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NEUROSURGICAL ANESTHESIOLOGY AND NEUROSCIENCE

A Comparison in Adolescents of Composite Auditory Evoked Potential Index and Bispectral Index During Propofol-Remifentanil Anesthesia for Scoliosis Surgery with Intraoperative Wake-Up Test

Heleen J. Blussé van Oud-Alblas, MD^*, Jeroen W. B. Peters, PhD^*, Tom G. de Leeuw, MD^*, Kris T. A. Vermeylen, MD^*, Luuk W. L. de Klerk, MD, PhD, Dick Tibboel, MD, PhD, Jan Klein, MD, PhD^*, and Frank Weber, MD^*

From the Departments of *Anesthesiology, Orthopedics, and Pediatric Surgery, Erasmus Medical Center–Sophia Children’s Hospital, Rotterdam, The Netherlands.

Address correspondence and reprint requests to Heleen Blussé van Oud-Alblas, Department of Anesthesiology, Erasmus Medical Center, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. Address e-mail to h.blussevanoudalblas{at}erasmusmc.nl.

Abstract

BACKGROUND: The electroencephalogram-derived Bispectral Index (BIS), and the composite A-line ARX index (cAAI), derived from the electroencephalogram and auditory evoked potentials, have been promoted as anesthesia depth monitors. Using an intraoperative wake-up test, we compared the performance of both indices in distinguishing different hypnotic states, as evaluated by the University of Michigan Sedation Scale, in children and adolescents during propofol-remifentanil anesthesia for scoliosis surgery. Postoperative explicit recall was also evaluated.

METHODS: Twenty patients (aged 10–20 yr) were enrolled. Prediction probabilities were calculated for induction, wake-up test, and emergence. BIS and cAAI were compared at the start of the wake-up test, at purposeful movement to command, and after the patient was reanesthetized. During the wake-up test, patients were instructed to remember a color, and were then interviewed for explicit recall.

RESULTS: Prediction probabilities of BIS and cAAI for induction were 0.82 and 0.63 (P < 0.001), for the wake-up test, 0.78 and 0.79 (P < 0.001), and 0.74 and 0.78 for emergence (P < 0.001). During the wake-up test, a significant increase in mean BIS and cAAI (P < 0.05) was demonstrated at purposeful movement, followed by a significant decline after reintroduction of anesthesia.

CONCLUSIONS: During induction, BIS performed better than cAAI. Although cAAI was statistically a better discriminator for the level of consciousness during the wake-up test and emergence, these differences do not appear to be clinically meaningful. Both indices increased during the wake-up test, indicating a higher level of consciousness. No explicit recall was demonstrated.

Both the Bispectral Index (BIS), derived from the electroencephalogram, and the composite A-Line ARX Index (cAAI), derived from auditory evoked potentials (AEP) and the electroencephalogram, continue to be evaluated as tools to measure depth of anesthesia and to detect intraoperative awareness. Two studies in adults comparing the usefulness of BIS and cAAI demonstrated that both monitors were comparable indicators of depth of hypnosis.1,2 Whereas BIS has been studied extensively in pediatric patients, there are only two published studies investigating the cAAI in children.3,4 Weber et al. demonstrated in an outcome study in children undergoing strabismus repair that cAAI-guided anesthesia resulted in less propofol consumption and shorter recovery times.4 Furthermore, a study from Ironfield and Davidson suggested that, in children under sevoflurane-based anesthesia, the cAAI is a poor predictor of depth of anesthesia compared to BIS.3 Until now there are, to our best knowledge, no published pediatric data comparing both indices under the condition of total IV anesthesia with short-acting drugs, such as propofol and remifentanil. Spinal cord fusion for idiopathic scoliosis, usually performed in adolescents, seems to be an almost perfect setting for comparing the performance of depth of anesthesia monitors. Besides general anesthesia, a period of planned intraoperative wakefulness, the so called "wake-up test," is a standard feature of this surgical procedure.

