Spectral entropy as a measure of hypnosis in children

BACKGROUND: The Datex-Ohmeda S/5 Entropy Module (Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland), using time-frequency balanced Spectral Entropy, is a novel tool for monitoring the hypnotic state during anesthesia. The Entropy Module produces two values, State Entropy (SE) and Response Entropy (RE), and in adults, it has been shown to measure reliably the hypnotic effects of various drugs. In children, Spectral Entropy has been only preliminary studied. The authors' aim was to study Spectral Entropy as a marker of hypnotic state during general anesthesia in infants and children. METHODS: Twenty infants (aged 1 month-1 yr) and 40 children (aged 1-15 yr) were anesthetized for surgery using standardized sevoflurane-nitrous oxide-based anesthesia. The relationships between SE, RE, or Bispectral Index (BIS) and (1) a modified Observer's Assessment of Alertness/Sedation Scale, (2) non-steady state end-tidal concentration of sevoflurane, (3) steady state end-tidal concentration of sevoflurane, and (4) hemodynamic values were calculated using prediction probability, nonlinear regression, and correlation coefficients, as appropriate. The performances of SE, RE, and BIS were compared. RESULTS: The prediction probability values (+/- SEM) of SE, RE, and BIS versus the modified Observer's Assessment of Alertness/Sedation Scale in the induction phase were 0.83 +/- 0.06, 0.88 +/- 0.06, and 0.87 +/- 0.08 for children and 0.76 +/- 0.08,0.79 +/- 0.08, and 0.73 +/- 0.10 for infants; values in the emergence phase were 0.68 +/- 0.05, 0.74 +/- 0.04, and 0.64 +/- 0.05 for children and 0.64 +/- 0.07, 0.69 +/- 0.06, and 0.72 +/- 0.06 for infants, respectively. SE, RE, and BIS values were inversely proportionally related to the end-tidal concentration of sevoflurane for children, but for infants, the correlation was much less clear. No significant correlations were found between SE, RE, or BIS values and the hemodynamic values. CONCLUSIONS: Spectral Entropy may be a useful tool for measuring the level of hypnosis in anesthetized children and seems to perform as well as BIS. In infants, the clinical usefulness of both these electroencephalogram-derived methods must be evaluated in further controlled studies.     

Spectral entropy and bispectral index as measures of the electroencephalographic effects of sevoflurane

BACKGROUND: Recently, entropy algorithms have been proposed as electroencephalographic measures of anesthetic drug effects. Datex-Ohmeda (Helsinki, Finland) introduced the Entropy Module, a new electroencephalographic monitor designed for measuring depth of anesthesia. The monitor calculates a state entropy (SE) computed over the frequency range of 0.8-32 Hz and a response entropy (RE) computed over the frequency range of 0.8-47 Hz. The authors investigated the dose-response relation of SE and RE during sevoflurane anesthesia in comparison with the Bispectral Index (BIS). METHODS: Sixteen patients were studied without surgical stimulus. Anesthesia was induced by sevoflurane inhalation with a tight-fitting facemask. Sevoflurane concentrations were increased and subsequently decreased and increased two to four times until the measurement was stopped and patients were intubated for surgery. The performances of SE, RE, and BIS to predict the estimated sevoflurane effect site concentration, obtained by simultaneous pharmacokinetic and pharmacodynamic modeling, were compared by calculating the correlation coefficients and the prediction probability. RESULTS: State entropy, RE, and BIS values decreased continuously over the observed concentration range of sevoflurane. Correlation coefficients were slightly but not significantly better for entropy parameters (0.87 +/- 0.09 and 0.86 +/- 0.10 for SE and RE, respectively) than for BIS (0.85 +/- 0.12). Calculating the prediction probability confirmed these results with a prediction probability of 0.84 +/- 0.05 and 0.82 +/- 0.06 for SE and RE, respectively, and 0.80 +/- 0.06 for BIS. CONCLUSION: State entropy and RE seem to be useful electroencephalographic measures of sevoflurane drug effect.     

