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Anesth Analg 2007;104:1481-1487
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000261516.45687.ee


NEUROSURGICAL ANESTHESIA

Section Editor:
Adrian W. Gelb

Bispectral Index Monitoring Does Not Improve Anesthesia Performance in Patients with Movement Disorders Undergoing Deep Brain Stimulating Electrode Implantation

Uwe Schulz, MD*, Didier Keh, MD{dagger}, Christoph Barner, MD{dagger}, Udo Kaisers, MD{ddagger}, and Willehad Boemke, MD{dagger}

From the *Department of Critical Care, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; {dagger}Department of Anesthesiology and Surgical Intensive Care Medicine, Charité—Universitaetsmedizin Berlin, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany; and {ddagger}Department of Anesthesiology and Intensive Care Medicine, Universitaet Leipzig, Leipzig, Germany.

Address correspondence and reprint requests to Willehad Boemke, MD, Klinik für Anästhesiologie und Operative Intensivmedizin, Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. Address e-mail to willehad.boemke{at}charite.de.


    Abstract
 Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
BACKGROUND: Deep brain stimulation (DBS) has emerged as a promising therapy for movement disorders. During the implantation procedure for the electrodes, the patient emerges from anesthesia repeatedly to facilitate neurological testing. We investigated whether Bispectral Index (BIS TM) monitoring would be beneficial in patients receiving "sleep-awake-sleep" anesthesia with respect to time of arousal, consumption of propofol, and cardiopulmonary stability (i.e., heart rate, arterial blood pressure, and end-tidal carbon dioxide).

METHODS: We investigated 21 patients scheduled for implantation of DBS electrodes. Depth of propofol anesthesia was controlled either with BIS guidance in 10 patients (BIS group) or without in 11 patients (non-BIS group). In the BIS group, a BIS score of 40–60 was targeted during sleep periods, whereas in the non-BIS group, a value of 1 (= no response to tactile stimulation [unconsciousness]) on the Observers’ Assessment of Alertness/Sedation Scale was targeted. For analgesia, the sites for the burr holes and for the pins of the stereotactic ring were infiltrated with 2% lidocaine; no opioids were used. For periods during which an awake patient required neurological testing, propofol was discontinued.

RESULTS: We found no difference between groups with respect to times of arousal, total amount of propofol consumption, and cardiopulmonary stability. However, significantly more propofol boluses had to be administered in the BIS group (30 ± 11.6 vs 17 ± 4.6) to maintain the BIS score within the target range (P < 0.05).

CONCLUSION: BIS monitoring does not improve anesthesia management for DBS electrode implantation in patients with movement disorders.


    Introduction
 Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Deep brain stimulation (DBS) is a well-recognized option in the therapy for patients with movement disorders (e.g., Parkinson’s disease, dystonia, essential tremor) (1,2). Herzog et al. (3) found a 50.9% reduction in the Unified Parkinson’s Disease Rating Scale compared with baseline after implantation of DBS electrodes, and Meissner et al. (4) reported a profound reduction in treatment costs for Parkinson’s disease from the second year on after implantation of DBS electrodes. These promising results and possible further indications for DBS, such as phantom limb pain, obsessive compulsive disorder, poststroke neuropathic pain, persistent vegetative state, and depression (5–9), may soon lead to more widespread use of DBS electrodes.

For patients with movement disorders, electrodes are usually implanted bilaterally into the subthalamic nucleus, internal segment of the globus pallidus, or thalamic nucleus ventralis intermedius. During the procedure, the patient is aroused from anesthesia at least twice, depending on the number of electrodes placed, to allow for neurological testing and confirmation of the position of the electrodes. The patient has to be fully alert and cooperative at these times.

During the sleep periods, the patient is at risk of hemodynamic and respiratory instability if anesthesia is too deep, whereas the surgical result is at risk when anesthesia is not deep enough. The Bispectral Index (BIS TM) monitor (Aspect medical Systems, Naptick, MA) has been shown to be a useful tool for measuring depth of anesthesia in nonneurosurgical procedures. The purpose of this study was to investigate whether BIS is helpful in titrating depth of anesthesia in patients with movement disorders undergoing stereotactic implantation of electrodes for DBS and whether it thereby improves hemodynamic and respiratory stability and shortens arousal time.


