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BackgroundA new potential target for multimodal pain management is the group-II metabotropic glutamate receptor subtypes, which can be activated by N-acetylcysteine. We investigated whether pre-emptive administration of N-acetylcysteine leads to a reduction in postoperative pain after laparoscopic inguinal hernia repair.MethodsSixty American Society of Anesthesiologists I-II patients scheduled for elective inguinal hernia repair were randomized to receive either N-acetylcysteine (150 mg/kg) or placebo intravenously 1 hour before surgery. The primary outcome was the visual analogue score during movement in the morning (approximately 24 hours) after surgery. Among secondary outcomes were postoperative opioid consumption and safety of intravenous N-acetylcysteine.ResultsIn total, 23 patients were analyzed per group. Pain scores were similar at all timepoints with a 24 hours median score of 34 (IQR of 19.0 to 42.5) in the N-acetylcysteine group and a median score of 26 (16.0 to 50.0) in the placebo group. The percentage of patients using opioids after surgery was 22% versus 39% day 1 (p=0.63); 9% versus 26% day 2 (p=0.14); 9% versus 17% day 3 (p=0.35) in the N-acetylcysteine group compared with placebo group. Side effects resembling anaphylactoid reactions in response to the administration of N-acetylcysteine were present in more than half of the patients.ConclusionsWithout finding important differences between N-acetylcysteine and placebo group in pain scores postoperatively, but with a high percentage of bothersome side effects for the N-acetylcysteine group, we would not recommend the use of pre-emptive intravenous N-acetylcysteine to reduce postoperative pain in laparoscopic inguinal hernia repair patients based on this study.Trial registration numberNCT03354572.

Geert-Jan van Geffen,1 Hielke Markerink,1 Marc van Barneveld,2 Frank Verhoeven,3 Gert Jan Scheffer,1 Jörgen Bruhn1 1Department of Anesthesiology, Pain and Palliative Care, Radboud University Medical Centre (RUMC), Nijmegen, The Netherlands; 2Medspray Anesthesia BV, Enschede, The Netherlands; 3Medspray T&M, Enschede, The NetherlandsCorrespondence: Geert-Jan van GeffenDepartment of Anesthesiology, Pain and Palliative Care, Radboud University Medical Center, Internal Mail 717, P.O. Box 9101, Nijmegen, HB 6500, The NetherlandsTel +31 24 36 15 24 4Email Geert-Jan.vanGeffen@radboudumc.nlBackground: Obtaining complete topical anaesthesia of the airway remains a clinical challenge. Particle size is one of the most important variables for the dose deposited and the distribution of aerosols in the airways. The mass median aerodynamic diameter of the particles should be in the range of 5– 20 μm. We developed the “Trachospray” as a soft mist spray device for local anaesthetics. This in-vitro comparative test was designed to compare the performance of the new Trachospray device with two existing medical devices. The performance was determined by comparing the spray deposition patterns in the mouth, throat, trachea and lungs.Methods: The human airway was simulated with an artificial idealized mouth and throat model, connected to a Next Generation Impactor. Four measurements were taken for each device (Trachospray, jet nebulizer and a spray pump) with 5.85% NaCl. A fifth measurement was carried out with 0.5% fluorescein solution for a visual inspection of the deposition patterns. The mass median aerodynamic diameter and geometric standard deviation of the droplets were measured.Results: The Trachospray produced an even coverage in the mouth, hypopharynx and vocal cords, with only a small lung fraction. The jet nebulizer produced a much thinner layer coverage of the tongue and surface around the vocal chords with a high lung deposition. The spray pump produced big droplets which deposited mainly at the hypopharynx.Conclusion: The Trachospray device deposits local anaesthetics in the targeted areas for topical anaesthesia of the airway and has promising characteristics for providing effective airway anaesthesia.Keywords: airway model, geometric standard deviation, mass median aerodynamic diameter, medical device, topical airway anaesthesia

Item does not contain fulltext PURPOSE OF REVIEW: The experience of intense postoperative pain remains a significant problem in perioperative medicine. The mainstay of postoperative analgetic therapy is the combination of nonopioid agents (e.g. paracetamol and NSAIDs) with strong opioids (e.g. morphine) according to the WHO analgesic ladder. But as the incidence and intensity of postoperative pain remains high, the search for and evaluation of additional concepts is ongoing. This review highlights the current trends of perioperative multimodal analgesia concepts. RECENT FINDINGS: Gabapentinoids, ketamine, dexamethasone and magnesium are effective parts of a multimodal analgesia concept without absolute contraindications and nearly without major negative side effects. Recent publications further define the role of these substances for perioperative use in terms of optimal dosing, positive side effects, relative potency and interaction. SUMMARY: Components of well tolerated and simple advanced multimodal analgesia concepts in the perioperative period are now easy to apply and ready to become a standard in the daily clinical practice.

Item does not contain fulltext PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) play an important role in multimodal pain management. In patients with a contraindication for NSAIDs, pain management is challenging. A recent Dutch anesthesiology guideline propagates the use of metamizole (dipyrone) in these patients. Metamizole is a controversial drug, its use being previously discouraged because of the risk for agranulocytosis. We discuss whether metamizole could be an alternative to classical NSAIDs and opioids in postoperative pain management despite this drawback. METHOD: Literature review and pharmacovigilance research based on World Health Organization adverse effect registrations. RESULTS: Metamizole causes fewer gastric and duodenal ulcers than other nonselective NSAIDs, and the risk for bleeding is limited. It is unknown whether it is safer than a nonselective NSAID combined with a proton pump inhibitor. Although the drug appears to be safe for renal function in healthy volunteers, data in high-risk patients (eg, those with heart or renal failure) are lacking. The incidence of metamizole-induced agranulocytosis is controversial, but the risk is likely to be limited with short-term postoperative use in this selected group of patients. CONCLUSION: Although firm evidence is lacking, metamizole may be safer for the upper intestinal tract and kidneys than other NSAIDs, and could alternatively be used in patients with an increased risk for stomach or renal problems. Hereby, improved postoperative pain relief can potentially be achieved. The risk for metamizole-induced agranulocytosis is judged to be acceptable.

