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Year : 2020  |  Volume : 14  |  Issue : 4  |  Page : 600-604  

Comparison of end-tidal anesthetic gas concentration versus bispectral index-guided protocol as directing tool on time to tracheal extubation for sevoflurane-based general anesthesia

Department of Anaesthesiology, Uttar Pradesh University of Medical Sciences, Saifai, Etawah, Uttar Pradesh, India

Date of Submission28-Feb-2021
Date of Decision01-Mar-2021
Date of Acceptance15-Mar-2021
Date of Web Publication27-May-2021

Correspondence Address:
Dr. Sanket Agrawal
Department of Anaesthesiology, Uttar Pradesh University of Medical Sciences, Saifai, Etawah, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aer.AER_25_21

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Background: Modalities for titrating anesthetic drug-like bispectral index (BIS) and end-tidal anesthetic gas (ETAG) concentration in predicting early extubation had been studied with old anesthetic agents such as isoflurane. Aim: The aim of this study is to compare the effect of ETAG concentration versus BIS-guided protocol as directing tool on time to tracheal extubation for sevoflurane-based general anesthesia. Materials and Methods: This prospective, randomized, double-blind trial studied sixty patients with American Society of Anesthesiologists physical status classes I and II who received sevoflurane-based general anesthesia and were allocated to either BIS–guided anesthesia group (n = 30) or ETAG–guided anesthesia group (n = 30). Time to tracheal extubation was measured. BIS value was kept between 40 and 60 in BIS group, whereas minimum alveolar concentration value was kept between 0.7 and 1.3 in ETAG group. The two groups were compared using Student's t-test, and P < 0.05 was considered statistically significant. The statistical analysis was performed using the open source “R” programming language. Results: Mean time to tracheal extubation was significantly shorter in BIS group (308.77 ± 20.48 s) as compared to ETAG group (377.90 ± 25.06 s) (P < 0.001). The sevoflurane concentration used was also significantly less in group BIS than group ETAG at multiple time intervals (P = 0.001). Conclusion: Prediction of extubation was significantly early with BIS monitoring as compared to ETAG monitoring in sevoflurane-based general anesthesia.

Keywords: Bispectral index, early extubation, end-tidal anesthetic gas concentration, sevoflurane

How to cite this article:
Shukla U, Yadav U, Yadav JB, Agrawal S. Comparison of end-tidal anesthetic gas concentration versus bispectral index-guided protocol as directing tool on time to tracheal extubation for sevoflurane-based general anesthesia. Anesth Essays Res 2020;14:600-4

How to cite this URL:
Shukla U, Yadav U, Yadav JB, Agrawal S. Comparison of end-tidal anesthetic gas concentration versus bispectral index-guided protocol as directing tool on time to tracheal extubation for sevoflurane-based general anesthesia. Anesth Essays Res [serial online] 2020 [cited 2022 May 16];14:600-4. Available from:

   Introduction Top

Monitored titration of inhaled anesthetics intraoperatively facilitate early emergence from general anesthesia. These monitored modalities may be bispectral index (BIS) and end-tidal anesthetic gas (ETAG) concentration. Compared with traditional inhaled anesthetics, less soluble sevoflurane (low blood: gas partition coefficient) helps in early extubation.

BIS gives a continuous assessment of patient with minimal stimulation and also enables titration of drug, whereas the ETAG concentration criteria relates to brain activity through concentration of anesthetic agent expired in lungs assuming it to be in equilibrium with brain concentration. About 50% of the participants do not respond to oral commands at ETAC equivalent to 0.33 times of minimum alveolar concentration (MAC) (MAC awake) and distressing (auditory) stimuli are not internalized at twice MAC–awake.[1] The B-Unaware and BAG-RECALL trials had reported no difference in awareness incidence with anesthetic protocol based on BIS range (40–60) and anesthetic protocol based on ETAG concentration (MAC range 0.7–1.3).[2],[3] These two modality are less studied with newer agents like sevoflurane.

We aimed to compare the effect of ETAG concentration versus BIS-guided protocol as directing tool on time to tracheal extubation for sevoflurane-based general anesthesia.

