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.     

Spectral Entropy as an Electroencephalographic Measure of Anesthetic Drug Effect: A Comparison with Bispectral Index and Processed Midlatency Auditory Evoked Response

Background: The authors compared the behavior of two calculations of electroencephalographic spectral entropy, state entropy (SE) and response entropy (RE), with the A-Line(R) ARX Index (AAI) and the Bispectral Index (BIS) and as measures of anesthetic drug effect. They compared the measures for baseline variability, burst suppression, and prediction probability. They also developed pharmacodynamic models relating SE, RE, AAI, and BIS to the calculated propofol effect-site concentration (Ceprop).

Methods: With institutional review board approval, the authors studied 10 patients. All patients received 50 mg/min propofol until either burst suppression greater than 80% or mean arterial pressure less than 50 mmHg was observed. SE, RE, AAI, and BIS were continuously recorded. Ceprop was calculated from the propofol infusion profile. Baseline variability, prediction of burst suppression, prediction probability, and Spearman rank correlation were calculated for SE, RE, AAI, and BIS. The relations between Ceprop and the electroencephalographic measures of drug effect were estimated using nonlinear mixed effect modeling.

Results: Baseline variability was lowest when using SE and RE. Burst suppression was most accurately detected by spectral entropy. Prediction probability and individualized Spearman rank correlation were highest for BIS and lowest for SE. Nonlinear mixed effect modeling generated reasonable models relating all four measures to Ceprop.     

Spectral entropy as an electroencephalographic measure of anesthetic drug effect: a comparison with bispectral index and processed midlatency auditory evoked response

BACKGROUND: The authors compared the behavior of two calculations of electroencephalographic spectral entropy, state entropy (SE) and response entropy (RE), with the A-Line ARX Index (AAI) and the Bispectral Index (BIS) and as measures of anesthetic drug effect. They compared the measures for baseline variability, burst suppression, and prediction probability. They also developed pharmacodynamic models relating SE, RE, AAI, and BIS to the calculated propofol effect-site concentration (Ceprop). METHODS: With institutional review board approval, the authors studied 10 patients. All patients received 50 mg/min propofol until either burst suppression greater than 80% or mean arterial pressure less than 50 mmHg was observed. SE, RE, AAI, and BIS were continuously recorded. Ceprop was calculated from the propofol infusion profile. Baseline variability, prediction of burst suppression, prediction probability, and Spearman rank correlation were calculated for SE, RE, AAI, and BIS. The relations between Ceprop and the electroencephalographic measures of drug effect were estimated using nonlinear mixed effect modeling. RESULTS: Baseline variability was lowest when using SE and RE. Burst suppression was most accurately detected by spectral entropy. Prediction probability and individualized Spearman rank correlation were highest for BIS and lowest for SE. Nonlinear mixed effect modeling generated reasonable models relating all four measures to Ceprop. CONCLUSIONS: Compared with BIS and AAI, both SE and RE seem to be useful electroencephalographic measures of anesthetic drug effect, with low baseline variability and accurate burst suppression prediction. The ability of the measures to predict Ceprop was best for BIS.     

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.     

Bispectral index and spectral entropy in neuroanesthesia

Spectral Entropy (SpEn) is an alternative tool to the bispectral index (BIS) for monitoring depth of hypnosis. SpEn measures response entropy (RE) and state entropy (SE). This open-label prospective study was designed to evaluate SpEn and BIS in 20 patients undergoing elective supratentorial neurosurgery with craniotomy and resection of brain tumors. SpEn and BIS were obtained continuously by Datex Ohmeda M-entropy module S/5 (Helsinki, Finland) and Aspect Medical System BIS (Newton), respectively. Total intravenous anesthesia was performed in all patients by Fresenius Vial infusion system (Brezins, France) to maintain a plasma concentration of propofol of 2.5 to 5 microg mL(-1) and sufentanil of 0.2 to 0.4 etag mL(-1). SpEn, BIS, the estimated propofol effect-site concentrations (Ce), the mean arterial pressure (MAP), and the heart rate (HR) were recorded during 12 specific events: induction of anesthesia, patient stop counting, loss of blinking reflex, intubation, mayfield pinning, craniotomy, termination of propofol infusion, recovery of blinking reflex, coughing, limb movement, order execution, and extubation. Stated that prediction probability or P(K) represents an indicator probability to predict correctly the rank order of an arbitrary pair of distinct observed indices of depth of hypnosis (ie, clinical settings and SpEn indices, or BIS, Ce, MAP, HR), PK of BIS, SE, RE, and Ce provided a better depth of hypnosis than MAP and HR; RE being the best for rapidity, SE for sensitivity, and BIS for specificity. There is good correlation between the 3 hypnosis indices and Ce. This study demonstrates that SpEn provides a reproducible hypnosis index for patients undergoing supratentorial neurosurgical procedures.     