Background and Aims: Pain reduction is important for rehabilitation after total knee arthroplasty. Intra- and peri-articular infiltration with local anesthetics may be an alternative to commonly used locoregional techniques. Adding pregabalin orally and s-ketamine intravenously may further reduce postoperative pain. Material and Methods: This prospective, randomized, double-blind, placebo-controlled study compared two methods of perioperative analgesia. Control patients received a standardized multimodal postoperative analgesic regime of paracetamol, diclofenac, and piritramide-patient-controlled analgesia, including ropivacaine knee infiltration during surgery. The study group received pregabalin orally and s-ketamine intravenously as an additional medication to the standard multimodal regimen. The control group received placebo. Results: The study group showed lower piritramide consumption during the first 24 h (P: 0.043), but with more side effects such as diplopia and dizziness. Conclusion: Addition of pregabalin and s-ketamine resulted in lower piritramide consumption during the first 24 h postoperatively. However, more investigation on benefits versus side effects of this medication is required.

Background The treatment of acute pain in the emergency department is not always optimal. Peripheral nerve blocks using “blind” or nerve stimulator techniques have substantial disadvantages. Ultrasound-guided regional anesthesia may provide quick, safe, and effective pain relief in patients with proximal femoral fractures with severe pain. However, no evidence exists on emergency physician-performed ultrasound-guided regional anesthesia in these patients in Dutch emergency departments. We hypothesized that emergency physicians can be effectively trained to safely perform and implement ultrasound-guided femoral nerve blocks, resulting in effective pain relief in patients with proximal femoral fractures. Methods In this prospective observational study, emergency physicians were trained by expert anesthesiologists to perform ultrasound-guided femoral nerve blocks during a single-day course. Femoral nerve blocks were performed on patients with proximal femoral fractures. A system of direct supervision by skilled anesthesiologists and residents was put in place. Results A total of 64 femoral nerve blocks were performed. After 30 min, blocks were effective in 69% of patients, and after 60 min, in 83.3%. The mean reduction in pain scores after 30 and 60 min was 3.84 and 4.77, respectively (both p

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Item does not contain fulltext Medical procedures and tests become a challenge when anxiety and pain make it difficult for the patient to cooperate or remain still when needed. Fortunately, a short intervention with hypnoidal language at the onset of a procedure induces a positive and sustained change in the way pain and anxiety are processed. Although anesthesia may appear to be a simple solution to eliminate pain, the adverse effects of preanesthesia anxiety on postoperative behavior and recovery are often not fully appreciated. This article discusses options for self-hypnotic relaxation that are applicable to interactions with children. The high suggestibility of children makes it relatively easy to engage them in make-believe scenarios. Avoidance of negative suggestions is key in avoiding nocebo effects that may be difficult to overcome later. Once a child is immersed in his or her preferred scenario or hobby/activity of choice, environmental and procedural stimuli can be easily integrated in the imagery. Ego-strengthening metaphors that tie in features of strength, confidence, or resilience are particularly empowering. Even when children are fully under general anesthesia, they may still have recall of what is said in the room, and therefore, caution in word choice should be maintained.

Intravenose Anasthetika sind ein wichtiges Handwerkszeug des Anasthesisten. Die Kenntnis ihrer Wirkungen – erwunscht und unerwunscht – sowie der Einsatzmoglichkeiten sind daher von groser Bedeutung. Die gangigen intravenosen Anasthetika sowie ihre Antagonisten werden in diesem Kapitel vorgestellt. Weiterhin wird auf die praktische Anwendung im Rahmen einer TIVA und TCI eingegangen.

Continuous peripheral nerve blocks can be used to provide effective and prolonged analgesia. A variety of needle/catheter assemblies exist, and perineural catheters can be installed using various guidance mechanisms, including nerve stimulation and ultrasound. Complications that may hinder the efficacy of a continuous regional block include inaccurate catheter tip location, catheter dislocation, infection at the catheter insertion site, and difficulty removing the catheter. Neurologic injury with continuous blocks is rare and related to multiple risk factors. Other complications that affect single-injection blocks, such as accidental vascular puncture and systemic local anesthetic toxicity, may also occur with continuous blocks. Complications associated closely with continuous blocks include increased risk of patient falls and problems with the infusion regimen or equipment.

Background The application of ultrasound (US) in peripheral nerve blocks has increased substantially during the last 15 years. However, this technique may have some drawbacks, one of which is the need of a high level of experience of the anaesthesiologist in performing US-guided blocks, a.o. in interpreting the cross-sections displayed in the ultrasound images. Sonoanatomical cross-sections produced by digitized anatomy are easier to understand. Methods From seven cadavers by cryomicrotomy a large series of consecutive high-resolution photographs with an interval of 0.078 mm were obtained from various regions. By multiplanar reformatting perpendicular reconstructions were made using self-developed software (E-MAC). Thus, 3-D tissue blocs were obtained with a voxel size of 78 μm that enabled the reconstruction of oblique cross-sections, in which sizes, angles and surface areas could be measured. Finally, a movie-like animation of consecutive cross-sections including a variable magnification display was built in. Results Reconstructions from the 3-D tissue blocs illustrate important sonoanatomical issues of the brachial plexus (BP). Its proximal nerve roots show varying angulations, whereas the nerves, towards distal, exhibit a shift in internal architecture and changing topography relative to the subclavian and axillary artery. Blood vessels that may hinder needle insertion are highlighted. Conclusion Multiplanar reformatting of digitized anatomy has made feasible the reconstructions of non-standard anatomical planes. The various (oblique) cross-sections explain the difference between hypo-echogenic vs hyper-echogenic structures of the BP-nerves, the position of the needle tip in the various BP-approaches, the topography of important blood vessels displayed in US images and illustrates why the US-probe needs a continuous change in angulation.