The main purpose of this study was to compare the performance of BIS and cAAI in children and adolescents with respect to their ability to distinguish between different hypnotic states, as evaluated by the responsiveness scores to the University of Michigan Sedation Scale (UMSS).5 This was specifically performed during the intraoperative wake-up test, which can be regarded as an intentional episode of intraoperative awareness. We hypothesized that both monitors performed equally, which was tested by calculating prediction probabilities (P_K) as the primary outcome parameter. The incidence of explicit recall was also evaluated.

METHODS

IRB approval and written informed consent of parents and patients was obtained. Twenty patients, ASA status I or II, undergoing correction of idiopathic scoliosis were enrolled in the study. Exclusion criteria were hypacusis or deafness, any neurological disease, medication affecting the central nervous system, or any contraindication to the protocol.

Patients were instructed during the preoperative visit about the wake-up test and told that during the wake-up test the anesthesiologist would first ask them to squeeze his hand with their fingers, then to wiggle their toes, and finally to remember a given color.

The principal investigator supervised recording of all data and was blinded to BIS and cAAI values. Values were recorded with a BIS monitor A-2000, software version 3.2; (Aspect Medical Systems, Newton, MA) and an AEP monitor/2 software version 1.6 (Danmeter A/S, Odense, Denmark). A BIS pediatric four sensor probe (BIS Pediatric Sensor, Aspect Medical Systems International BV, De Meern, The Netherlands) was placed on the patient’s forehead according to the manufacturer’s instructions. For the AEP monitor/2, headphones for auditory stimuli and three sensors (Danmeter A/S, Odense, Denmark) were positioned at the mid-forehead (+), right forehead (reference), and right mastoid (–). BIS and cAAI measurements started before induction to obtain preanesthetic awake values and continued until return of consciousness (ROC) after finishing anesthesia, defined as patient eye opening.

Patients received a standardized anesthetic regimen without premedication. Anesthesia was induced with remifentanil 1 µg/kg, infused over 1 min. Thereafter, propofol (4 mg/kg), and a single dose of rocuronium (0.6 mg/kg) were administered to facilitate endotracheal intubation. Patients’ lungs were mechanically ventilated to normocapnia (end-tidal CO₂ 35–40 mm Hg). An arterial line and a central venous catheter were inserted for invasive continuous measurement of arterial blood pressure and central venous pressure and a urinary catheter was placed. Thereafter, patients were moved to prone position.

Anesthesia was maintained with propofol by continuous infusion and remifentanil at the discretion of the anesthesiologist. During the procedure, no additional muscle relaxants were given. Intraoperatively intrathecal morphine (5 µg/kg) was administered for both intra- and postoperative pain treatment by the orthopedic surgeon.

For the wake-up test, propofol and remifentanil infusions were stopped. Patients were asked repeatedly to move their hands until they responded, and then to wiggle their feet. Thereafter, patients were verbally instructed to remember a color. After finishing the wake-up test, patients were reanesthetized and maintenance of anesthesia was continued as previously described.

Thirty minutes before the estimated end of surgery, 100 µg/kg morphine was administered IV. At the end of surgery, propofol and remifentanil infusions were discontinued, and patients were tracheally extubated when sufficient spontaneous breathing had returned and they responded to verbal commands. Thereafter, patients were transferred to the Pediatric Surgical Intensive Care.

The attending anesthesiologist was blinded to BIS and cAAI values throughout the study and estimated the level of consciousness using the UMSS (Table 1). UMSS level assessment started before induction until administration of rocuronium during induction, and was also performed during the wake-up test and emergence every 2 min.

The following events were specifically registered for further closed examination: 1) loss of consciousness (case milestone LOC), 2) start of the intraoperative wake-up test at stopping propofol and remifentanil (case milestone START), 3) purposeful patient movement to a verbal command during the wake-up test (case milestone MOVE), 4) patient reanesthetized after the wake-up test (case milestone REANES), 5) ROC during emergence (case milestone ROC). Furthermore, possible episodes of patient movement in response to tracheal intubation or surgical stimuli, indicating a low level of anesthesia, were specifically noted and linked to their corresponding BIS and cAAI values.