    METHODS
 Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
This prospective study was approved by the institutional ethics committee and written informed consent was obtained from every participant of the study. Included were all patients with movement disorders who were scheduled for electrode implantation in the time from December 2002 to April 2003 and from November 2003 to April 2004. Exclusion criteria were age <18 yr, ASA more than III, inability to communicate with the investigator in German language, and patient refusal to participate.

For the sleep periods, patients received anesthesia controlled either by BIS monitoring (A 2000 monitor; version XP software) (BIS group) or by clinical assessment performed by the neuroanesthesiologist in charge (non-BIS group). When controlled by the anesthesiologist’s assessment, a value of 1 (= no response to tactile stimulation [unconsciousness]) on the Observers’ Assessment of Alertness/Sedation Scale (OAA/S) was targeted. This scale was chosen because it demonstrated a good correlation with clinical evaluation of anesthesia or sedation (10). OAA/S was repeated every 5–6 min throughout the operation. When anesthesia was controlled by BIS, a value between 40 and 60 was targeted. This range is recommended for general anesthesia (11). According to the findings of Glass et al., an OAA/S score of 1–2 correlates with a BIS of 40–60 in healthy volunteers (12). To avoid "learning contamination bias" (13), we first investigated 11 patients anesthetized according to OAA/S assessment (non-BIS group). Thereafter, 10 patients underwent BIS-guided anesthesia (BIS group). BIS values were recorded in both groups, but for the non-BIS group, the anesthesiologist in charge was blinded to these values.

On the day before surgery, all patients were assessed by the anesthesiologist in charge and informed about anesthetic management. On the evening before surgery, 300 mg ranitidine (H2-receptor antagonist) was given orally, and on the morning of surgery, 150 mg ranitidine was given orally. Preoperative sedation was avoided to minimize respiratory impairment.

On arrival at the operating room, electrocardiogram, noninvasive arterial blood pressure and pulse oximetry were monitored. Thereafter, an arterial catheter (Leader-Cath; Vygon; Aachen, Germany) was placed in the radial artery under local anesthesia with 1% lidocaine. This catheter served for blood sampling (blood gas analysis) and invasive arterial blood pressure measurement. Finally, BIS electrodes were placed on the patient’s forehead according to the manufacturer’s recommendations. We used XP-electrodes which allow measurement of electromyogram (EMG)-activity (in dB) of the periorbital muscle, unlike previous versions. The smoothing time period was set at 30 s.

Before anesthetic induction all patients received 8 mg ondansetron IV and 8 mg dexamethason IV as prophylaxis for perioperative nausea and vomiting. The patients were breathing spontaneously during the entire procedure. The airway was secured using a Magill tube, introduced transnasally, with its tip positioned under direct vision just above the glottis, using a common laryngoscope and Magill’s forceps. Thus, the patient can speak without having to remove the tube during the awake periods, whereas in emergency situations, fiberoptic laryngeal intubation can be performed reliably and quickly with the tube in this position. Ideally, the inner diameter of the tube should be >6.5 mm. Before nasal intubation, lidocaine spray (10%) was administered for topical anesthesia of the nasopharynx, and naphazoline was dripped into both nostrils to reduce swelling of the nasal mucosa before insertion of the tube. Thereafter, the tube was connected to a Cato TM anesthesia circuit (Dräger GmbH, Lübeck, Germany). A proper end-tidal (ET)co2-Signal confirmed correct position of the tube, and additional oxygen could be administered if required (a Spo2 >95% was targeted).

