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Anesth Analg 2008; 107:545-548 © 2008 International Anesthesia Research Society doi: 10.1213/ane.0b013e318174deed
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Abstract |
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 Top Abstract IntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
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BACKGROUND: The click sounds of auditory evoked potentials (AEP) might have some effect on electroencephalogram indices and Bispectral Index (BIS) but many studies, unconcerned about this effect, have measured both indices simultaneously. In this study, I examined the effects, of AEP click sounds on the BIS, and also on the response entropy (RE) and state entropy (SE) of the entropy monitor.
METHODS: Forty patients aged 40–70 yr and scheduled for surgery of lower extremities under spinal anesthesia were anesthetized with 0.5% bupivacaine or tetracaine. Patients were sedated with midazolam 1 mg followed by propofol infusion started at 1 mg · kg–1 · h–1. Propofol infusion was controlled to keep BIS or SE at 80, 60, or 40 for several minutes, and then click sounds (65 dB) of the AEP were given for 60 s. The changes in BIS, RE, and SE were observed continuously for 60 s after the click sounds had stopped.
RESULTS: BIS, SE, and RE significantly increased during the click sounds. The longest duration of increase was at BIS or SE 60.
CONCLUSION: AEP monitor click sounds transiently increased the simultaneously measured BIS, RE, and SE during different levels of sedation by propofol infusion during spinal anesthesia. Therefore, the effects of the click sounds should be considered when these monitors are used simultaneously in the same patient.
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Introduction |
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TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
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Many electroencephalographic (EEG) monitors are used to infer hypnotic level during anesthesia. Variables, such as the Bispectral Index (BIS), spectral edge frequency, response entropy (RE), state entropy (SE), etc., are extracted from the cortical EEG, whereas the auditory evoked potentials (AEP) are measured from the EEG changes in response to auditory stimuli. Many studies have compared the BIS and AEP using the BIS and AEP monitors together in the same patient.1–4 However, if the BIS responds to stimuli such as intubation,5 laryngeal mask airway insertion,6 or skin incision,7 as reported, the click sounds of the AEP might also have some effects on the BIS. Other studies have evaluated the AEP and other EEG monitors by placing them on different patients and comparing the measured values.8–12 A relatively new EEG monitor of entropy calculates RE and SE, and is also reported to respond to electrical stimuli.13 The click sounds may therefore affect the entropy measurements, but there are no studies of the influence of auditory stimuli used for AEP monitoring on simultaneous entropy measurements. Clinically, there is little motivation to use two EEG monitors on the same patient, but for the purpose of comparing two monitoring devices it is better to compare the monitors on the same patient. However, if the AEP click sounds influence the other EEG monitors, monitors cannot be compared simultaneously. The purpose of the present study was to investigate the effects of the AEP click sounds on both BIS and entropy monitors. We used A-Line AEP (version 1.4, Alaris Medical Systems, Hampshire, UK, now distributed by Danmeter, Odense, Denmark), BIS (version 3.4, A-2000, Aspect Medical Systems, Newton, MA), and Entropy (S/5, GE Healthcare, Helsinki, Finland) monitors. The moving average windows used to calculate the entropy values are 2–15 s for the RE and 15–60 s for the SE, compared with a fixed 15 s for the BIS. The manufacturer’s recommended BIS range for general anesthesia is between 40 and 60, and it is the same for SE and RE. BIS uses a 100-point index, where 100 indicates awake and 0 indicates flat EEG, the SE uses the range 0–91, and RE 0–100. The frequency ranges used are 0.8–32 Hz for SE and 0.8–47 for RE.14
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METHODS |
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TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
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After approval of the ethics committee of the hospital and informed consent from patients, 40 patients aged 40–70 yr and scheduled for surgery of the lower extremities under spinal anesthesia were randomly divided into two groups. The BIS group was monitored using BIS and AEP monitors, whereas the entropy group was monitored with AEP and the entropy monitor. Patients with neurological disorders, hearing disturbance, liver or renal disease, mental impairment, or taking any drugs before surgery affecting cerebral function, such as hypnotics, antidepressants, etc., were excluded.
