Biomedical subjects

Helmut Schwilden

Publications and source records attributed to Helmut Schwilden.

10 recordsLinked to original sources

PubMed2006

Concepts of EEG processing: from power spectrum to bispectrum, fractals, entropies and all that.

Over the past two decades, methods of processing the EEG for monitoring anaesthesia have greatly expanded. Whereas power spectral analysis was once the most important tool for extracting EEG monitoring variables, higher-order spectra, wavelet decomposition and especially methods used in the analysis of complex dynamical systems such as non-linear dissipative systems are nowadays attracting much attention. This chapter reviews some of these methods in brief. However, a comparison of some of the newer approaches with the more traditional ones with respect to clinical end-points by association measures and to the signal-to-noise ratio raises some doubt over whether the newer EEG-processing techniques really do better than the more traditional ones.

Electroencephalography↗

PubMed2006

The discriminant power of simultaneous monitoring of spontaneous electroencephalogram and evoked potentials as a predictor of different clinical states of general anesthesia.

Spontaneous or evoked electrical brain activity is increasingly used to monitor general anesthesia. Previous studies investigated the variables from spontaneous electroencephalogram (EEG), acoustic (AEP), or somatosensory evoked potentials (SSEP). But, by monitoring them separately, the available information from simultaneous gathering could be missed. We investigated whether the combination of simultaneous information from EEG, AEP, and SSEP shows a more discriminant power to differentiate between anesthesia states than from information derived from each measurement alone. Therefore, we assessed changes of 30 EEG, 21 SSEP, and 29 AEP variables recorded from 59 patients during four clinical states of general anesthesia: "awake," "light anesthesia," "surgical anesthesia," and "deep surgical anesthesia." The single and combined discriminant powers of EEG, AEP, and SSEP variables as predictors of these states were investigated by discriminant analysis. EEG variables showed a higher discriminant power than AEP or SSEP variables: 85%, 46%, and 32% correctly classified cases, respectively. The frequency of correctly classified cases increased to 90% and 91% with information from EEG + AEP and EEG + AEP + SSEP, respectively. Thus, future anesthesia monitoring should consider combined information simultaneously distributed on different electrophysiological measurements, rather than single variables or their combination from EEG or AEP or SSEP.

Alfentanil↗

PubMed2005

Binding of propofol to human serum albumin.

The binding properties of the short-acting hypnotic agent propofol (CAS 2078-54-8) to human serum albumin were studied in vitro. Using centrifugation through ultrafiltration membranes the ratio of free and bound propofol as a function of the human serum albumin concentration was determined. In addition, a biomathematical approach was tested that allowed the determination of the number of binding sites from the measured binding profile. At a total propofol concentration of 8.81 +/- 0.25 microg/mL the concentration of the free fraction of propofol ranged from 338 +/- 11 ng/mL (mean +/- SE) at an albumin concentration of 0.5% to 15 +/- 2 ng/ mL at an albumin concentration of 8.0%. The corresponding percentage of propofol binding ranged from 96.07 +/- 0.14% to 99.83 +/- 0.02%. From this binding profile the binding site was estimated to be n(0) = 2. The measured influence of the albumin concentration on propofol binding might be of relevance in states of hypo- or hyperalbuminaemia which could result in an altered demand of propofol.

Algorithms↗

PubMed2005

Sedation with GPI 15715, a water-soluble prodrug of propofol, using target-controlled infusion in volunteers.

GPI 15715 is the first water-soluble propofol prodrug that has been studied in humans. Present propofol lipid formulations have well known undesirable properties, for example, pain on injection and increased triglyceride concentrations. We investigated whether GPI 15715 is suitable to achieve and maintain moderate sedation for 2 h. Six male and six female volunteers received a target-controlled infusion of GPI 15715, with an initial propofol target concentration of 1.8 microg/mL and the possibility to adjust the propofol target once after 1 h. Propofol concentrations, the bispectral index, and modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) scores were monitored. The median MOAA/S score was 4 during the first hour and was 3 during the second hour of infusion. The propofol target had to be changed to 2.4 microg/mL in seven volunteers and to 3.0 microg/mL in two volunteers. A propofol concentration of 1.9 microg/mL had the highest probability to result in an MOAA/S score of 3, which corresponds with moderate sedation. We observed no serious side effects. We conclude that GPI 15715 produces excellent sedation.

Adult↗

PubMed2005

Electroencephalogram monitoring during anesthesia with propofol and alfentanil: the impact of second order spectral analysis.