In addition to continuous BIS and cAAI monitoring, electrocardiogram, heart rate (HR), noninvasive and invasive mean arterial blood pressure (MAP), central venous pressure, end- tidal CO₂, oxygen saturation via pulse oximetry, and rectal temperature were continuously monitored, collected at 5-sec intervals using Rugloop (Demed, Temse, Belgium), and synchronized with Labgrab software (Demed).

Patients were interviewed by the principal investigator using a standard questionnaire based on the Brice-interview6 on three different occasions: on the first postoperative day, 1 wk, and 1 mo postoperatively. They were asked whether they remembered intraoperative events, the wake-up test, had any dreams and specifically whether they remembered pain or the color specified at the time of the wake-up test.

Statistics
All continuous data were tested for normality using the Kolgomorov-Smirnov method. For data sets that followed a normal distribution, parametric tests were used. For all other data sets, the appropriate nonparametric tests were applied. Data were analyzed using SPSS V12.0.1 (SPSS Inc., Chicago, IL) and MedCalc® V 9.3.1 (MedCalc Software, Mariakerke, Belgium). A P value smaller than 0.05 was considered statistically significant.

The ability of different indicators to describe the anesthetic drug effect was evaluated using P_K, which compares the performance of indicators having different units of measurements or different data types (i.e., continuous versus ordinal or categorical data). P_K was calculated using a custom spreadsheet macro P_K MACRO (written in Microsoft Excel; Microsoft Corp., Redmond), described and provided by Loveman et al.7 A P_K value of 1 means that the values of the predicting variable (e.g., BIS or cAAI) always correctly predicts the variable to be predicted (e.g., the UMSS). Alternatively, a P_K value of 0.5 means that the prediction is not better than chance alone; a P_K value below 0.5 indicates an inverse relationship. P_K values of paired measurements were calculated for all patients.

To assess the relation between BIS and cAAI versus UMSS, P_K data were analyzed for three study periods: (A) induction: the period from just before induction of anesthesia until administration of rocuronium; (B) the wake-up test: from the start of the wake-up test to reestablishment of anesthesia after finishing the wake-up test; and (C) emergence: from termination of surgery to final ROC. A Mann-Whitney test was used to evaluate whether P_K for BIS differed from cAAI. Repeated measure analysis of variance was used to compare BIS, cAAI, MAP, and HR at case milestones START, MOVE, and REANES.

We further investigated the performance of BIS and cAAI for discrimination between consciousness versus unconsciousness by computing values of cumulative occurrence.

According to recommendations by the manufacturer of the AEP monitor/2 and a study by Vereecke et al., we decided to analyze our cAAI data on a scale of 0–60 (all values above 60 are set to 60).2

RESULTS

Twenty patients were included in the study (male: female ratio = 3:17). The mean age was 15.6 ± 2.4 yr, and mean weight was 58.5 ± 12.8 kg.

The ability of BIS and cAAI to predict the UMSS score, as presented by the P_K values, is shown in Table 2. Three-hundred-twenty-five paired data were available for analysis at the different clinical states; cAAI was responsible for missing 26 data points, whereas 87 BIS points were missing. During induction, P_k values for BIS were significantly higher than for cAAI (P < 0.001) whereas, during the wake-up test and emergence, P_k values for cAAI were higher than for BIS. Awake BIS values varied between 32 and 98 (median 95), and awake cAAI values were between 14 and 60 (median 49). With increasing sedation (increase in UMSS score from level 0 to level 4), median BIS decreased significantly from 94 to 50 (P < 0.001), and median cAAI decreased significantly from 50 to 15 (P < 0.001) (Fig. 1). The transition from wakefulness to loss of consciousness occurred at a median BIS value of 46, and at a median value of 38 for cAAI.

View larger version (12K): [in this window] [in a new window]   Figure 1. Boxplot graphics (median and 25th and 75 percentiles [box top and bottom] and 5th and 95th percentiles [Whiskers]) and real data for (A) Bispectral Index (BIS), and (B) composite A-line ARX Index (cAAI), at different levels of the University of Michigan Sedation Scale (UMSS).

