Heiko Röpcke

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). Conclusions: The amount of regularity in the EEG increases with increasing desflurane concentrations. The approximate entropy could be a useful EEG measure of anesthetic drug effect.

Electroencephalogram approximate entropy correctly classifies the occurrence of burst suppression pattern as increasing anesthetic drug effect.

BackgroundApproximate entropy, a measure of signal complexity and regularity, quantifies electroencephalogram changes during anesthesia. With increasing doses of anesthetics, burst–suppression patterns occur. Because of the high-frequency bursts, spectrally based parameters such as median electroencephalogram frequency and spectral edge frequency 95 do not decrease, incorrectly suggesting lightening of anesthesia. The authors investigated whether the approximate entropy algorithm correctly classifies the occurrence of burst suppression as deepening of anesthesia. MethodsEleven female patients scheduled for elective major surgery were studied. After propofol induction, anesthesia was maintained with isoflurane only. Before surgery, the end-tidal isoflurane concentration was varied between 0.6 and 1.3 minimum alveolar concentration. The raw electroencephalogram was continuously recorded and sampled at 128 Hz. Approximate entropy, electroencephalogram median frequency, spectral edge frequency 95, burst–suppression ratio, and burst–compensated spectral edge frequency 95 were calculated offline from 8-s epochs. The relation between burst–suppression ratio and approximate entropy, electroencephalogram median frequency, spectral edge frequency 95, and burst–compensated spectral edge frequency 95 was analyzed using Pearson correlation coefficient. ResultsHigher isoflurane concentrations were associated with higher burst–suppression ratios. Electroencephalogram median frequency (r = 0.34) and spectral edge frequency 95 (r = 0.29) increased, approximate entropy (r = −0.94) and burst–compensated spectral edge frequency 95 (r = −0.88) decreased with increasing burst–suppression ratio. ConclusionElectroencephalogram approximate entropy, but not electroencephalogram median frequency or spectral edge frequency 95 without burst compensation, correctly classifies the occurrence of burst–suppression pattern as increasing anesthetic drug effect.

Shannon entropy applied to the measurement of the electroencephalographic effects of desflurane.

BackgroundThe Shannon entropy is a standard measure for the order state of sequences. It quantifies the degree of skew of the distribution of values. Increasing hypnotic drug concentrations increase electroencephalographic amplitude. The probability density function of the amplitude values broadens and flattens, thereby changing from a skew distribution towards equal distribution. We investigated the dose–response relation of the Shannon entropy of the electroencephalographic amplitude values during desflurane monoanesthesia in comparison with previously used electroencephalographic parameters. MethodsElectroencephalographic records previously obtained in 12 female patients during gynecologic laparotomies were reanalyzed. Between opening and closure of the peritoneum, desflurane vapor settings were varied between 0.5 and 1.6 minimum alveolar concentration. Electroencephalographic Shannon entropy, approximate entropy, median electroencephalographic frequency, SEF 95, total power, log total power, and Bispectral Index were determined, and their correlations with the desflurane effect compartment concentration, obtained by simultaneous pharmacokinetic–pharmacodynamic modeling, were compared. ResultsThe electroencephalographic Shannon entropy increased continuously over the observed concentration range of desflurane. The correlation of the Shannon entropy (R2 = 0.84 ± 0.08, mean ± SD) with the desflurane effect compartment concentrations is similar to approximate entropy (R2 = 0.85 ± 0.12), SEF 95 (R2 = 0.85 ± 0.10), and Bispectral Index (R2 = 0.82 ± 0.13) and is more statistically significant than median frequency (R2 = 0.72 ± 0.17), total power (R2 = 0.67 ± 0.18), and log total power (R2 = 0.80 ± 0.09). ConclusionsThe Shannon entropy seems to be a useful electroencephalographic measure of anesthetic drug effect.