Bispectral analysis of the electroencephalogram (EEG) has been used for monitoring anesthesia. The estimation of bicoherence allows us to determine whether a given time series represents a linear random process in cases where the bicoherence is trivial, i.e., a mere constant independent of frequency. In this study, we investigated the proportion of EEG epochs with nontrivial bicoherence during surgical anesthesia with propofol and alfentanil as an indicator for the degree of nonlinearity in the EEG. We reanalyzed 90 h of EEG recorded from 20 patients undergoing abdominal surgery using the Hinich procedure, which provides a statistical test for the following hypothesis: the EEG is a linear random process. In approximately 90% of all artifact-free, stationary EEG epochs, the bicoherence was found to be zero or a mere constant. Under these conditions, the EEG can be considered as a linear random process. Our findings suggest that the spectral information in the frequency domain delivered by the EEG monitoring during anesthesia is largely contained in the power spectrum of the signal. This calls into question the benefit of EEG bispectral analysis for monitoring anesthesia effect.

Adult↗

PubMed2004

Modelling acute tolerance to the EEG effect of two benzodiazepines.

AIMS: We studied the development of acute tolerance to the EEG effect of midazolam and the new benzodiazepine Ro 48-6791. METHODS: Nine young (24-28 years) and nine elderly (67-81 years) male volunteers received midazolam and Ro 48-6791 computer-controlled, targeting linearly increasing plasma concentrations for 30 min (targeted slopes: 40 and 20 ng ml-1 min-1 for midazolam, 3 and 1.5 ng ml-1 min-1 for Ro 48-6791, for young and elderly, respectively) and a constant concentration for the following 15 min. After recovery, the same infusion scheme was repeated. Plasma concentrations of midazolam, Ro 48-6791 and its metabolite Ro 48-6792 were determined from arterial blood samples. The hypnotic effect was assessed using the median frequency of the EEG power spectrum. RESULTS: The concentration-effect relationship in each infusion cycle could be described by a sigmoid Emax model. The half-maximum concentration EC50 was higher in the second infusion cycle compared with the first one (midazolam, 47% (2.3-91.6%) and 37% (5.3-69.5%); Ro 48-6791, 22% (-2.8% to 44.6%) and 43% (3.4-82.4%) for young and elderly; mean and 95% confidence interval). The complete time course of the EEG median frequency could be described by an interaction between the parent drug in an effect compartment and a hypothetical competitive drug in an additional tolerance compartment. For Ro 48-6791, the use of its metabolite Ro 48-6792 as competitive compound also gave appropriate results. CONCLUSION: Midzolam and Ro 48-6791 showed acute tolerance to the EEG effect which might be caused by competitive interaction with the metabolite.

Adult↗

PubMed2004

Comparative pharmacokinetics and pharmacodynamics of the new propofol prodrug GPI 15715 and propofol emulsion.

BACKGROUND: GPI 15715 is a new water-soluble prodrug that is hydrolyzed to release propofol. The objectives of this crossover study in volunteers were to investigate the pharmacokinetics and pharmacodynamics of GPI 15715 in comparison with propofol emulsion. METHODS: In two separate sessions, nine healthy male volunteers (19-35 yr, 70-86 kg) received GPI 15715 and propofol emulsion as a target controlled infusion over 60 min. In the first 20 min, the propofol target concentration increased linearly to 5 microg/ml. Subsequently, the targets were reduced to 3 microg/ml and 1.5 microg/ml for 20 min each. The plasma concentrations of GPI 15715 and propofol were measured from arterial and venous blood samples up to 24 h and pharmacokinetics were analyzed. The pharmacodynamic effect was measured by the median frequency of the power spectrum of the electroencephalogram, and a sigmoid model with effect compartment was fitted to the data. RESULTS: Compared with propofol emulsion, propofol from GPI 15715 showed a different disposition function and especially larger volumes of distribution. The propofol effect site concentration for half maximum effect was 2.0 +/- 0.5 microg/ml for GPI 15715 and 3.0 +/- 0.7 microg/ml for propofol emulsion (P < 0.05). Propofol from GPI 15715 did not show a hysteresis between plasma concentration and effect. CONCLUSIONS: Compared with propofol emulsion, propofol from GPI 15715 showed different pharmacokinetics and pharmacodynamics, particularly a higher potency with respect to concentration. These differences may indicate an influence of the formulation.

Adult↗

PubMed2004

Midazolam therapeutic drug monitoring in intensive care sedation: a 5-year survey.

