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Original Article

Tracheal intubation with volatile induction and target bispectral index of 25 versus 40

A randomized clinical trial

Khandelwal, Purva; Gombar, Kanti Kumar1; Ahuja, Vanita; Gombar, Satinder

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Journal of Anaesthesiology Clinical Pharmacology: Jul–Sep 2016 - Volume 32 - Issue 3 - p 349-352
doi: 10.4103/0970-9185.188831
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Intravenous (IV) induction during general anesthesia (GA) is common practice in modern anesthesia. Avoidance of neuromuscular blocking (NMB) drugs is an unusual requirement, in surgical procedures that mandates “no paralysis” (e.g., selective nerve stimulation to aid in dissection), anticipated difficult airway, or in children with difficult IV access.[123]

In an earlier study by van Twest et al. a target bispectral index (BIS) value of 25 provided good to excellent intubating conditions over target BIS of 40 with sevoflurane induction of anesthesia without the use of NMB drugs.[3] Studies are needed to evaluate the time required to achieve target BIS value of 25 versus 40 and tracheal intubation with sevoflurane inhalational induction as the primary outcome.

Hence we planned this study to compare the total time taken from inhalation induction to tracheal intubation at a BIS value of 25 or 40.

Material and Methods

After approval of the Institutional Ethics Committee and written informed consent, we enrolled 80 patients of American Society of Anesthesiologists physical status I and II, 20-60 years, of either sex scheduled for elective surgical procedures requiring GA with tracheal intubation. Exclusion criteria were; History of significant systemic dysfunction, gastro-oesophageal reflux or a hiatus hernia, alcohol or substance abuse, previous or predicted difficult intubation, body mass index (BMI) >30 kg/m2, and pregnancy.

This was a prospective, randomized, and observer-blinded clinical trial. All the patients received alprazolam 0.25 mg and ranitidine 150 mg per oral at night and 2 h before surgery as premedication. Using computer generated random number table, an anesthesiologist not part of the clinical trial allocated the patients to either of the following two groups. Group BIS40 (n = 40) - Intubation with oral cuffed tracheal tube (Portex, UK) after induction with sevoflurane to reach a target BIS value of 40 ± 5; Group BIS25 (n = 40) - Intubation with oral cuffed tracheal tube (Portex, UK) after induction with sevoflurane to reach a target BIS value of 25 ± 5.

Group allocation was concealed using opaque, coded, and sealed envelopes. On arrival of the patient in the operating room, IV access, and standard anesthesia monitoring (Aestiva S/5™ Critical Care Monitor, Datex Ohmeda, Helsinki, Finland) was started. Skin of the forehead was cleaned with an alcohol swab and dried with gauze before application of a disposable BIS - quatro sensor strip (Aspect Medical Systems Inc., Norwood, MA, USA) on the forehead in accordance to manufacturer's instructions. BIS was monitored and recorded using M-BIS module (Aestiva S/5™ Critical Care Monitor, Datex Ohmeda, Helsinki, Finland). IV midazolam 20 µg/kg, fentanyl 0.5 µg/kg, and glycopyrrolate 0.1 mg were given to all patients 5 min prior to induction of anesthesia.

The intubating anesthetist (P.K) started the induction of anesthesia using semi-closed Bain coaxial circuit at an oxygen gas flow rate of 6 L/min. The supervising anesthetist (K.K.G) increased sevoflurane (Drager Vapor 2000, Abbott Lab. Pvt. Ltd., Germany) in increments of 1-2% up to a maximum of 6-8% to achieve the target BIS value as per group allocation. The patient and intubating anesthetist were blinded to sevoflurane dial setting and the target BIS value that was concealed as the supervising anesthetist (K.K.G) managed the sevoflurane dial settings and BIS as per group allocation. The end-tidal sevoflurane concentration (EtSevo) was measured using module M-CAiOV (S/5™ Critical Care Monitor, Datex Ohmeda, Helsinki, Finland). Once the target BIS value was reached, the supervising anesthetist maintained the target BIS value for 2 min and the intubating anesthetist performed tracheal intubation. If the time to achieve target BIS value was more than 10 min or a second attempt for tracheal intubation was required, then the intubating anesthetist was allowed to proceed with technique as appropriate for the procedure. Following tracheal intubation, all patients received the standard anesthetic technique. An independent observer used a stopwatch to observe and record the time to reach the target BIS value and tracheal intubation confirmed on capnography. The intubating conditions were graded according to the intubating conditions scoring table; 3-4 = excellent, 5-6 = good, and 8-12 = poor/impossible.[3] Hemodynamic parameters were measured every one minute during preoxygenation, intubation, and up to 5 min following intubation. The patients were postoperatively followed for 24 h to observe any complications such as nausea, vomiting, awareness, sore throat, or any other adverse effect.