Midazolam 2–5 mg and atropine 0.2–0.5 mg were intramuscularly administered as routine premedication 15 min before entering the operating room. Spinal anesthesia was performed with patients in the lateral position with 0.5% plain or hyperbaric bupivacaine, or 0.5% hyperbaric tetracaine at the L4–5 interspace, after which patients were immediately returned to the supine position. Anesthesia level was checked by a cold test 5 min after spinal anesthesia to confirm that the level was adequate for surgery.
After the skin was prepared with alcohol and the AEP headphone was attached, the electrodes of the A-Line AEP and BIS or entropy were positioned as recommended by the manufacturers. Electrode impedances were considered acceptable if they were below 5, 7.5, and 10 kOhm for AEP, entropy and BIS, respectively. Continuous monitoring of EEG was started after checking the anesthesia level. A mean value of 10 s before sedation, arbitrarily selected, was taken as the control value of the BIS, RE, and SE.
Patients were sedated after the start of surgery with midazolam 1 mg followed by propofol infusion, which was started at 1 mg · kg–1 · h–1. Oxygen 6 L/min was administered by a mask. Propofol infusion was controlled to keep BIS or SE at 80 for several minutes then AEP click sounds (65 dB) were given for 60 s. The BIS or entropy (SE and RE) was monitored for another 60 s after stopping the click sounds. Several minutes later, the propofol infusion dose was increased to keep BIS or SE at 60 for several minutes to repeat the study with the click sounds. Finally, BIS or SE was kept at 40 for several minutes for the same measurements. The EEG value at time 0 was defined as the mean value for 10 s just before giving the click sounds. The value at each time point was the single value exactly at each time. The electromyographic bar of each monitor was also checked. Blood pressure, electrocardiogram, and percutaneous oxygen saturation were monitored as usual.
Statistical analysis was performed with the 
2 test and Student’s t-test for demographic data. The changes in BIS, SE, RE, blood pressure, heart rate, and propofol infusion dose were analyzed with repeated measures analysis of variance followed by Student–Newman–Keuls test as a post hoc analysis. The differences in propofol infusion dose between the groups were compared with factorial analysis of variance. A P value <0.05 was considered to be statistically significant.
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RESULTS |
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TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
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Demographic data were not different between the BIS and entropy groups (Table 1). Required propofol infusion dose matched sedation level (BIS or SE 40, 60, or 80) in a statistically significant manner, but no significant differences in the propofol dosage were observed between the BIS and entropy groups at the same index level (Table 2). The control values (awake values before sedation) were 91 ± 5, 93 ± 4, and 90 ± 4 in BIS, RE, and SE, respectively. Arterial blood pressure decreased after spinal anesthesia, but no difference between groups and no significant changes were seen during the study. Heart rate did not change significantly. Oxygen saturation was
97% in all patients during the study (data not shown).
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BIS significantly increased during click sounds compared to the value at time 0 (before click sounds) when BIS was 40, 60, or 80. The BIS increase continued the longest when BIS was 60 (Fig. 1, Table 3). SE also increased significantly during click sounds, with the longest duration of increase at SE of 60 (Fig. 2, Table 3). RE increased significantly during click sounds, but only when SE was 60. Increased electromyographic signals did not affect the measurements.
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DISCUSSION |
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TopAbstractIntroductionMETHODSRESULTSDISCUSSIONREFERENCES |
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The important findings of this study were that BIS, SE, and RE increased in response to the AEP click sounds, and the increase persisted longer when BIS or SE was 60 than when they were at 40 or 80.
Midazolam and atropine, administered as a premedication, and spinal anesthesia with tetracaine or bupivacaine might have some effects on EEG. However, the effects of the click sounds were studied at constant BIS or SE levels. Therefore, the results observed are independent of the effects of premedication or spinal anesthesia. Neither differences between the groups nor changes in hemodynamics can explain our findings.