Spectral Entropy and Bispectral Index as Measures of the Electroencephalographic Effects of Sevoflurane

Background: Recently, entropy algorithms have been proposed as electroencephalographic measures of anesthetic drug effects. Datex-Ohmeda (Helsinki, Finland) introduced the Entropy Module, a new electroencephalographic monitor designed for measuring depth of anesthesia. The monitor calculates a state entropy (SE) computed over the frequency range of 0.8-32 Hz and a response entropy (RE) computed over the frequency range of 0.8-47 Hz. The authors investigated the dose-response relation of SE and RE during sevoflurane anesthesia in comparison with the Bispectral Index (BIS).

Methods: Sixteen patients were studied without surgical stimulus. Anesthesia was induced by sevoflurane inhalation with a tight-fitting facemask. Sevoflurane concentrations were increased and subsequently decreased and increased two to four times until the measurement was stopped and patients were intubated for surgery. The performances of SE, RE, and BIS to predict the estimated sevoflurane effect site concentration, obtained by simultaneous pharmacokinetic and pharmacodynamic modeling, were compared by calculating the correlation coefficients and the prediction probability.

Results: State entropy, RE, and BIS values decreased continuously over the observed concentration range of sevoflurane. Correlation coefficients were slightly but not significantly better for entropy parameters (0.87 +/- 0.09 and 0.86 +/- 0.10 for SE and RE, respectively) than for BIS (0.85 +/- 0.12). Calculating the prediction probability confirmed these results with a prediction probability of 0.84 +/- 0.05 and 0.82 +/- 0.06 for SE and RE, respectively, and 0.80 +/- 0.06 for BIS.     

Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia

BACKGROUND: Time-frequency balanced spectral entropy of electroencephalogram (EEG) and frontal electromyogram (FEMG) is a novel measure of hypnosis during anesthesia. Two Entropy parameters are described: Response entropy (RE) is calculated from EEG and FEMG; and State Entropy (SE) is calculated mainly from EEG. This study was performed to validate their performance during transition from consciousness to unconsciousness under different anesthetic agents. METHODS: Response entropy, SE [S/5 Entropy Module, M-ENTROPY (later in text: Entropy), Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland] and BIS (BIS XP, A-2000, Aspect Medical Systems, Newton, MA) data were collected from 70 patients; 30 anesthetized with propofol 2 mg kg-1, 20 with sevoflurane inhalation, and 20 with thiopental 5 mg kg-1. Loss and regaining of consciousness (LOC, ROC) was tested every 10 s, and sensitivity, specificity, and prediction probability (Pk) were calculated. Behavior of the indices was studied. RESULTS: Sensitivity, specificity, and Pk values for consciousness were high and similar for all indices. During regaining of consciousness after propofol bolus, RE, SE, and BIS values recovered by 81 +/- 22%, 75 +/- 26%, and 59 +/- 18% (mean +/- SD), respectively, from the minimum relative to their baseline. After thiopental bolus, RE, SE, and BIS values recovered by 86+/-21%, 88 +/- 13%, and 63 +/- 14%, respectively. The relative rise was higher in RE and SE compared with BIS (P < 0.01). During deep levels of hypnosis, RE and SE decreased monotonously as a function of burst suppression ratio, while BIS showed biphasic behavior. On average, RE indicated emergence from anesthesia 11 s earlier than SE, and 12.4 s earlier than BIS. CONCLUSIONS: All indices, RE, SE, and BIS, distinguished excellently between conscious and unconscious states during propofol, sevoflurane, and thiopental anesthesia. During burst suppression, Entropy parameters RE and SE, but not BIS, behave monotonously. During regaining of consciousness after a thiopental or propofol bolus, RE and SE values recovered significantly closer to their baseline values than did BIS. Response entropy indicates emergence from anesthesia earlier than SE or BIS.     