Statistical analysis

The sample size was calculated based on an earlier study[3] in which mean total time to achieve BIS 25, and tracheal intubation were 8.6 ± 2.4, and 7.1 ±1.6 min for BIS 40. Considering α error of 0.05 and power of 90%, the sample size required was estimated to be 38 patients per group. To compensate for possible dropouts 40 patients were enrolled per group. Data were analyzed using statistical package for the social sciences (SPSS) version 15.0 for Windows. Statistical analysis was performed using two-tailed sample t-test and Chi-square test. Mann-Whitney U-test was used to compare intubation score between both the groups. P < 0.05 was considered statistically significant.


Eighty-five patients were enrolled for the study and of these five patients were excluded due to non-fulfilment of inclusion criteria; rest 80 patients completed the study. The patient's characteristics were similar in both the groups [Table 1]. The total time required from induction to tracheal intubation and mean values of Etsevo (%) was lower in group BIS40 as compared to BIS25 (P = 0.001) [Table 2]. The mean intubation score was superior in group BIS25 as compared to group BIS40 (P = 0.001) [Table 3]. On post-hoc analysis, it was found that patients with lower BMI (<20 kg/m2) exhibited better intubation scores and required lower EtSevo to achieve target BIS value (P = 0.001) [Table 3].

Table 1
Table 1:
Patient characteristics
Table 2
Table 2:
Induction and intubation parameters in patients
Table 3
Table 3:
Intubation score, EtSevo with different BMI

All the patients completed the study, and none of the patients in either group had a failure to achieve the target BIS or required alternative means for tracheal intubation. The patients did not have any significant perioperative hemodynamic instability or adverse events.


A target BIS of 40 was considered an adequate depth of anesthesia and hence one group was BIS40. We planned tracheal intubation without the use of NMB drugs so a lower BIS value of 25 was selected assuming that this may benefit in terms of tracheal intubation score. Kimura et al. used EtSevo concentration of 4.5 % and achieved a desirable intubating condition in 20 min without the use of BIS.[4] So far, a study by van Twest et al. was the only study available to address the issue of BIS guided intubation without the use of neuromuscular agents and there is no such study in the Indian population. van Twest et al. concluded that no difference existed in the time taken from induction to intubation with a target BIS 25 or 40.[3] In this study, patient's in-group BIS25 required greater time for induction to tracheal intubation possibly due to the greater time required for alveolar and the cerebral concentrations equilibration.[5] The longer induction time in group BIS25 and greater EtSevo (%) allowed for greater absorption of sevoflurane into the effect site tissues (brain, spinal cord) and provided greater relaxation of jaw muscles and obtunded airway reflexes to a greater degree.[3] The triad of anesthesia is sedation, analgesia, and muscle relaxation and omission one of these are likely to effect the time to achieve target BIS and tracheal intubation, which is a clinical outcome.[6] The present study proved that greater time required for induction to tracheal intubation in patients of group BIS25 relates to adequate intubating conditions to allow successful intubation without increasing the incidence of hemodynamic instability or side effects as compared to group BIS40.

Fentanyl when used in higher doses of 2-4 µg/kg reduces the required EtSevo and intubation response.[78] In this study, patients had lower mean BMI 22.4 ± 2.2 kg/m2 as compared to 26.2 ± 2.9 kg/m2 in the study conducted by van Twest et al.[3] Patients with BMI (<20 kg/m2) exhibited excellent intubation scores and needed lower values of EtSevo to achieve the target BIS (P = 0.001). The explanation in this regard is better jaw relaxation and lesser response to intubation in our patients due to lesser muscle mass. Therefore, BIS guided tracheal intubation during inhalational induction may be especially useful in patients with lower BMI, as it is a more accurate measurement of the depth of anesthesia and overcomes the physiological variability in these patients, which may not be alone possible with EtSevo.[3]

This study has a few limitations. The effect of BIS on tracheal intubation in patients with BMI <20 kg/m2 was underpowered and requires further randomized clinical trials. We used a low dose of fentanyl during the induction period, and the results may differ with a higher dosage of fentanyl.


The total time from induction to tracheal intubation was greater with sevoflurane induction at a target BIS value of 25 as compared to 40 but with better intubation score.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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Bispectral index; inhalational induction; neuromuscular blockers; sevoflurane; tracheal intubation

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