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The Effect of Bispectral Index Monitoring on Anesthetic Use and Recovery in Children Anesthetized with Sevoflurane in Nitrous Oxide

Bannister, Carolyn F. MD; Brosius, Keith K. MD; Sigl, Jeffrey C. PhD*; Meyer, Barbara J. RN; Sebel, Peter S. MB, BS, PhD, MBA

doi: 10.1097/00000539-200104000-00015
Pediatric Anesthesia: Research Report

The utility of bispectral index (BIS) monitoring to guide anesthetic administration has been demonstrated in adults. This prospective, randomized observer-blinded study was designed to evaluate the effect of BIS monitoring on anesthetic use and recovery characteristics in pediatric patients. After data collection in 38 historical controls, 202 patients age 0–18 yr were randomized into one of two groups: standard practice (SP) and BIS guided (BIS). Patients age 0–3 yr undergoing inguinal hernia repair (IH) and patients age 3–18 yr undergoing tonsillectomy and/or adenoidectomy (TA) were selected. All patients were anesthetized with sevoflurane in 60% N2O/O2. Hernia patients also received a caudal epidural anesthetic before surgery. In the BIS group, anesthetic delivery was adjusted in an effort to achieve a target BIS of 45–60 during maintenance and 60–70 during the last 15 min of the procedure. BIS was recorded throughout surgery in all patients, but data were unavailable to the anesthesiologist in the SP group. In the TA patients, BIS monitoring was associated with a significant reduction in end-tidal sevoflurane concentration during maintenance (2.4 ± 0.6%, SP and 1.8 ± 0.4% BIS, mean ± sd) and during the last 15 min of the procedure (2.1 ± 0.7, SP and 1.6 ± 0.6, BIS). There was a 25%–40% decrease in measured recovery times. In the patients 0–6 mo of age undergoing IH, sevoflurane concentrations during maintenance (2.0 ± 0.4% SP, 0.9 ± 0.8 BIS), during the last 15 min (1.6 ± 0.4% SP, 0.6 ± 0.6% BIS), and at the end of the procedure (1.1 ± 0.6% SP, 0.3 ± 0.3% BIS) were smaller in the BIS group. Emergence and recovery measures were unaffected by BIS titration. In the children 6 mo-3 yr of age, there were no significant differences between the SP and BIS groups in anesthetic use or recovery measures.

Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, and *Aspect Medical Systems, Newton, Massachusetts

Supported, in part, by a grant from Aspect Medical Systems. Dr. Jeffrey Sigl is an employee of and Dr. Peter Sebel a paid consultant to Aspect Medical Systems, Inc.

October 31, 2000.

Address correspondence and reprint requests to Carolyn F. Bannister, MD, Department of Anesthesiology, Children’s Healthcare of Atlanta at Egleston, 1405 Clifton Road, NE, Atlanta, GA 30322-1101. Address e-mail to

IMPLICATIONS: Bispectral index monitoring in children results in less anesthetic use and faster recovery than standard practice.

The bispectral index (BIS) correlates with the level of hypnosis in adult patients during general anesthesia (1–3). Anesthetic titration using BIS monitoring reduces anesthetic requirements and shortens recovery in adult surgical patients (4–5). The BIS algorithm is based on a retrospective analysis of adult electroencephalogram (EEG) data (6), and there are limited data on its applicability in pediatric practice. The studies relating anesthetic concentration to clinical end points performed in adults cannot be replicated in the pediatric population. Children cannot be expected to participate in volunteer studies involving general anesthesia, and assessments relying on response to verbal command or memory function are unreliable in this population. However, a recently published report indicates that the relationship between BIS and sevoflurane concentration in children aged 0–12 years (7) is similar to that seen in adult patients (2). Although a similar BIS/anesthetic concentration relationship may exist in pediatric patients, there are no data in pediatric patients demonstrating the utility of BIS monitoring in reducing anesthetic requirements or recovery times.

