Biomedical subjects

B Rehberg

Publications and source records attributed to B Rehberg.

At least 19 recordsLinked to original sources

PubMed2006

Fast-track surgery in laparoscopic radical prostatectomy: basic principles.

Fast-track surgery describes innovative treatment concepts ensuring a faster convalescence phase. The aim of this study was to allow hospital discharge 3 days after surgery without additional complications in patients receiving LRPE for localized prostate cancer. Twenty-five patients each were randomized in the study groups to verify if a fast-track regimen could be transferred into clinical routine. The perioperative data, early complications, hospital stay as well as readmission rate were analyzed. The mean postoperative stay was 3.6 days in the fast-track group versus 6.7 days in the conventional group. The overall complications were significantly less in the fast-track procedure. The readmission rate was low and not significant. Patients receiving an LRPE benefit from a suitable fast-track concept. The postoperative hospital stay could be shortened nearly by half with a significantly decreased overall complication rate. Thus, fast-track concepts might contribute to saving resources in the long term. However, more evidence based on larger prospective trials is needed to achieve optimal quality of life for patients perioperatively.

Aged↗

PubMed2006

Correlation of the A-Line ARX index with acoustically evoked potential amplitude.

BACKGROUND: Automated indices derived from mid-latency auditory evoked potentials (MLAEP) have been proposed for monitoring the state of anaesthesia. The A-Line ARX index (AAI) has been implemented in the A-Line monitor (Danmeter, V1.4). Several studies have reported variable and, in awake patients, sometimes surprisingly low AAI values. The purpose of this study was to reproduce these findings under steady-state conditions and to investigate their causes. METHODS: Ten awake unmedicated volunteers were studied under steady-state conditions. For each subject, the raw EEG and the AAI were recorded with an A-Line monitor (V1.4) during three separate sessions of 45.0 (1.6) min duration each. MATLAB (Mathworks) routines were used to derive MLAEP responses from EEG data and to calculate maximal MLAEP amplitudes. RESULTS: The AAI values ranged from 15 to 99, while 11.4% fell below levels which, according to the manufacturer, indicate an anaesthetic depth suitable for surgery. Inter-individual and intra-individual variation was observed despite stable recording conditions. The amplitudes of the MLAEP varied from 0.8 to 42.0 microV. The MLAEP amplitude exceeded 2 microV in 75.3% of readings. The Spearman's rank correlation coefficient between the MLAEP amplitude and the AAI value was r=0.89 (P<0.0001). CONCLUSIONS: The version of the A-Line monitor used in this study does not exclude contaminated MLAEP signals. Previous publications involving this version of the A-Line monitor (as opposed to the newer A-Line/2 monitor series) should be reassessed in the light of these findings. Before exclusively MLAEP-based monitors can be evaluated as suitable monitors of depth of anaesthesia, it is essential to ensure that inbuilt validity tests eliminate contaminated MLAEP signals.

Acoustic Stimulation↗

PubMed2006

Comparison of a new composite index based on midlatency auditory evoked potentials and electroencephalographic parameters with bispectral index (BIS) during moderate propofol sedation.

BACKGROUND AND OBJECTIVE: Derived parameters of the electroencephalogram and auditory evoked potentials can be used to determine depth of anaesthesia and sedation. However, it is not known whether any parameter can identify the occurrence of awareness in individual patients. We have compared the performance of bispectral index and a new composite index derived from auditory evoked potentials and the electroencephalogram (AAI 1.61) in predicting consciousness, explicit and implicit memory during moderate sedation with propofol. METHODS: Twenty-one patients with spinal anaesthesia received intraoperatively propofol at the age-corrected C(50) for loss of consciousness and were presented test words via headphones. Bispectral index and AAI 1.61 (auditory evoked potentials, AEP-Monitor2) were recorded in parallel as well as the Observer's Assessment of Alertness/Sedation-score. Postoperatively, testing for explicit and implicit memory formation was performed. RESULTS: Bispectral index and AAI 1.61 correlated well with loss of consciousness defined by an Observer's Assessment of Alertness/Sedation-score of 2 (identical P(K) of 0.87), but did not allow a prediction of postoperative explicit or implicit recall. CONCLUSIONS: Both bispectral index and AAI may be indices of depth of sedation rather than indicators of memory formation, which persists during propofol sedation even after loss of consciousness.