Spectral entropy and bispectral index as measures of the electroencephalographic effects of propofol

Recently, Datex-Ohmeda introduced the Entropy Moduletrade mark for measuring depth of anesthesia. Based on the Shannon entropy of the electroencephalogram, state entropy (SE) and response entropy (RE) are computed. We investigated the dose-response relationship of SE and RE during propofol anesthesia in comparison with the Bispectral Indextrade mark (BIS). Twenty patients were studied without surgical stimulus. Anesthesia was induced by a constant propofol infusion of 2000 mg/h (451 +/- 77 microg x min(-1) x kg(-1)) via a large forearm vein. Propofol was infused until substantial burst suppression occurred (more than 50%) or mean arterial blood pressure decreased to <60 mm Hg. Hereafter, infusions were stopped until recovery of BIS values up to 60 was reached. Subsequently, the constant propofol infusion of 2000 mg/h was restarted to increase depth of anesthesia and again decreased (infusion was stopped) within the BIS value range of 40-60. The coefficient of determination (R2) and the prediction probability (P(K)) were calculated to evaluate the performance of SE, RE, and BIS to predict changing propofol effect-site concentrations. R2 values for SE, RE, and BIS of 0.88 +/- 0.08, 0.89 +/- 0.07, and 0.92 +/- 0.06, respectively, were similar. The calculated P(K) values, however, revealed a significant difference between SE and RE compared with BIS, with P(K) = 0.77 +/- 0.09, 0.76 +/- 0.10, and 0.84 +/- 0.06, respectively. BIS seems to show slight advantages in predicting propofol effect-site concentrations compared with SE and RE, as measured by P(K) but not as measured by R2.     

Comparative evaluation of the Datex-Ohmeda S/5 Entropy Module and the Bispectral Index monitor during propofol-remifentanil anesthesia

BACKGROUND: Different analytical concepts were introduced to quantify the changes of the electroencephalogram. The Datex-Ohmeda S/5 Entropy Module (Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland) was the first commercial monitor based on the entropy generating two indices, the state entropy (SE) and the response entropy (RE). The aim of the current study was to compare the accuracy of SE and RE with the Bispectral Index(R) monitor (BIS(R); Aspect Medical Systems, Newton, MA) during propofol-remifentanil anesthesia. METHODS: The authors investigated 20 female patients during minor gynecologic surgery. SE, RE, BIS, mean arterial blood pressure, heart rate, and sedation level were recorded every 20 s during stepwise increase (target-controlled infusion, 0.5 microg/ml) of propofol until the patients lost response. Five minutes after loss of response, remifentanil infusion (0.4 microg . kg(-1) . min(-1)) was started. Spearman correlation coefficient and prediction probability were calculated for sedation levels with SE, RE, BIS, mean arterial blood pressure, and heart rate. The ability of the investigated parameters to distinguish between the anesthesia steps awake versus loss of response, awake versus anesthesia, anesthesia versus first reaction, and anesthesia versus extubation was analyzed with the prediction probability. RESULTS: SE correlates best with sedation levels, but no significant differences of the prediction probability values among SE, RE, and BIS were found. The prediction probability for all investigated steps of anesthesia did not show significant differences among SE, RE, and BIS. SE, RE, and BIS were superior to mean arterial blood pressure and heart rate. CONCLUSION: SE, RE, and BIS revealed similar information about the level of sedation and allowed the authors to distinguish between different steps of anesthesia. Both monitors provided useful additional information for the anesthesiologist.     

Comparative Evaluation of the Datex-Ohmeda S/5 Entropy Module and the Bispectral Index® Monitor during Propofol-Remifentanil Anesthesia

Background: Different analytical concepts were introduced to quantify the changes of the electroencephalogram. The Datex-Ohmeda S/5 Entropy Module (Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland) was the first commercial monitor based on the entropy generating two indices, the state entropy (SE) and the response entropy (RE). The aim of the current study was to compare the accuracy of SE and RE with the Bispectral Index(R) monitor (BIS(R); Aspect Medical Systems, Newton, MA) during propofol-remifentanil anesthesia.

