PEDIATRIC ANESTHESIA: Research Report
Bispectral index (BIS) is a continuously processed electroencephalography (EEG) variable that correlates with the level of sedation in adults (1–4). A linear correlation between BIS and end-tidal sevoflurane concentration has also been observed in infants and children (5). Reliability of BIS in children with mental delay has not been reported. However, the presence of nonprogressive encephalopathy in children with cerebral palsy (CP) may influence BIS values and their correlation with the administration of anesthetics. We performed this study to compare the correlation of BIS values with different sevoflurane concentrations between normal children and those with quadriplegic CP with mental retardation (CPMR).
After IRB approval and parental consent were obtained, 20 profoundly delayed, nonverbal, and noncommunicative children with CPMR (Group I) and 21 mentally normal children with ASA physical status I or II (control group, Group II) between 2 and 14 yr of age and scheduled for elective, nonneurologic surgical procedures were included in the study.
All patients were sedated 15 min before anesthetic induction with midazolam 0.5 mg/kg to a maximum of 15 mg, administered orally. All patients were monitored with an electrocardiograph, pulse oximeter, noninvasive blood pressure, capnograph, oxygen analyzer, and BIS monitor. Anesthesia was induced by inhaled technique with 8% sevoflurane administered for 60 s and 66% nitrous oxide in oxygen with a total fresh gas flow of 6 L/min. After rocuronium administration and endotracheal intubation, anesthesia was maintained with 66% nitrous oxide in oxygen and sevoflurane with a total fresh gas flow of 6 L/min. High fresh gas flow was used to facilitate equilibration of end-tidal sevoflurane with inspired drug concentration.
BIS values were recorded on an Aspect Medical Systems monitor (model A2000, software version 3.21; Natick, MA) using commercially available BIS sensor strips (Aspect Medical Systems) that are designed for use in adults. Placements of the leads was also as recommended in adults—the proximal lead placed above the nasion and the distal lead midway between the outer canthus of the eye and the tragus of the ear. Leads were placed before the induction of anesthesia.
The end-tidal sevoflurane concentrations were measured with a drug monitor (Ohmeda RGM 5250, Hanover, MA). The BIS values were recorded before induction of anesthesia after midazolam premedication; at induction of anesthesia with 8% inspired sevoflurane concentration for 60 s; at steady-state end-tidal sevoflurane concentrations of 1%, 3%, and again at 1%; and after emergence from the anesthetic. A steady state of sevoflurane was considered achieved when the end-tidal concentration reached the desired value and then stayed at that value for 5 min and the BIS value had reached a steady number. It was observed that even at a steady-state end-tidal sevoflurane concentration, BIS values oscillated in a narrow range of approximately five to six points. When a steady state had been achieved, the arithmetic mean of the highest and the lowest BIS values was recorded. All measurements, except the final postanesthetic BIS values, were taken before opioid administration and the commencement of surgery to eliminate the possible influence of these two factors on BIS. Final BIS values were obtained at the end of the surgical procedure when patients reached the preoperative level of consciousness.
The data were analyzed by using SPSSfor Windows(version 10.0; SPSS, Chicago, IL) and expressed as mean ± sd with P < 0.05 considered significant. Statistical analysis included χ2 test for nominal data and t-test for interval data.
There was no significant difference between Group I and Group II in age and sex distribution (P > 0.05). However, children in Group I weighed less than those in Group II (P < 0.05). Seventeen patients in Group I had a history of seizures. Of these 17 patients, 13 were receiving antiseizure medications. No patient in Group II (control group) had any history of seizures.
The BIS values changed inversely with changes in end-tidal sevoflurane concentration in both groups. However, these values were observed to be significantly lower in Group I compared with Group II after sedation before anesthetic induction, at 1% end-tidal sevoflurane concentrations measured at two different times, and after termination of the anesthetic. No significant difference was observed between the two groups at induction of anesthesia when 8% sevoflurane was administered and at 3% end-tidal sevoflurane concentration (Table 1). Also, when the relative changes in BIS were compared at different measurement points with the baseline in that group, no significant difference between the two groups was observed (Fig. 1).
