THE Bispectral Index (BIS) is a derived parameter from the scalp electroencephalogram used for monitoring the level of consciousness during administration of anesthetics and hypnotics. 1BIS has been shown to correlate well with anesthetic depth for a number of agents, but it has not been studied with halothane. 1–4Typically, BIS values of 65–80 are indicative of loss of conscious information processing and recall, and when appropriately used, BIS can be useful for reducing the risk of intraoperative awareness. 5 

During halothane anesthesia, however, we observed BIS values to be higher (55–70 U) than those observed with equi-potent concentrations of isoflurane or sevoflurane (35–50 U) and desflurane (∼ 45–50 U). These observations suggest that BIS values obtained during halothane might lead an unwary clinician to underestimate the depth of anesthesia. The present study was undertaken to investigate whether BIS remains elevated throughout the range of clinical halothane anesthetic concentrations.

With the approval of the Institutional Review Board at the University of South Florida, Tampa, Florida, we studied 19 consenting patients of American Society of Anesthesiologists physical status I or II who were scheduled for breast surgery. The choice of anesthetic was randomized, and exclusion criteria included subjects receiving β-adrenergic antagonists, those who received preoperative sedatives or any medication that might affect the electroencephalogram, and pregnancy. No patient received premedication or other sedatives/hypnotics. In the operating room, standard American Society of Anesthesiologists monitors and an adult sensor strip (Aspect A-2000, Bispectral Index® XP version 4.0; Aspect Medical Systems, Newton, MA) were applied. All measured impedances were under 5.0 kΩ. Baseline BIS values were recorded for 3 min before induction of anesthesia. A mask induction with halothane or sevoflurane with 100% oxygen was performed, and patients breathed spontaneously via  a laryngeal mask airway. End-tidal concentrations of anesthetic, oxygen, and carbon dioxide were monitored continuously (Datex Capnomatic, Helsinki, Finland). Volatile anesthetic concentration was titrated to maintain hemodynamic stability during surgical stimulation with a goal of reaching an end-tidal anesthetic concentration equal to 1.3 minimum alveolar concentration (MAC1.3) adjusted for patient age. 6BIS was recorded every 2.5 min throughout the operation. Values recorded at MAC1.3were obtained during a 10-min period of minimal surgical stimulation (e.g. , while awaiting for frozen section results). To ensure end-tidal equilibration of the anesthetic to the brain, BIS values were recorded after maintaining end-tidal concentrations constant for at least 15 min.

Categorical data are presented as raw values, and intergroup statistical contrasts were made using the Pearson chi-square test. Demographic data are summarized as mean ± 1 SD, and intergroup comparisons were made with the Student t  test for independent observations. Outcome data are summarized as mean ± 1 SD, and intergroup statistical comparisons were made with a repeated measures analysis of variance. When the F ratio was significant at the 0.05 level, the Tukey honestly significant difference post hoc  test was used to distinguish intergroup differences. Statistical analyses were performed using Statistica software (version 6.0, StatSoft, Tulsa, OK).

All patients completed the protocol, although one did not complete the awakening portion of the study because of propofol administration at the end of surgery. The two study groups were comparable with respect to demographic data and hemodynamic parameters. The overall mean ages (± SD) for halothane and sevoflurane were 58 ± 15 and 54 ± 14, respectively; similarly, the overall weights were 73 ± 18 and 75 ± 27, respectively. Mean heart rates at MAC1.3were 72 ± 7 and 71 ± 11 for halothane and sevoflurane, respectively; similarly, blood pressure readings at MAC1.3were 76 ± 11 and 74 ± 11, respectively. The mean BIS value at MAC1.3for halothane was significantly higher than that of sevoflurane at equi-potent end-tidal anesthetic concentrations (table 1). Given the differences in BIS at MAC1.3, an unexpected finding was that during emergence, the mean BIS-value at eye opening was the same for both halothane and sevoflurane.