   Materials and Methods Top

The study was conducted after the approval of the Institutional Ethical Committee. Randomized double-blind trial comparing sixty patients allocated in two groups: Group E-(ETAG concentration) (n = 30) and Group B-(BIS) (n = 30) of either sex, age group 18–50 years, with American Society of Anesthesiologists (ASA) physical status classes I and II, body mass index (BMI) between 18 and 30 kg.m−2 scheduled for elective general surgery lasting up to 120 min receiving Sevoflurane (Sevoflurane [250 mL], Piramal Healthcare Ltd.,)-based general anesthesia.

Patients refusal, patients on psychoactive medication, psychiatric patients, known or suspected electroencephalographic (EEG) abnormality (e.g. epilepsy and previous brain surgery), abnormal kidney function, pregnant or lactating females, history of alcohol and drug abuse were excluded from the study.

Group allocation was done using sequentially sealed opaque envelopes. A trained nurse not involved in the study generated the random allocation sequence, enrolled study participants and assigned participants to interventions. Both the study patients and the anesthesiologist who recorded the data were blinded to the group allocation. For ETAG group, monitor configuration that omitted BIS number was used while in BIS group, an opaque screen was placed over the MAC value on the monitor.

All patients had full relevant preanesthetic checkup including general, systemic and laboratory investigations, written and informed consent was taken and patients were kept nil per oral for 6 h before surgery. In the operating room, patient's basal parameters: blood pressure, heart rate, baseline ECG, and SpO2 were noted. A 18 G intravenous (i.v.) cannula with an IV Ringer lactate @8−1 was started.

In Group B patients, BIS electrodes were applied before starting the procedure to note the baseline awake BIS value. A thorough skin preparation of forehead was done to remove any skin oils. The sensors of the BIS monitor (BIS LoC 2 channel, ©2011 Covidien, made in Singapore) were placed. Sensor impedance check was initiated; impedance value was measured; and electrode status was in pass status.

In Group E patients, ETAG concentration was measured using the adult multigas sidestream analyzer module. The infrared gas analyzer was calibrated before the start of each surgery. The MAC values of nitrous oxide and sevoflurane were considered to be additive; therefore, total MAC was taken as a measure of ETAG concentration. The vaporizer used was Mindray V60 Pour Fill type sevoflurane vaporizer for both the groups.

All patients were preoxygenated for 3 min and premedicated with i.v. 4−1 glycopyrrolate, 0.05−1 midazolam, 2−1 fentanyl, induction was achieved by i.v. 2−1 propofol and intubation was facilitated with i.v. 0.08−1 vecuronium. Anesthesia was maintained with 60% of nitrous oxide in oxygen on controlled ventilation at low flow anesthesia (2.5 Lpm) and sevoflurane was titrated according to respective group protocols (BIS value of 40–60 in Group B and 0.7–1.3 MAC value in Group E) along with i.v. 0.02−1 vecuronium maintenance dose as required. Paracetamol (15−1 i.v.) was given as analgesic.

After the last skin suture, all anesthetic agents were stopped and after the onset of spontaneous respiration, residual neuromuscular blockade was reversed with i.v. 0.05−1 neostigmine and 0.01−1 glycopyrrolate. Extubation was done when the patient started following verbal commands, had sustained head lift for 5 s and was maintaining adequate SpO2 (>95% on disconnection from ventilatory circuit).

Hemodynamic parameters were recorded at baseline and at every 5 min interval until tracheal extubation. Duration of anesthesia (time from premedications to last skin suture), duration of surgery (time from skin incision to last skin suture) and time to tracheal extubation (time from last skin suture to extubation of endotracheal tube from trachea) were measured. BIS value and sevoflurane concentration on vaporizer were noted in Group B, and similarly, MAC value and sevoflurane concentration on vaporizer were noted in Group E. The satisfaction of the patient was assessed using a seven-point Likert verbal rating scale immediately and 12 h after the surgery. Scores between 5 and 7 were considered as acceptable score.

