[Transparency and anticorruption]. / Transparenz und Antikorruption.

Transparency in healthcare has been demanded and promoted for years. The aim of such transparency is disclosure of relationships and interests, so that patients can draw their own conclusions regarding the economic relations of their treating physician. Furthermore, transparency measures aim to prevent illegitimate payments. Overall, transparency should keep healthcare free from non-medical considerations, which may stand in contrast to the patient's wellbeing. Part of this strategy is the legislation aimed at fighting corruption in healthcare passed 13 April 2016, the so-called Anticorruption Act.

Can remifentanil use in obstetrics be improved by optimal patient-controlled analgesia bolus timing?

BACKGROUND: The safety of patient-controlled i.v. analgesia (PCA) with remifentanil for obstetrical analgesia remains a matter of concern. The efficacy of remifentanil bolus application, that is, the coincidence between pain and remifentanil effect-site concentration, may be improved by forecasting contractions, but it is not known whether such a technique would also improve safety. METHODS: We recorded pain intensity during labour continuously using a handheld dynamometer in 43 parturients. Using these data, we compared different models in their ability to predict future contractions. In addition, we modelled remifentanil effect-site concentration using three simulated modes of bolus administration, with and without prediction of future contractions. RESULTS: The average duration of pain during contractions recorded by the dynamometer was 45 [14 standard deviation (sd)] s. The time interval between painful contractions was highly variable, with a mean of 151 (31 sd) s during the first and 154 (52 sd) s during the second recording. Using a simple algorithm (three-point moving average), the sd of the difference between predicted and observed inter-contraction intervals can be reduced from 0.95 to 0.79 min. However, the coincidence between remifentanil concentration and pain during contraction is not substantially improved when using these models to guide remifentanil bolus application. CONCLUSIONS: Because of the large variability of inter-contraction intervals, the use of prediction models will not influence the mean remifentanil concentration in-between contractions. Using models predicting future contractions to improve the timing of remifentanil PCA bolus administration will not diminish the need of continuous clinical surveillance and other safety measures.

Nitrous oxide does not produce a clinically important sparing effect during closed-loop delivered propofol-remifentanil anaesthesia guided by the bispectral index: a randomized multicentre study.

BACKGROUND: Nitrous oxide (N2O) offers both hypnotic and analgesic characteristics. We therefore tested the hypothesis that N2O administration decreases the amount of propofol and remifentanil given by a closed-loop automated controller to maintain a similar bispectral index (BIS). METHODS: In a randomized multicentre double-blind study, patients undergoing elective surgery were randomly assigned to breathe 60% inspired N2O (N2O group) or 40% oxygen (AIR group). Anaesthesia depth was evaluated by the proportion of time where BIS was within the range of 40-60 (BIS40-60). The primary outcomes were propofol and remifentanil consumption, with reductions of 20% in either being considered clinically important. RESULTS: A total of 302 patients were randomized to the N2O group and 299 to the AIR group. At similar BIS40-60 [79 (67-86)% vs 76 (65-85)%], N2O slightly decreased propofol consumption [4.5 (3.7-5.5) vs 4.8 (4.0-5.9) mg kg(-1) h(-1), P=0.032], but not remifentanil consumption [0.17 (0.12-0.23) vs 0.18 (0.14-0.24) µg kg(-1) min(-1)]. For the subgroups of men, at similar BIS40-60 [80 (72-88)% vs 80 (70-87)%], propofol [4.2 (3.4-5.3) vs 4.4 (3.6-5.4) mg kg(-1) h(-1)] and remifentanil [0.19 (0.13-0.25) vs 0.18 (0.15-0.23) µg kg(-1) min(-1)] consumptions were similar in the N2O vs AIR group, respectively. For the subgroups of women, at similar BIS40-60 [76 (64-84)% vs 72 (62-82)%], propofol [4.7 (4.0-5.8) vs 5.3 (4.5-6.6) mg kg(-1) h(-1), P=0.004] and remifentanil [0.18 (0.13-0.25) vs 0.20 (0.15-0.27) µg kg(-1) min(-1), P=0.029] consumptions decreased with the co-administration of N2O. CONCLUSIONS: With automated drug administration titrated to comparable BIS, N2O only slightly reduced propofol consumption and did not reduce remifentanil consumption. There was a minor gender dependence, but not by a clinically important amount. Clinical trial registration This study was registered at ClinicalTrials.gov, number NCT00547209.

Utility of Nociceptive Flexion Reflex Threshold, Bispectral Index, Composite Variability Index and Noxious Stimulation Response Index as measures for nociception during general anaesthesia.