Acoustic Stimulation↗

PubMed2006

Subjective assessment of depth of anaesthesia by experienced and inexperienced anaesthetists.

BACKGROUND AND OBJECTIVE: To measure 'depth of anaesthesia', anaesthesiologists use a combination of observable end-points such as immobility and autonomic stability. Unconsciousness and amnesia are not reliably observable end-points, but correlate with parameters derived from the electroencephalogram. We investigated the association of subjective assessment and electroencephalographic measures of anaesthetic depth in a group of experienced (>4 yr of experience) and a group of inexperienced (<2 yr of experience) anaesthesiologists. METHODS: One hundred ASA I or II patients were assigned to either group. Anaesthesiologists assessed 'anaesthetic depth' using an 11-point numeric and a 5-point verbal scale. Bispectral index and spectral entropy were recorded as electroencephalogram parameters. The association between the subjective assessment and the electroencephalogram parameters was calculated using the prediction probability, PK. RESULTS: Association between subjective assessment and electroencephalographic parameters showed a tendency to a better prediction probability in the experienced group. The difference was significant (P < 0.05) for the bispectral index (PK 0.76 +/- 0.01 for experienced and 0.71 +/- 0.01 for inexperienced anaesthesiologists). In both groups, a large percentage of the data points recorded during surgery showed bispectral index values above the recommended value of 60 (13.2% in the experienced and 34.3% in the inexperienced group) despite a subjective assessment of 'deep' or 'very deep' anaesthetic depth. CONCLUSION: The study demonstrates that the association between subjectively assigned values of anaesthetic depth and electroencephalographic parameters of anaesthetic depth is better for anaesthesiologists with more clinical experience. However, in the 'inexperienced' as well as 'experienced' group a high percentage of bispectral index and entropy values above 60 occurred despite a subjective assessment of adequate anaesthetic depth. Although there was no evidence for explicit memory, this may indicate a risk for memory formation.

Adult↗

PubMed2006

Suppression of the human spinal H-reflex by propofol: a quantitative analysis.

BACKGROUND: The spinal cord is an important site of anaesthetic action because it mediates surgical immobility. During anaesthesia with volatile anaesthetics, it has been shown that the suppression of the spinal H-reflex correlates with surgical immobility. To evaluate whether the H-reflex could also be a possible candidate for monitoring immobility during propofol anaesthesia, this study assessed the concentration-dependent suppression of the H-reflex by propofol. To discriminate different effect sites, the individual concentration response-curves and the t(1/2ke0) of the H-reflex have been compared with those of two EEG parameters. METHODS: In 18 patients, anaesthesia was induced and maintained with propofol infused using a target-controlled infusion pump at stepwise increasing and decreasing plasma concentrations between 0.5 and 4.5 mg/l. The H-reflex of the soleus muscle was recorded at a frequency of 0.1 Hz. Calculated propofol concentrations and H-reflex amplitude were analysed in terms of a pharmacokinetic-pharmacodynamic (PKPD) model with a sigmoid concentration-response function. RESULTS: For slowly increasing propofol concentrations, computer fits of the PKPD model for H-reflex suppression by propofol yielded the following median parameters: EC50 1.1 (0.8-1.7) mg/l, slope parameter 2.4 (2.0-3.7), and a t(1/2ke0) of 6.7 (2.8-7.5, 25-75% quantiles) min. For the bispectral index, the t(1/2ke0) was 2.2 (1.8-3.1) min and for the spectral edge frequency at the 95th percentile of the power spectrum 2.8 (1.9-3.2) min. CONCLUSIONS: Propofol, unlike sevoflurane, suppresses the spinal H-reflex at concentrations far lower than the C50 skin incision. The differences in t(1/2ke0)-values indicate the presence of different effect compartments for effects on the H-reflex and the EEG.