During a 5-year period, 1997 to 2002, therapeutic drug monitoring of midazolam plasma concentrations in combination with the level of sedation as assessed by the Ramsay sedation scale was performed in 648 critically ill patients requiring artificial ventilation. In a subgroup of 189 patients sepsis-related organ failure assessment procedure was additionally performed. A total number of 3354 samples were analyzed. Significantly reduced clearance of midazolam was observed within the first 4 days of midazolam treatment of critically ill patients. As a result, accumulation of midazolam and its metabolites occurred within the first week of treatment. In contrast, parameters such as serum bilirubin or creatinine, which are commonly used to adapt drug therapy to organ dysfunction, showed significant changes with a delay of more than 10 days as compared with the findings of midazolam monitoring. Midazolam plasma concentrations showed a good correlation with the sedative capacity of the drug (r2 = 0.906). However, a great variability of the drug effect between patients could be demonstrated, which, as a consequence, may complicate the development of dosing strategies based on midazolam plasma concentrations to better control sedation in critically ill patients. Furthermore, patient age seems to be an important factor for the considerable variability of the sedative effect of midazolam. To achieve a certain levels of sedation, significantly lower midazolam infusion rates as well as plasma concentrations were required as the patients age increased. No significant sex-related differences could be observed for any pharmacologic parameter obtained in this study. Our findings suggest that midazolam therapeutic drug monitoring might be a useful tool to individualize midazolam therapy, especially in critically ill patients developing organ dysfunction and requiring long-term sedation to minimize the risk of drug accumulation and excessive sedation.

Adult↗

PubMed2003

Pharmacokinetics and clinical pharmacodynamics of the new propofol prodrug GPI 15715 in volunteers.

BACKGROUND: GPI 15715 (AQUAVAN injection) is a new water-soluble prodrug which is hydrolyzed to release propofol. The objectives of this first study in humans were to investigate the safety, tolerability, pharmacokinetics, and clinical pharmacodynamics of GPI 15715. METHODS: Three groups of three healthy male volunteers (aged 19-35 y, 67-102 kg) received 290, 580, and 1,160 mg GPI 15715 as a constant rate infusion over 10 min. The plasma concentrations of GPI 15715 and propofol were measured from arterial and venous blood samples up to 24 h. Pharmacokinetics were analyzed with compartment models. Pharmacodynamics were assessed by clinical signs. RESULTS: GPI 15715 was well tolerated without pain on injection. Two subjects reported a transient unpleasant sensation of burning or tingling at start of infusion. Loss of consciousness was achieved in none with 290 mg and in one subject with 580 mg. After 1,160 mg, all subjects experienced loss of consciousness at propofol concentrations of 2.1 +/- 0.6 microg/ml. A two-compartment model for GPI 15715 (central volume of distribution, 0.07 l/kg; clearance, 7 ml. kg-1 min-1; terminal half-life, 46 min) and a three-compartment model for propofol (half-lives: 2.2, 20, 477 min) best described the data. The maximum decrease of blood pressure was 25%; the heart rate increased by approximately 35%. There were no significant laboratory abnormalities. CONCLUSIONS: Compared with propofol lipid emulsion, the potency seemed to be higher with respect to plasma concentration but was apparently less with respect to dose. Pharmacokinetic simulations showed a longer time to peak propofol concentration after a bolus dose and a longer context-sensitive half-time.

Adult↗

PubMed2002

Does the EEG during isoflurane/alfentanil anesthesia differ from linear random data?

OBJECTIVE: Bispectral analysis of the electroencephalogram (EEG) has been used to monitor depth of anesthesia. In the majority of publications this has been done using the so called Bispectral (BIS) Index. The exact relation of this index to bispectral quantities like the bispectrum and its normalized version the bicoherence has not yet been published. In case the EEG is a linear random process the bicoherence is trivial. It is a mere constant independent of the EEG frequency. If the signal is a linear Gaussian random process this constant is zero. In this case both the bispectrum and bicoherence are zero. The aim of this study was to determine the proportion of EEG epochs with non-trivial bicoherence during anesthesia with isoflurane/nitrous oxide. METHODS: We reanalyzed 26.4 hr of EEG signal recorded in 8 patients during anesthesia for general abdominal surgery which were stored in digitized form on CD-Rom. The test developed by Hinich for Gaussianity and linearity was applied to these data. The test was validated with various kinds of surrogate data; especially the phase randomized (pr) EEG, synthetic Gaussian random data and the z-component of the Lorenz attractor and its pr version. RESULTS: The proportion of epochs for which a non-trivial bicoherence was detected by the test was as follows: Lorenz data 95%, pr Lorenz data 5%, synthetic Gaussian data 13.8%, pr EEG 5.4%, original EEG 6.2%. CONCLUSION: As expected the test procedure correctly identified for the Lorenz data for 95% of all epochs a non-trivial bicoherence. For the original EEG data we could not find a significant greater percentage of epochs with non-trivial bicoherence than for the pr data and the synthetic Gaussian data. We conclude that the EEG during anesthesia with isoflurane/alfentanil appears to be largely a linear random process.

Alfentanil↗