Comparative evaluation of the cerebral state index and the bispectral index during target-controlled infusion of propofol

T. Zhong*, Q. L. Guo, Y. D. Pang, L. F. Peng and C. L. Li

Department of Anesthesiology and Intensive Care Medicine, Xiangya Hospital, Central Southern University, Changsha 410008, China

* Corresponding author. E-mail: zhongtao88{at}tom.com

Accepted for publication August 24, 2005.


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. Cerebral state index (CSI) has recently been introduced as an intra-operative monitor of anaesthetic depth. We compared the performance of the CSI to the bispectral index (BIS) in measuring depth of anaesthesia during target-controlled infusion (TCI) of propofol.

Methods. Twenty Chinese patients undergoing general anaesthesia were recruited. CSI and BIS, and predicted effect-site concentration of propofol were recorded. The level of sedation was tested by Modified Observer's Assessment of Alertness/Sedation Scale (MOAAS) every 20 s during stepwise increase (TCI, 0.5 µg ml–1) of propofol. The loss of verbal contact (LVC) and loss of response (LOR) were defined by MOAAS values of 2–3 and less than 2, respectively. Baseline variability and the prediction probability (PK) were calculated for the BIS and CSI. The values of BIS05 and CSI05, BIS50 and CSI50, BIS95 and CSI95 were calculated at each end-point (LVC and LOR).

Results. Baseline variability of CSI was more than that of BIS. Both CSI and BIS showed a high prediction probability for the steps awake vs LVC, awake vs LOR, and LVC vs LOR, and good correlations with MOAAS values.

Conclusion. Despite larger baseline variation, CSI performed as well as BIS in terms of PK values and correlations with step changes in sedation.

Keywords: anaesthesia, depth ; anaesthetics i.v., propofol ; monitoring, cerebral state index ; monitoring, bispectral index


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Electroencephalography has been introduced in anaesthesia to monitor the hypnotic state of patients. Different analytical concepts have been presented to quantify the changes in the electroencephalogram during anaesthesia. In 1992, the bispectral index monitor (BIS; Aspect Medical Systems, Newton, MA), became available; this monitor is based on the bispectral analysis that relies on the correlation of the phase between different frequency components of the electroencephalogram.1 The effects of anaesthetic drugs and the anaesthetized state on BIS monitoring have been well characterized.2 5 More recently, the cerebral state index (CSI) monitoring (CSITM, Danmeter, Odense, Denmark) has been certified for clinical use in China. The value of CSI, like BIS, ranges from 0 to 100 (awake).

The aim of the current study was to give a first impression of the new CSI during target-controlled infusion (TCI) of propofol. In particular, we were interested in whether the CSI monitor is as reliable or better or worse than BIS monitor in reflecting changes during increasing propofol infusions and sedation levels, and whether CSI or BIS better predicted loss of verbal contact (LVC) and loss of response (LOR) during blood propofol concentrations held constant for 5 min.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Twenty patients, aged between 18 and 65 yr, ASA I or II, undergoing general anaesthesia were entered into the study. Approval was granted by the local institutional ethics committee and written informed consent was obtained from all the participants. Exclusion criteria were recent administration of sedative or opioid drugs, impairment of renal, hepatic, cardiac or respiratory function, and body weight less than 80% or greater than 120% of ideal weight.

All patients were pre-medicated with atropine 0.5 mg i.m. 30 min before induction of anaesthesia. After arrival in the induction room, standard monitoring was started. The skin of the forehead was prepared with isopropanol 70%, and BIS and CSI monitoring electrodes were positioned as recommended by the manufacturers. The electroencephalogram was recorded continuously using a BIS monitor (Aspect A-2000, Aspect Medical Systems, Newton, MA; version XP) and the CSI monitor (CSITM Danmeter, Odense, Denmark). The data were automatically recorded in intervals of 1–5 s. BIS values were recorded and transferred to computer hard disk for off-line analysis. The smoothing time period for the BIS monitor was set at 15 s. The values of CSI were recorded using the Danmeter A/S CSM capture V2.02 onto the computer hard disk.