Statistical analysis

Sample size calculation was based on assuming a difference of 4.34 min in both groups with 95% confidence interval, 5% alpha error using G-power 3.1 Software [Heinrich Heine University, Dusseldorf, Germany].[4] The quantitative variables were compared using unpaired t-test and qualitative variables were compared using the Chi-square/Fisher's exact test. P < 0.05 was considered statistically significant. The data were stored in MS Excel spreadsheet and statistical analysis performed using open source “R” programming language.

   Results Top

All sixty patients were analyzed, and none were excluded at the end of the study [Figure 1]. The groups were well-matched regarding age, gender, BMI and ASA physical status [Table 1]. In our study, type of surgery mainly comprised laparoscopic cholecystectomy and also excision of fibroadenoma, pyelolithotomy and transabdominal preperitoneal hernia repair. Both groups were comparable regarding type and duration of surgery as well as anesthesia [Table 2].
Figure 1: Consort flow diagram

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Table 1: Demographic profile of patients

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Table 2: Mean duration of surgery, anesthesia and time to tracheal extubation

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All hemodynamic parameters remained within normal limits (20% of baseline) throughout the course of anesthesia [Figure 2]. Mean baseline BIS value was 91.33 and it was maintained between 40 and 60 in Group B intraoperatively, whereas in Group E, mean MAC value increased from 0 to 0.7 after induction and was maintained between 0.7 and 1.3 intraoperatively [Figure 3].
Figure 2: Comparison of vital parameters. BIS = Bispectral, ETAG = End-tidal anesthetic gas

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Figure 3: Bispectral index score and minimum alveolar concentration values among the groups across the time periods. BIS = Bispectral, ETAG = End.tidal anesthetic gas

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In our study, mean time to tracheal extubation in BIS group was found to be shorter than ETAG group with P < 0.001. It was 308.77 ± 20.48 s in BIS group as compared to 377.90 ± 25.06 s in ETAG group. Furthermore, we compared sevoflurane concentration (%) set to maintain decided protocols in both the groups. Sevoflurane concentration was lower significantly in Group B during the maximum course of surgery [Figure 4].
Figure 4: Comparison of sevoflurane concentration among the groups across the time periods. BIS = Bispectral, ETAG = End-tidal anesthetic gas

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All the patients were extubated in the operating room and no complications were noted. Postoperatively, patient's satisfaction score, assessed using Likert scale score was acceptable in both the groups. Patients were also inquired about intraoperative recall and none of the patient reported the same.

   Discussion Top

Recovery from anesthesia is a critical period from the perspective of both physiological stability and patient satisfaction. Hence, early extubation is desirable. We observed BIS monitoring is associated with statistically significant reduction in time to tracheal extubation and also indirectly predicting less sevoflurane consumption when compared with ETAG-guided anesthesia.

On a similar observations with our study, Persec et al.[5] used sevoflurane and compared extubation time and concluded that time to extubation was significantly shorter in the BIS-guided group than routine anesthesia care group (17.5 min vs. 75 min, P < 0.001). Akçali et al.[6] also found extubation time to be significantly shorter in the BIS group (3.7 ± 1.9 min) than control group (5.7 ± 3.1 min) (P < 0.01) during TIVA for lumbar discectomies. Recart et al.[7] found significantly early extubation time in BIS group (6 ± 4 min) than control group (11 ± 10 min) (P < 0.05). Similarly, Song et al.[8] concluded BIS titrated group (5.5 ± 2.2 min) predict early recovery than non-BIS titrated group (7.7 ± 3.5 min) using sevoflurane.

However, Jain et al.[4] performed a study with halothane and found contrarily significantly (P < 0.05) shorter extubation time in the ETAG-guided group (5.29 ± 1.51 min) as compared to BIS-guided group (9.63 ± 3.02 min) (mean difference 4.34 min with 95% confidence interval [3.106, 5.982]). The probable reason may be the inhalational agent used, i.e. halothane. At equal-MAC values, halothane produces higher BIS values than other inhalational agent. This drug-specific changes in BIS values were observed by Schwab et al.[9] who studied the effect of sevoflurane and halothane on BIS values and concluded that sevoflurane causes a greater decrease in BIS values than halothane at equal MAC multiples (mean BIS value was 54 ± 7 with halothane vs. 34 ± 6 with sevoflurane at 1 MAC). Similarly, at equi-MAC end-tidal concentrations, Bharti and Devrajan[10] concluded isoflurane produces lower BIS values than halothane and Gupta et al.[11] found sevoflurane produces lower BIS values as compared to isoflurane.

