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Year : 2007  |  Volume : 51  |  Issue : 5  |  Page : 401 Table of Contents     

Comparison of Bispectral Index Values Produced by Isoflurane and Halothane at Equal End-tidal MAC Concentrations

1 MD, Assistant Professor, PGIMER, Chandigarh, India
2 MD, Senior Resident, AIIMS, New Delhi, India

Date of Acceptance04-Jul-2007
Date of Web Publication20-Mar-2010

Correspondence Address:
Neerja Bharti
Assistant Professor, Department of Anaesthesia & Intensive Care, PGIMER, Chandigarh-160012
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Source of Support: None, Conflict of Interest: None

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The bispectral index (BIS) has been validated as a measure of hypnotic effect for various anaesthetic agents. There are limited data correlating the BIS with minimum alveolar concentration (MAC) of different volatile anaesthetics. We compared the BIS values using halothane and isoflurane at equal end-tidal MAC multiples. Forty adult patients of ASAI-II undergoing elective abdominal surgeries were randomly assigned into two groups. After a standardized induction, anaesthesia was maintained with either halothane (Group H) or isoflurane (Group I) in combination with nitrous oxide 66% in oxygen and fentanyl.BIS values were measured before induction, during anaesthesia at 0.5 MAC, 1 MAC, 1.5 MAC concentration of the volatile anaesthetics and then at awakening of the patient. BIS measurements were made after meeting steady state concentrations of volatile anaesthetic agents.
BIS values at 0.5 MAC, 1.0 MAC and 1.5 MAC for patients receiving halothane exceeded those for patients receiving isoflurane. BIS value at awakening did not differ between the halothane and isoflurane groups.
We concluded that at equal MAC concentrations of halothane and isoflurane BIS values were significantly lower with isoflurane.

Keywords: Bispectral index; Halothane; Isoflurane, Minimum alveolar concentration

How to cite this article:
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

How to cite this URL:
Bharti N, Devrajan J. Comparison of Bispectral Index Values Produced by Isoflurane and Halothane at Equal End-tidal MAC Concentrations. Indian J Anaesth [serial online] 2007 [cited 2021 Jul 24];51:401. Available from: https://www.ijaweb.org/text.asp?2007/51/5/401/61170

   Introduction Top

Minimum alveolar concentration (MAC) is the most common method of titration of volatile anaesthetics in clinical practice. However, this value describes mainly the immobilizing potency (prevents movement to skin in­cision in 50% of patients) of the anaesthetic agent and most likely reflects more the effects on the spinal cord rather than the brain [1] . To obtain more complete concen­tration-response curves for the hypnotic effects of vari­ous volatile anaesthetics a novel EEG-derived param­eter bispectral index (BIS) is more specific. Previous studies have shown that BIS correlates well with the brain metabolism and with hypnotic and sedative effects of various anaesthetic agents including isoflurane, sevoflurane, midazolam and propofol [2],[3] .

Anaesthetic agents vary in their relative hypnotic and immobilizing potentials. Therefore, equal MAC con­centrations of various volatile agents may produce dif­ferent BIS values. Limited data allow a comparison of BIS values with equal end-tidal MAC concentrations of volatile anaesthetics [4],[5] . Olofsen and Dhaman [4] demon­strated an inhibitory sigmoid E max model for the dynamic relationship between isoflurane and sevoflurane end-tidal concentrations and the BIS values, and found that isoflurane is more potent hypnotic than sevoflurane. In a comparative study Schwad et al [5] found that sevoflurane decreases BIS values more than does halothane at equal MAC multiples. Halothane has different EEG effects from sevoflurane and isoflurane [5],[6] . The present study was aimed to compare the BIS values at various end-­tidal MAC concentrations of halothane and isoflurane.

   Methods Top

After obtaining institutional ethical committee ap­proval and informed written consent, forty patients with ASA physical status I-II, scheduled for elective abdomi­nal surgeries lasting >60min were randomly allocated into two groups receiving either halothane (Group H) or isoflurane (Group I). Patients with morbid obesity (weight >130% of IBW), uncontrolled hypertension or diabetes mellitus, impaired renal or hepatic function, or having history of drug or alcohol abuse were excluded.