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.     

Spectral entropy measurement of patient responsiveness during propofol and remifentanil. A comparison with the bispectral index

Background. We compared two spectral entropies, state entropy(SE) and response entropy (RE), based on the irregularity ofthe EEG, to measure loss of response to verbal command (LOR_verbal)and noxious stimulus (LOR_noxious) with the bispectral index(BIS) during propofol infusion with and without remifentanil. Methods. Three groups of 20 patients received an effect-sitecontrolled propofol infusion (Ce_PROP) starting at 1 µgml^–1 and increased in steps of 0.5 µg ml^–1at 4 min intervals. In addition, a remifentanil infusion wasmaintained at a group-dependent, fixed effect-site target concentration(Ce_REMI) (0, 2 or 4 ng ml^–1). The ability of BIS, SE orRE to predict LOR_verbal and LOR_noxious were compared with thechanges in BIS, SE and RE using logistic regression, predictionprobability (P_K), and sensitivity/specificity. Results. In all groups, BIS, SE and RE decreased with increasingCe_PROP. However, BIS decreased more smoothly than SE and REat deeper levels of sedation. At LOR_verbal, BIS₅₀, SE₅₀ andRE₅₀ increased with increasing Ce_REMI. BIS, SE and RE all detectedLOR_verbal accurately but BIS performed better at 100% sensitivity.Sensitivity/specificity for detection of LOR_verbal decreasedfor all methods with increasing Ce_REMI. LOR_noxious was poorlydescribed by all measures. Conclusion. LOR_verbal was detected accurately by BIS, SE andRE except for 100% sensitivity, where BIS performed better.Though BIS, SE and RE were influenced by remifentanil duringpropofol administration, their ability to detect LOR_verbal remainedaccurate. None of the measures predicted LOR_noxious.      

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.     

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.     

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.     

Target-controlled infusion of propofol for intraoperative sedation: determination of effect-site concentration and assessment of bispectral index

OBJECTIVES: To determine the effect-site concentration (Ce) of propofol, required to achieving adequate sedation. To assess the efficacy and safety of a target-controlled infusion system during monitored anaesthesia care and to evaluate the ability of bispectral index (BIS) to predict sedation level. Study design. - Prospective clinical study. PATIENTS: Women scheduled for insertion of tension-free vaginal tape under local anaesthetic infiltration. METHODS: After premedication with hydroxyzine, 1% propofol was infused using the Diprifusor system at an initial target plasma concentration (Cc) of 1 microg/ml and then adjusted by steps of 0.2 microg/ml at 5 min intervals. The level of sedation was assessed using the observer's assessment of alertness/sedation (OAA/S) scale; the objective was to obtain an OAA/S level at 4 or 3 (response to verbal stimulation). Ce of propofol and BIS were noted every 5 min. Relation between Ce or BIS and OAA/S scale was analysed by linear regression and probability of prediction (P(K)). RESULTS: Fifty patients aged 62 +/- 12 years were studied. Sedation at level 4 or 3 was observed in all patients. Ce of propofol and BIS to maintain this OAA/S score were, respectively, 1.0 +/- 0.2 microg/ml and 87 +/- 7. There was a linear relation between OAA/S scale and BIS or Ce; however, individual values demonstrate wide variability. The average of P(K) values computed for each patient for the BIS and Ce was 0.84 and 0.83, respectively. CONCLUSIONS: Target-controlled infusion of propofol provides easy and safe management of intraoperative sedation, allowing a fast and precise adjustment of the propofol concentration to the clinical response of the patient.     