There is controversy regarding whether BIS is influenced by noxious stimuli. Because BIS measures cortical function, it is considered to monitor only the sedative/hypnotic state and is a poor indicator of the sensitivities to noxious stimuli.15 However, the sudden appearance of the electromyographic signal in BIS data often indicates that the patient is responding to some external stimulus, such as pain.16 We did not observe any increases in electromyographic signals that coincided with BIS changes in response to the audible click. In addition, BIS accurately predicts response to verbal commands during sedation and hypnosis with propofol.17 Takamatsu et al. reported that noxious stimulation increased BIS, RE, SE, and the difference between RE and SE, which is consistent with the effects of the click sounds in the present study. However, in their study, these indices could not quantify the intensity of stimulation, and are therefore inadequate for quantifying noxious stimulation.13 The present study could not confirm their results because the intensity of the click sounds were not varied. The click sounds could have an arousal effect, aggravating the excitation,18 thus increasing BIS, RE, and SE.
Repetitive auditory stimuli may alter BIS by causing sufficient stimulation to increase the level of consciousness. Absalom et al.11 studied the effects of the click sounds on the BIS during sedation and anesthesia. In their study, AEP click sounds were switched on and off during sedation with propofol at a target concentration 1.6 µg/mL and anesthesia with propofol concentration 3.6 µg/mL. They showed that click sounds did not have any effects on the clinical signs of depth of sedation or BIS when BIS was around 75 in sedation (propofol 1.6 µg/mL) and 40 in anesthesia (propofol 3.6 µg/mL). These results were different from those of the present study, in which click sounds increased BIS when BIS was around 40 or 80. However, whether their sedation levels were the same as mine or not cannot be determined because, to avoid the effects of evaluating hypnosis on the BIS and entropy, I did not examine sedation/hypnotic levels. In addition, Absalom et al. did not indicate how they determined the BIS value during a 5 min epoch of on-and-off click sounds. If they used the value at the end of each epoch, which means 5 min after click sounds on or off, or the mean value during 5 min, they could have missed the BIS increase that might have occurred after 1 min, as shown in the present study.
The increase of BIS, RE, or SE began about 10–20 s after the start of the click sounds. This delay can be explained by the time windows applied in the evaluation of each indicator.14 The moving average windows used to calculate the entropy values are 2–15 s for RE, 15–60 s for SE, and 15 s for BIS. These averaging intervals would delay the BIS, RE, and SE response. BIS decreased to the baseline level during the click sounds, whereas the increase of SE continued after stopping the sounds. The reason for this difference was not clear from this study. However, it seems that both monitors responded only to the changes of the stimuli (i.e., starting click sounds). Thus, BIS, RE, and SE might increase when click sounds begin and decrease thereafter, depending on the characteristics of each monitor.
The increase of the index seemed to be the largest, and its duration longest, when BIS or SE was 60. When BIS or SE was 40, the auditory cortex might have been too deeply sedated to be aroused by click sounds of 65 dB, and at BIS or SE of 80 it might have been almost fully aroused, so that the click sounds could not induce any more arousal.
From the results of this study, click sounds of differing intensities might have had different effects, and other sounds in the operating room, such as background music, electrocardiogram, alarms, or the sounds of surgical apparatus might have some effects on EEG parameters. These possibilities should be further investigated.
In conclusion, AEP monitor click sounds increased BIS, RE, and SE during different levels of sedation by propofol infusion during spinal anesthesia. Therefore, in studies comparing AEP with the BIS or entropy, either both monitors should not be put on the same patient or the effects of the click sounds on these monitors should be considered.
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Footnotes |
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Accepted for publication March 12, 2008.
This work was done at the Department of Anesthesiology, Ofuna Chuo Hospital, Kanagawa, Japan.