Analysis of Variance↗

PubMed2005

The suppression of spinal F-waves by propofol does not predict immobility to painful stimuli in humans.

BACKGROUND: The immobilizing effects of volatile anaesthetics are primarily mediated at the spinal level. A suppression of recurrent spinal responses (F-waves), which reflect spinal excitability, has been shown for propofol. We have assessed the concentration-dependent F-wave suppression by propofol and related it to the logistic regression curve for suppression of movement to noxious stimuli and the effect on the bispectral index (BIS). The predictive power of drug effects on F-waves and BIS for movement responses to noxious stimuli was tested. METHODS: In 24 patients anaesthesia was induced and maintained with propofol infused by a target controlled infusion pump at stepwise increasing and decreasing plasma concentrations between 0.5 and 4.5 mg litre(-1). The F-waves of the abductor hallucis muscle were recorded at a frequency of 0.2 Hz. BIS values were recorded continuously. Calculated propofol concentrations and F-wave amplitude and persistence were analyzed in terms of a pharmacokinetic-pharmacodynamic (PK/PD) model with a simple sigmoid concentration-response function. Motor responses to tetanic electrical stimulation (50 Hz, 60 mA, 5 s, volar forearm) were tested and the EC(50tetanus) was calculated using logistic regression. RESULTS: For slowly increasing propofol concentrations, computer fits of the PK/PD model for the suppression by propofol yielded a median EC50 of 1.26 (0.4-2.3) and 1.9 (1.0-2.8) mg litre(-1) for the F-wave amplitude and persistence, respectively. These values are far lower than the calculated EC(50) for noxious electrical stimulation of 3.75 mg litre(-1). This difference results in a poor prediction probability of movement to noxious stimuli of 0.59 for the F-wave amplitude. CONCLUSIONS: F-waves are almost completely suppressed at subclinical propofol concentrations and they are therefore not suitable for prediction of motor responses to noxious stimuli under propofol mono-anaesthesia.

Adult↗

PubMed2005

Concentration-dependent suppression of F-waves by sevoflurane does not predict immobility to painful stimuli in humans.

BACKGROUND: Decreased spinal excitability contributes to the immobilizing effects of halogenated ethers during general anaesthesia. Recurrent spinal responses such as F-waves reflect spinal excitability and are suppressed by volatile anaesthetics. To evaluate whether F-waves are suitable for monitoring immobility, the concentration-dependent effects of sevoflurane on F-waves were compared with effects on the Bispectral Index (BIS). The predictive power of all parameters for movement responses to noxious stimuli was tested. In addition, the effect of the noxious stimulus itself on F-waves was investigated. METHODS: In 28 patients, F-waves were recorded during sevoflurane anaesthesia at a frequency of 0.2 Hz at the lower limb. To insert a laryngeal mask, the sevoflurane concentration was initially increased to approximately 4%, which caused a complete extinction of F-waves. The sevoflurane concentration was then reduced until the F-waves recovered. BIS and spectral edge frequency (SEF(95)) were recorded continuously. The t(1/2ke0) and EC(50) values of the F-wave persistence and amplitude were calculated using a standard pharmacokinetic-pharmacodynamic model. During decreasing sevoflurane concentration motor responses to tetanic electrical stimulation (50 Hz, 60 mA, 5 s, volar forearm) were tested in seven patients and MAC(tetanus) was calculated using logistic regression. RESULTS: Sevoflurane reduces the F-wave amplitude with an EC(50) of 0.79 vol% at a far lower concentration than the calculated MAC(tetanus) (1.5 vol%), whereas the F-wave persistence yields an EC(50) of 1.4 vol%. Spinal and EEG parameters predicted the motor responses to movement better than chance alone, but did not differ significantly from each other. CONCLUSION: F-waves, especially the F-wave amplitude, cannot be used to predict movement to noxious stimuli during sevoflurane anaesthesia because they are almost completely suppressed at subclinical sevoflurane concentrations. Either the particular motoneurone pool (the largest motoneurones) assessed by F-waves is not involved in generating movement to painful stimuli or direct effects on motoneurone excitability are not involved in the suppression of movement to painful stimuli by sevoflurane.