Methods: The authors investigated 20 female patients during minor gynecologic surgery. SE, RE, BIS, mean arterial blood pressure, heart rate, and sedation level were recorded every 20 s during stepwise increase (target-controlled infusion, 0.5 [mu]g/ml) of propofol until the patients lost response. Five minutes after loss of response, remifentanil infusion (0.4 [mu]g [middle dot] kg-1 [middle dot] min-1) was started. Spearman correlation coefficient and prediction probability were calculated for sedation levels with SE, RE, BIS, mean arterial blood pressure, and heart rate. The ability of the investigated parameters to distinguish between the anesthesia steps awake versus loss of response, awake versus anesthesia, anesthesia versus first reaction, and anesthesia versus extubation was analyzed with the prediction probability.

Results: SE correlates best with sedation levels, but no significant differences of the prediction probability values among SE, RE, and BIS were found. The prediction probability for all investigated steps of anesthesia did not show significant differences among SE, RE, and BIS. SE, RE, and BIS were superior to mean arterial blood pressure and heart rate.     

The differences in the bispectral index between infants and children during emergence from anesthesia after circumcision surgery

The bispectral index (BIS) correlates with consciousness during adult anesthesia. In this prospective, blinded study of children (n = 24) and infants (n = 25) undergoing elective circumcision, we evaluated BIS and consciousness level during emergence from anesthesia. Anesthesia was maintained with sevoflurane, and a penile nerve block was performed in each patient before surgical stimulation. At the completion of surgery, the sevoflurane was decreased stepwise from 0.9% in increments of 0.2%, and arousal was tested with a uniform auditory stimulus given after a steady state of end-tidal sevoflurane concentration was achieved at each step. The BIS increased significantly as the sevoflurane concentrations decreased in children (0.9%, 62.5 +/- 8.1; 0.7%, 70.8 +/- 7.4; and 0.5%, 74.1 +/- 7.1; P < 0.001 for 0.7% and 0.5% compared with 0.9%), but a similar relationship was not demonstrated in infants. The BIS values at 0.7% and 0.5% sevoflurane were significantly higher in children than infants (P < 0.02 and P < 0.002, respectively). In both children and infants, the BIS increased significantly from pre- to postarousal (children, 73.5 +/- 7 to 83.1 +/- 12, P = 0.01; infants, 67.8 +/- 10 to 85.6 +/- 13.6, P < 0.001). The BIS at which arousal was possible with the stimulus tended to be higher in children than in infants (P = 0.06). IMPLICATIONS: In this study comparing the Bispectral index (BIS) in infants and children undergoing circumcision surgery by use of a standardized surgical and anesthetic technique, a significant decrease in BIS was detected in children during a stepwise decrease in end-tidal sevoflurane concentration. A similar relationship was not demonstrated in infants less than 1 yr old. In both children and infants, BIS increased significantly from pre- to postarousal. Additional studies are necessary to determine changes in BIS with maturational changes in the electroencephalogram.     

