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Contains fulltext : 70879.pdf (publisher's version ) (Closed access), BACKGROUND: We compared two pharmacodynamic models, one with and one without a plateau effect. Bispectral indices (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend (NCT, MonitorTechnik, Bad Bramstedt, Germany, version 4.0) were used as an electroencephalographic measure of sevoflurane drug effect. In addition, we tried to analyze the origin of the plateau. METHODS: We investigated 26 adult patients scheduled for radical prostatectomy. At least 45 min after induction of general anesthesia, end-tidal sevoflurane concentrations were varied between 1 vol% and 4 vol%. To evaluate the relationship between concentrations and electroencephalographic indices, two different pharmacodynamic models were applied: a conventional model based on a single sigmoidal curve, and a novel model based on two sigmoidal curves for BIS and NCT values with and without burst suppression. The parameters of the models were estimated by NONMEM V (GloboMax, Hanover) by minimizing log likelihood. Statistical significance between the two models was calculated by the likelihood ratio test. RESULTS: The end-tidal sevoflurane concentration ranged from 1.04 +/- 0.17 vol% to 4.43 +/- 0.43 vol%. The difference between the log likelihood values of the new pharmacokinetic/pharmacodynamic model with two connected sigmoidal curves and the classical E(max) model with one sigmoidal curve is 396 (P < 0.001) for the BIS monitor and 1121 (P < 0.001) for the NCT. The plateau is positioned at the change between the maximum delta power and the increase of burst suppression ratio. CONCLUSION: A pharmacokinetic/pharmacodynamic model consisting of two sigmoid curves with an intervening plateau describes the effect of sevoflurane on BIS and NCT indices better than a model with a single sigmoid curve.

Contains fulltext : 69032.pdf (publisher's version ) (Closed access)

Contains fulltext : 69264.pdf (publisher's version ) (Closed access), Over the last 10 years the technique of target-controlled infusion (TCI) has substantially influenced the development and practice of intravenous anaesthesia. It opened the possibility of many new and exciting applications of perioperative anaesthetic care. More recent and current developments, such as open TCI (target-controlled infusion) and the availability of generic anaesthetic agents combined with modern infusion pumps, means that TCI can become a standard procedure in anaesthesia and is no longer just a research tool for specialists and enthusiasts. This review explains the fundamentals and applications of intravenous drug delivery by TCI and gives practice guidelines to successfully implement the technique into clinical practice. The aim is to provide a comprehensive reference based on clinically proven evidence.

Contains fulltext : 70983.pdf (publisher's version ) (Closed access), BACKGROUND: The Bispectral Index (BIS) and the Patient State Index (PSI) quantify depth of anesthesia by analyzing the electroencephalogram. The authors examined the response of BIS and PSI to sevoflurane anesthesia. METHODS: In 22 patients, sevoflurane anesthesia was induced by inhalation with a tight-fitting facemask and was maintained via a laryngeal mask. Sevoflurane concentrations were increased until burst suppression occurred and subsequently decreased until BIS recovered to values above 60. This procedure was repeated twice until patients underwent intubation for subsequent surgery. End-tidal sevoflurane concentrations, BIS, and PSI were recorded simultaneously. The performance of PSI and BIS to predict the estimated sevoflurane effect site concentration, as derived from simultaneous pharmacokinetic and pharmacodynamic modeling, was compared by determination coefficients (rho(2)) and prediction probabilities (P(K)). RESULTS: A significant (P < 0.001) correlation between BIS and PSI was found (r(2) = 0.75), and a close sigmoid relation between sevoflurane effect site concentration and both BIS (rho(2) = 0.84 +/- 0.09) and PSI (rho(2) = 0.85 +/- 0.15) was observed. The maximum sevoflurane electroencephalographic effect resulted in PSI values (1.3 +/- 4.3) that were significantly (P = 0.019) lower than BIS values (7.9 +/- 12.1), and the effect site efflux constant k(e0) was significantly smaller (P = 0.001) for PSI (0.13 +/- 0.08 min(-1)) than for BIS (0.24 +/- 0.15 min(-1)). The probability of BIS (P(K) = 0.80 +/- 0.11) to predict sevoflurane effect site concentration did not differ (P = 0.76) from that of PSI (P(K) = 0.79 +/- 0.09). CONCLUSIONS: The BIS reacted faster to changes in sevoflurane concentrations, whereas the PSI made better use of the predefined index range. However, despite major differences in their algorithms and minor differences in their dose-response relations, both PSI and BIS predicted depth of sevoflurane anesthesia equally well.