All patients were fasted overnight and received diazepam 5 mg orally at night and 2 hr before surgery. On arrival in the operation theatre, intravenous cannula­tion was secured and routine monitoring of ECG, oxygen saturation and blood pressure was started. The BIS was recorded continuously with soothing rate of 15sec by using an Aspect EEG monitor. After obtaining base line values of heart rate, blood pressure and BIS, anaesthe­sia was induced with fentanyl 2 µg.kg -1 followed by propofol 2-3 mg.kg -1 till loss of verbal response. Tra­cheal intubation was facilitated with vecuronium 0.1 mg.kg -1 . Anaesthesia was maintained with 66% N 2 O in oxygen along with either halothane or isoflurane. The patients' lungs were mechanically ventilated to maintain an end-tidal carbon-di-oxide concentration of 32-35 mmHg. Total flow through a semicircle system was kept constant to 3L.min -1 throughout the study period. Fenta­nyl infusion was started after induction of anaesthesia at the rate of 0.5 µg.kg -1 .hr -1 . Intermittent bolus doses of vecuronium 0.02 mg.kg -1 were administered at one twitch response using the train-of-four (TOF) monitor for as­sessing the degree of neuromuscular blockade. Supple­mental doses of fentanyl (25-50µg) were given if there was a persistent increase in heart rate (> 100 beats/min) or blood pressure (> 20% of baseline). Body tempera­ture was maintained above 35.5 0 C in all cases. The in­spired and end-tidal concentrations of inhalational agents, oxygen and carbon-di-oxide were measured by using a Datex Capnomac monitor.

During the maintenance phase, 10 min after inci­sion, the end-tidal concentration of inhalational anaes­thetic was adjusted at 0.5 MAC for 10 min. When BIS values were stabilized, the inspired concentrations of halothane or isoflurane were increased from 0.5 to 1.0 MAC and then 1.5 MAC, and then decreased to 0.5 MAC in same graded manner. The end tidal MAC was

calculated according to the use of nitrous oxide. After each increment or decrement, the concentration was kept constant for 10 min, to reduce the difference between inspired and end-tidal concentration of inhalational an­aesthetic to <10%. The BIS values were recorded at the end of 10 min at each end-tidal concentration.

Fentanyl infusion was stopped 15 min before the end of procedure. The inhalational anaesthetic was dis­continued just before skin closure. The residual neuro­muscular blockade was reversed with neostigmine 0.05 mg.kg -1 and atropine 0.02 mg.kg -1 at the end of surgery. While the end-tidal concentration of inhalational anaes­thetic was decreasing the patients were asked to open their eyes. The BIS value (BIS-awake) and end-tidal concentration of inhalational agent at eye opening was recorded. Patients were extubated and shifted to post­operative care unit for monitoring of vitals and recovery.

   Statistical analysis Top

The data were collected and presented as mean ± SD. Two sample unpaired student's t-test was used to compare demographic data and duration of surgery. Friedman two-way analysis of variance was applied to see the trends of BIS value in each group. Mann­Whitney U test was used to compare the BIS values between the two groups. P value <0.05 was considered significant.

   Results Top

The demographic data and duration of surgery were comparable among groups [Table 1].

In both groups the pre-induction BIS values were between 96 and 98, and then decreased precipitously after induction. The BIS values for each milestone are presented in [Figure 1].

[Figure 1] shows a significant correlation of BIS with the end-tidal anaesthetic concentrations in each group. The BIS values decreased significantly with increasing MAC concentrations during wash-in phase and increased significantly with decreasing MAC concentrations dur­ing wash-out phase in both the groups. However, for similar anaesthetic agent the BIS values were compa­rable at equi-MAC concentrations during wash-in and wash-out phases. The BIS values were 66.5 ± 3.1 and 55.3 ± 5.5 at 0.5 MAC, and 54.2 ± 3.7 and 42.4 ± 5.8 at1 MAC in halothane and isoflurane groups respectively. At 1.5 MAC, BIS values were 40.1 ± 5.2 and 34.7 ± 4.5 respectively. BIS values were significantly (P<0.05) lower in isoflurane group as compared to halothane group at each target MAC value during anaesthesia. How­ever, BIS-awake did not differ between the halothane and isoflurane groups (89.6 ± 4.2 vs 88.2 ± 3.3). The time taken for awakening was 9.2 ± 3.4 min in hal­othane group and 6.3 ± 2.8 min in isoflurane group (P<0.05).

There was no significant difference in heart rate, mean arterial pressure, end-tidal carbon-di-oxide con­centration and oxygen saturation in both groups at vari­ous MAC concentrations. At 1.5 MAC 3 patients in ha­lothane group developed mild hypotension which was corrected by fluid administration. No other adverse ef­fect was recorded in any group.

