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 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.     

Approximate Entropy as an Electroencephalographic Measure of Anesthetic Drug Effect during Desflurane Anesthesia

Background: The authors hypothesized that the electroencephalogram (EEG) during higher anesthetic concentrations would show more "order" and less "randomness" than at lower anesthetic concentrations. "Approximate entropy" is a new statistical parameter derived from the Kolmogorov-Sinai entropy formula which quantifies the amount of regularity in data. The approximate entropy quantifies the predictability of subsequent amplitude values of the EEG based on the knowledge of the previous amplitude values. The authors investigated the dose-response relation of the EEG approximate entropy during desflurane anesthesia in comparison with spectral edge frequency 95, median frequency, and bispectral index.

Methods: Twelve female patients were studied during gynecologic laparotomies. Between opening and closure of the peritoneum, end-tidal desflurane concentrations were varied between 0.5 and 1.6 minimum alveolar concentration (MAC). The EEG approximate entropy, median EEG frequency, spectral edge frequency 95, and bispectral index were determined and the performance of each to predict the desflurane effect compartment concentration, obtained by simultaneous pharmacokinetic-pharmacodynamic modeling, was compared.

Results: Electroencephalogram approximate entropy decreased continuously over the observed concentration range of desflurane. The performance of the approximate entropy (prediction probability PK = 0.86 +/- 0.06) as an indicator for desflurane concentrations is similar to spectral edge frequency 95 (PK = 0.86 +/- 0.06) and bispectral index (PK = 0.82 +/- 0.06) and is statistically significantly better than median frequency (PK = 0.78 +/- 0.06).     

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.     

Using Permutation Entropy to Measure the Electroencephalographic Effects of Sevoflurane

Background: Approximate entropy (AE) has been proposed as a measure of anesthetic drug effect in electroencephalographic data. Recently, a new method called permutation entropy (PE) based on symbolic dynamics was also proposed to measure the complexity in an electroencephalographic series. In this study, the AE and PE were applied to electroencephalographic recordings for revealing the effect of sevoflurane on brain activity. The dose-response relation of PE during sevoflurane anesthesia was compared with that of AE.

Methods: Nineteen patients' electroencephalographic data were collected during the induction of general anesthesia with sevoflurane. PE and AE were applied to the electroencephalographic recordings, and the performance of both measures was assessed by pharmacokinetic-pharmacodynamic modeling and prediction probability. To ensure an accurate complexity measure of electroencephalographic recordings, a wavelet-based preprocessor was built in advance.

Results: Both PE and AE could distinguish between the awake and anesthetized states and were highly correlated to each other (r = 0.8, P = 0.004). The pharmacokinetic-pharmacodynamic model adequately described the dose-response relation between PE and AE and sevoflurane effect site concentration. The coefficient R2 between PE and effect site concentration was 0.89 +/- 0.07 for all patients, compared with 0.60 +/- 0.14 for AE. Prediction probabilities of 0.86 +/- 0.04 and 0.79 +/- 0.09 for PE and AE showed that PE has a stronger ability to differentiate between the awake and anesthetic states.     

Hypnosis as sole anaesthesia for skin tumour removal in a patient with multiple chemical sensitivity

A female patient with multiple chemical sensitivity and previous anaphylactoid reactions to local anaesthetics was admitted for removal of a thigh skin tumour under hypnosis as sole anaesthesia. The hypnotic protocol included hypnotic focused analgesia and a pre‐operative pain threshold test. After inducing hypnosis, a wide excision was performed, preserving the deep fascia, and the tumour was removed; the patient's heart rate and blood pressure did not increase during the procedure. When the patient was de‐hypnotised, she reported no pain and was discharged immediately. Our case confirms the efficacy of hypnosis and demonstrates that it may be valuable as a sole anaesthetic method in selected cases. Hypnosis can prevent pain perception and surgical stress as a whole, comparing well with anaesthetic drugs.     

Comparison of Bispectral Index and Composite Auditory Evoked Potential Index for Monitoring Depth of Hypnosis in Children

Background: In pediatric patients, the Bispectral Index (BIS), derived from the electroencephalogram, and the composite A-Line autoregressive index (cAAI), derived from auditory evoked potentials and the electroencephalogram, have been used as measurements of depth of hypnosis during anesthesia. The performance and reliability of BIS and cAAI in distinguishing different hypnotic states in children, as evaluated with the University of Michigan Sedation Scale, were compared.

Methods: Thirty-nine children (aged 2-16 yr) scheduled to undergo elective inguinal hernia surgery were studied. For all patients, standardized anesthesia was used. Prediction probabilities of BIS and cAAI versus the University of Michigan Sedation Scale and sensitivity/specificity were calculated.

Results: Prediction probabilities for BIS and cAAI during induction were 0.84 for both and during emergence were 0.75 and 0.74, respectively. At loss of consciousness, the median BIS remained unaltered (94 to 90; not significant), whereas cAAI values decreased (60 to 43; P < 0.001). During emergence, median BIS and cAAI increased from 51 to 74 (P < 0.003) and from 46 to 58 (P < 0.001), respectively. With respect to indicate consciousness or unconsciousness, 100% sensitivity was reached at cutoff values of 17 for BIS and 12 for cAAI. One hundred percent specificity was associated with a BIS of 71 and a cAAI of 60. To ascertain consciousness, BIS values greater than 78 and cAAI values above 52 were required.