The anaesthesia was induced with a TCI of propofol starting at the target of 0.5 µg ml–1; this was followed by a stepwise increase in TCI with each step increase amounting to 0.5 µg ml–1 and maintained over 5 min. We used Diprifusor (software version 2; AstraZeneca), which contains the pharmacokinetic model described by Marsh and colleagues,6 for administering propofol. This system displays both the predicted blood propofol concentration and the effect-site propofol concentration. The model uses an equilibration rate constant, keo, of 0.2 min–1.7 8 The Modified Observer's Assessment of Alertness/Sedation Scale (MOAAS; Table 1)9 was tested every 20 s; the LVC was defined as MOAAS values from 3 to 2, and the LOR was defined as MOAAS values less than 2. Fentanyl and muscle relaxants were given 5 min after MOAAS values reached zero.


View this table:
[in this window]
[in a new window]
 
Table 1 MOAAS

 
Heart rate (HR), non-invasive mean arterial pressure (MAP), and oxygen saturation were measured and registered at every point of measurement by Agilent A3 patient monitor (Agilent A3®, Agilent Technologies, Palo Alto, CA, USA). The predicted effect-site concentrations of propofol in TCI system were recorded when they increased by more than 0.1 µg ml–1.

The baseline variability of BIS and CSI values was calculated by computing the coefficient of variation (CV) on the values that were obtained during the last 1 min before starting propofol infusion. Correlations were made between MOAAS and CSI, BIS, MAP and HR, and Spearman correlation coefficients were calculated. For BIS and CSI, we calculated the prediction probability (PK) as described by Smith and colleagues.10 11 PK was calculated as the Somers d statistic using SPSS version 12. The Somers d statistic was then rescaled from the –1 to +1 range of the Somers d statistic to the 0 to 1 range of PK so that

Assessment of the linear association between BIS, CSI or predicted effect-site concentrations and the probability of LVC and LOR were performed using logistic regression. A quantal response model (Probit analysis) was used to calculate EC05 (BIS05 or CSI05), EC50 (BIS50 or CSI50) and EC95 (BIS95 or CSI95) at each end-point (LVC and LOR) based on recordings of predicted effect site concentrations, CSI and BIS values. Statistical analyses were performed using the SPSS package (version 12.0; SPSS, Chicago, IL) and SigmaPlot (version 9.0). A P-value less than 0.05 was considered statistically significant.


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
We studied eight men and 12 women. The mean (SD) value of their age, weight and height were 37.7 (16.2) yr, 62.0 (3.8) kg, and 165 (6.5) cm, respectively. Induction of anaesthesia was smooth in all patients, although seven patients reported pain on injection of propofol. All measured data were included in the analysis.

The baseline (awake) values [mean (SD)] of CSI and BIS were 93.9 (5.0) and 95.3 (2.9), respectively. Compared with BIS, CSI had larger baseline variability as defined by the coefficient of variation (5.4 vs 3.3).

CSI and BIS decreased after induction of anaesthesia (Fig. 1). The increase in sedation (MOAAS decreasing from 5 to 0) was associated with decreases in the median values of CSI (from 90.2 to 40.1) as well as BIS (from 94.1 to 34.1). CSI correlated best with MOAAS (r=0.929), but the difference from BIS was not statistically significant (Table 2). The coefficients of correlation between MOAAS, and CSI and BIS, were higher than those between MOAAS, and MAP and HR (Table 2). CSI and BIS showed a high prediction probability (PK>0.9) for the steps awake vs LVC, awake vs LOR, and LVC vs LOR. PK was higher for CSI and BIS than for MAP and HR, and there were no significant differences in PK values between CSI and BIS.



View larger version (16K):
[in this window]
[in a new window]
 
Fig 1 (A) BIS, (B) CSI, (C) HR and (D) MAP, during different sedation levels (MOAAS 5 to 0). To demonstrate the scatter of the data 95th, 90th, 75th, 50th, 25th, 10th, and 5th centiles are represented.

