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In this prospective study, we evaluated the bispectral index (BIS) and postoperative recall during the intraoperative wake-up examination in 34 children and adolescents undergoing scoliosis surgery. Each anesthesiologist was blinded to BIS values throughout surgery and the wake-up test. The BIS, mean arterial blood pressure, and heart rate were compared at: before starting the wake-up test, patient movement to command, and after the patient was reanesthetized. The anesthetic technique for Group 1 was small-dose isoflurane, nitrous oxide, fentanyl, and midazolam and for Group 2 was nitrous oxide, fentanyl, and midazolam. Controlled hypotension was used for all cases. At patient movement to command, the patients were told a specific color to remember (teal) and on the second postoperative day were interviewed for explicit recall of the color and other intraoperative events. A total of 37 wake-up tests were performed in 34 patients. There was a significant increase in both groups of BIS (P < 0.001), mean arterial blood pressure (P < 0.001), and heart rate (P < 0.01) at the time of purposeful patient movement followed by a significant decline in BIS after reintroduction of anesthesia (P < 0.01). No patient recalled intraoperative pain, one patient recalled the wake-up test but not the color, and five patients recalled the specified color. We conclude that BIS may be a useful clinical monitor for predicting patient movement to command during the intraoperative wake-up test, particularly when controlled hypotension is used and hemodynamic responses to emergence of anesthesia are blunted. IMPLICATIONS: The relationship between bispectral index (BIS) and purposeful intraoperative patient movement is consistent with previous BIS utility studies. We conclude that BIS may be a useful clinical monitor for predicting patient movement to command during the intraoperative wake-up test, particularly when controlled hypotension is used and hemodynamic responses to emergence of anesthesia are blunted.
Spinal cord injury is a potential complication after distraction, instrumentation, and vertebral fusion to correct idiopathic or acquired scoliosis. Somatosensory evoked potentials (SSEPs) and an intraoperative wake-up test have been used to monitor spinal cord function during surgery (15). The purpose of the wake-up test is to monitor voluntary motor function of the lower limbs once the vertebrae have been instrumented and distracted. The wake-up test involves a gradual lightening of the anesthetic depth to the point where patients are able to respond to verbal commands. After voluntary movement of the patients lower extremities has been demonstrated, the anesthetic depth is increased and surgery completed (6,7). At our institution, anesthesia for scoliosis surgery is often maintained using incremental IV doses or a continuous infusion of fentanyl, midazolam, nitrous oxide, or small-dose isoflurane. Because volatile anesthetics can decrease the amplitude and latency of the SSEP waveforms and, thereby, decrease the utility of the SSEP monitoring, they are administered in a small concentration (8,9). Antihypertensive drugs are also given to induce controlled hypotension during the surgery. However, these drugs alter the autonomic responses and hemodynamic changes used to assess the depth of anesthesia during the maintenance phase of anesthesia and the wake-up test, making the depth of anesthesia difficult to evaluate. The bispectral index (BIS) (Aspect Medical Systems, Newton, MA), developed from the processed electroencephalogram, has been proposed as a direct measure of consciousness level during anesthesia (10,11). A correlation between BIS and movement, level of consciousness, and recall in adults has been reported after propofol, midazolam, and isoflurane sedation and anesthesia (12,13). Because we routinely use an intraoperative wake-up test and voluntary patient movement in response to a verbal stimulus during scoliosis surgery, this prospective study was undertaken to determine whether an increase in the BIS occurred during the intraoperative wake-up test. In addition, we evaluated the incidence of postoperative explicit recall in children and adolescents undergoing two different anesthesia techniques.