Adult↗

PubMed2005

Human mediotemporal EEG characteristics during propofol anesthesia.

Evidence for a response-control-related kind of declarative memory during deep propofol anesthesia has recently been reported. Connectivity within the mediotemporal lobe (MTL), and in particular rhinal-hippocampal synchronization within the gamma band, has been shown to be crucial for declarative memory formation. Thus, we analyzed EEG recordings obtained from the scalp, as well as directly from within the hippocampus and from the anterior parahippocampal gyrus, which is covered by rhinal cortex, in patients with unilateral temporal lobe epilepsy during propofol anesthesia, which preceded electrode explantation. For the gamma band a power decrease starting with induction of anesthesia was observed at scalp position Cz, but a power increase was detected at MTL locations. In contrast to prior results for sleep recordings, rhinal-hippocampal coherence did not decrease within the gamma band at deeper levels of anesthesia. These findings may represent an indirect electrophysiological correlate of partially intact declarative memory formation during deep propofol sedation. Furthermore, we investigated how well the plasma propofol level, as well as different stages of anesthesia including the burst suppression phase, could be monitored by different spectral as well as by nonlinear EEG measures. We observed that conventional spectral power measures, most prominently those recorded from mediotemporal locations, are most closely correlated with the plasma propofol level, whereas different stages of anesthesia can be distinguished best by nonconventional spectral as well as nonlinear measures.

Adult↗

PubMed2004

Comparison of the concentration-dependent effect of sevoflurane on the spinal H-reflex and the EEG in humans.

BACKGROUND: It has been shown that spinal reflexes such as the H-reflex predict motor responses to painful stimuli better than cortical parameters derived from the EEG. The precise concentration-dependence of H-reflex suppression by anaesthetics, however, is not known. Here we investigated this concentration-response relationship and the equilibration between the alveolar and the effect compartment for sevoflurane. METHODS: In 26 patients, the H-reflex was recorded at a frequency of 0.1 Hz while anaesthesia was induced and maintained with sevoflurane at increasing and decreasing concentrations. Population pharmacodynamic modelling was performed using the NONMEM software package, yielding population mean parameters as well as indicators of interindividual variability. RESULTS: Suppression of H-reflex amplitude occurred at lower concentrations (mean EC(50) 1.04 +/- 0.10 vol%, SE of NONMEM estimate) than the effect on either BIS or SEF(95) of the EEG (mean EC(50) 1.55 +/- 0.08 and 1.72 +/- 0.18 vol%, respectively), and exhibited a higher interindividual variability. The concentration-response function for the H-reflex was also steeper (mean ë 2.83 +/- 0.25). In addition, the equilibration between alveolar and effect compartment was slower for the H-reflex (mean k(e0) 0.15 +/- 0.01 min(-1)) than for BIS or SEF(95) (mean k(e0) 0.22 +/- 0.02 and 0.41 +/- 0.05 min(-1)). CONCLUSION: The differences in EC(50) and slope of the concentration-response relationships for H-reflex suppression and the EEG parameters point to different underlying mechanisms. In addition, the differences in time constant for equilibration between alveolar and effect compartment confirm the notion that immobility is caused at a different anatomic site than suppression of the EEG.

Adult↗

PubMed2002

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.

Analysis of Variance↗

PubMed2001

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.

Abdomen↗

PubMed2000

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

BACKGROUND: Approximate 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. METHODS: Eleven 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. RESULTS: Higher 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. CONCLUSION: Electroencephalogram 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.