Surgical Stimulation Shifts EEG Concentration–Response Relationship of Desflurane

Background Anesthesiologists routinely increase the delivered anesthetic concentration before surgical stimulation in anticipation of increased anesthetic requirement to achieve certain goals (e.g., amnesia, unconsciousness, and immobility). Electroencephalographic monitoring is one method of determining indirectly anesthetic effect on the brain. The present study investigated the effect of surgical stimuli on the concentration–response relation of desflurane-induced electroencephalographic changes. Methods The electroencephalographic activity was recorded from 24 female patients who received only desflurane after a single induction dose of propofol. Twelve patients served as a control group before surgical stimulation. The other 12 patients, all undergoing lower abdominal surgery, were investigated between opening and closure of the peritoneum. Desflurane vaporizer settings were randomly increased and decreased between 0.5 and 1.6 minimum alveolar concentration as long as anesthesia was considered adequate. Spectral edge frequency 95, median power frequency, and Bispectral Index were calculated. Desflurane effect-site concentrations and the concentration–effect curves for spectral edge frequency 95, median power frequency, and Bispectral Index were determined by simultaneous pharmacokinetic and pharmacodynamic modeling. Results Surgical stimulation shifted the desflurane concentration–electroencephalographic effect curves for spectral edge frequency 95, median power frequency, and Bispectral Index toward higher desflurane concentrations. In the unstimulated group, 2.2 ± 0.74 vol% desflurane were necessary to achieve a Bispectral Index of 50, whereas during surgery, 6.8 ± 0.98 vol% (mean ± SE) were required. Conclusions During surgery, higher concentrations of the volatile anesthetic are required to achieve a desired level of cortical electrical activity and, presumably, anesthesia.

Interaction of Isoflurane and Nitrous Oxide Combinations Similar for Median Electroencephalographic Frequency and Clinical Anesthesia

Background The volatile anesthetic sparing effect of nitrous oxide in clinical studies is less than might be expected from the additivity of minimum alveolar concentration values. Other studies identify nonadditive interactions between isoflurane and nitrous oxide. The aim of this study was to quantify the interaction of isoflurane and nitrous oxide at a constant median electroencephalographic frequency. Methods Twenty-five patients were studied during laparotomies. Nitrous oxide was randomly administered in concentrations of 0, 20, 40, 60, and 75 vol%, to ten patients for each nitrous oxide concentration. Isoflurane vaporizer settings were chosen so that the median electroencephalographic frequency was held between 2 and 3 Hz. The relationship between nitrous oxide concentrations and required isoflurane concentrations was examined with the method of isoboles. Results Nitrous oxide linearly decreased the isoflurane requirement. Addition of every 10 vol% of nitrous oxide decreases the isoflurane requirement by approximately 0.04 vol%. The total anesthetic requirement of isoflurane and nitrous oxide, expressed in terms of previously reported minimum alveolar concentration values, increased significantly with increasing nitrous oxide concentrations. Conclusions The interaction of isoflurane and nitrous oxide in the dose range 0-75 vol% on median electroencephalographic frequency is compatible with additivity. The potency of nitrous oxide as a substitute for isoflurane is less than on a minimum alveolar concentration basis. Maintaining median electroencephalographic frequency more appropriately reflects the clinical usage of isoflurane and nitrous oxide than does maintaining minimum alveolar concentration.

A manual slide rule for target-controlled infusion of propofol: development and evaluation

UNLABELLED We describe the development and evaluation of a simple slide rule that enables the bedside determination of the infusion rate for a particular target plasma concentration of propofol. The infusion rate to reach this target concentration at time (t) is the product of the target concentration, body weight, and a correction factor that depends on the time elapsed from the start of the initial infusion. Our target-controlled infusion (TCI) slide rule, constructed along this principle, performs the multiplications, analogous to the principle of the classical slide rule, as addition of logarithms. We calculated the percentage deviation of the predicted concentration obtained by STANPUMP versus predicted concentrations obtained using the infusion rates determined from the TCI slide rule. The evaluation using STANPUMP simulations showed, for a constant target concentration of 3 micro g/mL of propofol, a mean deviation of 4.05% (max, 6.97%) in the first 15 min and a mean deviation of 0.5% (max, 2.03%) between 16 and 300 min. The mean deviation after changing the target from 3 micro g/mL to 1, 2, 4, or 5 micro g/mL ranged from 1.15% to 17.76%. This pocket-sized TCI slide rule combines the advantages of minimal financial and technical cost with reasonable accuracy. IMPLICATIONS We describe the development and evaluation of a simple slide rule that enables the bedside determination of the required infusion rate for a particular target plasma concentration. This pocket-sized target-controlled infusion slide rule combines the advantages of minimal financial and technical cost with reasonable accuracy.