Some trials have inferred comparable results between the study groups in the past. Sudhakaran et al.[12] studied recovery characteristics including time to tracheal extubation in BIS monitoring, ETAG monitoring and standard monitoring in desflurane-based spine surgeries. They found that extubation time in ETAG and BIS guided group was significantly lower than standard group (P < 0.001) but ETAG-guided anesthesia was comparable to BIS-guided anesthesia. The probable reason of comparability could have been of using a narrow range of MAC value (0.8–1) and BIS value (45–55) allowing less titration of inhaled anesthetic. Similarly, study on fast track cardiac surgery by Vance et al.[13] (median time to extubation 307 [215–771] min in the BIS group and 323 [196–730] min in the ETAG group [P = 0.61]) and Villafranca et al.[14] study showing time to tracheal extubation in majority of patients (75% in the BIS group; 78% in the ETAG group, P = 0.426) were successfully extubated within 8 h after chest closure but with no significant difference. The possible explanation would have been extra volume of drug being delivered in postoperative intensive care unit till extubation as these periods were not monitored by BIS and ETAG.

Sevoflurane consumption can be indirectly assessed by observing concentration of sevoflurane used in surgery provided other contributing factors are comparable.

Where VA = fluid volatile agent volume (in ml), FGF = fresh gas flow in ml/minute, mean agent concentration = in %, duration of anesthesia = in minutes, saturated gas volume = constant (184 mL for sevoflurane). In our study, mean sevoflurane concentration set on vaporizer was statistically less in group BIS than group ETAG in maximum course of the surgery indicating titration of sevoflurane according to our criteria helps in less usage of drug in group BIS.

Punjasawadwong et al.[15] reported BIS-guided anesthesia reduced the requirement for volatile anesthetics by 0.65 times of standardized mean difference of MAC equivalents. Similarly, Ibraheim et al.[16] found significantly lower sevoflurane consumption in BIS group (mean sevoflurane consumption per hour was 15.66 ± 4.04 mL liquid in BIS group vs. 19.60 ± 3.94 mL liquid in non-BIS group, P < 0.05). Aimé et al.[17] reported BIS-guided anesthesia required 29% less sevoflurane than non-BIS guided anesthesia, the consumption was estimated by weighing sevoflurane vaporizers before and after anesthesia. Another study conducted by Basar et al.[18] reported that BIS-guided anesthesia reduced sevoflurane usage by 4.37% and 2.19 mL.h−1 was saved. Yli-Hankala et al.[19] studied EEG-BIS monitoring in sevoflurane or propofol anesthesia and concluded that BIS guidance helped to reduce sevoflurane consumption by 40%.


First, the small sample size and second the observations cannot be generalized to all types of surgeries and anesthesia protocols. Furthermore, the cost of sevoflurane and BIS electrodes are high comparatively.