Movement and haemodynamic responses to noxious stimuli during general anaesthesia are regarded as signs of nociception. We compared the Nociceptive Flexion Reflex Threshold (NFRT), Bispectral Index (BIS), Composite Variability Index (CVI), Noxious Stimulation Response Index (NSRI) and the calculated propofol/remifentanil effect-compartment concentrations (Ce) as predictors for such responses in 50 female subjects at laryngeal mask airway insertion and skin incision. The following prediction probabilities (PK-values) were obtained at laryngeal mask airway insertion and skin incision, respectively. For movement responses: NFRT = 0.77 and 0.72; p = 0.0001 and 0.004, respectively; BIS = 0.41 and 0.56, p = 0.29 and 0.5, respectively; CVI = 0.48 and 0.57, p = 0.76 and 0.88, respectively; NSRI = 0.49 and 0.76, p = 0.92 and 0.0001, respectively; propofol-Ce = 0.35 and 0.66, p = 0.04 and 0.03, respectively; remifentanil-Ce = 0.68 and 0.72, p = 0.01 and 0.003, respectively. For heart rate responses: NFRT = 0.68 and 0.75, p = 0.04 and 0.01, respectively; BIS = 0.37 and 0.59, p = 0.15 and 0.41, respectively; CVI = 0.41 and 0.44, p = 0.39 and 0.37, respectively; NSRI = 0.48 and 0.53, p = 0.84 and 0.78, respectively; propofol-Ce = 0.42 and 0.56, p = 0.39 and 0.53, respectively; remifentanil-Ce = 0.58 and 0.54, p = 0.35 and 0.73, respectively. We conclude that the NFRT best predicts movement and heart rate responses to noxious stimuli. Effect-compartment concentrations and NSRI also predict movement (but not heart rate) responses satisfactorily.

Sevoflurane reduces spinal reciprocal Ia-inhibition in humans.

BACKGROUND: Potentiation of inhibitory transmissions in the spinal cord is considered to be an important mechanism for the mediation of the immobilizing effects of anesthetics. However, the depressant effects on motoneurons could be counterbalanced by presynaptic effects that inhibit the depressant pathways. Here we investigated the effect of sevoflurane on a disynaptic inhibitory pathway onto motoneurons in a human reflex model. METHODS: The study was performed with 9 volunteers receiving sevoflurane anesthesia (end tidal: 0.8% sevoflurane). Reciprocal inhibition was estimated from the depression of the H-reflex following a conditioning stimulation of the muscle spindle afferents from the tibialis anterior muscle. Measurements were performed before, during and after drug administration. RESULTS: The inhibition (mean ± SE) amounted to 15.4% ± 6.8%, 1.9% ± 4.2% and 15.7% ± 8.8% for measurements before, during and after sevoflurane administration, respectively. Differences between the anesthetic state and the two controls were statistically significant (mixed-effect ANOVA, p<0.01). CONCLUSION: Sevoflurane reduces reciprocal Ia-inhibition on motoneurons in humans. These findings seem to contradict the accepted view that sevoflurane enhances inhibitory synaptic transmission. This contradiction might be explained by the inhibitory actions of sevoflurane within the disynaptic pathway prior to the final glycinergic transmission onto the motoneuron. Our results suggest that even in presumably simple pathways, postsynaptic effects of anesthetics could be superimposed by their presynaptic effects.

Monitoring of the responsiveness to noxious stimuli during sevoflurane mono-anaesthesia by using RIII reflex threshold and bispectral index.

BACKGROUND: We investigated the accuracy of the (normalized) RIII reflex threshold, the bispectral index (BIS), and the end-tidal sevoflurane concentration for predicting movement responses during mono-anaesthesia using sevoflurane. METHODS: Fourteen male subjects were included. Each received a sevoflurane mono-anaesthesia for which the end-tidal concentration was increased in steps of 0.2 vol% every 10 min. Every 5 min, the reactions to noxious stimuli (10 s trapezius squeeze and 30 s 80 mA tetanic stimulus) were tested. The administration of sevoflurane was halted after no movement reactions occurred for three concentration steps. RIII reflex threshold and BIS were recorded continually in all subjects. RESULTS: Thirteen subjects completed the study. The prediction probabilities for movement reactions to the noxious stimuli were 0.79 for the BIS, 0.91 for the RIII threshold, and 0.89 for the end-tidal sevoflurane concentration (PKDMACRO-Statistics: BIS vs RIII, P<0.05; BIS vs C(sevo), P<0.05; RIII vs C(sevo), P>0.05). All population prediction probability values differed significantly from 0.5 (P<0.01, PKDMACRO). CONCLUSIONS: All three instruments can be used for a prediction of movement responses to a noxious stimulus under sevoflurane mono-anaesthesia with an accuracy exceeding prediction by chance. The accuracy of the BIS to predict these responses appears to be lower compared with the RIII reflex threshold or the end-tidal sevoflurane concentration.

Monitoring of the responsiveness to noxious stimuli during anaesthesia with propofol and remifentanil by using RIII reflex threshold and bispectral index.