Contains fulltext : 87561.pdf (Publisher’s version ) (Closed access) STUDY OBJECTIVE: To present the use of ultrasonography for the performance of proximal subgluteal and distal sciatic nerve blocks in children. DESIGN: Prospective descriptive study. SETTING: University hospital. PATIENTS: 45 ASA physical status I, II, and III patients, aged between 8 months and 16 years, scheduled for lower limb surgery. INTERVENTIONS: During general anesthesia, proximal, subgluteal, and distal sciatic nerve blocks using ultrasonography were performed. If severe postoperative pain was expected, a catheter technique was used. MEASUREMENTS: The injected amount of local anesthetic was noted. Based on the spread of local anesthetic, prediction for successful block was made. Complications, adverse effects, postoperative pain scores, and parent satisfaction scores were noted. MAIN RESULTS: 21 proximal sciatic nerve blocks (12 single-injection and 9 continuous blocks) and 35 distal sciatic nerve blocks (17 single-injection, 6 bilateral single-injection, 4 continuous, and one bilateral continuous block) were performed. A mean initial dose of 0.25 mL.kg(-1) of ropivacaine 0.375% was injected. A successful block was obtained in all children. Excellent postoperative pain relief was obtained. All parents were satisfied with the postoperative pain relief. No complications occurred. CONCLUSION: Ultrasonography is useful in the identification of the sciatic nerve and it facilitates needle and catheter placement for proximal and distal nerve blocks in children. 01 juni 2010

Contains fulltext : 89815.pdf (Publisher’s version ) (Open Access) BACKGROUND: The patient state index (PSI) and the bispectral index (BIS) quantify anaesthetic depth based on the EEG using different algorithms. We compared both indices with regard to the prediction of the depth of propofol anaesthesia. METHODS: In 17 patients, propofol was infused until burst suppression occurred and stopped thereafter until BIS recovered to values above 60. This was repeated; afterwards, patients were intubated, for subsequent surgery. Without surgical stimulus, PSI and BIS were measured simultaneously and compared with the estimated effect-site concentrations of propofol. These were derived from simultaneous pharmacokinetic and -dynamic modelling in an individual two-stage and a population-based NONMEM approach. RESULTS: A close sigmoid relationship was observed between the propofol effect-site concentration and both PSI [coefficient of determination rho(2)=0.91 (sd 0.05)] and BIS [rho(2)=0.92 (0.03)], which was significantly steeper for PSI [gamma=2.2 (0.6)] than for BIS [gamma=1.8 (0.4)], and reached significantly lower values for PSI [E(max)=0.3 (1.1)] than for BIS [E(max)=5.3 (6.7)] at maximal propofol concentrations. A significantly smaller k(e0) was obtained for PSI [0.09 (0.03) min(-1)] compared with BIS [0.10 (0.02) min(-1)]. PSI and BIS correlated significantly with each other (rho(2)=0.866) and predicted propofol effect-site concentration with a comparable probability [P(K)=0.87 (0.05) and 0.86 (0.05), respectively]. NONMEM revealed E(0)=89.3 and 92.3, E(max)=1.9 and 8.6, C(e50)=1.38 and 1.92 microg ml(-1), gamma=1.6 and 1.48, and k(e0)=0.103 and 0.131 min(-1) as typical values for PSI and BIS, respectively. CONCLUSIONS: The PSI and the BIS monitors performed equally well in predicting depth of propofol anaesthesia. However, PSI was lower than BIS by approximately 10-15 points at high propofol concentrations. 01 augustus 2010

Contains fulltext : 87659.pdf (Publisher’s version ) (Closed access) BACKGROUND AND OBJECTIVES: Efficient identification of the sciatic nerve (SN) requires a thorough knowledge of its topography in relation to the surrounding structures. Anatomic cross sections in similar oblique planes as observed during SN ultrasonography are lacking. A survey of sonoanatomy matched with ultrasound views of the major SN block sites will be helpful in pattern recognition, especially when combined with images that show the internal architecture of the nerve. METHODS: From 1 cadaver, consecutive parts of the upper leg corresponding to the 4 major blocks sites were sectioned and deeply frozen. Using cryomicrotomy, consecutive transverse sections were acquired and photographed at 78-microm intervals, along with histologic sections at 5-mm intervals. Multiplanar reformatting was done to reconstruct the optimal planes for an accurate comparison of ultrasonography and gross anatomy. The anatomic and histologic images were matched with ultrasound images that were obtained from 2 healthy volunteers. RESULTS: By simulating the exact position and angulation as in the ultrasonographic images, detailed anatomic overviews of SN and adjacent structures were reconstructed in the gluteal, subgluteal, midfemoral, and popliteal regions. Throughout its trajectory, SN contains numerous fascicles with connective and adipose tissues. CONCLUSIONS: In this study, we provide an optimal matching between histology, anatomic cross sections, and short-axis ultrasound images of SN. Reconstructing ultrasonographic planes with this high-resolution digitized anatomy not only enables an overview but also shows detailed views of the architecture of internal SN. The undulating course of the nerve fascicles within SN may explain its varying echogenic appearance during probe manipulation.

Contains fulltext : 81509.pdf (Publisher’s version ) (Closed access) BACKGROUND AND OBJECTIVES: The sciatic nerve block represents one of the more difficult ultrasound-guided nerve blocks. Easy and reliable internal ultrasound landmarks would be helpful for localization of the sciatic nerve. Earlier, during ultrasound-guided posterior approaches to the infragluteal sciatic nerve, the authors recognized a hyperechoic structure at the medial border of the long head of biceps femoris muscle (BFL). The present study was performed to determine whether this is a potential internal landmark to identify the infragluteal sciatic nerve. METHODS: The depth and the thickness of this hyperechoic structure, its relationship with the sciatic nerve and the ultrasound visibility of both were recorded in the proximal upper leg of 21 adult volunteers using a linear ultrasound probe in the range of 7-13 MHz. The findings were verified by an anatomical study in two cadavers. RESULTS: The hyperechoic structure at the medial border of the BFL extended in a dorsoventral direction between 1.4+/-0.6 cm (mean+/-SD) and 2.8+/-0.8 cm deep from the surface, with a width of 2.2+/-0.9 mm. Between 2.6+/-0.9 and 10.0+/-1.5 cm distal to the subgluteal fold, the sciatic nerve was consistently identified directly at the ventral end of the hyperechoic structure in all volunteers. The anatomical study revealed that this hyperechoic structure corresponds to tendinous fibres inside and at the medial border of the BFL. CONCLUSION: The hyperechoic BFL tendon might be a reliable soft tissue landmark for ultrasound localization of the infragluteal sciatic nerve.