 

View this table:
[in this window]
[in a new window]
 
Table 2 Spearman correlation coefficient (r) for the MOAAS and PK for distinguishing different investigated states. SEE, standard error of the estimate; BIS, bispectral index; CSI, cerebral state index; HR, heart rate

 
The probabilities of LVC and LOR vs predicted effect-site propofol concentrations are shown in Figure 2. The probabilities of LOV and LOR vs BIS and CSI are respectively shown in Figures 3 and 4. Good correlations between BIS and the predicted effect-site concentration of propofol (r2=0.787, P<0.001) and between CSI and the predicted effect-site concentration of propofol (r2=0.792, P<0.001) were noted. Predicted effect-site propofol concentrations, and the values of BIS and CSI at LVC and LOR for 5, 50 and 95% of the patients are shown in Tables 3 and 4, respectively.



View larger version (17K):
[in this window]
[in a new window]
 
Fig 2 Predicted effect-site concentrations of propofol vs probability of loss of verbal contact and probability of loss of response.

 


View larger version (14K):
[in this window]
[in a new window]
 
Fig 3 BIS vs probability of loss of verbal contact and probability of loss of response.

 


View larger version (14K):
[in this window]
[in a new window]
 
Fig 4 CSI vs probability of loss of verbal contact and probability of loss of response.

 

View this table:
[in this window]
[in a new window]
 
Table 3 Predicted effect-site propofol concentrations and values of BIS and CSI at LVC for 5, 50 and 95% of patients. Values in parentheses are 95% CI. BIS, bispectral index; CSI, cerebral state index

 

View this table:
[in this window]
[in a new window]
 
Table 4 Predicted effect-site propofol concentrations and values of BIS and CSI at LOR for 5, 50 and 95% of patients. Values in parentheses are 95% CI. BIS, bispectral index; CSI, cerebral state index

 

    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
This study was designed to compare the effect of induction of anaesthesia using propofol on the derived EEG variable CSI. The study demonstrates that induction with propofol alone resulted in a progressive decrease in CSI values, similar to a progressive decrease in BIS values, during decreasing values of MOAAS.

In this study, we compared CSI and BIS, as two measures of depth of anaesthesia, during increasing predicted effect-site concentration of propofol. Baseline variability can profoundly affect EEG-based pharmacodynamic estimation of parameters assessing depth of anaesthesia.12 Therefore, we calculated CV on the data before administering the anaesthetic. BIS showed the higher baseline stability between the two measures. Baseline variation might decrease the predictive ability of the univariate parameter, as stated by Bruhn and collaeagues.12 Baseline variation was considered to be related to the smoothing times. Smoothing time of BIS monitor was 15 s and that for CSI monitor was around 10 s, the shorter smoothing time of CSI could have resulted in relatively increased variability.

One strategy to test a depth-of-anaesthesia monitor is to compare its performance with the clinically observed level of sedation in the patient.13 Using this approach, we studied CSI, BIS, MAP and HR during different sedation levels. We used the MOAAS because it provides a good correlation with different degrees of sedation and has been tested in many other studies.14 16 In this study, decreases in sedation level were associated with decreases in CSI and BIS. In contrast, changes in MAP and HR did not correlate well with the changes in MOAAS.

A depth-of-anaesthesia monitor should distinguish accurately between different steps of anaesthesia such as awake, LVC or LOR. Thus, for an index to be accurate, the values indicating different steps should not overlap.17 In this study, we used the PK10 11 to detect the accuracy of the two indices in distinguishing between the investigated steps of anaesthesia. A PK value of 0.5 would indicate that the index distinguishes between the two steps by 50:50 chance; a PK value of 1.0 would indicate a correct distinction with no overlap. Our study has shown that CSI and BSI have high prediction probability (PK>0.9) for the steps awake vs LVC, awake vs LOR, and LVC vs LOR. But the PK values of CSI were not significantly different from BIS. Thus CSI, as an index of depth of anaesthesia, was able to distinguish all investigated states of anaesthesia as accurately as BIS.

