Technology, Computing, and Simulation: Research Report
The bispectral index (BIS) is a processed electroencephalographic (EEG) monitoring modality that has been validated as a quantifiable measure of the hypnotic effect of anesthetic drugs (1).
We have noted a marked decrease in the BIS number and the 95% spectral edge frequency (SEF95) in association with the appearance of large δ waves on the EEG during abdominal surgery when the peritoneal cavity was irrigated with normal saline. These EEG patterns have been termed a “paradoxical arousal” (PA). It is thought that PA can be provoked by strong, noxious stimuli (2–4). Other investigators have noted decreases in SEF or BIS during PA (3,4). These changes can be attenuated by a bolus of narcotics (3) or epidural anesthesia (4). We hypothesized that distention of the peritoneal cavity during intraabdominal irrigation might cause a paradoxical arousal response and a decrease in BIS. Therefore, in the present study, we sought to evaluate the changes in the BIS number and study the effect of fentanyl on the changes of BIS during intraabdominal irrigation in patients anesthetized with nitrous oxide and sevoflurane.
The study protocol was approved by our IRB and informed consent was obtained from all patients. Eighteen ASA physical status I–II patients scheduled for elective abdominal surgery were enrolled in the study and randomly allocated to one of two groups: a control group (group C) or the fentanyl pretreatment group (group F). Group F patients received IV fentanyl (1.5 μg/kg) before intraabdominal irrigation. Patients with neurologic or psychiatric disorders were not included in this study.
All patients received 0.5 mg of atropine by IM injection approximately 30 min before the start of anesthesia. Anesthesia was induced with 3 mg/kg of thiopental and 5% sevoflurane. After tracheal intubation, anesthesia was maintained with sevoflurane and nitrous oxide in 50% oxygen. Sevoflurane concentrations were adjusted to maintain the BIS value between 40 and 60. Vecuronium was given as required. Mechanical ventilation was adjusted to maintain an end-tidal carbon dioxide partial pressure of 35–40 mm Hg. Noninvasive mean arterial blood pressure (MAP), heart rate (HR), and pulse oximetry (Spo2) were monitored continuously and maintained within normal range (MAP >60 mm Hg, 50< HR <100, Spo2>95%). To maintain the MAP at more than 60 mm Hg, 100 μg boluses of phenylephrine were administered. The bladder temperature was monitored and was maintained at 36.0°C–36.5°C using a water blanket (Medi-Therm II; Gaymer, New York, NY). The expired concentration of anesthetics was monitored using Capnomac Ultima (Datex, Helsinki, Finland).
The electrodes for the BIS monitor (Aspect Medical Systems, Natick, MA) were applied to the forehead regions before the induction of anesthesia. The EEG was monitored continuously by using an Aspect A-1050 monitor (BIS version 3.4; Aspect Medical Systems). The raw EEG signal was transferred from the Aspect monitor to a personal computer with Microsoft Windows ME. Then BIS, SEF95, burst suppression ratio (BSR), and signal quality index (SQI) were recorded at 1-min intervals using custom software (5).
Near the conclusion of the case, and approximately 3 min before the start of intraabdominal irrigation, group F received an IV injection of 1.5 μg/kg fentanyl; group C did not. Intraabdominal irrigation was performed using 2000–3000 mL of warm (35°C) normal saline before closure of the abdominal wall. BIS, SEF95, BSR, MAP and HR were recorded just before abdominal irrigation, 2 min after the start of irrigation, at the end of irrigation, and 10 min after the end of abdominal irrigation. BIS values reported by the A-1050 monitor represent an average value derived from the previous 60 s of data (6). To consider this time lag, we recorded the values at 2 min after the start of irrigation.
BIS, SEF95, and BSR values were analyzed by Friedman’s test followed by the Scheffe’s test for intragroup comparisons. MAP and HR were analyzed by one-way analysis of variance. Intergroup comparisons were performed by the Mann-Whitney U-test for BIS, SEF95, and BSR. For other data, unpaired Student’s t-test or χ2 test were performed when appropriate. P values <0.05 were considered significant. BIS, SEF95, and BSR are expressed as medians, whereas the other data are expressed as means ± sd.
Table 1 shows the demographic data. There were no significant differences between the groups. In the recorded EEG data, no electromyographic (EMG) artifact was observed in any of the measurements. Furthermore, all patients provided reliable EEG derivatives with SQI >0.8.
Table 2 shows changes in MAP and HR during the study. MAP and HR did not change significantly over time during the measurement period in either of the groups. There were also no significant differences between the two groups.
Table 3 shows the changes in BIS and SEF95 during the study. BIS and SEF95 values decreased significantly from 42 and 14.2 (preirrigation) to 32 and 8.4 (2 min after start of irrigation). The BIS and SEF95 at 2 min after start of irrigation in group C patients were significantly lower than those in group F. In group F, BIS and SEF95 did not change significantly during irrigation. Figure 1 shows the changes in BIS in individual patients in groups C and F. BIS decreased (ΔBIS >5) during abdominal irrigation in all patients in group C (Fig. 1A), whereas BIS decreased in three patients but did not decrease in six patients in group F (Fig. 1B). BSR values were almost 0 during the measurement period in either group.