Since its commercial introduction in 1996, target-controlled infusion (TCI) has become an established technique for administration of intravenous anaesthetics. Modern TCI systems, however, are characterized by an increasing number of additional options and features, such as the choice between different pharmacokinetic models and modes of application, which may confuse the less experienced user. This review describes the differences between pharmacokinetic models, modes of application and the effect of covariates as well as the consequences for dosing. The aim is to explicate for the user of modern TCI systems the underlying scientific concepts and the relevance for clinical practice.

BACKGROUND: The sciatic nerve block by the posterior approaches represents one of the more difficult ultrasound-guided nerve blocks. Our clinical experiences with these blocks indicated a point slightly distal to the subgluteal fold as an advantageous position to allow good ultrasonic visibility. In this study, we systematically scanned the sciatic nerve from the subgluteal fold to the popliteal crease, to determine an optimal point for ultrasonographic visualization. METHODS: After institutional approval and written informed consent, we recruited 15 volunteers to visualize the sciatic nerve from the subgluteal fold to the popliteal crease using a linear ultrasound probe in the range of 7-13 MHz. The ultrasonographic visibility of the sciatic nerve, nerve diameter (width and thickness), and skin-to-nerve distance at 20 equidistant points between the subgluteal fold and the popliteal crease were recorded. RESULTS: The sciatic nerve could be successfully visualized in cross-section as a hyperechoic structure on ultrasound in all volunteers. In the course from subgluteal to the popliteal area, the shape of the sciatic nerve changed from flat to round, while the skin-nerve distance varied with the smallest skin-nerve distances at the popliteal crease and at 5.4 cm (on average) distal to the subgluteal fold. The best ultrasonographic visibility scores were found between 7.2 and 10.8 cm (on average) distal to the gluteal fold. CONCLUSION: Between 5.4 and 10.8 cm from the subgluteal fold seems to be the best area to scan the sciatic nerve in terms of superficial nerve position and good ultrasonic visibility.

In this in vitro study, a needle guidance device and a 'free hand' technique for ultrasound guided needle insertion were compared in a simulated ultrasound-guided interventional task using a porcine phantom. Residents inexperienced in using ultrasonography were asked to insert a needle, using an in-plane techniques, and to make contact with metal rods at a depth of 2 and 4 cm in the phantom. The transducer made angles of 90 degrees, 60 degrees and 45 degrees with the surface of the phantom. The times to perform the procedures were significantly shorter and the needle visualisation was significantly better when using the needle guidance device. The residents ranked their satisfaction with the needle-guidance device significantly better than the 'free-hand' technique. This device may be beneficial when performing ultrasound guided peripheral nerve blocks, especially by inexperienced operators.

Item does not contain fulltext Brain-Computer Interface (BCI) systems are traditionally designed by taking into account user-specific data to enable practical use. More recently, subject independent (SI) classification algorithms have been developed which bypass the subject specific adaptation and enable rapid use of the system. A brain switch is a particular BCI system where the system is required to distinguish from two separate mental tasks corresponding to the on-off commands of a switch. Such applications require a low false positive rate (FPR) while having an acceptable response time (RT) until the switch is activated. In this work, we develop a methodology that produces optimal brain switch behavior through subject specific (SS) adaptation of: a) a multitrial prediction combination model and b) an SI classification model. We propose a statistical model of combining classifier predictions that enables optimal FPR calibration through a short calibration session. We trained an SI classifier on a training synchronous dataset and tested our method on separate holdout synchronous and asynchronous brain switch experiments. Although our SI model obtained similar performance between training and holdout datasets, 86% and 85% for the synchronous and 69% and 66% for the asynchronous the between subject FPR and TPR variability was high (up to 62%). The short calibration session was then employed to alleviate that problem and provide decision thresholds that achieve when possible a target FPR=1% with good accuracy for both datasets. 10 p.

Contains fulltext : 157484.pdf (Publisher’s version ) (Open Access) Objective. Patients undergoing general anesthesia may awaken and become aware of the surgical procedure. Due to neuromuscular blocking agents, patients could be conscious yet unable to move. Using brain–computer interface (BCI) technology, it may be possible to detect movement attempts from the EEG. However, it is unknown how an anesthetic influences the brain response to motor tasks. Approach. We tested the offline classification performance of a movement-based BCI in 12 healthy subjects at two effect-site concentrations of propofol. For each subject a second classifier was trained on the subject’s data obtained before sedation, then tested on the data obtained during sedation (‘transfer classification’). Main results. At concentration 0.5 μ g ml -1 , despite an overall propofol EEG effect, the mean single trial classification accuracy was 85% (95% CI 81%- 89%), and 83% (79%-88%) for the transfer classification. At 1.0 μ g ml -1 , the accuracies were 81% (76%-86%), and 72% (66%-79%), respectively. At the highest propofol concentration for four subjects, unlike the remaining subjects, the movement-related brain response had been largely diminished, and the transfer classification accuracy was not significantly above chance. These subjects showed a slower and more erratic task response, indicating an altered state of consciousness distinct from that of the other subjects. Significance. The results show the potential of using a BCI to detect intra-operative awareness and justify further development of this paradigm. At the same time, the relationship between motor responses and consciousness and its clinical relevance for intraoperative awareness requires further investigation. 9 p.

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 : 154964.pdf (Publisher’s version ) (Open Access) Brain-Computer Interfaces (BCIs) have the potential to detect intraoperative awareness during general anaesthesia. Traditionally, BCI research is aimed at establishing or improving communication and control for patients with permanent paralysis. Patients experiencing intraoperative awareness also lack the means to communicate after administration of a neuromuscular blocker, but may attempt to move. This study evaluates the principle of detecting attempted movements from the electroencephalogram (EEG) during local temporary neuromuscular blockade. EEG was obtained from four healthy volunteers making 3-second hand movements, both before and after local administration of rocuronium in one isolated forearm. Using offline classification analysis we investigated whether the attempted movements the participants made during paralysis could be distinguished from the periods when they did not move or attempt to move. Attempted movement trials were correctly identified in 81 (68-94)% (mean (95% CI)) and 84 (74-93)% of the cases using 30 and 9 EEG channels, respectively. Similar accuracies were obtained when training the classifier on the participants' actual movements. These results provide proof of the principle that a BCI can detect movement attempts during neuromuscular blockade. Based on this, in the future a BCI may serve as a communication channel between a patient under general anaesthesia and the anaesthesiologist. 11 p.