Anesthetic data are shown in Table 3, and BIS, cAAI, MAP, and HR during the wake-up test are displayed in Table 4. The cumulative occurrence curves for consciousness and unconsciousness are shown in Figure 2A for BIS and Figure 2B for cAAI.

View larger version (9K): [in this window] [in a new window]   Figure 2. Cumulative occurrence for consciousness and unconsciousness as a function of the University of Michigan Sedation Scale for the (A) Bispectral Index (BIS), and the (B) composite A-line ARX Index (cAAI).

During the three postoperative interviews, no explicit recall or intraoperative pain was reported. Even after having been given associations of the color, no patient could remember what color had been presented during the wake-up test. Although there was no attempt to test for implicit recall in this study, one patient who was instructed to remember the color yellow, dreamed of yellow bananas, smileys, and toys. Patients were unable to recall any other intraoperative events before or after the wake-up test.

DISCUSSION

This study was conducted to compare the performance of BIS and cAAI in distinguishing different hypnotic states and to evaluate the incidence of explicit recall in children and adolescents as a consequence of the mandatory intraoperative wake-up test during scoliosis surgery.

During induction, we found BIS to perform better than cAAI, as indicated by P_k values. During the wake-up test and emergence, P_k values for cAAI were statistically higher. In terms of clinical relevance, however, these differences do not seem to be meaningful. Both monitors were not found to be ideal, as considerable overlap in both BIS and cAAI values was present when compared with each level of the UMSS. Furthermore, the cumulative occurrence data in Figure 2A and B showed a remarkable overlap between "conscious" and "not conscious" data, which means that BIS and cAAI data within the commonly accepted target ranges for general anesthesia do not always indicate an unconscious patient. This also applies for the conscious patient, who may present with index values usually associated with deep levels of anesthesia. Our results correspond with findings previously reported in adults, indicating some overlap of both monitors during propofol anesthesia.8

Ironfield and Davidson compared BIS and cAAI during sevoflurane anesthesia in children aged 0 to 12 yr undergoing cardiac catherization.3 In their study, BIS appeared to be a better predictor of sevoflurane steady-state concentrations compared to cAAI. In the 2 to 12 yr group, the P_K for BIS (0.89) was significantly higher than the P_K for cAAI (0.53). When comparing our results with the data published by Ironfield and Davidson, P_K for BIS in both studies were comparable. However, P_k values for cAAI in our study are higher compared to the results of Ironfield and Davidson.

In our study, patients were capable of cognitive action during the wake-up test with mean BIS values of 70 ± 7 and mean cAAI values of 48 ± 15. Thus, our patients were fully awake with low mean BIS values, whereas mean cAAI values were within a typical range of wakefulness. Interestingly, no patient recalled the wake-up test or any other intraoperative event. A possible reason that explicit recall was absent in our study may be that the use of propofol has led to memory impairment, as previously described in adults.9,10 In contrast to our results, Nordstrom and Sandin showed that 35% of their adult study patients undergoing incontinence surgery under propofol anesthesia with an intraoperative wake-up test recalled awareness.11 Unfortunately no data on depth of anesthesia was provided. Therefore, we found it inappropriate to compare both studies. Glass et al.12 reported absence of recall at BIS values of 70 ± 18 whereas Liu et al.13 demonstrated that only 8% of shown pictures were recalled at BIS levels below 80. Our findings are consistent with the aforementioned studies with respect to the relationship between the BIS and the rate of explicit recall.

Another possible reason is that our patients underwent a rapid recovery during the wake-up test, rather than a long period of arousal. In addition, patients were in a deep anesthesia before and after the wake-up test.

Finally, negative stimuli are commonly better remembered than pleasant ones. (Intraoperative) pain, for example, secondary to hormonal responses affecting the amygdala, enhances the ability to remember events.14 Nociceptive stimuli during the procedure were depressed by intrathecal morphine, which made patients wake up comfortably without pain. As no patient reported any intraoperative pain, this may, in part, explain the absence of recall in our study.

