia practitioner attempts to titrate the drug to optimize patient comfort, while maintaining cardiorespiratory stability and intact protective airway reflexes. Based on the OAA/S scores and BIS index, these data would suggest that a BIS index in the range of 85-90 correlates with an OAA/S score of 3. However, for an individual patient, a BIS index in this range may result in a depth of sedation which is either too high or too low (Figure 1). Further studies are necessary to determine whether it will be possible to improve the administration of propofol by using BIS monitoring as an adjunct to routine clinical assessment. To minimize the possibility to intraoperative recall during propofol-induced sedation or anesthesia, the BIS value should be maintained below 80. Since the BIS value corresponded to an OAA/S score of 2 (or less), use of propofol alone to achieve intraoperative amnesia may result in an excessive depth of sedation and associated cardiorespiratory depression. Taylor et al.  demonstrated that the adjunctive use of small doses of midazolam (1-3 mg IV) as part of a co-sedation technique can decrease intraoperative recall without significantly altering the cardiorespiratory variables during propofol-induced sedation. However, the effect of midazolam premedication on the BIS index during propofol sedation has not been evaluated.
In summary, the BIS index correlates with the depth of sedation as measured by the OAA/S score in patients receiving propofol for sedation during regional anesthesia. Lower BIS values and OAA/S scores were associated with progressively decreased recall during propofol-induced sedation.
The authors thank the postanesthesia care unit nurses, CRNAs, and residents of the Department of Anesthesiology and Pain Management for their cooperation during this study. Support for this study was also provided by Paul Manberg, PhD, Pat Embree, CRNA, and Nassib Chamoun of the Aspect Medical Systems, Inc.
1. Smith I, White PF, Nathanson M, Gouldson R. Propofol: an update on its clinical use. Anesthesiology 1994;81:1005-43.
2. Smith I, Monk TG, White PF, Ding Y. Propofol infusion during regional anesthesia: sedative, amnestic and anxiolytic properties. Anesth Analg 1994;79:313-9.
3. Taylor E, Ghouri AF, White PF. Midazolam in combination with propofol for sedation during local anesthesia. J Clin Anesth 1992;4:213-6.
4. Chernik DA, Gillings D, Laine H, et al. Validity and reliability of the observer's assessment of alertness/sedation scale: study with intravenous midazolam. J Clin Psychopharmacol 1990;10:244-51.
5. Liu J, Singh H, White PF. Electroencepohalogram bispectral analysis predicts the depth of midazolam-induced sedation. Anesthesiology 1996;84:64-9.
6. Kearse LA, Manberg P, Chamoun N, et al. Bispectral analysis of the electroencephalogram correlates with patient movement to skin incision during propofol/nitrous oxide anesthesia. Anesthesiology 1994;81:1365-70.
7. Vernon JM, Lang E, Sebel PS, Manberg P. Prediction of movement using bispectral electroencephalographic analysis during propofol/alfentanil or isoflurane/alfentanil anesthesia. Anesth Analg 1995;80:780-5.
8. Sebel PS, Bonke B, Winograd E. Memory and awareness in anesthesia. Englewood Cliffs, NJ: Prentice Hall, 1993.
9. Sandin R, Nordstrom O. Awareness during total i.v. anaesthesia. Br J Anaesth 1993;71:782-7.
10. Leslie K, Sessler DI, Schroeder M, Walters K. Propofol blood concentration and bispectral index predict suppression of learning during propofol/epidural anesthesia in volunteers. Anesth Analg 1995;81:1269-74.
11. Glass P, Gan TJ, Sebel PS, et al. Comparison of the bispectral index (BIS) and measured drug concentrations for monitoring the effects of propofol, midazolam, alfentanil and isoflurane [abstract]. Anesthesiology 1995;83:A374.
12. Kearse L, Rosow C, Connors P, et al. Propofol sedation/hypnosis and bispectral EEG analysis in volunteers [abstract]. Anesthesiology 1995;83:A506.
13. Veselis RA, Reinsel RA, Wronski M, et al. EEG and memory effects of low-dose infusions of propofol. Br J Anaesth 1992;69:246-54.