Representative EEG patterns in a patient in group C are shown in Figure 2. After intraabdominal irrigation, the EEG pattern changed from waves with a dominant frequency of approximately 10 Hz to one with large δ waves and BIS decreased from 42 to 25. Eight patients in group F showed almost no change or a mixed pattern with fast wave and δ wave activity. One patient in group F whose BIS decreased more than 10 during irrigation also showed large δ waves similar to those seen in group C.
All patients were interviewed on the first postoperative day and none exhibited intraoperative recall.
In the present study, BIS and SEF95 decreased during intraabdominal irrigation in patients anesthetized with nitrous oxide-sevoflurane. Pretreatment with a small dose of fentanyl before intraabdominal irrigation prevented the decrease in BIS and SEF95.
A variety of factors have been reported to show spurious BIS numbers, including deepening of anesthesia, hypothermia, cerebral hypoperfusion (7), and artifact to the EEG signal (8,9). In the present study, end-tidal sevoflurane concentration was maintained constant during the study. Body temperature, MAP, and HR were also maintained within normal ranges. The common causes of spurious BIS values are electrical artifact (8) and EMG activity (9). However, in this study, a neuromuscular relaxant was used and contamination with EMG activity was minimized. Furthermore, in most cases, noise or EMG contamination would result in an increase in the BIS value. Although almost all erroneous BIS values are high, one condition that will cause a sudden decrease has been referred to as a PA response (2). This response can be provoked by a strong noxious stimulus in the presence of inadequate anesthesia/analgesia.
Kiyama and Takeda (4) reported that in patients anesthetized with 1.0% isoflurane and 66% nitrous oxide there was a significant decrease in the SEF90 after surgical incision whereas no decrease was observed when the patients received epidural anesthesia in addition to nitrous oxide-isoflurane. Kochs et al. (10) have reported that, during 1.2% isoflurane with 66% nitrous oxide anesthesia, noxious stimuli provoked a decrease in α EEG activity in 53% of the patients and increased δ activity in 44% of patients. Hagihira et al. (3) also reported that during 1.0% isoflurane or 1.5% sevoflurane with air, BIS and SEF95 showed individual variability after incision. High amplitude δ wave activity was the predominant EEG pattern when the BIS number decreased in association with surgical stimulation. These results suggest that PA can be observed when intense noxious stimuli occur in the presence of moderate levels of anesthesia. In our study, anesthesia was produced using sevoflurane with an end-tidal concentration of 1.2–1.3%. Avramov et al. (11) reported the appearance of δ waves in the EEG when the surgeons placed traction on the intestine during nitrous oxide and halothane anesthesia. This manipulation is common during intraabdominal irrigation. When the peritoneum is distended for intraabdominal irrigation, this sudden noxious event may be a sufficient stimulus to induce PA.
Previous reports indicate that, in anesthetized patients, sensory stimulation typically increases the dominant EEG frequency (12). The physiological basis of the appearance of δ waves during PA response is unclear. Animal studies indicate that the activation of reticular formation of the brainstem may have a close relation to slow EEG activity (13). As nitrous oxide is a stimulator to reticular neurons (14), use of nitrous oxide in this study might have promoted the induction of δ wave.
Pretreatment with 1.5 μg/kg of fentanyl prevented the decrease in BIS and SEF95 in this study. Administration of fentanyl (3) or epidural anesthesia (4) has been shown to suppress PA. Hagihira et al. (3) reported that 3 μg/kg of fentanyl given 5 minutes before skin incision similarly suppressed the changes of BIS and SEF95 during isoflurane or sevoflurane anesthesia for elective abdominal surgery. In our study, we used 50% nitrous oxide with sevoflurane. The dose of fentanyl used in our study was smaller than that used by Hagihira et al. (3). In the present study, BIS decreased in three of nine patients in group F. The one patient in whom BIS decreased to less than 20 in group F was a 41-year-old male who was the youngest patient in the study. As there was wide individual variation in sensitivity to narcotics, more fentanyl might have been needed, especially for the young patients, to prevent PA.
During PA, δ waves were dominant in the EEG. The decrease in SEF95 in this situation is well understood; however, the reason for the decrease in BIS is unclear because the algorithm used to calculate the BIS number remains proprietary. Usually, low BIS values are accompanied by an increase in BSR that is the percentage of the suppression period during the time of analysis. Koitabashi (15) reported that BSR >40% was inversely correlated with BIS values in the range of 30 to 0. However, BSR did not increase during PA in the present study. We have previously evaluated the relationship between BIS and other EEG parameters (16). In that study, changes in BIS correlated well with the SEF95 and a low SEF without increase in BSR also corresponded to a BIS <30. Therefore, in the situation of a δ wave-dominant EEG, there should be a decrease in the BIS number.
By topographic EEG analysis, the increase in δ wave activity induced by surgical stimulation during abdominal surgery has been reported to be dominant at the frontal areas of brain (10). Because the sensor of the BIS monitor is usually applied to the frontal areas, this might indicate that the BIS monitor is sensitive to EEG changes during PA.
Anesthesiologists should be aware of the PA response during abdominal surgery. If the anesthesiologist were to decrease the anesthetic concentration when BIS decreases, there would be an increased chance of intraoperative awareness. Our data suggest that adequate analgesia corresponding to the surgical procedure is required to assess anesthetic depth correctly by EEG monitoring during abdominal surgery.
The authors thank Dr. Mark H. Zornow, MD (Department of Anesthesiology, OR Health and Science University), for his help in editing the manuscript.
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© 2005 International Anesthesia Research Society
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