Contains fulltext : 51677.pdf (publisher's version ) (Closed access), Pharmacokinetic models can be differentiated into two groups: physiological-based models and empirical models. Traditionally the pharmacokinetics of volatile anaesthetics are described using physiological-based models together with the respective tissue-blood distribution coefficients. The compartments of the empirical model have no anatomical equivalents and are merely the product of the mathematical procedure for parameter estimation. The end expiratory concentration of volatile anaesthetics is approximately equal to the arterial concentration and, therefore, the description of the transition between plasma and effect site for volatile anaesthetics plays a central role. The most important parameter here is the k(e0) value which is a time constant and describes the time delay for the transition from the central compartment to the calculated effect compartment. The k(e0) values for sevoflurane and isoflurane are the same but the concentration balance between the end-tidal concentration and the effect compartment occurs twice as quickly with desflurane. In clinical practice volatile anaesthetics are normally combined with N(2)O and/or opioids. This results in an additive interaction between volatile anaesthetics and N(2)O but a synergistic interaction of volatile anaesthetics with opioids. However, there are relatively few investigations on the interactions between the clinically widely used combination of volatile anaesthetics, N(2)O and opioids.

Contains fulltext : 49611.pdf (publisher's version ) (Closed access), Autoregressive modeling with exogenous input of middle-latency auditory evoked potentials (A-Line AEP index, AAI) has been developed for monitoring depth of anesthesia. We investigated the prediction of recovery and dose-response relationship of desflurane and AAI or bispectral index (BIS) values. Twenty adult men scheduled for radical prostatectomy were recruited. To minimize opioid effects, analgesia was provided by a concurrent epidural in addition to the general anesthetic. Electrodes for AAI and BIS monitoring and a headphone for auditory stimuli were applied. Propofol and remifentanil were used for anesthetic induction. Maintenance of anesthesia was with desflurane only. For comparison to AAI and BIS monitor parameters, pharmacokinetic models for desflurane and propofol distribution and effect-site concentrations were used to predict clinical end-points (Prediction probability P(K)). Patients opened their eyes at an AAI value of 47 +/- 20 and a BIS value of 77 +/- 14 (mean +/- sd), and the prediction probability for eye opening was P(K) = 0.81 for AAI, P(K) = 0.89 for BIS, and P(K) = 0.91 for desflurane effect-site concentration. The opening of eyes was best predicted by the calculated desflurane effect-site concentration. The relationship between predicted desflurane effect-site concentration versus AAI and BIS was calculated by nonlinear regression analysis (r = 0.75 for AAI and r = 0.80 for BIS). The correlation between BIS and clinical end-points of anesthesia or the desflurane effect-compartment concentration is better than for the AAI.

Contains fulltext : 50473.pdf (publisher's version ) (Closed access), BACKGROUND: Several studies have shown a reduction in anaesthetic drug consumption with Bispectral Index (BIS) titration compared with standard clinical practice. However, the amount of reduction varied widely between 1% and 40%. We investigated the correlation between reduction in anaesthetic drug consumption and mean titrated BIS values. METHODS: An analysis upon randomized controlled trials cited until January 2006 in MEDLINE and other databases investigating the potential reduction in anaesthetic (hypnotic) drug consumption with BIS titration was performed. Investigations with a marked difference (> 15%) in opioid drug consumption between the BIS group and the standard practice group were excluded. Correlations between amount of reduction in hypnotic drug use and the mean titrated BIS value were analysed with linear regression. RESULTS: Fourteen manuscripts covering 2582 patients were included into the analysis. The mean BIS value in the standard clinical practice group averaged over all studies was 43.6 +/- 3.2 and the mean BIS value in the BIS-titrated group was 49.9 +/- 5.4. The amount of reduction in hypnotic drug use correlated significantly with the mean BIS values in the BIS-titrated groups (r =0.68) and with the differences between the mean BIS value in the BIS-titrated group and the mean BIS value in the standard clinical practice group (r = 0.70). Every point of BIS difference between the two groups resulted in a reduced hypnotic drug use of approximately 2%. CONCLUSION: Despite differences in the study designs and in the drugs used, a linear correlation between the mean titrated BIS value and the hypnotic drug saving potential was found.

Contains fulltext : 50138.pdf (publisher's version ) (Closed access), 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.

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Four main dammarane-type aglycones of gypenosides, extracted from the aerial parts of Gynostemma pentaphyllum were identified by gas chromatography-mass spectrometry. By detecting these aglycones as well as the aglycones of ginsenosides, a difference in sapogenin composition between Gynostemma pentaphyllum and Panax species was observed, which can be used in the differentiation of these plant drugs.