Isoflurane, nitrous oxide, and fentanyl pharmacodynamic interactions in surgical patients as measured by effects on median power frequency

STUDY OBJECTIVE To identify and quantify the simultaneous interactions of isoflurane, nitrous oxide (N2O), and fentanyl during surgical procedures. The slowing of the EEG to a median power frequency of 2 Hz to 3 Hz was chosen as the measure of pharmacodynamic drug effect. DESIGN Prospective, randomized, open label. SETTING Operating room of a university hospital. PATIENTS 65 ASA physical status I and II patients undergoing gynecological laparatomies. INTERVENTIONS 25 patients received no fentanyl. 20 patients received a loading dose of 100 micrograms fentanyl and a continuous infusion of 70 micrograms.h-1 fentanyl. Calculated effect compartment concentrations were 0.7 ng.ml-1 between the first and second hours after induction of anesthesia. Another 20 patients received a loading dose of 200 micrograms fentanyl and a continuous infusion of 150 micrograms.h-1 fentanyl; the respective effect compartment concentrations were 1.5 ng.ml-1. N2O was randomly administered in concentrations of 0, 20, 40, and 60 vol%; in the group that did not receive fentanyl, we additionally investigated 75 vol% N2O. Each patient received two different N2O concentrations, with each combination of N2O and fentanyl finally applied to ten patients. Isoflurane vaporizer settings were chosen so that the median power frequency was held between 2 Hz and 3 Hz. The type and degree of interaction among the three anesthetic drugs was analyzed based on a generalized isobole approach. MEASUREMENTS AND MAIN RESULTS The interaction of isoflurane, N2O, and fentanyl is compatible with additivity. A model with regard to the relative potencies and age dependency is given by: [formula: see text] with C0,iso = 1.30 vol%, C0,N2O = 177 vol%, C0,fen = 10.6 ng.ml-1, and a = -0.0031 yr-1. where conc. = end-tidal or effect compartment concentrations. CONCLUSION The potency of N2O and fentanyl to substitute isoflurane in maintaining a median power frequency of 2 Hz to 3 Hz during surgery is less than anticipated from minimum alveolar concentration studies.

Application of semilinear canonical correlation to the measurement of the electroencephalographic effects of volatile anaesthetics

Background and objective: The common parameters of the electroencephalogram quantify a shift of its power spectrum towards lower frequencies with increasing anaesthetic drug concentrations (e.g. spectral-edge frequency 95). These ad hoc parameters are not optimized for the content of information with regard to drug effect. Using semilinear canonical correlation, different frequency ranges (bins) of the power spectrum can be weighted for sensitivity to changes of drug concentration by multiplying their power with iteratively determined coefficients, yielding a new (canonical univariate) electroencephalographic parameter. Methods: Electroencephalographic data obtained during application of volatile anaesthetics were used: isoflurane (n = 6), desflurane (7), sevoflurane (7), desflurane during surgical stimulation (12). Volatile anaesthetic end-tidal concentrations varied between 0.5 and 1.6 minimum alveolar concentration (MAC). The canonical univariate parameter and spectral-edge frequency 95 were determined and their correlation with the volatile anaesthetic effect compartment concentration, obtained by simultaneous pharmacokinetic-pharmacodynamic modelling, were compared. Results: The canonical univariate parameter with individually optimized coefficients, but not with mean coefficients, was superior to the spectral-edge frequency 95 as a measure of anaesthetic drug effect. No significant differences of the coefficients were found between the three volatile anaesthetics or between the data with or without surgical stimulus. The coefficients for volatile anaesthetics were similar to the coefficients for opioids, but different from coefficients for propofol and midazolam. Conclusions: The canonical univariate parameter calculated with individually optimized coefficients, but not with mean coefficients, correlates more accurately and consistently with the effect site concentrations of volatile anaesthetics than with spectral-edge frequency 95.