Auditory steady-state response and bispectral index for assessing level of consciousness during propofol sedation and hypnosis

We assessed the effect of propofol on the auditory steady-state response (ASSR), bispectral (BIS) index, and level of consciousness in two experiments. In Experiment 1, propofol was infused in 11 subjects to obtain effect-site concentrations of 1, 2, 3, and 4 microg/mL. The ASSR and BIS index were recorded during baseline and at each concentration. The ASSR was evoked by monaural stimuli. Propofol caused a concentration-dependent decrease of the ASSR and BIS index values (r(2) = 0.76 and 0.93, respectively; P<0.0001). The prediction probability for loss of consciousness was 0.89, 0.96, and 0.94 for ASSR, BIS, and arterial blood concentration of propofol, respectively. In Experiment 2, we compared the effects of binaural versus monaural stimulus delivery on the ASSR in six subjects during awake baseline and propofol-induced unconsciousness. During baseline, the ASSR amplitude with binaural stimulation (0.47+/-0.13 microV, mean +/- SD) was significantly (P<0.002) larger than with monaural stimulation (0.35+/-0.11 microV). During unconsciousness, the amplitude was 0.09+/-0.09 microV with monaural and 0.06+/-0.04 microV with binaural stimulation (NS). The prediction probability for loss of consciousness was 0.97 (0.04 SE) for monaural and 1.00 (0.00 SE) for binaural delivery. We conclude that the ASSR and BIS index are attenuated in a concentration-dependent manner by propofol and provide a useful measure of its sedative and hypnotic effect. BIS was easier to use and slightly more sensitive. The ASSR should be recorded with binaural stimulation. The ASSR and BIS index are both useful for assessing the level of consciousness during sedation and hypnosis with propofol. However, the BIS index was simpler to use and provided a more sensitive measure of sedation. Implications: We have compared two methods for predicting whether the amount of propofol given to a human subject is sufficient to cause unconsciousness, defined as failure to respond to a simple verbal command. The two methods studied are the auditory steady-state response, which measures the electrical response of the brain to sound, and the bispectral index, which is a number derived from the electroencephalogram. The results showed that both methods are very good predictors of the level of consciousness; however, bispectral was easier to use.     

Changes of bispectral index during recovery from general anesthesia with 2% propofol and remifentanil in children

BACKGROUND: The bispectral (BIS) index is a pharmacodynamic measure of the effect of anesthesia on the central nervous system. The aim of this study was to investigate the relationship between BIS index and predicted plasma concentration of propofol delivered by target controlled infusion (TCI) during emergence in children. METHODS: With approval of IRB, 30 patients (2-7 years) were included in this study. Anesthesia was with TCI propofol 3-5 microg.ml(-1) and remifentanil 7.5 ng.ml(-1) to maintain BIS 40-60 and the propofol concentration was fixed at 3 microg.ml(-1) Remifentanil infusion was stopped 10 min before the end of surgery. BIS values were recorded after reducing propofol in decrement of 0.2 microg.ml(-1). BIS values were checked when spontaneous respiration occurred and children were able to obey a command (eye opening or hand grasping). RESULTS: Spearman's correlation analysis showed negative correlation between BIS and propofol plasma concentration (r = -0.559, P < 0.001). When respiration returned, mean BIS was 77.2 +/- 5.3 and propofol plasma concentration 1.6 +/- 0.3 microg.ml(-1) and when a verbal command was obeyed, BIS was 82.4 +/- 5.6 and propofol plasma concentration 1.5 +/- 0.3 microg.ml(-1). CONCLUSIONS: In preschool children, BIS moderately correlated with the predicted plasma concentration of propofol.     

Bispectral Analysis of the Electroencephalogram Predicts Conscious Processing of Information during Propofol Sedation and Hypnosis

Background: The bispectral index (BIS) measures changes in the interfrequency coupling of the electroencephalogram (EEG). The purposes of this study were (1) to determine whether BIS correlates with responses to command during sedation and hypnosis induced by propofol or propofol and nitrous oxide, and (2) to compare BIS to targeted and measured concentrations of propofol in predicting participants' responses to commands.

Methods: Twenty volunteers (15 men and 5 women, aged 22-50 yr) were given propofol by computer-controlled infusion, and EEG was recorded for off-line analysis of BIS. Responses to randomly ordered verbal commands or voice plus touch were measured with two categorical scales (CS1 and CS2, respectively). All subjects received a propofol infusion targeted to achieve effect site concentrations of 1, 2, 4, 2, 1, and 0 micro gram/ml. Ten participants had repeated infusion, whereas 10 others breathed 30% nitrous oxide and oxygen and received a propofol infusion targeted for 0.5, 1, 2, 4, 2, 1, 0.5, and 0 micro gram/ml. Five minutes after each targeted concentration had been reached, CS1, CS2, and arterial propofol concentration were determined. The area under the receiver operating characteristic curve was used to compare the accuracy of (1) BIS, (2) targeted propofol concentration, (3) measured concentration, and (4) treatment history as predictors of response.