Before tube insertion, anesthesia was induced by propofol boluses (0.5 mg/kg body weight [BW]) (Fig. 1, Table 1). These boluses were repeated every 30 s until the desired level of either OAA/S or BIS was achieved. In the BIS group, further propofol was given if the BIS level of 40–60 was not yet reached, even if the investigator clinically judged the patient to be asleep. To maintain anesthesia, continuous propofol infusion (70–130 µg · kg bw–1 · min–1) was given. The propofol infusion rate required regular adjustments and propofol boluses (0.5 mg/kg BW) had to be given to maintain anesthesia at the appropriate level during various stimuli, such as placement of the tube, fixation of the stereotactic ring, skin incision, noise during magnetic resonance imaging (MRI) and burr hole drilling (Fig. 3). Analgesia was achieved by infiltrating the area of skin incision for the burr holes and the position of the pin holders for the stereotactic ring with 2% lidocaine. Repetitive lidocaine infiltration was usually not required. No opioids were given. For postoperative pain, patients received 3 mg piritramide IV on demand (according to the institutional protocol for postoperative pain treatment). Because of long periods of motionless positioning on the operating table, some patients complained of musculosceletal pain. This pain is ideally controlled by a peripheral analgesic (we used metamizole 2 g IV). Because of the extended motionless supine position, patients are also at risk of developing pulmonary atelectasis; respiratory therapy is therefore recommended in the postoperative period.


Figure 129
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Figure 1. Time course of the procedure and study end-points. Exemplary data of one patient. Thin vertical lines indicate study end-points. Thick horizontal lines indicate different phases of the procedure. 1 = Induction, including connection to monitor, intubation, insertion of arterial line and Foley catheter. 2 = surgical preparation including hair cut and fixation of stereotactic ring. 3 = magnetic resonance imaging. 4 = calculation of entry and target coordinates. 5 = burr holes for ventriculography and first electrode. 6 = Testing of first electrode. 7 = Burr hole for second electrode. 8 = Testing of second electrode. 9 = Skin closure, band aid, and transport to intensive care unit.

 

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Table 1. Definition of Time Points (See Figs. 1–3)

 

Figure 329
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Figure 3. Effect site concentration assessed post hoc after Bruhn and Boullion (18).

 

After placing the stereotactic ring on the patients’ heads, the sleeping patients were transferred to the MRI and thereafter brought back to the operating room, where the burr hole for placement of the ventriculography cannula was drilled. After calculation of entry and target coordinates from the MRI and ventriculography images, the burr hole for the first electrode was drilled, the first electrode placed and propofol infusion stopped to allow for neurological testing. The propofol infusion was restarted after both the neurologist and surgeon were satisfied with the result. The infusion was stopped a second time upon placement of the contralateral electrode to continue neurological testing. The patient was reanesthetized a final time to facilitate skin closure. To avoid a decrease of body temperature the patients were wrapped in blankets. For postoperative care, the patients were transferred to our neurosurgical intensive care unit overnight. For a detailed description of the sleep-awake-sleep technique used in our institution, we refer to Schulz et al. (14).

During the procedure, arterial blood pressure, heart rate, ETco2, oxygen saturation, and BIS values (including raw electroencephalogram [EEG] and EMG) were collected on a personal computer using the Dataplore® software (DATAN GmbH, Teltow, Germany). In addition, samples for blood gas analysis were taken (ABL 505; Radiometer, Copenhagen, Denmark).

The primary end points were total amount of propofol infused, amount of propofol used for anesthetic induction, and time from the discontinuation of propofol infusion until the patient could squeeze the investigator’s hand repeatedly on command (arousal time).

Arterial blood pressure, heart rate, and BIS scores are presented for specific time points during the course of the procedure: at the times of induction and arousal, and at the three occasions when the scalp was infiltrated with lidocaine before skin incisions for the three burr holes (Table 1). For each time point, three values are reported: a baseline value (120 s before the respective intervention), the value at onset of the respective intervention, and finally, the value 30 s after the intervention (Table 1).