   Discussion Top

The results of our study showed that the BIS val­ues were less during isoflurane anaesthesia than during halothane anaesthesia at equivalent MAC levels. This observation is probably consistent with the greater meta­bolic suppression caused by isoflurane and also its abil­ity to produce a higher degree of brain electrical activity suppression than halothane [6] . BIS incorporates different information from the raw EEG : power and frequency, (3 activation, and burst suppression are integrated in a single number. Halothane and isoflurane differently affect spectral power and median power of EEG . Halothane produces relatively fast EEG rhythms whereas isoflurane produces mainly slow waves. In addition isoflurane pro­duces burst suppression within the clinical dosage range whereas halothane does not [7],[8] . These known differences in the effects of halothane and isoflurane on EEG are expected to influence the BIS value differently at a similar depth of anaesthesia.

The difference in BIS values between the two groups may be due to the different mechanism of anaesthetic action of the two agents. Halothane is known to have a greater analgesic and immobilizing effect (through its spi­nal action) as compared to isoflurane [9] . The BIS does in­deed selectively measure the hypnotic or obtunding as­pects of anaesthesia rather than the immobilizing action of anaesthesia. At low concentrations of anaesthetic agent the predominant EEG determinant is arousal and the BIS is less agent specific. This is consistent with the findings that BIS-awake values were similar between the agents. As the concentration increases, the effects of arousal are less, and the effects of anaesthetics are greater and the BIS may be more agent-specific [5] . In a previous study in children, Davidson et al, also reported significant low BIS values with isoflurane than halothane at 1MAC but not at awakening10.

BIS values in a range of 40-60 have been proposed for producing adequate degree of hypnosis during ana­esthesia. In present study we found that the BIS value at 1 MAC of halothane (54.2 ± 3.7) was adequate for hypnotic effect .In contrast the BIS value at 1 MAC of isoflurane was 42.4 ± 5.8. which shows the possibility that 1 MAC of isoflurane is more than enough for ad­equate hypnotic effect. This finding is in consistent with the fact that the use of BIS monitoring for titration of anaesthetic agent reduces intraoperative isoflurane con­sumption [11] . However, the use of BIS for titration of ana­esthesia in unparalyzed patients cannot predict the like­lihood of movement [12] .

In conclusion, at equi-MAC end tidal concentrations isoflurane produces less BIS values than halothane. The BIS values for volatile anaesthetics may be drug specific.

   References Top

1.RampilIJ, MasonP, SinghH. Anestheticpotency (MAC) is independent of forebrain structures in the rat. Anesthesiology 1993;78:707-12.  Back to cited text no. 1      
2.Glass PS, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997; 86: 836-47.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.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. 3  [PUBMED]  [FULLTEXT]  
4.Olofsen E, Dahan Albert. The dynamic relationship between end-tidal sevoflurane and isoflurane concentrations and bispectral index and spectral edge frequency of the electroen­cephalogram. Anesthesiology 1999; 90: 1345-53.  Back to cited text no. 4      
5.Schwab H S, Seeberger MD, Eger II EI, Kindler CH, Fillipovic 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. 5      
6.Johnson CB, Taylor PM. Comparison of the effects of hal­othane, isoflurane and methoxyflurane on the electroencepha­logram of the horse. Br J Anaesth 1998; 81: 748-53.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]  
7.Lioyd-Thomas AR, Cole PV, Prior PF. Quantitative EEG and brainstem auditory evoked potentials: comparison of isoflurane with halothane using the cerebral function analyzing monitor. Br J Anaesth 1990; 65: 306-12.  Back to cited text no. 7      
8.Yli-Hankala A, Eskola H, Kaukinen S. EEG spectral power during halothane anesthesia. Acomparison of spectral bands in the monitoring of anaesthesia level. Acta Anaesthesiol Scand 1989; 33: 304-308.  Back to cited text no. 8  [PUBMED]    
9.Jinks SL, Martin JT, Carstens E, Jung SW, Antogini JF. Peri­MAC depression of a nociceptive withdrawal reflex is accom­panied by reduced dorsal horn activity with halothane but not isoflurane. Anesthesiology 2003; 98: 1128-38.  Back to cited text no. 9      
10.Davidson AJ, Czarnecki C. The bispectral index in children: com­paring isoflurane and halothane. Br J Anaesth 2004; 92: 14-17.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Guignard B, Coste C, Mentgaux C, Chauvin M. Reduced isoflurane consumption with bispectral index monitoring. Acta Anaesthesiol Scand 2001; 45: 308-14.  Back to cited text no. 11      
12.Vernon J M, Lang E, Sebel P S, Manberg P. Prediction of movement using bispectral encephalographic analysis during propofol/alfentanil or isoflurane/alfentanil anesthesia. AnesthAnalg1995;80:780-5.  Back to cited text no. 12      


  [Figure 1]

  [Table 1]


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