Adult↗

PubMed2000

Quantification of depth of anesthesia by nonlinear time series analysis of brain electrical activity

We investigate several quantifiers of the electroencephalogram (EEG) signal with respect to their ability to indicate depth of anesthesia. For 17 patients anesthetized with sevoflurane, three established measures (two spectral and one based on the bispectrum), as well as a phase space based nonlinear correlation index were computed from consecutive EEG epochs. In the absence of an independent way to determine anesthesia depth, the standard was derived from measured blood plasma concentrations of the anesthetic via a pharmacokinetic/pharmacodynamic model for the estimated effective brain concentration of sevoflurane. In most patients, the highest correlation is observed for the nonlinear correlation index D*. In contrast to spectral measures, D* is found to decrease monotonically with increasing (estimated) depth of anesthesia, even when a "burst-suppression" pattern occurs in the EEG. The findings show the potential for applications of concepts derived from the theory of nonlinear dynamics, even if little can be assumed about the process under investigation.

Journal Article↗

PubMed1999

Sodium channels (from rat, mouse, and man) in neuroblastoma cells and different expression systems have similar sensitivities to pentobarbital.

Current understanding of the molecular mechanisms of anaesthesia entails multiple molecular sites of anaesthetic action, each more or less important for a specific anaesthetic drug used. For some molecular anaesthetic targets such as the GABA(A), and acetylcholine receptors as well as potassium channels, large differences in anaesthetic effects and sensitivity between different receptor subtypes have been found. Voltage-gated sodium channels have been shown to be affected at clinical concentrations of pentobarbital. However, these results were obtained in an expression system, and anaesthetic sensitivity may be dependent on sodium channel subtype and subunit composition, too. Therefore, we compared the sensitivity of voltage-gated sodium channels to pentobarbital in human (SHSYSY) and mouse (N1 E-115) neuroblastoma cell lines as well as an HEK293-cell expression system with previously reported data with other sodium channel subtypes. Remarkably, for all sodium channel subtypes studied as well as all subtypes reported in the literature, pentobarbital had qualitatively identical effects with some quantitative differences, and at potentials near the action potential threshold sodium currents were significantly reduced by clinical concentrations of pentobarbital.

Action Potentials↗

PubMed1999

Comparative pharmacodynamic modeling of the electroencephalography-slowing effect of isoflurane, sevoflurane, and desflurane.

BACKGROUND: The most common measure to compare potencies of volatile anesthetics is minimum alveolar concentration (MAC), although this value describes only a single point on a quantal concentration-response curve and most likely reflects more the effects on the spinal cord rather than on the brain. To obtain more complete concentration-response curves for the cerebral effects of isoflurane, sevoflurane, and desflurane, the authors used the spectral edge frequency at the 95th percentile of the power spectrum (SEF95) as a measure of cerebral effect. METHODS: Thirty-nine patients were randomized to isoflurane, sevoflurane, or desflurane groups. After induction with propofol, intubation, and a waiting period, end-tidal anesthetic concentrations were randomly varied between 0.6 and 1.3 MAC, and the EEG was recorded continuously. Population pharmacodynamic modeling was performed using the software package NONMEM. RESULTS: The population mean EC50 values of the final model for SEF95 suppression were 0.66+/-0.08 (+/- SE of estimate) vol% for isoflurane, 1.18+/-0.10 vol% for sevoflurane, and 3.48+/-0.66 vol% for desflurane. The slopes of the concentration-response curves were not significantly different; the common value was lambda = 0.86+/-0.06. The Ke0 value was significantly higher for desflurane (0.61+/-0.11 min(-1)), whereas separate values for isoflurane and sevoflurane yielded no better fit than the common value of 0.29+/-0.04 min(-1). When concentration data were converted into fractions of the respective MAC values, no significant difference of the C50 values for the three anesthetic agents was found. CONCLUSIONS: This study demonstrated that (1) the concentration-response curves for spectral edge frequency slowing have the same slope, and (2) the ratio C50(SEF95)/MAC is the same for all three anesthetic agents. The authors conclude that MAC and MAC multiples, for the three volatile anesthetics studied, are valid representations of the concentration-response curve for anesthetic suppression of SEF95.

Adult↗

PubMed1999

Suppression of central nervous system sodium channels by propofol.