BACKGROUND: Movement responses are an important indicator of noxious perception in the unconscious state. To allow for a continual monitoring of the responsiveness to noxious stimuli during general anaesthesia, surrogate parameters are needed. Here we compare the performance of the bispectral index (BIS) and the RIII threshold in predicting reactions to noxious stimuli during anaesthesia with propofol and remifentanil. METHODS: Twenty male volunteers were included. The first 10 subjects received constant concentrations of propofol while remifentanil concentrations were increased stepwise. The other 10 subjects each received high propofol concentrations combined with different low remifentanil concentrations and also low propofol concentrations combined with different high remifentanil concentrations. In all subjects, the reactions to an 80 mA 30 s tetanic stimulus were tested every 5 min. BIS and RIII threshold were recorded continually in all subjects. RESULTS: Nineteen subjects completed the study. The population prediction probability for reactions to the noxious stimuli amounted to 0.86 for the BIS and to 0.84 for the RIII threshold in the first 10 subjects (P>0.05, PKDMACRO). In the other nine subjects, the prediction probabilities amounted to 0.64 for the BIS and to 0.77 for the RIII threshold (P<0.05, PKDMACRO). All population prediction probability values differed significantly from 0.5 (P<0.01, PKDMACRO). CONCLUSIONS: RIII threshold and BIS are both influenced dose-dependently by remifentanil at those concentrations that suppress reactions to noxious stimuli. The susceptibility of the parameters to remifentanil concentration seems to be of a similar quality. Under different ratios of propofol and remifentanil concentrations, the RIII threshold correlates with non-responsiveness better than the BIS.

Comparison of the nociceptive flexion reflex threshold and the bispectral index as monitors of movement responses to noxious stimuli under propofol mono-anaesthesia.

BACKGROUND: Prediction of movement responses to noxious stimuli during anaesthesia is of clinical importance. Susceptibility of a parameter of immobility to both hypnotic and analgesic influences could pose an advantage. Here, nociceptive reflexes might be useful, but data regarding the suppression by hypnotic substances are scarce. Therefore, we compared the prediction of movement responses by the RIII reflex threshold and the bispectral index (BIS) during propofol mono-anaesthesia. METHODS: Fifteen male volunteers were included. Propofol effect compartment concentration was increased every 15 min in steps of 1 microg ml(-1) (max 7 microg ml(-1)). Every 5 min, the reactions to trapezius squeezes and 30 s tetanic stimulations (80 mA) of the right ulnar nerve were tested. The RIII reflex threshold was estimated continuously using an automated threshold tracking system that analyses the nociceptive RIII response at the left biceps femoris muscle to stimulation of the left sural nerve. RESULTS: Twelve subjects completed the study. RIII threshold values were normalized by subtraction of the first threshold that was estimated after the subject's loss of consciousness. The population prediction probability P(K) amounted to 0.84 for the RIII threshold and to 0.86 for the BIS (difference not significant). CONCLUSIONS: Movement responses to noxious stimuli under propofol can be predicted by the RIII threshold with a comparable accuracy as the BIS. Therefore, the RIII threshold seems to be influenced by hypnotic effects. Since susceptibility of the RIII threshold to analgesic influences is well established, an advantage for the RIII threshold in the prediction of motor responses could be expected when analgesic substances are used in addition to propofol.

Use of a target-controlled infusion system for propofol does not improve subjective assessment of anaesthetic depth by inexperienced anaesthesiologists.

BACKGROUND AND OBJECTIVES: Target-controlled infusion, via the calculated effect compartment concentrations, may help anaesthesiologists to titrate anaesthetic depth and to shorten recovery from anaesthesia. METHODS: In this prospective, randomized clinical study, we compared the performance of six inexperienced anaesthesiologists with <1 yr of training when using target- or manually controlled infusion of propofol, combined with manual dosing of fentanyl. Ninety-two premedicated ASA I-III patients undergoing minor elective urological or gynaecological surgery were assigned to the manual- or target-controlled infusion group. Bispectral index was recorded in a blinded manner. Subjective assessment of anaesthetic depth on a 10 point numerical scale (1 = very deep anaesthesia, 10 = awake) was asked at regular intervals and the correlation with the blinded bispectral index was analysed using the prediction probability, PK. The propofol concentration profile was calculated post hoc. RESULTS: Propofol administration was similar in both groups with no significant difference for the administered amount and concentrations of propofol. Recovery times were also not different. In both groups, a large percentage of the bispectral index data points recorded during surgery showed bispectral index values below the recommended value of 40, but in the target-controlled infusion group there were significantly less bispectral index values above the recommended upper limit of 60 (2.5% vs. 5.1%). CONCLUSIONS: A target-controlled infusion system does not help inexperienced anaesthesiologists to assess anaesthetic depth or to shorten recovery times, but may reduce episodes of overly light anaesthesia and thus help to prevent awareness.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.