The CO2-tension in arterial blood (Paco2) was measured three to five times during the course of the operation with the patient being asleep and was used together with simultaneously recorded ETco2 values to determine the individual Paco2-ETco2 gradient. The difference between Paco2 and ETco2 of any patient was added to the continuous ETco2 readings (using Dataplore TM) to assess Paco2. A Paco2 >59 mm Hg was considered significant hypercapnia. It is notable that a reliable ETco2-signal can be achieved only with the patient being sleep.

For numeric data with a normal distribution, Student’s t-test was used. For analyzing data collected over time, analysis of variance and post hoct-testing with Bonferroni’s correction were used. Categorical data were analyzed using the {chi}2 test. P < 0.05 was considered statistically significant (NCSS 2001 TM, Kaysville, UT). Values are reported as means ± sd.


    RESULTS
 Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Twenty-three patients were investigated; however, two patients from the non-BIS group were not included in the analysis because of complete or partial loss of data. Eleven patients were evaluated in the non-BIS group and 10 patients in the BIS group. There were no demographic differences between the two groups (Table 2). The mean duration of the procedure was 14.6 ± 1.3 h in the BIS group and 13.0 ± 1.9 h in the non-BIS group (P = 0.04; Table 3). The mean duration of propofol infusion was similar in both groups: 9.4 ± 1.3 h in the BIS group and 9.3 ± 1.1 h in the non-BIS group (P = 0.88; Table 3). There was no difference in total propofol consumption between the BIS and non-BIS groups. Mean infusion rates between groups did not differ, but larger amounts of propofol were needed for induction after the awake periods in the BIS group (P = 0.004) (Table 3). Additionally, almost twice as many bolus injections of propofol were necessary intraoperatively in the BIS group when compared with that in the non-BIS group (P = 0.0001) (Table 3).


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Table 2. Patients Characteristics

 

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Table 3. Rates of Propofol Infusion

 

No difference between groups was found for times of arousal (Table 4). One patient had to be excluded from this calculation because of his inability to squeeze the investigator’s hand. This patient suffered from akinetic crisis after preoperative discontinuation of medication for Parkinson’s disease. Even the day after the procedure, he was not able to obey commands.


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Table 4. Time of Arousal

 

Three to five blood gas analyses were taken from each patient. Hypercapnic episodes, i.e., periods with assessed Paco2 values more than 59 mm Hg, were of similar duration in both groups (on average 4.0 ± 8.9 min in the BIS group vs 8.4 ± 2.2 min in the non-BIS group [P = 0.49]). Mean pH was 7.36 ± 0.02 in the BIS and 7.36 ± 0.03 in the non-BIS group (P = 0.38). The mean PAo2/Fio2 ratio was 354 ± 67.9 in the BIS and 368 ± 57.7 in the non-BIS group (P = 0.30). Hemodynamic data did not differ between groups (Fig. 2).


Figure 229
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Figure 2. Heart rate and arterial blood pressure in the course of implantation of deep brain stimulating electrodes. For definition of the time points depicted see Table 1.

 


    DISCUSSION
 Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
This study evaluated whether BIS monitoring would reduce propofol consumption, shorten arousal times, and improve hemodynamic stability in patients undergoing sleep-awake-sleep anesthesia for deep brain electrode implantation. There were no cases of hemodynamic instability in either group under our anesthesia regimen. However, in this group of patients with movement disorders, we were unable to replicate previous findings in nonneurosurgical patients that lower doses of anesthetics and shorter arousal times can be achieved when BIS monitoring is used (Table 3) (15). In fact, we found increased propofol demands, especially at induction of the second and third sleep period when BIS monitoring was used. This reflected our observations that OAA/S scores of 1 were often achieved with significantly smaller doses of propofol than those required to acquire BIS values of 40–60. BIS does not seem to correlate well with clinical assessment of patients with movement disorders, and the effect is most pronounced during anesthetic induction. Moreover, in some patients, we even found a slight increase in BIS readings during induction.