BIS analysis is a statistical technique that allows study of phenomena with a nonlinear character and provides a description of a continuous pseudo-randomly varying signal like EEG (6). BIS analysis measures not only the constituent frequencies and the power that each contributes to the signal, similar to power spectral analysis, it also quantifies the amount of phase coupling among the component sine waves of a signal. It quantifies the level of synchronization in the EEG, which can change as the hypnotic state changes. Several studies indicate that BIS is an effective measure of depth of sedation with propofol, midazolam, isoflurane, and sevoflurane (1–3).
CP is the result of damage in the developing brain and encompasses several symptoms of heterogeneous etiology. Although motor dysfunction is the most common characteristic in these patients, other features commonly seen are epilepsy, mental retardation, and sensory defects. Because there is a wide spectrum of neurologic deficits in children with CPMR, we included in this study only nonverbal and noncommunicative children with spastic quadriplegic CP.
We observed that in both groups, there was an inverse correlation between different end-tidal sevoflurane concentrations at steady state and BIS values. However, in children with CPMR, this correlation was not as close as observed in normal children, indicated by greater variability in BIS values from mean in the former group. Significantly lower BIS values in children with CPMR were observed at four of six measurement points when compared with normal children (Fig. 2).
When larger sevoflurane concentrations were administered at induction (8%) and at steady-state end-tidal concentration of 3%, BIS values were lower in both groups, but the difference between Group I and Group II was not significant. This finding may be related to the loss of linearity in relationship between BIS values and sevoflurane concentration when large concentrations are administered (1). It has been observed that the relationship between sevoflurane concentration and BIS values reaches a plateau before a sevoflurane concentration that completely suppresses clinical response is reached (1). One study actually indicates a paradoxical increase in EEG BIS when inhaled isoflurane concentration is increased. 1
All patients were sedated before obtaining a baseline BIS value. It was observed that unsedated children with CPMR had high muscle tone with strong EMG signals, and, consequently, baseline BIS values in these children were difficult to obtain before sedation. Therefore, we decided to obtain the baseline BIS value in all patients only after sedation in both groups.
A few questions emerged from our study. First, although BIS has been tested and validated in prospective, randomized clinical trials, only adults were used to develop and test the BIS, and values based on adult data may not apply to the pediatric population (7). Formation of synapses and brain maturation continues up to five years of age, and EEG changes have been observed during this period (8). The effect of neuronal and physiologic maturation of the brain on BIS is unknown in pediatric patients. Although the correlation among awareness, level of sedation, and anesthetic outcome with BIS in children has not been published, data from a clinical study in children indicate that BIS values in children are inversely proportional to the end-tidal sevoflurane concentration (5). There is no difference in sevoflurane/BIS dose-response relationship in older children before induction, during maintenance, and on emergence compared with adult values. However, Denman et al. (5) found a concentration-response difference between infants and older children that is consistent with data that minimum alveolar concentration for preventing movement in response to skin incision was larger in children less than one year of age. Another study performed by Davidson et al. (9) in infants and older children observed a progressive increase in BIS values in older children when the end-tidal concentration of sevoflurane was decreased from 0.9% to 0.5%; no such relationship could be established in infants.
Second, development of BIS is based on the studies conducted on mentally normal patients and, therefore, suitability and reliability of such a monitor on neurologically abnormal children is questionable. Validation of BIS in mentally normal children with validated sedation scales may be possible, but such validation in mentally subnormal children may be tenuous. In one patient with genetically determined low-voltage EEG, BIS was observed to be abnormally low (awake baseline = 40) (10). Also, the majority of patients in the CPMR group (Group I) had a history of seizures and were taking antiseizure medications. It is unknown whether the presence of seizures or the administration of various antiseizure medications affects BIS values.
With the available data and our present understanding of this depth of sedation monitor, we concluded from our study that, in children with CPMR, BIS monitoring exhibited a similar pattern of change as observed in normal children. However, absolute BIS values obtained in such children are lower than those in normal children while awake and at different end-tidal sevoflurane concentrations at steady state.
1 Detsch O, Schneider G, Hapfelmeier G, et al. Increasing isoflurane may induce paradoxical increase in EEG bispectral index (BIS) [abstract]. Anesthesiology 1998;89:A363.
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© 2002 International Anesthesia Research Society
10. Schnider TW, Luginbuhl M, Petersen-Felix S, Mathis J. Unreasonably low bispectral index values in a volunteer with genetically determined low-voltage electroencephalographic signal. Anesthesiology 1998; 89: 1607–8.