This study was designed to evaluate in a prospective, randomized, observer-blinded manner, the effect of BIS monitoring on the anesthetic requirements and recovery times in pediatric patients undergoing general anesthesia with sevoflurane. We hypothesized that the utility of BIS titration during sevoflurane/nitrous oxide (N2O) anesthesia in children aged 0–18 years would be similar to that demonstrated in adult patients and would reduce anesthetic requirements and shorten recovery times.

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After IRB approval and written parental informed consent, 240 patients were enrolled in the study. During a preliminary baseline phase before starting randomization, we collected relevant data from 38 of these patients, designated in the results as “historical controls.” These control patients were anesthetized according to our usual standard practice. BIS monitoring was used solely for data collection. The anesthetic team was blinded to BIS and no anesthetic titration occurred. These patients were used to test for learning bias (8) or changing clinical practice in the Standard Practice group during the trial.

The 202 patients entered into the main study were divided into 2 age groups: 0–3 yr and 3–18 yr. The most common surgical procedure performed in each age group in our institution was chosen to define the study population. On that basis, the study was limited to inguinal hernia repair (IH) in the 0–3 yr group and to tonsillectomy and/or adenoidectomy (TA) in the 3–18 yr group. Patients were randomized within each age group to one of the two treatment groups, standard practice (SP) or BIS-guided (BIS).

Before induction of anesthesia, frontotemporal EEG electrodes were applied to the forehead using standard adult sensor strips (Aspect Medical Systems, Newton, MA). All impedances were <5 kΩ. EEG signals were recorded using an A-1050 EEG monitor(Aspect Medical Systems, Newton, MA) and BIS (v 3.3) was calculated. Raw EEG and BIS values were recorded on a microcomputer for subsequent offline analysis. In the control and SP groups, BIS was recorded, but the anesthesiologist was blinded as to BIS data. In the BIS group, BIS data were visible and used to guide anesthetic administration.

Patients less than 6 mo old were unpremedicated. In the patients age 6 mo to 3 yr, oral midazolam 0.3–0.75 mg/kg was used at the discretion of the anesthesiologist on the basis of accepted criteria for the administration of preoperative medication in pediatric patients. Induction of anesthesia was with sevoflurane 8% in 60% N2O in oxygen. After loss of consciousness, IV access was obtained and a nondepolarizing neuromuscular blocking drug was administered to facilitate endotracheal intubation. After endotracheal intubation, in the IH group, a caudal epidural block was performed with 0.75–1.0 mL/kg bupivacaine 0.25% containing epinephrine 5 μg/mL. Maintenance anesthesia consisted of sevoflurane in 60% N2O/oxygen. No other sedatives or hypnotics were administered. In patients over 6 mo of age, fentanyl 1–2 μg/kg or morphine 0.05–0.1 mg/kg was administered at the discretion of the anesthesiologist in accordance with usual clinical indications.

In the control and SP groups, sevoflurane administration was at the discretion of the anesthesiologist using clinical signs and hemodynamic changes to adjust anesthetic concentration. In the BIS groups, sevoflurane was adjusted in an effort to achieve a target BIS of 40–60 during maintenance of anesthesia and 60–70 during the last 15 min of surgery. Sevoflurane concentrations were measured using a Capnomac Ultima gas analyzer (Datex Medical Instrumentation, Inc., Helsinki, Finland) and end-tidal concentrations were continuously recorded by a microcomputer. At the completion of surgery, and after confirmation of return of neuromuscular function, sevoflurane and N2O were simultaneously discontinued. The following times were measured:

  • End of surgery to first movement response
  • End of surgery to extubation
  • End of surgery to postanesthesia care unit (PACU) discharge readiness

Extubation was performed when the patients demonstrated purposeful movement, facial grimace, or eye opening to jaw thrust. PACU discharge readiness was defined as a score of 12 or more, with no zeros, on a modified 16-point Aldrete scale (9) and a room air O2 saturation ≥ 94%. A single observer, blinded as to patient group, was responsible for all PACU discharge assessments.