BACKGROUND: Previous studies have provided evidence that clinical levels of propofol alter the functions of voltage-dependent sodium channels, thereby inhibiting synaptic release of glutamate. However, most of these experiments were conducted in the presence of sodium-channel activators, which alter channel inactivation. This study electrophysiologically characterized the interactions of propofol with unmodified sodium channels. METHODS: Sodium currents were measured using whole-cell patch-clamp recordings of rat brain IIa sodium channels expressed in a stably transfected Chinese hamster ovary cell line. Standard electrophysiologic protocols were used to record sodium currents in the presence or absence of externally applied propofol. RESULTS: Propofol, at concentrations achieved clinically in the brain, significantly altered sodium channel currents by two mechanisms: a voltage-independent block of peak currents and a concentration-dependent shift in steady-state inactivation to hyperpolarized potentials, leading to a voltage dependence of current suppression. The two effects combined to give an apparent concentration yielding a half-maximal inhibitory effect of 10 microM near the threshold potential of action potential firing (about -60 mV). Propofol inhibition was also use-dependent, causing a further block of sodium currents at these anesthetic concentrations. CONCLUSIONS: In these experiments with pharmacologically unaltered sodium channels, propofol inhibition of currents occurred at concentrations about eight-fold above clinical plasma levels and thus at brain concentrations reached during clinical anesthesia. Therefore, the results indicate a possible role for sodium-channel suppression in propofol anesthesia.

Anesthetics, Inhalation↗

PubMed1998

Volatile anesthetics significantly suppress central and peripheral mammalian sodium channels.

1. Voltage-dependent sodium channels are important for neuronal signal propagation and integration. 2. Non-mammalian preparations, such as squid giant axon, have sodium channels which have been found to be insensitive to clinical anesthetic concentrations. 3. On the other hand, sodium channels from mammalian neurons are much more sensitive to block by volatile anesthetics. 4. Due to a significant hyperpolarizing shift in steady-state inactivation, IC50s for sodium channel block at potentials close to the resting membrane potential overlapped with clinical anesthetic concentrations. 5. Hence, sodium channels in mammalian neurons may be sensitive molecular targets of volatile anesthetics.

Anesthetics, Inhalation↗

PubMed1998

[Concentration-dependent changes in the latency and amplitude of somatosensory-evoked potentials by desflurane, isoflurane and sevoflurane].

PURPOSE: Comparison of the influence of desflurane, isoflurane, and sevoflurane on the parameters of cortical somatosensory evoked potentials (SEP). METHODS: A total of 41 patients were randomly allocated to either the isoflurane, desflurane or sevoflurane group. Following induction with propofol and intubation, concentration of the volatile anaesthetic was kept constant at 1.3, 1.0, and 0.7 MAC for 15 minutes each in randomised sequences. No opioids or N2O were used. Cortical somatosensory evoked potentials were recorded following median nerve stimulation at the wrist with 1.5 times motor threshold current. SEP were evaluated for latencies of peak N20 and P25 as well as peak-to-peak amplitude N20P25. Measurements at the end of the 15 minute equilibration intervals were compared by analysis of variance for repeated measurements. Latencies and the logarithm of the amplitudes were assumed to be normally distributed. RESULTS: SEP could be recorded in all patients and at all concentrations. Latency of cortical SEP increased with anaesthetic concentration in a linear manner. No differences in latency increase were found between the three anaesthetics (ANOVA). In contrast, the decrease in amplitude with increasing anaesthetic concentration was non-linear. It was large from control to 0.7 MAC, but small in the range between 0.7 and 1.3 MAC. Amplitude reduction was larger with isoflurane than with sevoflurane or desflurane. CONCLUSION: 1) Sevoflurane and desflurane are better suited for anaesthetic management during intraoperative electrophysiological monitoring than isoflurane, because SEP amplitudes are better preserved. 2) SEP amplitude is less altered by changing anaesthetic concentrations in the concentration range from 0.7 to 1.3 MAC than SEP latency.

Adult↗