七氟醚和依托咪酯镇静催眠效应的相互作用

目的 评价七氟醚和依托咪酯镇静催眠效应的相互作用.方法 择期全麻手术患者24例,ASA Ⅰ或Ⅱ级,年龄18～59岁,体重指数17～27 kg/m2.试验Ⅰ 12例患者靶控输注依托咪酯,效应室靶浓度依次为0.05、0.1、0.2、0.3、0.4、0.5 μg/ml.效应室浓度依次达到预设浓度2 min时,记录反应熵(RE)、状态熵(SE)和警觉/镇静(OAA/S)评分,然后停止输注依托咪酯.随机分为3组(n=4),A1组、B1组、C1组吸入七氟醚,呼气末浓度分别为0.5%、1%、2%.七氟醚呼气末浓度达预定浓度的95%或以上时,靶控输注依托咪酯,效应室靶浓度依次为0.2、0.3、0.4、0.5 μg/ml.效应室浓度依次达到预设浓度2 min时,记录RE、SE和OAA/S评分.试验Ⅱ 12例患者吸入七氟醚,呼气末浓度依次为0.5%、1%、2%、3%、4%、5%.依次达到预定呼气末浓度时,记录RE、SE和OAA/S评分,然后停止吸人七氟醚,吸氧洗脱七氟醚.随机分为3组(n=4),A2组、B2组、C2组靶控输注依托咪酯,效应室靶浓度分别为0.05、0.1、0.2 μg/ml.效应室浓度达到预设浓度2 min时,吸入七氟醚,呼气末浓度依次为0.5%、1%、2%、3%、4%、5%.依次达到预定呼气末浓度时,记录RE、SE和OAA/S评分.采用反应曲面法评价RE、SE和OAA/S评分,判断七氟醚和依托咪酯镇静催眠效应的相互作用.结果 RE和SE的相互作用指数的拟合值及其95%可信区间分别为0.32(-0.07～0.71)、0.25(-0.12～0.63)(P>0.05).OAA/S评分的相互作用指数的拟合值及其95%可信区间为2.25(0.58～3.93)(P<0.05).结论 以脑电熵指数反映镇静催眠效应时七氟醚和依托咪酯为相加作用;以OAA/S评分反映镇静催眠效应时七氟醚和依托咪酯为协同作用.     

Pediatric evaluation of the bispectral index (BIS) monitor and correlation of BIS with end-tidal sevoflurane concentration in infants and children

The bispectral index (BIS) has been developed in adults and correlates well with clinical hypnotic effects of anesthetics. We investigated whether BIS reflects clinical markers of hypnosis and demonstrates agent dose-responsiveness in infants and children. In an observational arm of this study, BIS values in children undergoing general anesthesia were observed and compared with similar data collected previously in a study of adults. In a second arm of the study, a range of steady-state end-tidal concentrations of sevoflurane was administered and corresponding BIS documented. Data were examined for differences between infants (0-2 yr) and children (2-12 yr). No difference was seen in BIS values in children before induction, during maintenance, and on emergence compared with adult values. There was no difference in BIS between infants and children at similar clinical levels of anesthesia. In children and infants, BIS was inversely proportional to the end-tidal concentration of sevoflurane. The sevoflurane concentration for a BIS = 50 (95% confidence interval) was significantly different: 1. 55% (1.40-1.70) for infants versus 1.25% (1.12-1.37) for children. Although validation with specific behavioral end points was not possible, BIS correlated with clinical indicators of anesthesia in children as it did in adults: as depth of anesthesia increased, BIS diminished. BIS correlated with sevoflurane concentration in infants and children. The concentration-response difference between infants and children was consistent with data showing that minimum alveolar concentration is higher in children less than 1 yr of age. IMPLICATIONS: The use of bispectral index (BIS) during general anesthesia improves the titration of anesthetics in adults. The data from this study suggest that the same equipment and method of electroencephalogram analysis may be applied to infants and children.     

熵指数监测全麻患者镇静水平的准确性

目的 评价反应熵和状态熵监测全麻患者镇静水平的准确性.方法 择期行腹部手术患者20例,ASAⅠ或Ⅱ级,入室后监测反应熵(RE)、状态熵(SE)及脑电双频谱指数(BIS),静脉注射异丙酚、维库溴铵和芬太尼麻醉诱导,气管插管后机械通气,吸入七氟烷、间断静脉注射维库溴铵和芬太尼维持麻醉.分别于入室时、意识消失前10min、意识消失即刻、气管插管时、手术1 h、意识恢复前10 min、意识恢复即刻、拔管后10 min时记录RE、SE和BIS.结果 RE、SE和BIS在意识改变前后差异均有统计学意义(P＜0.05),RE、SE和BIS判断意识消失的临界值分别为76、73和68,灵敏度分别为94%、95%和92%,特异度分别为92%、94%和9l%,临界值判断意识消失的准确度分别为93%、95%、94%;判断意识恢复的临界值分别为82、75和70,灵敏度分别为95%、95%和91%,特异度分别为93%、96%和93%,临界值判断意识恢复的准确度分别为98%、96%和97%.结论 熵指数能够准确地监测全麻患者镇静水平.     