The average end-tidal sevoflurane concentration during maintenance and the BIS during maintenance were calculated using data from time of skin incision to 15 min before end of surgery. All data points were used to calculate an average for each patient and then pooled for each group. Similarly, the end-tidal sevoflurane concentration during the last 15 min of the procedure and BIS during the last 15 min of the procedure were calculated using the data from 15 min before end of surgery. The end-tidal sevoflurane concentration at the end of the procedure and BIS at the end of the procedure are the last values recorded before discontinuation of the anesthetic. A log transform was applied to variables that were not normally distributed, as determined by the Kolmogorov-Smirnov statistic. Parametric data between the BIS group and SP group as well as between the SP group and historical controls were compared by using Bonferroni-corrected t-tests. χ2 was used to compare gender distribution. Data are reported as mean ± sd. A P value of <0.05 was considered significant.

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There were no statistically significant differences in demographic data among the groups (Table 1). Patients <6 mo of age received neither premedication nor opioids. In the 6 mo-3 yr age group, 9 controls, 28 SP patients, and 28 BIS patients received oral midazolam premedication. In the patients over 3 yr of age (TA), 19 controls, 31 SP patients, and 31 BIS patients received midazolam premedication. In the 6 mo-3 yr age group, 2 controls, 2 SP patients, and 3 BIS patients received fentanyl. In the patients over 3 yr of age (TA), 19 controls, 35 SP patients, and 37 BIS patients received opioids. There were no statistically significant differences among groups for mean arterial pressure or heart rate recorded during surgery. There were no differences in any measured variable between historical control and SP groups in all age ranges.

Table 1

Table 1

During the conduct of the study, we unexpectedly discovered that the BIS response of infants under 6 mo of age was uncharacteristic of that seen in older children and adults. For this reason, we report results in the IH patients subdivided into two groups, 0–6 mo of age and 6 mo to 3 yr of age rather than the single 0–3 yr age group defined in the protocol. The data for patients undergoing IH are displayed in Tables 1–3 stratified by age.

Table 2

Table 2

Table 3

Table 3

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Children Aged 3–18 Yr (TA Group)

End-tidal sevoflurane concentrations during maintenance and during the last 15 min of the case were significantly smaller in the BIS group compared with SP. BIS values in this group were also significantly higher during the last 15 min of the case and at the end of the procedure compared with SP group. There were no intergroup differences between SP and control group (Table 2).

Patients in the BIS group responded earlier, were extubated earlier, and were ready for PACU discharge significantly earlier than the SP group with time differences varying from 25% to 40%. There were no intergroup differences between SP and control (Table 3).

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Children Aged 6 Mo–3 Yr (IH Group)

In patients aged 6 mo-3 yr, there were no intergroup differences in sevoflurane concentrations, intraoperative BIS values, or recovery measures.

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Patients Aged 0–6 Mo (IH Group)

In the 0–6 mo BIS-monitored IH group, adjustment of sevoflurane concentration to target BIS values proved problematic. We frequently found that, despite severe reductions in sevoflurane administration, BIS values remained below the minimum target of 40. Maintenance BIS in the 0–6 mo age group was 35.7 ± 9.6 despite significantly smaller than anticipated end-tidal sevoflurane concentrations. In this subset of patients, because of difficulties associated with achieving target BIS values that occasionally required early discontinuation of sevoflurane, simultaneous discontinuation of sevoflurane and N2O could not be performed at the end of surgery according to protocol in all cases.

Average end-tidal sevoflurane concentrations during maintenance, during the last 15 min of the procedure, and at the end of the procedure were significantly and markedly smaller in the BIS versus SP group (Table 2). There were no differences among control, SP, and BIS groups in any recovery variables (Table 3).

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BIS is a measure of anesthetic effect in adult volunteers (1) and relates to return of consciousness in adult unstimulated patients (10). Guided anesthetic administration using a BIS target range of 45–60 is associated with a reduction in propofol use and faster anesthetic recovery (4,11). Similar reductions in volatile anesthetic usage and faster recovery were seen with inhaled anesthesia based on sevoflurane (5), desflurane (5,11), and isoflurane (12).