After obtaining IRB approval and informed consent from parents and assent from patients, we enrolled 34 children and adolescents (ASA physical status I and II) onto this prospective study. Patients were instructed about the wake-up test and told that during the wake-up test the anesthesiologist would first ask them to squeeze the anesthesiologists hand with their fingers, then wiggle their toes, and then to remember a color. Each anesthesiologist was blinded to the changes in BIS throughout the surgery. An independent study nurse recorded all data. Routine intraoperative monitoring was used in all patients and included pulse oximetry, electrocardiogram, intraarterial blood pressure, end-tidal capnography, and end-tidal inhaled anesthetic concentration measurement (Capnomac, Datex, Tewksbury, MA). Electrodes for continuous SSEP were also placed by an electrophysiologist for continuous intraoperative monitoring. The disposable BisSensor (Aspect Medical Systems) was applied to the forehead of each patient after the induction of anesthesia and connected to a BIS A-1050 monitor (Aspect Medical Systems). Once all monitoring had been established, the patients were placed in the prone position on the Relton-Hall frame (14). The BIS was monitored continuously in all patients throughout the procedure and specifically recorded at three time points: immediately before starting the intraoperative wake-up (T1), time of patient movement to verbal command (T2), and after the patient was reanesthetized after the wake-up test (T3). Mean arterial blood pressure (MAP) and heart rate (HR) were also recorded at these specific time points. Although the anesthetic technique was not randomized during this study, two distinct techniques were used to maintain anesthesia according to the anesthesiologists preference. It was therefore possible to divide patients into two groups according to the anesthetic technique. Patients in Group 1 (isoflurane, n = 19) were premedicated with IV midazolam, and anesthesia was induced with fentanyl and thiopentone or propofol. Anesthesia was maintained with fentanyl, nitrous oxide, oxygen, and small-dose isoflurane; 10 of the patients in this group also received supplemental doses of midazolam before the wake-up test. In Group 2 (no isoflurane, n = 15), patients were premedicated with IV midazolam, and anesthesia was induced with fentanyl, thiopentone or propofol and was maintained with fentanyl, nitrous oxide, and oxygen. No volatile anesthetics were used in patients in this group, and all patients received intermittent doses of midazolam before the wake-up test. Pancuronium was used for all patients to maintain neuromuscular blockade (three of four twitches, train-of-four). To minimize blood loss, controlled hypotension to maintain a mean blood pressure of 5565 mm Hg was attempted in all patients with IV labetalol. In addition, some patients also received hydralazine, nitroprusside, or esmolol as required to accomplish this goal. After the wake-up test, patients were reanesthetized with either a bolus of midazolam or propofol, a reintroduction of isoflurane, or both. At the time of the wake-up test, the anesthesiologist asked the patient to squeeze his or her hand. This request was repeated every 30 s until they responded. Next, the patient was instructed to wiggle their toes and to remember the color teal. On the second postoperative day, the patient was interviewed by the study nurse and asked whether they remembered intraoperative events, the wake-up test, and specifically whether they remembered pain or the color specified at the time of the wake-up test. Parametric methods were used for statistical analysis after the Kolmogorov-Smirnov goodness-of-fit test had indicated that each variable followed a normal distribution. Differences in BIS, MAP, and HR level at each time point were evaluated within each group using repeated-measures ANOVA with a Greenhouse-Geisser F-test for small samples followed by multiple paired t-tests. The BIS at T1 and T2 were compared within each group using a paired Students t-test and between each group using an unpaired Students t-test. Data are expressed as mean ± SD. Statistical analysis was performed with the SigmaStat (version 1.0, Jandel Corp, San Rafael, CA), and significance was accepted at P < 0.05.
A total of 37 wake-up tests were performed in 34 patients. One patient underwent two separate wake-up tests, and a second patient underwent three separate wake-up tests during the surgery. The mean age for all patients was 14.3 ± 2.8 yr, and mean weight was 57.7 ± 21.3 kg. The mean BIS value, MAP, and mean HR at each time point for all patients are shown in Table 1. From T1 to T2, there was a significant increase in BIS (P < 0.001), MAP (P < 0.001), and HR (P < 0.01). After a positive wake-up test and at T3, the BIS level significantly decreased (P < 0.01).