We chose to study the Diprifusor system for TCI administration of propofol because it is widely available. It should be mentioned that we did not measure propofol blood/plasma concentrations but used calculated effect-site concentrations. We increased the target concentration of propofol by small increments every 5 min. There was insufficient time for the propofol to equilibrate with the brain. Equilibration of the effect-site with the blood concentration takes four to five times the keo half-life [T1/2 (keo)], where T1/2 (keo)=0.693/keo. The Diprifusor uses a keo of 0.2 min–1. Therefore, it will take approximately 15 min for blood and effect-site concentrations to equilibrate. Because of this there was considerable discrepancy between the predicted blood and effect-site concentrations, emphasizing that during induction and recovery the effect-site concentration is a more useful clinical correlate than the predicted blood concentration.18 19 Several previous studies18 20 have evaluated the relationship of predicted effect-site propofol concentrations to investigated state of consciousness. These studies, unlike our study, showed large differences in EC50 for effect-site propofol concentration at LOR. We believe that the differences in EC50 can be caused by different criteria used for the clinical state of consciousness, and the different ethnic groups of patients. In this study, we found good correlations between BIS and the predicted effect-site concentration of propofol (r2=0.787) and between CSI and the predicted effect-site concentration of propofol (r2=0.792).

Ninety per cent of patients will have no response to verbal commands and will lose response at CSI between the CSI95 and the CSI05 for these responses. For LVC, this range was 58.3–72.9 and for LOR it was 38.2–71.3; the corresponding ranges for BIS values were 55.8–79.7 and 35.6–78.0, respectively (Tables 3 and 4). The ranges for CSI are somewhat smaller than that of BIS. It is possible that CSI is slightly better than BIS in detecting LVC and LOR.

In this study, using a specific anaesthetic technique and a single anaesthetic agent, CSI and BIS show nearly similar changes at different sedation levels. Despite larger baseline variation, CSI performed as well as BIS in terms of PK and correlation with level of sedation. There is an indication that CSI may be more useful than BIS in predicting LVC and LOR because of the smaller range of values for the two clinical end-points. However, one study has shown CSI to be not sensitive in detecting LOR achieved with nitrous oxide.21 Therefore, further studies using other anaesthetic agents and other anaesthetic techniques are necessary to determine the future role of the CSI monitor.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Rampil IJ. A primer for EEG signal processing in anesthesia. Anesthesiology 1998; 89: 980–1002[CrossRef][ISI][Medline]

2 Drummond JC. Monitoring depth of anesthesia: With emphasis on the application of the Bispectral Index and the middle latency auditory evoked response to the prevention of recall. Anesthesiology 2000; 93: 876–82[ISI][Medline]

3 Gan TJ, Glass PS, Windsor A, et al. Bispectral Index monitoring allows faster emergence and improved recovery from propofol, alfentanil, and nitrous oxide anesthesia. BIS Utility Study Group. Anesthesiology 1997; 87: 808–15[CrossRef][ISI][Medline]

4 Kreuer S, Biedler A, Larsen R, Altmann S, Wilhelm W. Narcotrend monitoring allows faster emergence and a reduction of drug consumption in propofol–remifentanil anesthesia. Anesthesiology 2003; 99: 34–41[CrossRef][ISI][Medline]

5 Luginbuhl M, Wuthrich S, Petersen-Felix S, Zbinden AM, Schnider TW. Different benefit of bispectral index (BIS) in desflurane and propofol anesthesia. Acta Anaesthesiol Scand 2003; 47: 165–73[CrossRef][ISI][Medline]

6 Marsh B, White M, Morton N, Kenny GN. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 1991; 67: 41–8[ISI][Medline]