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REFERENCES |
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- Kreuer S, Bruhn J, Larsen R, Bauer C, Wilhelm W. Comparison of BIS and AAI as measures of anaesthetic drug effect during desflurane-remifentanil anaesthesia. Acta Anaesthesiol Scand 2004;48:1168–73[Web of Science][Medline]
- Iselin-Chaves IA, El Moalem HE, Gan TJ, Ginsberg B, Glass PSA. Changes in the auditory evoked potentials and the Bispectral Index following propofol or propofol and alfentanil. Anesthesiology 2000;92:1300–10[Web of Science][Medline]
- Kreuer S, Bruhn J, Larsen R, Buchinger H, Wilhelm W. A-line, Bispectral Index, and estimated effect-site concentrations: a prediction of clinical end-points of anesthesia. Anesth Analg 2006;102:1141–6
[Abstract/Free Full Text] - Jeleazcov C, Schneider G, Daunderer M, Scheller B, Schuttler J, Schwilden H. The discriminant power of simultaneous monitoring of spontaneous electroencephalogram and evoked potentials as a predictor of different clinical states of general anesthesia. Anesth Analg 2006;103:894–901
[Abstract/Free Full Text] - Kearse LA Jr, Manberg P, DeBros F, Chamoun N, Sinai V. Bispectral analysis of the electroencephalogram during induction of anesthesia may predict hemodynamic responses to laryngoscopy and intubation. Electroenceph Clin Neurophysiol 1994;90:194–200[Web of Science][Medline]
- Doi M, Gajraj RJ, Mantzaridis H, Kenny GNC. Prediction of movement at laryngeal mask airway insertion: comparison of auditory evoked potential index, Bispectral Index, spectral edge frequency, and median frequency. Br J Anaesth 1999; 82:203–7
[Abstract/Free Full Text] - 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[Abstract]
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[Abstract/Free Full Text] - Nishiyama T, Matsukawa T, Hanaoka K. Is the ARX index a more sensitive indicator of anesthetic depth than the Bispectral Index during sevoflurane/nitrous oxide anesthesia? Acta Anaesthesiol Scand 2004;48:1028–32[Web of Science][Medline]
- Nishiyama T, Hanaoka K. The A-line ARX index may be a more sensitive detector of arousal than the Bispectral Index during propofol-fentanyl-nitrous oxide anesthesia: a preliminary investigation. Can J Anaesth 2004;51:539–44[Web of Science][Medline]
- Absalom AR, Sutcliffe N, Kenny GNC. Effects of the auditory stimuli of an auditory evoked potential system on levels of consciousness, and on the Bispectral Index. Br J Anaesth 2001;87:778–80
[Abstract/Free Full Text] - Recart A, Gasanova I, White PF, Thomas T, Ogunnaike B, Hamza M, Wang A. The effect of cerebral monitoring on recovery after general anesthesia: a comparison of the auditory evoked potential and Bispectral Index devices with standard clinical practice. Anesth Analg 2003;97:1667–74
[Abstract/Free Full Text] - Takamatsu I, Ozaki M, Kazama T. Entropy indices vs the Bispectral IndexTM for estimating nociception during sevoflurane anaesthesia. Br J Anaesth 2006;96:620–6
[Abstract/Free Full Text] - Vierto-Oja H, Maja V, Sarkela M, Talja P, Tenkanen N, Tolvanen-Laakso H, Paloheimo M, Vakkuri A, Yli-Hankala A, Meriläinen P. Description of the EntropyTM algorithm as applied in the Datex-Ohmeda S/5TM Entropy module. Acta Anaesthesiol Scand 2004;48:154–61[Web of Science][Medline]
- Mi WD, Sakai T, Takahashi S, Matsuki A. Haemodynamic and electroencephalograph responses to intubation during induction with propofol and propofol/fentanyl. Can J Anaesth 1998;45:19–22[Web of Science][Medline]
- Struys M, Versichelen L, Mortier E, Ryckaert D, De Mey JC, De Deyne C, Rolly G. Comparison of spontaneous frontal EMG, EEG power spectrum and Bispectral Index to monitor propofol drug effect and emergence. Acta Anaesthesiol Scand 1998;42: 628–36[Web of Science][Medline]
- Kearse LA, Rosow C, Zaslavsky A, Connors P, Dershwitz M, Denman W. Bispectral analysis of the electroencephalogram predicts conscious processing of information during propofol sedation and hypnosis. Anesthesiology 1998;88:25–34[Web of Science][Medline]
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