Bispectral Index values are higher during halothane vs. sevoflurane anesthesia in children, but not in infants

BACKGROUND: Previously, we have shown in adult patients that bispectral index score (BIS) values are significantly higher during halothane anesthesia (53-61 units) as compared with those observed during equipotent concentrations of sevoflurane (39-43 units). Because halothane is frequently used in the pediatric setting, we tested the hypothesis that BIS values observed in children might also be higher during general anesthesia with halothane than with sevoflurane. METHODS: Forty-one healthy, unpremedicated pediatric patients scheduled for elective operations received either halothane or sevoflurane titrated as appropriate for surgical stimulation. RESULTS: During maintenance sevoflurane anesthesia (n=20), the mean BIS values and percent end-tidal concentrations were 44+/-14 and 2.1+/-0.6, respectively, whereas for the halothane group (n=21) the corresponding values were 61+/-7 and 1.1+/-0.4, respectively. CONCLUSION: These findings suggest that BIS values are higher during halothane vs. sevoflurane anesthesia in children, but not in infants.     

Opioid-Volatile Anesthetic Synergy: A Response Surface Model with Remifentanil and Sevoflurane as Prototypes

Background: Combining a hypnotic and an analgesic to produce sedation, analgesia, and surgical immobility required for clinical anesthesia is more common than administration of a volatile anesthetic alone. The aim of this study was to apply response surface methods to characterize the interactions between remifentanil and sevoflurane.

Methods: Sixteen adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the Observer's Assessment of Alertness/Sedation score and response to a series of randomly applied experimental pain stimuli (pressure algometry, electrical tetany, and thermal stimulation) were observed for each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for sedation and analgesic endpoints. Using computer simulation, the pharmacodynamic interaction models were combined with previously reported pharmacokinetic models to identify the combination of remifentanil and sevoflurane that yielded the fastest recovery (Observer's Assessment of Alertness/Sedation score >= 4) for anesthetics lasting 30-900 min.

Results: Remifentanil synergistically decreased the amount of sevoflurane necessary to produce sedation and analgesia. Simulations revealed that as the duration of the procedure increased, faster recovery was produced by concentration target pairs containing higher amounts of remifentanil. This trend plateaued at a combination of 0.75 vol% sevoflurane and 6.2 ng/ml remifentanil.     

Opioid-volatile anesthetic synergy: a response surface model with remifentanil and sevoflurane as prototypes

BACKGROUND: Combining a hypnotic and an analgesic to produce sedation, analgesia, and surgical immobility required for clinical anesthesia is more common than administration of a volatile anesthetic alone. The aim of this study was to apply response surface methods to characterize the interactions between remifentanil and sevoflurane. METHODS: Sixteen adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the Observer's Assessment of Alertness/Sedation score and response to a series of randomly applied experimental pain stimuli (pressure algometry, electrical tetany, and thermal stimulation) were observed for each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for sedation and analgesic endpoints. Using computer simulation, the pharmacodynamic interaction models were combined with previously reported pharmacokinetic models to identify the combination of remifentanil and sevoflurane that yielded the fastest recovery (Observer's Assessment of Alertness/Sedation score > or = 4) for anesthetics lasting 30-900 min. RESULTS: Remifentanil synergistically decreased the amount of sevoflurane necessary to produce sedation and analgesia. Simulations revealed that as the duration of the procedure increased, faster recovery was produced by concentration target pairs containing higher amounts of remifentanil. This trend plateaued at a combination of 0.75 vol% sevoflurane and 6.2 ng/ml remifentanil. CONCLUSION: Response surface analyses demonstrate a synergistic interaction between remifentanil and sevoflurane for sedation and all analgesic endpoints.     