7 Glen JB. The development of ‘Diprifusor’: a TCI system for propofol. Anaesthesia 1998; 53: 13–21[CrossRef][Medline]

8 Gray JM, Kenny GN. Development of the technology for ‘Diprifusor’ TCI systems. Anaesthesia 1998; 53: 22–7[ISI][Medline]

9 Chernik DA, Gillings D, Laine H, et al. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: Study with intravenous midazolam. J Clin Psychopharmacol 1990; 10: 244–51[ISI][Medline]

10 Smith WD, Dutton RC, Smith NT. A measure of association for assessing prediction accuracy that is a generalization of non-parametric ROC area. Stat Med 1996; 15: 1199–215[CrossRef][ISI][Medline]

11 Smith WD, Dutton RC, Smith NT. Measuring the performance of anesthetic depth indicators. Anesthesiology 1996; 84: 38–51[CrossRef][ISI][Medline]

12 Bruhn J, Bouillon TW, Hoeft A, Shafer SL. Artifact robustness, inter- and intraindividual baseline stability, and rational EEG parameter selection. Anesthesiology 2002; 96: 54–9[CrossRef][ISI][Medline]

13 Struys MM, Jensen EW, Smith W, et al. Performance of the ARX-derived auditory evoked potential index as an indicator of anesthetic depth: A comparison with bispectral index and hemodynamic measures during propofol administration. Anesthesiology 2002; 96: 803–16[CrossRef][ISI][Medline]

14 Schmidt GN, Bischoff P, Standl T, Hellstern A, Teuber O, Schulte EJ. Comparative evaluation of the Datex-Ohmeda S/5 Entropy Module and the Bispectral Index monitor during propofol-remifentanil anesthesia. Anesthesiology 2004; 101: 1283–90[CrossRef][ISI][Medline]

15 Bruhn J, Bouillon TW, Radulescu L, Hoeft A, Bertaccini E, Shafer SL. Correlation of approximate entropy, bispectral index, and spectral edge frequency 95 (SEF95) with clinical signs of "anesthetic depth" during coadministration of propofol and remifentanil. Anesthesiology 2003; 98: 621–7[CrossRef][ISI][Medline]

16 Drummond JC. Monitoring depth of anesthesia: With emphasis on the application of the Bispectral Index and the middle latency auditory evoked response to the prevention of recall. Anesthesiology 2000; 93: 876–82[ISI][Medline]

17 Wakeling HG, Zimmerman JB, Howell S, Glass PS. Targeting effect compartment or central compartment concentration of propofol: what predicts loss of consciousness? Anesthesiology 1999; 90: 92–7[CrossRef][ISI][Medline]

18 Milne SE, Troy A, Irwin MG, Kenny GN. Relationship between bispectral index, auditory evoked potential index and effect-site EC50 for propofol at two clinical end-points. Br J Anaesth 2003; 90: 127–31[Abstract/Free Full Text]

19 Irwin MG, Hui TW, Milne SE, Kenny GN. Propofol effective concentration 50 and its relationship to bispectral index. Anaesthesia 2002; 57: 242–8[CrossRef][ISI][Medline]

20 Iannuzzi M, Iannuzzi E, Rossi F, Berrino L, Chiefari M. Relationship between bispectral index, electroencephalographic state entropy and effect-site EC50 for propofol at different clinical endpoints. Br J Anaesth 2005; 94: 492–5[Abstract/Free Full Text]

21 Anderson RE, Barr G, Jakobsson JG. Cerebral state index during anaesthetic induction: a comparative study with propofol or nitrous oxide. Acta Anaesthesiol Scand 2005; 49: 750–3[CrossRef][ISI][Medline]





This Article
Abstract
Full Text (PDF)
All Versions of this Article:
95/6/798    most recent
aei253v1
E-Letters: Submit a response to the article
Alert me when this article is cited
Alert me when E-letters are posted
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Zhong, T.
Articles by Li, C. L.
PubMed
PubMed Citation
Articles by Zhong, T.
Articles by Li, C. L.