Given the fast development and increasing clinical relevance of ultrasound guidance for thoracic paravertebral blockade, this review article strives (1) to provide comprehensive information on thoracic paravertebral space anatomy, tailored to the needs of a regional anesthesia practitioner, (2) to interpret ultrasound images of the thoracic paravertebral space using cross-sectional anatomical images that are matched in location and plane, and (3) to briefly describe and discuss different ultrasound-guided approaches to thoracic paravertebral blockade. To illustrate the pertinent anatomy, high-resolution photographs of anatomical cross-sections are used. By using voxel anatomy, it is possible to visualize the needle pathway of different approaches in the same human specimen. This offers a unique presentation of this complex anatomical region and is inherently more realistic than anatomical drawings.

Bispectral Index (BIS) (Aspect Medical Systems, Newton, MA) and Narcotrend (MonitorTechnik, Bad Bramstedt, Germany) are monitoring devices that were, as others, designed to assess the depth of anesthesia. Meanwhile, a number of studies indicate that with total IV anesthesia, BIS and Narcotrend have comparable effects on drug consumption and recovery times whereas comparative clinical data for volatile anesthetics are still missing. Therefore, we designed the present prospective, randomized, and double-blinded study to compare the effects of BIS and Narcotrend monitoring during desflurane-remifentanil anesthesia and versus a standard anesthetic practice protocol. One-hundred-twenty adult patients scheduled for minor orthopedic surgery were randomized to receive a desflurane-remifentanil anesthetic controlled either by Narcotrend or by BIS or solely by clinical variables. Anesthesia was induced with 0.4 microg x kg(-1) x min(-1) remifentanil and 2 mg/kg propofol. After tracheal intubation, remifentanil was infused at a constant rate of 0.2 microg x kg(-1) x min(-1) whereas desflurane in 1.5 L/min O(2)/air was adjusted according to clinical variables or the following target values: during maintenance of anesthesia to a value of "D(0)" (Narcotrend) or "50" (BIS), 15 min before the end of surgery to "C(1)" (Narcotrend) or "60" (BIS), whereas in the standard protocol group, desflurane was controlled according to clinical variables, e.g., heart rate, arterial blood pressure, movements. Recovery times and desflurane consumption were recorded by a blinded investigator. The desflurane vaporizer was weighed before and after anesthesia and consumption per minute was calculated. Data are mean +/- sd. The groups were comparable for demographic data, duration of anesthesia, and mean remifentanil dosages. Compared with standard practice, patients with Narcotrend or BIS monitoring needed significantly less desflurane (standard practice 443 +/- 71 mg/min, Narcotrend 374 +/- 124 mg/min, BIS monitoring 416 +/- 99 mg/min desflurane [both P0.05]). However, recovery times were not significantly different between the groups, e.g., opening of eyes 4.7 +/- 2.2 versus 3.7 +/- 2.0 versus 4.2 +/- 2.1 min. During desflurane-remifentanil anesthesia, Narcotrend and BIS monitoring seem to be equally effective compared with standard anesthetic practice: BIS and Narcotrend allow for a small reduction of desflurane consumption whereas recovery times are only slightly reduced.Monitoring the electroencephalogram with Narcotrend or Bispectral Index during desflurane-remifentanil anesthesia only slightly reduces recovery times when compared with a standard practice protocol.

Background.Thisstudywasdesignedtoinvestigatetheimpactofbispectralindex(BIS)orA-line AAI index (based on middle-latency auditory evoked potential) monitoring on recovery times and drug consumption when compared with standard anaesthetic practice during desfluraneremifentanil anaesthesia. Methods. After having obtained approval from the institutional review board and written informed consent, 200 adult patients undergoing minor surgical procedures were randomized to receive a desflurane-remifentanil anaesthetic controlled either solely by clinical parameters or by BIS or AAI to the following target values: during maintenance of anaesthesia to a value of ‘50’ (BIS) or ‘30’ (AAI), 15 minbefore the end ofsurgery to ‘60’ (BIS)or ‘45’ (AAI). Recovery times and drug consumption were recorded by a blinded investigator. Results. Compared with standard practice, patients with BIS or AAI monitoring needed similar desfluraneconcentrations(standardpractice2.9[0.5]vol%,BIS3.3[0.9]vol%,AAI2.6[0.5]vol%), and had similar recovery times (open eyes 5.6 [2.5] min, 5.9 [3.4] min, 5.0 [3.1] min; extubation 6.3 [2.4] min, 6.6 [3.5] min, 5.6 [3.0] min; stating name 7.3 [2.4] min, 7.6 [3.5] min, 7.3 [6.6] min). Conclusions. Compared with standard anaesthetic practice BIS and AAI guided titration to the used target ranges did not result in a reduction of desflurane consumption or recovery times during minor surgery with use of remifentanil. Br J Anaesth 2005; 94: 63‐9

Background Recently, entropy algorithms have been proposed as electroencephalographic measures of anesthetic drug effects. Datex-Ohmeda (Helsinki, Finland) introduced the Entropy Module, a new electroencephalographic monitor designed for measuring depth of anesthesia. The monitor calculates a state entropy (SE) computed over the frequency range of 0.8-32 Hz and a response entropy (RE) computed over the frequency range of 0.8-47 Hz. The authors investigated the dose-response relation of SE and RE during sevoflurane anesthesia in comparison with the Bispectral Index (BIS). Methods Sixteen patients were studied without surgical stimulus. Anesthesia was induced by sevoflurane inhalation with a tight-fitting facemask. Sevoflurane concentrations were increased and subsequently decreased and increased two to four times until the measurement was stopped and patients were intubated for surgery. The performances of SE, RE, and BIS to predict the estimated sevoflurane effect site concentration, obtained by simultaneous pharmacokinetic and pharmacodynamic modeling, were compared by calculating the correlation coefficients and the prediction probability. Results State entropy, RE, and BIS values decreased continuously over the observed concentration range of sevoflurane. Correlation coefficients were slightly but not significantly better for entropy parameters (0.87 +/- 0.09 and 0.86 +/- 0.10 for SE and RE, respectively) than for BIS (0.85 +/- 0.12). Calculating the prediction probability confirmed these results with a prediction probability of 0.84 +/- 0.05 and 0.82 +/- 0.06 for SE and RE, respectively, and 0.80 +/- 0.06 for BIS. Conclusion State entropy and RE seem to be useful electroencephalographic measures of sevoflurane drug effect.