Effect of nitrous oxide on the bispectral index during sevoflurane anesthesia

We studied the effects of nitrous oxide on the relationship between end-tidal sevoflurane concentration and bispectral index (BIS) in patients undergoing abdominal surgery. Anesthesia was maintained with combination of epidural and sevoflurane anesthesia in air (control group; n = 15) or with 67% nitrous oxide (nitrous oxide group; n = 15). The end-tidal sevoflurane concentration was increased by 0.5% every 15 min to 3% and BIS values were recorded at each step. In both groups, sevoflurane decreased BIS values in a dose-dependent manner and the decrease in BIS reached plateau at 2% of sevoflurane. Nitrous oxide with sevoflurane caused more reduction in BIS in comparison with sevoflurane alone. The sevoflurane concentration for BIS at 50 in the nitrous oxide group (0.9 +/- 0.4%) was significantly lower than that in the control group (1.2 +/- 0.4%). The results suggest that the hypnotic effect of sevoflurane was enhanced by the addition of nitrous oxide during abdominal surgery.     

When is a bispectral index of 60 too low?: Rational processed electroencephalographic targets are dependent on the sedative-opioid ratio

BACKGROUND: Opioids are commonly used in conjunction with sedative drugs to provide anesthesia. Previous studies have shown that opioids reduce the clinical requirements of sedatives needed to provide adequate anesthesia. Processed electroencephalographic parameters, such as the Bispectral Index (BIS; Aspect Medical Systems, Newton, MA) and Auditory Evoked Potential Index (AAI; Alaris Medical Systems, San Diego, CA), can be used intraoperatively to assess the depth of sedation. The aim of this study was to characterize how the addition of opioids sufficient to change the clinical level of sedation influenced the BIS and AAI. METHODS: Twenty-four adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the modified Observer's Assessment of Alertness/Sedation score, BIS, and AAI were measured at each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for each pharmacodynamic endpoint. RESULTS: Response surface models adequately characterized all pharmacodynamic endpoints. Despite the fact that sevoflurane-remifentanil interactions were strongly synergistic for clinical sedation, BIS and AAI were minimally affected by the addition of remifentanil to sevoflurane anesthetics. CONCLUSION: Although clinical sedation increases significantly even with the addition of a small to moderate dose of remifentanil to a sevoflurane anesthetic, the BIS and AAI are insensitive to this change in clinical state. Therefore, during "opioid-heavy" sevoflurane-remifentanil anesthetics, targeting a BIS less than 60 or an AAI less than 30 may result in an unnecessarily deep anesthetic state.     

A comparison of state and response entropy versus bispectral index values during the perioperative period

Cerebral monitoring indices are associated with a large degree of inter-patient variability and electrical signal interference during surgery. We designed this clinical study to test the hypothesis that use of the spectral entropy (Entropy) module is associated with less frequent intraoperative interference with the displayed indices than the bispectral index (BIS) monitor when used during general anesthesia with propofol and desflurane. Thirty consenting patients scheduled for major laparoscopic surgery procedures were enrolled in this prospective study. The elapsed time to obtain a baseline index value was recorded, as well as the simultaneous state entropy (SE), response entropy (RE), and BIS values at specific time intervals during the induction, maintenance, and emergence periods in patients administered a standardized general anesthetic technique. During the maintenance period, the changes in these indices were evaluated after a bolus dose of propofol (20 mg IV) and a 2% increase or decrease in the inspired concentration of desflurane. As expected, the baseline SE values were less than the RE and BIS values (88 +/- 2 versus 96 +/- 3 and 96 +/- 4, respectively). However, the SE and RE values correlated with the BIS value during the induction (r = 0.77 and 0.78, respectively) and emergence (r = 0.86 and 0.91, respectively) periods. The area under the receiver operating characteristic curve for detection of consciousness also indicated a similar performance of the SE (0.93 +/- 0.04) relative to the RE (0.98 +/- 0.04) and BIS (0.97 +/- 0.04). During the maintenance period, the responses to changes in propofol and desflurane concentrations were consistent with all three indices. Finally, the entropy indices were less interfered with by the electrocautery unit during the operation (12% versus 62% for the BIS monitor). Because the average selling prices of the Entropy and BIS disposable electrode strips (14.25 dollars versus 14.95 dollars USD, respectively) are comparable, we conclude that the Entropy module is a cost-equivalent alternative to the BIS monitor.     