Results: Bispectral index was a strong predictor of CS1 and CS2 (P < 0.0001) and significantly more accurate than targeted or measured propofol concentrations (P < 0.0003 and P < 0.003, respectively). It also provided additional predictive power when combined with treatment history (P < 0.02). Nitrous oxide slightly decreased the probability of response at a given value of BIS (P < 0.05), but accuracy was unaffected.     

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.     

听觉诱发相关电位，脑电双频指数和熵用于判断重症监护病房患者的不同镇静状态

背景包括镇静评分和常规镇静暂停在内的镇静方案,有助干减少机械通气时间和重症监护病房（ICU）入住时间。因临床上对于镇静深度的评估工作量大、仅能间断进行且干扰镇静和睡眠,所以通过脑电生理信号评估镇静深度的替代方法已经开始倍受青睐：我们想明确听觉诱发相关电位（ERPs）、脑电双频指数（BIS）和墒（Entropy）是否也能够评估临床镇静深度。方法选择10例择期全麻下行胸部或腹部手术的患者。手术后进入ICU,逐渐减少丙泊酚和瑞芬太尼靶控镇静程度[采用Rickmond Agitation镇静评分（RASS）,-5分极深镇静,-4分深度镇静,-3～-1分中度镇静,0分清醒]期间,记录脑电图、BIS、状态熵（SE）、反应墒（RE）和ERPs。手术前或手术后数天测量指标的相关基础水平。结果基线、PASS-5分、RASS-4分、RASS-3至-1分和PASS-0分,对应的BIS值分别是94[4]（中位数,四分位数间距）、47[15]、68[9]、75[10]和88[6];对应的SE值分别是87[3]、46[10]、60[22]、74[21]和87[5];对应的RE值分别是97[4]、48[9]、71[25]、81[8]和96[3]（P〈0．05,Friedman检验）。BIS和墒都有高变异度。当单独考虑ERP振幅100时,各个镇静水平的ERPs值差异无显著性：但是、复括双参数主要变量分析的ERP辨别分析显示区别深度镇静、中度镇静和清醒状态的推算概率PK大约是0．89。与PK对应的RE,SE和BIS值分别是0．88、0．89和0．85。结论ERPs、BIS和熵均不能替代基于标准评分系统的临床镇静评估。全麻后对于极深镇静、深度到中度镇静和清醒的辨别,ERPs和脑电图仅能提供相似的PK值。BIS和熵存在较高的个体间和个体自身变异度,使其难以确定预测镇静水平的目标值范围,因而在危重患者中的使用受到限制。ERPs的变异度还不清楚。     

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.     

Ability of the bispectral index, autoregressive modelling with exogenous input-derived auditory evoked potentials, and predicted propofol concentrations to measure patient responsiveness during anesthesia with propofol and remifentanil

BACKGROUND: This study was conducted to compare the performance accuracy of the independent variables Bispectral Index (BIS), A-Line ARX index (AAI), and predicted propofol effect-site concentration (CePROP) to measure the dependent variables of loss of responses to different stimulation defined as loss of response to verbal command (LORverbal), eyelash reflex (LORlash), and noxious stimulus (LORnoxious) during stepwise increased levels of propofol infusion with and without remifentanil. METHODS: Forty-five patients were randomly allocated to one of three groups (0, 2, and 4 ng/ml remifentanil) to receive graded CePROP and predicted effect compartment controlled remifentanil (CeREMI). At every step, the ability to respond to verbal command using the Observer's Assessment of Alertness/Sedation Scale (OAA/S), eyelash reflex, and electrical tetanic noxious stimulus were compared against BIS, AAI, and CePROP. Prediction probability and sensitivity/specificity were calculated. RESULTS: Increasing CeREMI increased BIS and AAI values at LORverbal and LORlash and decreased CePROP. Similar findings were found for LORnoxious. The overall prediction probability to measure the hypnotic component of anesthesia remained accurate in the three groups for BIS, AAI, and CePROP. Combined information from CePROP, CeREMI, and BIS or AAI increased the overall prediction probability for predicting the OAA/S scale and LORlash. Less accuracy to LORnoxious was found in all independent variables. CONCLUSIONS: Although BIS, AAI, and CePROP were influenced by remifentanil during propofol administration, their ability to detect OAA/S and LORlash remained accurate. Improved performance is obtained when BIS and AAI are measured in conjunction with drug targeted effect-site concentrations. Remifentanil decreases the ability of these independent variables to detect LORnoxious.