Patient demographics and the changes in mean BIS, MAP, and HR between the anesthesia Groups 1 (isoflurane) and 2 (no isoflurane) are shown in Table 2. Of the 19 patients in Group 1, 13 had a posterior fusion alone, and six underwent an anterior and posterior fusion; of the 15 patients in Group 2, 12 underwent a posterior fusion, and three had an anterior and posterior fusion. The time from the induction of anesthesia to starting the wake-up test was not significantly different between the two groups (Group 1, 340.3 ± 96.2 min and Group 2, 300.7 ± 78.5 min, P = 0.2). No patient responded to the first request to wake-up, and the mean time from T1 to T2 was not significantly different between the two groups. The BIS at T1 was significantly lower in Group 1 (P < 0.05) but not at the other time points. For both groups, there was a significant increase in BIS level from T1 to T2 (P < 0.001) but no significant difference between the two groups at T2. The BIS level decreased significantly in both groups after resuming anesthesia (P < 0.001), but there was no significant difference between the two groups at T3. Between groups, there were no significant differences with respect to MAP or HR at each time point. Within each group, the MAP increased significantly during the wake-up test (P < 0.01). There was also a significant decrease in MAP when anesthesia resumed (P < 0.01). HR increased significantly only in Group 1 from T1 to T2 (P < 0.01).
There was no difference between the two groups for the mean dose of midazolam administered as premedication (Group 1, 0.048 ± 0.01 mg/kg and Group 2, 0.045 ± 0.03 mg/kg, P = 0.5), but the mean dose of midazolam administered during the maintenance of anesthesia and before the wake-up test was significantly less in Group 1 compared with Group 2 (0.03 ± 0.05 mg/kg and 0.07 ± 0.04 mg/kg, respectively, P < 0.02). The mean dose of fentanyl administered at the time of the induction was significantly less for patients in Group 1 compared with those in Group 2 (10.9 ± 5.4 µg/kg and 16.7 ± 5.6 µg/kg, respectively, P = 0.007), but there was no difference in the mean total dose of fentanyl administered during maintenance of anesthesia before the wake-up test (Group 1, 18.0 ± 10.0 µg/kg and Group 2, 13.1 ± 6.1 µg/kg, P = 0.12). The mean end-tidal concentration of isoflurane administered during the maintenance of anesthesia before the wake-up test in Group 1 patients was 0.4% ± 0.1%. Controlled hypotension with labetalol was used for all patients. The mean dose of labetalol used for patients in Group 1 and Group 2 was not significantly different (1.3 ± 0.4 mg/kg and 1.0 ± 0.7 mg/kg, respectively, P = 0.5). However, only two patients in Group 1 received additional antihypertensive drugs (hydralazine, n = 1 and sodium nitroprusside, n = 1), whereas 10 patients in Group 2 required additional antihypertensive drugs (hydralazine, n = 8 and esmolol, n = 2). At the postoperative interview, explicit auditory recall was demonstrated in six patients (17.6%), but no patient recalled intraoperative pain. One patient in Group 1 recalled the wake-up test but not the color, and five patients (two in Group 1 and three in Group 2) recalled the color teal. Although there was no attempt to test for implicit recall in this study, three patients in Group 1 recalled the color as turquoise (n = 2) or aquamarine (n = 1). Patients were unable to recall other intraoperative events before or after the wake-up test. All patients had a satisfactory postoperative recovery without significant morbidity.