Table 1. Observed BIS Values at Data Collection Points

Values are mean ± SD.

*P < 0.001 comparing halothane and sevoflurane BIS at MAC1.3. Baseline BIS is prior to induction of anesthesia; MAC1.3is during a 10-min period of minimal surgical stimulation.

BIS = bispectral index; MAC = minimum alveolar concentration; SD = standard deviation.

Table 1. Observed BIS Values at Data Collection Points
Table 1. Observed BIS Values at Data Collection Points

Figure 1shows the observed mean BIS values at various end-tidal halothane and sevoflurane concentrations during surgical anesthesia. There was a nearly dose-independent relationship for both agents. Most BIS values for sevoflurane were clustered between 25 and 60; no BIS value was below 38 for halothane and some values were above 70 at MAC > 1.0.

Fig. 1. Mean Bispectral Index (BIS) values recorded at various end-tidal sevoflurane and halothane concentrations during steady-state conditions with minimal surgical stimulation. The triangles  represent halothane and the circles  represent sevoflurane. Note the separation between the halothane and sevoflurane values as well as the dose-independent relationship between BIS values and end-tidal anesthetic concentrations.

Fig. 1. Mean Bispectral Index (BIS) values recorded at various end-tidal sevoflurane and halothane concentrations during steady-state conditions with minimal surgical stimulation. The triangles  represent halothane and the circles  represent sevoflurane. Note the separation between the halothane and sevoflurane values as well as the dose-independent relationship between BIS values and end-tidal anesthetic concentrations.

At MAC1.3,anesthesia was maintained with a mean end-tidal concentration of 0.9%± 0.1 (± SD) halothane and 2.5%± 0.2 sevoflurane. No recall of events occurred in any of the patients studied in either group, as assessed by questioning each subject at the time of discharge from the hospital.

Halothane is a commonly used anesthetic agent in American pediatric anesthesia practice, and it is still used in over 30 countries worldwide. Because BIS values during surgical halothane anesthesia are significantly higher than those seen with other volatile anesthetics, intraoperative BIS values do not accurately reflect the depth of halothane anesthesia and may lead to inadvertent overdosage if vital signs are not closely monitored.

We believe our findings are the result of the differences in electroencephalogram signature of halothane compared to that of sevoflurane. 7Constant et al.  found that clinical concentrations of halothane produce relatively fast electroencephalogram rhythms, whereas sevoflurane produces progressively slower electroencephalogram activity with relatively few fast rhythms. 7 

Because the algorithm for deriving BIS remains proprietary, the impact of halothane anesthesia on BIS values could not have been predicted without clinically derived data. Indeed, the BIS value at MAC1.3for the halothane group is comparable to values observed during light anesthesia with sevoflurane. 8We chose 1.3 MAC as a clinical endpoint to compare halothane and sevoflurane to achieve adequate depth of anesthesia during airway manipulations and surgical stimulation. By contrast, the fact that BIS values at eye opening during emergence were identical for both halothane and sevoflurane supports the use of BIS for monitoring hypnosis during halothane.

Because halothane is widely used in pediatric anesthesia practice, these data may also have significant implications for patient safety in children. BIS monitoring seems to be a promising method for gauging depth of anesthesia in children, 9and the BIS-sevoflurane dose response appears to be similar to that seen in adults. 10Our data, however, suggest that BIS values during halothane anesthesia are likely to be higher than those seen with sevoflurane and may lead an unsuspecting clinician to administer excessive halothane in an attempt to achieve an “adequate” BIS value. Because halothane overdosage is an ongoing source of concern in pediatric anesthesia, understanding how halothane affects the BIS in this population seems warranted.

In summary, we have found that BIS values during surgical levels of halothane anesthesia are significantly higher than those found at equi-potent concentrations of sevoflurane. Caution is warranted when BIS monitoring is used during halothane anesthesia, because unexpectedly high BIS values might give the impression of inadequate anesthetic depth and result in inadvertent overdosage.

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