Background The purpose of this investigation was to describe the pharmacodynamic interaction between propofol and remifentanil for probability of no response to shaking and shouting, probability of no response to laryngoscopy, Bispectral Index (BIS), and electroencephalographic approximate entropy (AE). Methods Twenty healthy volunteers received either propofol or remifentanil alone and then concurrently with a fixed concentration of remifentanil or propofol, respectively, via a target-controlled infusion. Responses to shaking and shouting and to laryngoscopy were assessed multiple times after allowing for plasma effect site equilibration. The raw electroencephalogram and BIS were recorded throughout the study, and AE was calculated off-line. Response surfaces were fit to the clinical response data using logistic regression or hierarchical response models. Response surfaces were also estimated for BIS and AE. Surfaces were visualized using three-dimensional rotations. Model parameters were estimated with NONMEM. Results Remifentanil alone had no appreciable effect on response to shaking and shouting or response to laryngoscopy. Propofol could ablate both responses. Modest remifentanil concentrations dramatically reduced the concentrations of propofol required to ablate both responses. The hierarchical response surface described the data better than empirical logistic regression. BIS and AE are more sensitive to propofol than to remifentanil. Conclusions Remifentanil alone is ineffective at ablating response to stimuli but demonstrates potent synergy with propofol. BIS and AE values corresponding to 95% probability of ablating response are influenced by the combination of propofol and remifentanil to achieve this endpoint, with higher propofol concentrations producing lower values for BIS and AE.

Background Several studies relating electroencephalogram parameter values to clinical endpoints using a single (mostly hypnotic) drug at relatively low levels of central nervous system depression (sedation) have been published. However, the usefulness of a parameter derived from the electroencephalogram for clinical anesthesia largely depends on its ability to predict the response to stimuli of different intensity or painfulness under a combination of a hypnotic and an (opioid) analgesic. This study was designed to evaluate the predictive performance of spectral edge frequency 95 (SEF95), BIS, and approximate entropy for the response to increasingly intense stimuli under different concentrations of both propofol and remifentanil in the therapeutic range. Methods Ten healthy male and ten healthy female volunteers were studied during coadministration of propofol and remifentanil. After having maintained a specific target concentration for 10 min, the depth of sedation-anesthesia was assessed using the responsiveness component of the Observer's Assessment of Alertness/Sedation (OAA/S) rating scale, which was modified by adding insertion of a laryngeal mask and laryngoscopy. The electroencephalogram derived parameters approximate entropy, bispectral index, and SEF95 were recorded just before sedation level was assessed. Results The prediction probability values for approximate entropy were slightly, but not significantly, better than those for bispectral index, SEF95, and the combination of drug concentrations. A much lower prediction ability was observed for tolerance of airway manipulation than for hypnotic endpoints. Conclusion Approximate entropy revealed informations on hypnotic and analgesic endpoints using coadministration of propofol and remifentanil comparable to bispectral index, SEF95, and the combination of drug concentrations.

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

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Background and objective This study investigates the interaction of sevoflurane and nitrous oxide on EEG median power frequency of 2.5 Hz during surgery. Methods Sevoflurane concentrations required for electroencephalographic median power frequency between 2 and 3 Hz were measured in 25 patients during gynaecological laparotomies. Nitrous oxide was randomly administered at 0, 20, 40, 60 and 75 vol%, subsequently two different concentrations in each patient. The data were analysed using isobolographic analysis together with previously published data on nitrous oxide-isoflurane, -enflurane, or -desflurane interaction. Results The interaction is described by the equation: C volatile anaesthetic/CO volatile anaesthetic + C N 2 O/ CO N 2 O = 1 (C is the concentrations for a drug combination to achieve the desired effect; CO is the concentration for single drug use). The parameters are CO isoflurane = 1.11 vol% (95% Cl 1.03-1.19), CO enflurane = 1.64 (1.52-1.77), CO desflurane = 5.31 (4.92-5.73), CO sevoflurane = 2.12 (1.96-2.29), CO N 2 O = 174 (153-202). These parameters decrease by 6% (2.5-10) for every 10 years of patients' age > 40 years. Conclusions The interaction is compatible with additivity. The potency of nitrous oxide to substitute the volatile anaesthetics is less than anticipated from previously reported MAC values.

Background The authors hypothesized that the electroencephalogram (EEG) during higher anesthetic concentrations would show more "order" and less "randomness" than at lower anesthetic concentrations. "Approximate entropy" is a new statistical parameter derived from the Kolmogorov-Sinai entropy formula which quantifies the amount of regularity in data. The approximate entropy quantifies the predictability of subsequent amplitude values of the EEG based on the knowledge of the previous amplitude values. The authors investigated the dose-response relation of the EEG approximate entropy during desflurane anesthesia in comparison with spectral edge frequency 95, median frequency, and bispectral index. Methods Twelve female patients were studied during gynecologic laparotomies. Between opening and closure of the peritoneum, end-tidal desflurane concentrations were varied between 0.5 and 1.6 minimum alveolar concentration (MAC). The EEG approximate entropy, median EEG frequency, spectral edge frequency 95, and bispectral index were determined and the performance of each to predict the desflurane effect compartment concentration, obtained by simultaneous pharmacokinetic-pharmacodynamic modeling, was compared. Results Electroencephalogram approximate entropy decreased continuously over the observed concentration range of desflurane. The performance of the approximate entropy (prediction probability PK = 0.86 +/- 0.06) as an indicator for desflurane concentrations is similar to spectral edge frequency 95 (PK = 0.86 +/- 0.06) and bispectral index (PK = 0.82 +/- 0.06) and is statistically significantly better than median frequency (PK = 0.78 +/- 0.06). Conclusions The amount of regularity in the EEG increases with increasing desflurane concentrations. The approximate entropy could be a useful EEG measure of anesthetic drug effect.