In this study, we demonstrated a significant increase in BIS during the intraoperative wake-up test with a small incidence of explicit recall, which was independent of anesthetic technique. This increase is consistent with previous studies that have correlated BIS with involuntary patient movement and response to surgical stimulation and during emergence from anesthesia (12,1517). The concomitant use of vasoactive drugs for controlled hypotension can alter the autonomic response during emergence from anesthesia, and the BIS may be a useful monitor of consciousness level in this circumstance. The patients in our study demonstrated a less frequent incidence of explicit recall of events during the intraoperative wake-up test than would be predicted by their BIS numbers alone. In volunteer and clinical utility studies in adults, the change in BIS has been related to a change in the consciousness level or hypnotic state of an individual (12,15). Using logistic regression analysis of volunteers receiving increasing doses of propofol, isoflurane, or midazolam, a BIS level of <60 was associated with a small probability for response to verbal command (12). At a BIS level between 60 and 70, the probability for response to verbal command increased along with the potential for explicit recall, and at a BIS level more than 70, the probability of free recall significantly increased (12). However, there seems to be considerable overlap in the threshold BIS values that predict responsiveness to command or ability to form memory. In our patients, the mean BIS level of 72 before the wake-up test was at a level that has been associated with explicit recall in adults (12). The mean BIS level of 90 at the time of purposeful patient movement has, in one study, been associated with conscious patients (12). Glass et al. (12) reported the BIS50 of 86 for recall in adult volunteers receiving propofol, midazolam, or isoflurane sedation. The incidence of explicit recall in our patients was only 17.6% (five remembered the color and one recalled the test), which is a smaller incidence than would be expected based on adult studies (12,18,19). Importantly, no patient recalled intraoperative pain or distress during the intraoperative wake-up test. There was no difference in the incidence of explicit recall between the two anesthesia techniques. The reasons why patients in our study had a relatively small incidence of recall are speculative. One possible reason is that they received more than one drug during anesthesia rather than a single anesthetic at controlled and titrated doses (12,18,19). Another possible reason is that our patients underwent a prolonged anesthetic before the wake-up tests, rather than a short period of sedation, as was done in the adult studies (12,18,19). A third possible reason is that the BIS algorithm is inaccurate for predicting the state of consciousness in children and adolescents. However, this seems unlikely because several pediatric studies have demonstrated a close correlation between the BIS and anesthetic depth in children older than one year of age (2022). The current BIS algorithm was derived from patients anesthetized with a variety of anesthetics that have predominantly hypnotic properties, such as propofol and inhaled anesthetics, and may not be applicable to patients undergoing a primarily opioid-based anesthetic (10,23). The effect of narcotics on BIS levels is complicated. In a study of adult volunteers undergoing propofol sedation, the addition of an opioid did not change the BIS level when the subjects were not stimulated. However, in this same study, the addition of an opioid attenuated the BIS response to painful stimuli (24). In a study of 10 patients undergoing coronary bypass surgery, the BIS did not correlate with midazolam or fentanyl drug concentrations. Despite a wide range of BIS numbers (range, 3691), there was no evidence of recall (23). Although our patients in Group 2 had a mean BIS level of 75.6 ± 8.0 at the start of the wake-up test, no patient in either group had explicit recall of intraoperative events or pain during maintenance anesthesia. In our study, the point at which patients were given the command to move their lower limbs was at the discretion of each anesthesiologist based upon his or her clinical experience of evaluating hemodynamic changes as the patients emerged from anesthesia. The concurrent use of hypotensive drugs such as labetalol, esmolol, hydralazine, and sodium nitroprusside to induce controlled hypotension during surgery can be expected to modify this hemodynamic response during the wake-up process. More patients in Group 2, who received fentanyl primarily for maintenance of anesthesia, received additional antihypertensive drugs before the wake-up test. They also had a significantly larger BIS value immediately before starting the wake-up test compared with those patients in Group 1 who received isoflurane for anesthesia maintenance. This may suggest that patients in Group 2 were at a lighter plane of anesthesia. However, there was no difference between groups in the incidence of recall, and no patient had explicit recall of pain or intraoperative events before the wake-up test. In addition, the mean time from starting the wake-up test to spontaneous patient movement in response to verbal stimulus was 8.2 ± 4.8 minutes, which was not influenced by anesthetic technique. Whereas the BIS varies in sensitivity and specificity between anesthetic techniques and individual patients, it may provide useful trend information in any given patient. In this study, we evaluated BIS in the setting of a complex surgical procedure in which vasoactive drugs were used to modify hemodynamic responses and in which movement during an intraoperative wake-up test and postoperative recall could be used as discrete end points. Independent of the anesthetic techniques used in our patients, there was a significant increase in BIS during the wake-up process that indicated a higher level of consciousness but with an infrequent incidence of explicit recall. Additional prospective studies using BIS-directed anesthetic management along with more detailed explicit and implicit memory testing are required to determine the utility of BIS for routine monitoring in this setting.
Accepted for publication
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