Despite the absence of explicit recall in our study, the occurrence of unconscious implicit memory cannot be entirely precluded. Although there was no attempt to test for implicit recall in this study, one patient who was instructed to remember the color yellow, dreamed of yellow bananas, smileys, and toys. BIS, cAAI, and hemodynamic data of this patient did not differ from other patients. The importance and possible psychological consequences of this kind of implicit memory process during general anesthesia are, however, not known.

The absence of recall in our study contradicts to recent studies by McCann et al.15 and Ting et al.,16 who evaluated BIS and explicit recall for an intraoperative wake-up test. McCann et al. demonstrated explicit auditory recall in 18% of their patients. Ting et al. showed that desflurane anesthesia was not associated with recall, whereas anesthesia with fentanyl and nitrous oxide, led to a 25% rate of explicit auditory recall of the wake-up test. Interestingly, BIS levels at which patients responded during the wake-up test in our study (70 ± 7) were significantly lower than the corresponding mean BIS levels reported by McCann et al. (BIS >88) and Ting et al. (BIS >90). This may possibly be a consequence of the different anesthesia regimen in the studies.

The performance of wake-up tests requires an anesthetic regimen that provides fast recovery and fast return of cognition to allow immediate neurological evaluation. Therefore, total IV anesthesia with propofol and remifentanil is chosen as the standard anesthetic regimen in our institution to perform intraoperative wake-up tests during scoliosis surgery. It might be criticized that we used conventional infusion pump technology for administration of both propofol and remifentanil, though target-controlled infusion systems are increasingly becoming a standard. As surgical procedures, such as scoliosis repair, are commonly associated with significant blood loss and substantial changes in circulating volume, target-controlled infusion might not be a meaningful choice.

The wake-up onset time in our study is much longer than 9.4 ± 2.4 min reported by Grottke et al. in their propofol-remifentanil maintenance groups.17 The differences between our findings and these observations may have been due to intrathecal administration of morphine.

A shortcoming of our study is the lack of the ideal tool to assess our patients’ hypnotic states. We selected the UMSS because it provides good correlation with clinical reflection of the hypnotic component of anesthesia and has been validated in children.5 However, subjective clinical scoring systems, such as the UMSS, are only indicative for a specific time, and by their nature introduce potential error via individual implementation and interpretation. Furthermore, depending on the intensity of potentially distressing painful physical stimulation they are not necessarily only a measure of cortical activity, but also of spinal reflexes. Therefore, we cannot expect total agreement between the UMSS and BIS and cAAI scores.

In conclusion, when comparing BIS and cAAI with the level of consciousness as defined by the UMSS, we found BIS to perform significantly better than cAAI during induction, whereas during the wake-up test and emergence both indices performed equally. BIS and cAAI values increased significantly during the wake-up test, indicating a higher level of consciousness, however, no explicit recall was demonstrated. Care has to be taken not to extrapolate our results, which are probably specific for propofol - remifentanil anesthesia in adolescents, to other anesthesia regimens or younger children.

Footnotes

Accepted for publication June 18, 2008.

Supported by Departmental funding. Rugloop software was provided by Aspect Medical Systems (Newton, MA), Labgrab software and AEP electrodes were provided by Danmeter A/S (Odense, Denmark). Aspect Medical Systems and Danmeter A/S were not involved in the design, conduct or analysis of this study.

All authors have participated in the work to the extent that each of them could defend its contents and have read the manuscript before its submission for publication, and are prepared to sign a statement to the effect that he has read the manuscript and agrees with its publication.

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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 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 Blussé van Oud-Alblas, H. J. Articles by Weber, F. Search for Related Content PubMed PubMed Citation Articles by Blussé van Oud-Alblas, H. J. Articles by Weber, F. Related Collections Neuroanesthesia Anesthetic Techniques Monitoring (Non-cardiac) Clinical Pharmacology Pediatrics Technology Pharmacology