   Conclusion Top

We conclude that BIS monitoring predicts earlier extubation of patients and also in the less consumption of sevoflurane as compared to ETAG monitoring in sevoflurane-based anesthesia.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Eger EI 2nd. Age, minimum alveolar anaesthetic concentration and minimum alveolar anaesthetic concentration-awake. Anaesth Analg 2001;93:947-53.  Back to cited text no. 1
Avidan MS, Zhang L, Burnside BA, Finkel KJ, Searleman AC, Selvidge JA, et al. Anesthesia awareness and the bispectral index. N Engl J Med 2008;358:1097-108.  Back to cited text no. 2
Avidan MS, Jacobsohn E, Glick D, Burnside BA, Zhang L, Villafranca A, et al. Prevention of intraoperative awareness in a high-risk surgical population. N Engl J Med 2011;365:591-600.  Back to cited text no. 3
Jain N, Mathur PR, Khan S, Khare A, Mathur V, Sethi S. Effect of bispectral index versus end-tidal anesthetic gas concentration-guided protocol on time to tracheal extubation for halothane-based general anesthesia. Anesth Essays Res 2016;10:591-6.  Back to cited text no. 4
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Persec J, Persec Z, Kopljar M, Sojcic N, Husedzinovic I. Effect of bispectral index monitoring on extubation time and analgesic consumption in abdominal surgery: A randomised clinical trial. Swiss Med Wkly 2012;142:w13689.  Back to cited text no. 5
Akçali DT, Ozköse Z, Yardim S. Do we need bispectral index monitoring during total intravenous anesthesia for lumbar discectomies? Turk Neurosurg 2008;18:125-33.  Back to cited text no. 6
Recart A, Gasanova I, White PF, Thomas T, Ogunnaike B, Hamza M, et al. The effect of cerebral monitoring on recovery after general anaesthesia: A comparison of the auditory evoked potential and bispectral index devices with standard clinical practice. Anaesth Analg 2003;97:1667-74.  Back to cited text no. 7
Song D, Joshi GP, White PF. Titration of volatile anesthetics using bispectral index facilitates recovery after ambulatory anesthesia. Anesthesiology 1997;87:842-8.  Back to cited text no. 8
Schwab HS, Seeberger MD, Eger EI 2nd, Kindler CH, Filipovic M. Sevoflurane decreases bispectral index values more than does halothane at equal MAC multiples. Anesth Analg 2004;99:1723-7.  Back to cited text no. 9
Bharti N, Devrajan J. Comparison of bispectral index values produced by isoflurane and halothane at equal end-tidal MAC concentrations. Indian J Anaesth 2007;51:401-4.  Back to cited text no. 10
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Gupta M, Shri I, Sakia P, Govil D. Comparison of equi-minimum alveolar concentration of sevoflurane and isoflurane on bispectral index values during both wash in and wash out phases: A prospective randomised study. Indian J Anaesth 2015;59:79-84.  Back to cited text no. 11
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Sudhakaran R, Makkar JK, Jain D, Wig J, Chabra R. Comparison of bispectral index and end-tidal anaesthetic concentration monitoring on recovery profile of desflurane in patients undergoing lumbar spine surgery. Indian J Anaesth 2018;62:516-23.  Back to cited text no. 12
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Vance JL, Shanks AM, Woodrum DT. Intraoperative bispectral index monitoring and time to extubation after cardiac surgery: Secondary analysis of a randomized controlled trial. BMC Anesthesiol 2014;14:79.  Back to cited text no. 13
Villafranca A, Thomson IA, Grocott HP, Avidan MS, Kahn S, Jacobsohn E. The impact of bispectral index versus end-tidal anesthetic concentration-guided anesthesia on time to tracheal extubation in fast-track cardiac surgery. Anesth Analg 2013;116:541-8.  Back to cited text no. 14
Punjasawadwong Y, Phongchiewboon A, Bunchungmongkol N. Bispectral index for improving anaesthetic delivery and postoperative recovery. Cochrane Database Syst Rev 2014;2014:CD003843.  Back to cited text no. 15
Ibraheim O, Alshaer A, Mazen K, El-Dawlaty A, Turkistani A, Alkathery K, et al. Effect of BIS monitoring on postoperative recovery and sevoflurane consumption among morbidly obese patients undergoing laparascopic gastric banding. Middle East J Anaesthesiol 2008;19:819-30.  Back to cited text no. 16
Aimé I, Verroust N, Masson-Lefoll C, Taylor G, Laloë PA, Liu N, et al. Does monitoring bispectral index or spectral entropy reduce sevoflurane use? Anesth Analg 2006;103:1469-77.  Back to cited text no. 17
Basar H, Ozcan S, Buyukkocak U, Akpinar S, Apan A. Effect of bispectral index monitoring on sevofurane consumption. Eur J Anaesthesiol 2003;20:396-400.  Back to cited text no. 18
Yli-Hankala A, Vakkuri A, Annila P, Korttila K. EEG bispectral index monitoring in sevoflurane or propofol anaesthesia: Analysis of direct costs and immediate recovery. Acta Anaesthesiol Scand 1999;43:545-9.  Back to cited text no. 19


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]


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