Objective. The bispectral index (BIS) is a complex EEG parameter which integrates several disparate descriptors of the EEG into a single variable. One of the subparameters incorporated in the BIS is the suppression ratio, quantifying the percentage of suppression during burst suppression pattern. The exact algorithm used to synthetize the information to the BIS value is unpublished and still unknown. This study provides insight into the integration of the suppression ratio into the BIS algorithm. Methods. EEG data of 10 healthy volunteers during propofol infusion were analyzed. Propofol concentrations were ramped up to 4 predetermined concentrations (1, 2, 3, 4, 6, 8, 9, or 12 µg/ml) using a computer controlled infusion pump (STANPUMP). EEG recordings were performed with an Aspect A-1000 EEG monitor (Version 3.22). The relationship of the processed EEG variables bispectral index and suppression ratio, calculated by the Aspect A-1000 monitor, was analyzed. Results. Up to 40% suppression ratio the average BIS values remained constant regardless of suppression ratios (r= 0.13). Beyond a suppression ratio of 40%, BIS and suppression ratio were invariably linearly correlated (r= −1). At a suppression ratio ≥ 40% the BIS value could be calculated as BIS = 50 – suppression ratio/2. Conclusions. Suppression ratio values > 40% are linearly correlated with BIS values from 30 to 0. An increasing anesthetic drug effect resulting in an increase of the duration of suppression to a suppression ratio up to 40% is not adequately reflected by the BIS value.

Item does not contain fulltext Combining electrophysiological and hemodynamic features is a novel approach for improving current performance of brain switches based on sensorimotor rhythms (SMR). This study was conducted with a dual purpose: to test the feasibility of using a combined electroencephalogram/functional near-infrared spectroscopy (EEG-fNIRS) SMR-based brain switch in patients with tetraplegia, and to examine the performance difference between motor imagery and motor attempt for this user group. A general improvement was found when using both EEG and fNIRS features for classification as compared to using the single-modality EEG classifier, with average classification rates of 79% for attempted movement and 70% for imagined movement. For the control group, rates of 87% and 79% were obtained, respectively, where the "attempted movement" condition was replaced with "actual movement." A combined EEG-fNIRS system might be especially beneficial for users who lack sufficient control of current EEG-based brain switches. The average classification performance in the patient group for attempted movement was significantly higher than for imagined movement using the EEG-only as well as the combined classifier, arguing for the case of a paradigm shift in current brain switch research. 8 p.

Contains fulltext : 133861.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Patients with a proximal femur fracture are often difficult to evacuate from the accident scene. Prehospital pain management for this vulnerable group of patients may be challenging. Multiple co-morbidities, polypharmacy and increased age may limit the choice of suitable analgesics. The fascia iliaca compartment (FIC) block may be an alternative to intravenous analgesics. However this peripheral nerve block is mainly applied by physicians.In the Netherlands, prehospital emergency care is mostly provided by EMS-nurses. Therefore we examined whether well-trained EMS-nurses are able to successfully perform a FIC block in order to ensure timely and appropriate effective analgesia.The study was study was registered in the Netherlands Trial Register (NTR-nr 3824). METHODS: Ten EMS nurses were educated in the performance of a FIC-block. Indications, technique, side-effects and complications were discussed. Hereafter the trained EMS-nurses staffed ambulance teams were dispatched to patients with a suspicion for a proximal femur fracture. After confirmation of the diagnosis, the block was performed and 0.3 ml/kg lidocaine (10 mg/ml) with adrenaline 5 mug/ml was injected. The quality of pain relief, occurrence of complications and patient satisfaction were evaluated. RESULTS: In 108 patients a block was performed. One hundred patients could be included. Every EMS nurse performed at least 10 FIC blocks. The block was effective in 96 patients. The initial median (NRS)-pain score decreased after block performance to a score of 6 (after 10 minutes), 4 (after 20 minutes) and 3 (after 30 minutes). At arrival at the Emergency Department the median pain score was 3. Dynamic NRS-pain scores when transferring the patient from the accident scene to the ambulance stretcher, during transportation to the hospital and when transferring the patient to a hospital bed were, 4, 3 and 3.5 respectively. Patient satisfaction was very high. No complications were noted. CONCLUSION: Additional educated EMS-nurses are able to successfully perform a FIC-block for providing acute pain relief to patients with a suspected proximal femur fracture.

Item does not contain fulltext The SonixGPS needle guidance positioning system provides navigation assistance to facilitate needle handling during ultrasound-guided procedures. Each of 20 inexperienced nurse anaesthetists performed 12 different ultrasound-guided tasks in a porcine phantom. Using both in-plane and out-of-plane approaches, they inserted a needle and made contact with metal rods at depths of 2, 4 and 6 cm. We compared their performances without and with navigation as paired observations. Using the out-of-plane approach, navigation yielded shorter execution times (26 s vs 14 s, respectively; p = 0.01) and fewer needle repositionings (8 vs 3, respectively; p = 0.001). Using the in-plane approach, the needle was more visible with navigation assistance: 24% vs 52% of execution time, respectively (95% CI: 44%-12%; p = 0.0025). Better needle visibility was associated with shorter execution times and fewer needle repositionings. Combining ultrasound-guided techniques with the needle guidance positioning system may reduce tissue manipulation, thus improving patient comfort and safety.

Item does not contain fulltext INTRODUCTION: The Episure Autodetect syringe, a spring-loaded syringe, is a loss-of-resistance syringe with an internal compression that applies constant pressure on the plunger. As the principle of loss-of-resistance is the same for adult and for pediatric patients, the Episure Autodetect syringe should be able to identify correctly the epidural space also in pediatric patients. METHODS: A retrospective review was carried out for all pediatric patients, in which the Episure Autodetect syringe was used for locating the epidural space between 2007 and 2011 in our department. RESULTS: In 17 pediatric patients (9 months-14 years, 7.5-43 kg weight), the Episure syringe was used. In all 17 patients, the epidural space was correctly identified using the spring-loaded syringe as evidenced by satisfactory analgesia. No accidental dural punctures or false loss-of-resistances were observed. CONCLUSION: The spring-loaded Episure Autodetect syringe might be a potentially useful loss-of-resistance syringe for identification of the epidural space in pediatric patients.