To maintain BIS values between 40–60 in the BIS protocol, the infusion rate had to be changed repeatedly and propofol boluses administered. Overall, BIS guidance did not reduce the mean propofol infusion rate (Table 3) and arousal times were not shorter under BIS guidance in our patients (Table 4). Consequently, even before considering the additional cost of the BIS device, there were no cost benefits.

On reviewing the literature, we found that patients undergoing neurosurgical procedures or suffering from neurological diseases were frequently excluded from validation studies of the BIS monitoring device. It is argued that the EEG may be altered under these circumstances and hence produce invalid BIS readings (16). Pemberton and Dinsmore (17) studied patients undergoing tumor or epilepsy surgery using a sleep-awake-sleep anesthesia technique similar to ours. In their patients, they also found a poor correlation between BIS values and the observer’s assessment of anesthesia level, suggesting that BIS is not a reliable tool for patients with brain abnormalities.

The results in our patients with movement disorders do not provide us with sufficient information to define a BIS range that first clearly discriminates between sleep and awake and second is applicable to all stages of the procedure. At induction of the second and third sleep periods (i.e., after placement of the first and second deep brain electrode), we observed BIS values >95 (i.e., values which are usually found in patients who are fully awake) at the clinical time point of loss of consciousness (Fig. 2) (11).

The acquisition of BIS values in a range indicating surgical tolerance (40–60) was associated with considerable delay (>30 s) when compared with that using OAA/S-based clinical assessment by the anesthesiologist in charge. This may have been due to the smoothing time period of the BIS device which was set at 30 s. However, the decrease in BIS values often occurred parallel with a decrease in EMG activity. Patients with movement disorders often have more EMG activity than those without movement disorders. The average EMG activity 10 min before the first induction was 55.1 dB in this group of patients compared with 46.3 dB in 10 patients scheduled for abdominal surgery in this department (historical data, unpublished). High EMG activity can significantly influence BIS values because the EMG frequencies overlap the BIS algorithm’s Beta Ratio in the 30–47 Hz range (16), and may therefore cause falsely high BIS readings in patients with movement disorders. An alternative, though unlikely, explanation is that we may not have judged the patients’ level of consciousness correctly atthe second and third inductions. On these occasions, the patient’s head is, unlike the first induction, fixed in the stereotactic ring which makes it more difficult to judge loss of consciousness as accurately.

There was no difference in the calculated effect site concentrations between the OAA/S and BIS-guided groups throughout the procedure (Fig. 3), indicating that depth of anesthesia was quite similar in both groups [effect site concentrations were assessed post hoc using the excel table introduced by Bruhn and Boullion (18)].

To define the influence of moderately painful stimuli on BIS, the effect of scalp infiltration for the three burr holes during the course of the procedure was recorded (local anesthetic 1, 2, and 3 in Fig. 2). We could not detect any change in BIS, heart rate, or arterial blood pressure at infiltration of local anesthesia for the burr holes, indicating that the patients seemed to be well protected against moderately painful stimuli when propofol anesthesia was used. Against more painful stimuli, when the patient is protected through the properties of the local anesthetic, no IV opioids were necessary.

In summary, in patients with movement disorders undergoing sleep-awake-sleep anesthesia for deep brain electrode implantation, BIS monitoring does not reduce propofol consumption during anesthesia, nor does the patient arouse faster for the test periods. In addition, there may be interference between EMG signals and EEG signals that make BIS values unreliable in this patient group. We noted this especially during the induction periods. Therefore, BIS monitoring does not further improve the anesthesiologist’s management of these patients. An exception to this rule may be a patient experiencing an akinetic crisis. In our study, we saw one patient who was akinetic and did not squeeze the investigator’s hand on command, even 1 h after propofol infusion was stopped. It is noteworthy that patients experiencing an akinetic crisis are awake and are aware of their environment but are unable to communicate or move. Sometimes they appear to be asleep. Under these circumstances, continuous BIS values between 90–100 in a patient who does not move or respond to questions could be a readily available and valuable tool for differential diagnosis.


    Footnotes
 
Accepted for publication February 13, 2007.


    REFERENCES
 Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2007 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press