频谱熵和双频指数用于测定依托咪酯血浆效应室平衡速率常数的比较

目的 比较用熵指数和脑电双频指数(BIS)测定依托咪酯单次注射后的最大效应时间(TpEAK),并藉以估计依托咪酯的血浆-效应室平衡速率常数(Ke0).方法 22例患者静脉注射最大效应负荷剂量依托咪酯后,用熵指数模块和听觉诱发电化监测仪测定从注射开始至反应熵(RE)、状态熵(SE)、BIS最低的时间(TPEAK),用TpEAx和Arden等报道的依托咪酯药代学模型,按照Minto等提出的方法计算KeO.结果 RE、SE、BIS的TpEAx中位数分别为70、70和80 s,Ke0中位数分别是1.10/min、1.10/min和1.02/min.结论 单次注射依托咪酯后,熵指数和BIS监测的TpESK和计算的Ke0相同,且有别于国外研究报道的结果.     

When Is a Bispectral Index of 60 Too Low?: Rational Processed Electroencephalographic Targets Are Dependent on the Sedative-Opioid Ratio

Background: Opioids are commonly used in conjunction with sedative drugs to provide anesthesia. Previous studies have shown that opioids reduce the clinical requirements of sedatives needed to provide adequate anesthesia. Processed electroencephalographic parameters, such as the Bispectral Index (BIS; Aspect Medical Systems, Newton, MA) and Auditory Evoked Potential Index (AAI; Alaris Medical Systems, San Diego, CA), can be used intraoperatively to assess the depth of sedation. The aim of this study was to characterize how the addition of opioids sufficient to change the clinical level of sedation influenced the BIS and AAI.

Methods: Twenty-four adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the modified Observer's Assessment of Alertness/Sedation score, BIS, and AAI were measured at each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for each pharmacodynamic endpoint.

Results: Response surface models adequately characterized all pharmacodynamic endpoints. Despite the fact that sevoflurane-remifentanil interactions were strongly synergistic for clinical sedation, BIS and AAI were minimally affected by the addition of remifentanil to sevoflurane anesthetics.     

Response entropy increases during painful stimulation

Frontal electromyography (FEMG) may increase during painful stimulation and indicate patient arousal. The Datex-Ohmeda Entropy Module calculates state entropy (SE) of the electroencephalogram (EEG; 0.8-32 Hz) and response entropy (RE) of EEG and FEMG (0.8-47 Hz). We determined whether RE increases above SE (RE--SE), an indication of FEMG, increase during painful stimuli and if this is related to paralysis or level of anesthesia. With the unanesthetized baseline measurement, SE was 89 +/- 2 and RE was 98 +/- 2. During paralysis and anesthesia with either 0.8% (n = 10) or 1.4% (n = 10) isoflurane, SE decreased to 63 +/- 7 and 34 +/- 14, respectively, and the RE--SE difference decreased 90%. Before recovery from paralysis, arterial catheter or head pin placement increased RE--SE above unanesthetized levels in eight patients (five treated with 0.8% and three with 1.4% isoflurane), consistent with an increase in FEMG. The elevated RE--SE difference was related to a significant increase in SE, blood pressure, and heart rate. After recovery from paralysis, tetanic stimulation of the ulnar nerve increased the RE--SE difference above unanesthetized levels in 8 of 20 patients (6 treated with 0.8% and 2 with 1.4% isoflurane). In these patients, SE increased significantly. The remaining 12 patients did not show an increase in RE--SE during tetanic stimulation and SE did not increase. We conclude that increased RE during painful stimulation was not dependent on recovery from paralysis but was seen more often in patients anesthetized with 0.8% compared with 1.4% isoflurane. This suggests that RE reflects FEMG and may be useful to identify inadequate anesthesia and patient arousal during painful stimuli.