Motor-impaired individuals such as tetraplegics could benefit from Brain-Computer Interfaces with an intuitive control mechanism, for instance for the control of a neuroprosthesis. Whereas BCI studies in healthy users commonly focus on motor imagery, for the eventual target users, namely patients, attempted movements could potentially be a more promising alternative. In the current study, EEG frequency information was used for classification of both imagined and attempted movements in tetraplegics. Although overall classification rates were considerably lower for tetraplegics than for the control group, both imagined and attempted movement were detectable. Classification rates were significantly higher for the attempted movement condition, with a mean rate of 77%. These results suggest that attempted movement is an appropriate task for BCI control in long-term paralysis patients.

The bispectral index (BIS) is a complex EEG variable that combines several disparate descriptors of the EEG into a single value. Approximate entropy is a novel EEG measure that quantifies the regularity of a data time series such as EEG. We report two patients in which the EEG effect of propofol was quantified very similarly by BIS and approximate entropy. However, at the beginning of burst suppression of the EEG, BIS did not indicate an increased anaesthetic drug effect, while approximate entropy did.

Background and Objectives: Thoracic paravertebral block (TPVB) can be used for unilateral surgical procedures. Modifications of the classic approach have been proposed to minimize the risk of pleural puncture. In this study, we evaluated the feasibility and success rate of a transverse in-plane ultrasound (US)-guided TPVB with radiologic confirmation of catheter position. Methods: A total of 36 patients scheduled for unilateral surgery with a TPVB catheter were included in this prospective study. Ultrasonographically, the transverse process of the thoracic vertebra and rib were identified at the appropriate thoracic level. The transducer was moved cranially until an intercostal US view was obtained, indicated by visualization of the parietal pleura. An in-plane needle insertion approach from lateral to medial was used, and a total of 20 mL ropivacaine 0.75% was injected through the needle and a subsequently threaded catheter, while the spread of local anesthetic was observed. Sensory spread of the block was evaluated by loss of cold sensation in the dermatomes. Catheter position was radiologically evaluated with radiopaque dye. Results: Block success rate was 100%. In all patients, correct radiologic thoracic paravertebral catheter position was confirmed; 1 patient also showed additional epidural spread. The median number of total dermatomal segments with loss of cold sensation was 6. No pneumothorax or contralateral loss of cold sensation occurred. Conclusion: An in-plane transverse US-guided TPVB using the described technique is feasible and has a high success rate. In all patients, correct catheter position in the thoracic paravertebral space was radiologically confirmed.

This study was designed to investigate the impact of the Entropy Module® and Bispectral Index® (BIS) monitoring on drug consumption and recovery times compared with standard anaesthetic practice in patients undergoing orthopaedic surgery using a combination of regional and general anaesthesia as performed by an experienced anaesthesiologist. We hypothesised that electroencephalogram monitoring would lead to a lower drug consumption as well as shorter recovery times. With institutional review board approval and written informed consent, 90 adult patients undergoing surgery to the upper or lower extremity received regional anaesthesia for post- and intraoperative pain control and were randomised to receive general anaesthesia by propofol/remifentanil infusion controlled either solely by clinical parameters or by targeting Entropy or BIS values of 50. Recovery times and drug consumption were recorded. Data from 79 patients were analysed. Compared with standard practice, patients with Entropy or BIS monitoring showed a similar propofol consumption (standard practice 101±22 μg/kg/minute, Entropy 106±24 μg/kg/minute, BIS 104±20 μg/kg/minute) and showed similar Aldrete scores (10/10) one minute after extubation: 9.1∓0.3, 9.2±0.6 and 9.3±0.5, respectively. Time points of extubation were 7.3±2.9 minutes, 9.2∓3.9 minutes and 6.8±2.9 minutes, respectively, demonstrating a significant difference between Entropy and BIS (P=0.023). Compared with standard practice, targeting an Entropy or BIS value of 50 did not result in a reduction of propofol consumption during general anaesthesia combined with regional anaesthesia as performed by an experienced anaesthesiologist in orthopaedic patients.

Contains fulltext : 87296.pdf (Publisher’s version ) (Closed access) Noma, also known as cancrum oris, is an infectious disease that results in a loss of orofacial tissue, due to gangrene of soft and bony tissue. It is especially seen in young children in the sub-Saharan region. Among the sequelae of patients who survive noma, trismus is one of the most disabling. This retrospective research studied the long-term results of trismus release in noma patients. Thirty-six patients could be traced in the villages and were included in the study. The mean mouth opening in this group was 10.3mm (95% CI: 7.0; 13.6mm) and the mean period after discharge from hospital was 43 months. Better mouth opening was observed in patients who continued physiotherapy after discharge, were older, and those with a 'soft' (vs. 'hard') inner and outer cheek on palpation. The result of trismus release in noma patients in the long term was extremely poor in this study. 01 september 2010

Contains fulltext : 81731.pdf (Publisher’s version ) (Closed access) BACKGROUND: We compared dose-response curves of the hypnotic effects of desflurane, sevoflurane and isoflurane. In addition, we analyzed the k(e0) values of the different anesthetics. The EEG parameters Bispectral index (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend index (MonitorTechnik, Bad Bramstedt, Germany, version 4.0) were used as measures of the pharmacodynamic effect. METHODS: With IRB approval and informed consent we analyzed the data of three studies including 61 adult patients scheduled for radical prostatectomies. At least 45 min after induction of general anesthesia, end-tidal concentrations of desflurane, sevoflurane or isoflurane were varied between 0.5 and 2 MAC. We transferred the end-tidal concentrations into age-related MAC values. The relationship between MAC effect compartment concentrations and EEG was modeled with a variation of the classical fractional sigmoid E(max) model with two linked sigmoidal curves. All parameters were calculated as a population fit by NONMEM V (GloboMax, Hanover, USA) by minimizing log likelihood. RESULTS: The k(e0) values of the population fit derived from BIS data were 0.54 min(-1) for desflurane, 0.24 min(-1) for sevoflurane and 0.16 min(-1) for isoflurane, from the Narcotrend index 0.43 min(-1) for desflurane, 0.26 min(-1) for sevoflurane and 0.18 min(-1) for isoflurane. The change between the first and the second sigmoidal curve was positioned at nearly the same Narcotrend- and BIS index values between 41 and 44. CONCLUSIONS: The first order rate constant (k(e0) value) determining the equilibration between age-related MAC values and MAC effect site concentration is substantially higher for desflurane than for sevoflurane or isoflurane.