However, there are limited data on the use of BIS monitoring in children. The index was derived from adult EEGs (6), but data from children age 0–12 years of age (7) indicate that the sevoflurane/BIS dose-response relationship is similar in children breathing sevoflurane/N2O to that seen in adults breathing sevoflurane/O2(2). The concentration of sevoflurane for BIS = 50 (95% CI) was 1.55% (1.40–1.70) for infants < 2 years and 1.25% (1.12–1.37) for children age 2–12 years (7). In adults breathing sevoflurane/oxygen, sevoflurane concentration for BIS = 45 is 1.4%(2).

Our findings in patients aged 3–18 years undergoing TA are consistent with previous findings in adults. BIS-guided anesthetic management was associated with a significant reduction in anesthetic consumption and faster recovery. We found a 25% reduction in maintenance concentration of sevoflurane compared with non-BIS-titrated patients. Recovery times were 25%–40% faster in BIS-titrated patients.

In our population of children aged 6 months to 3 years undergoing IH with combined caudal epidural/general anesthesia, titrating anesthetic to BIS values did not reduce anesthetic requirements or speed recovery. Anesthetic concentrations, drug usage, BIS values, and recovery times in the SP group were not different from those in the BIS-titrated group. All patients undergoing IH had a caudal epidural anesthetic placed after anesthetic induction and before surgical incision. Thus, the expected effects of surgical stimulation on anesthetic requirements may have been attenuated. Additionally, in the setting of a caudal epidural block, less anesthetic is required to maintain hemodynamic stability (13). The anesthesiologist, aware that a caudal epidural block had been placed, may have made adjustments in anesthetic dose based on that information alone. Thus, the presence of a regional block likely influenced the conduct of the anesthetic in the direction of “lighter” anesthesia, whether or not BIS was used to guide anesthetic administration. This is supported by the similarity in BIS values during surgery in the historical control, SP, and BIS-guided groups. In IH patients 6 months-3 years of age, the historical control and SP groups demonstrated maintenance BIS values in the target range in the absence of active BIS titration.

As we gained experience in using BIS to guide anesthetic administration in patients <6 months old with a caudal epidural block in place, it became apparent that, in an effort to attain target BIS values, it was necessary to markedly reduce or discontinue volatile anesthetic administration. This represented a separate population because BIS values associated with unconsciousness in adults could be maintained in these infants with a caudal anesthetic, N2O, and minimal sevoflurane. Despite markedly reduced anesthetic administration, there were no differences among study groups in this age range with respect to mean arterial pressure and heart rate, and neither the BIS nor the SP group exhibited hemodynamic signs of light anesthesia. We found that emergence and recovery times were not affected by the presence of BIS. All patients in this group had caudal epidural blocks in place, and therefore these data should not be extrapolated to children without regional blockade.

Our inability to achieve target BIS values in the 0–6 month age group may be because of a fundamental difference in EEG in this population. EEGs in small infants are different than those in adults because brain maturation and synapse formation is occurring in the early months of life (14–16). Another potential explanation for our observation may be that 60% N2O alone is in fact sufficient to maintain a deep hypnotic state in this infant population. Until additional data are available relating inhaled anesthetic concentration to BIS in children <6 months of age, BIS data should be interpreted with caution.

In summary, in our patients 0–6 months of age undergoing IH with combined general/regional anesthesia, BIS-guided anesthetic titration led to decreased anesthetic use but did not affect emergence or recovery times. In our population of children age 6 months-3 years undergoing IH with combined regional/general anesthesia, titrating anesthetic to BIS values did not reduce anesthetic requirements or speed recovery. In older children undergoing TA surgery, we found that BIS-guided anesthetic management was associated with a significant reduction in anesthetic use, earlier emergence, and shorter recovery.

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