Anaesthetic efficacy and postinduction hypotension with remimazolam compared with propofol: a multicentre randomised controlled trial.

Remimazolam, a short-acting benzodiazepine, may be used for induction and maintenance of total intravenous anaesthesia, but its role in the management of patients with multiple comorbidities remains unclear. In this phase 3 randomised controlled trial, we compared the anaesthetic efficacy and the incidence of postinduction hypotension during total intravenous anaesthesia with remimazolam vs. propofol. A total of 365 patients (ASA physical status 3 or 4) scheduled for elective surgery were assigned randomly to receive total intravenous anaesthesia with remimazolam (n = 270) or propofol (n = 95). Primary outcome was anaesthetic effect, quantified as the percentage of time with Narcotrend® Index values ≤ 60, during surgery (skin incision to last skin suture), with a non-inferiority margin of -10%. Secondary outcome was the incidence of postinduction hypotensive events. Mean (SD) percentage of time with Narcotrend Index values ≤ 60 during surgery across all patients receiving remimazolam (93% (20.7)) was non-inferior to propofol (99% (4.2)), mean difference (97.5%CI) -6.28% (-8.89-infinite); p = 0.003. Mean (SD) number of postinduction hypotension events was 62 (38.1) and 71 (41.1) for patients allocated to the remimazolam and propofol groups, respectively; p = 0.015. Noradrenaline administration events (requirement for a bolus and/or infusion) were also lower in patients allocated to remimazolam compared with propofol (14 (13.5) vs. 20 (14.6), respectively; p < 0.001). In conclusion, in patients who were ASA physical status 3 or 4, the anaesthetic effect of remimazolam was non-inferior to propofol.

[Preoperative patient-oriented advance planning of emergency and intensive care treatment--Necessary or imposition? : Questionnaire survey]. / Präoperative patientenorientierte Vorausplanung von Notfall- und Intensivbehandlung--Bedarf oder Zumutung? : Fragebogenerhebung.

BACKGROUND: Traditional advance directives can often not be satisfactorily implemented into patient care; therefore, patient-oriented decision-making prior to scheduled interventions and beyond the actual surgery is of particular importance. Data on inpatient advance care planning (ACP) in Germany are lacking. OBJECTIVES: This proof-of-concept study was carried out to determine the needs of inpatients undergoing surgery for advance preoperative planning of emergency care and to assess potential discomfort caused by such a program. MATERIAL AND METHODS: A voluntary and anonymous standardized questionnaire survey was carried out in scheduled surgery inpatients over 50 years old. Data collection was structured in a demographic part and statements dealing with preoperative advance planning of emergency care in hospital evaluated as Likert items. RESULTS: Out of 579 patients (mean age 66 years, 51% male) 43% indicated a basic interest in being informed about advance planning of emergency care individually during the current hospital stay. Desire for patient self-determination represented an independent factor of information needs [p = 0.036, 95% confidence interval (95% CI) 0.027-0.793]. The survey was perceived as a burden by only 7.3% of patients. This perception was independently associated with less concern about perioperative complication risks (p = 0.008, 95% CI 0.144-0.975). CONCLUSION: The results confirmed a substantial interest in patient-oriented advance planning of emergency care in a preoperative setting; however, no demographic group criteria for patients with information requirements could be defined. As the burden evoked by the topic is low, advance planning of emergency and intensive care treatment of inpatients undergoing surgery should be actively provided in the future.

[Survey on the need for information during the preanesthesia visit]. / Fragebogenstudie zum Informationsbedarf in der Prämedikationsambulanz.

BACKGROUND: The preanesthesia informed consent document is regarded mainly as a legal prerequisite but patient autonomy in the authorization of a proposed intervention requires that the relevant information is provided in a suitable and useful way. AIM: The information needs of patients was determined in relation to demographic parameters. This study carried out to evaluate if the expected extent of information regarding anesthesia during the preanesthesia visit was dependent on group-specific variables. MATERIAL AND METHODS: A total of 699 adult patients with forthcoming elective non-cardiac surgery were anonymously interviewed concerning their expectations and informational needs during the preanesthesiavisit. The questionnaire contained 15 demographic variables, one being the question on health-related quality of life (HRQoL). The ASA classification was the only patient data assessed by the anesthesiologist after the consultation. In the second part of the questionnaire statements regarding the kind and extent of information (n = 10) as well as structural aspects of the preanesthesia visit (n = 5) could be rated using a four-step Likert scale. Point values from questions 1-10 were added to a sum score of need for information for each patient with 0 to ± 3 allotted for each question according to the direction of the question wording (i.e. more or less information desired) and the individual patient scores on the Likert scale. Variables associated with this score of need for information were assessed by regression analysis. RESULTS: Of the patients, 80.6% were classified as American Society of Anesthesiologists (ASA) physical status I and II. The HRQoL was rated fair or good by a total of 80%. On average patients were satisfied with the extent and the kind of information offered during the preanesthesia visit with a mean of the sum score of 0 (min. -10 and max. +10, SD ± 3.2). This applied to the written material to prepare for informed consent; however, the consultation was much more appreciated as a source of information. Of the patients, 278 wanted more information and 268 patients wanted less. Linear regression analysis determined education [p = 0.00018, 95% CI: 0.405 (0.194-0.615)], ASA physical status [(p = 0.047, 95% CI: - 0.558 (- 1.107 to - 0.009)] and HRQoL [(p = 0.025, 95% CI: - 0.412 (- 0.771 to - 0.053)] as being independently related to information needs, including perioperative processes as well as rare risks and complications. Interest in being educated about patient autonomy in end of life situations in the hospital was significantly correlated to the score (p < 0.001, r = 0.143). The results of this study demonstrate for the first time in a German surgical cohort a wide acceptance of preoperative healthcare planning (77.4 %). CONCLUSION: Demographic criteria can help to tailor pre-anesthetic information to individual patient needs. The explanatory power of these variables was, however, low. The relationship between self-assessed HRQoL and the demand for information underlines the necessity to adapt the amount and kind of information provided during the consultation to individual patients preferences.

Burst suppression-MAC and burst suppression-CP50 as measures of cerebral effects of anaesthetics.

BACKGROUND: MAC (minimum alveolar concentration of an inhaled anaesthetic) and CP50i (minimum plasma concentration of i.v. anaesthetics) are well-established measures to compare potencies of anaesthetics. The underlying clinical endpoint immobility reflects mainly effects of anaesthetics on the spinal cord, which limits the use of this measure for comparison of effects on the main target organ of general anaesthesia--the brain. The present study determines the median concentration of sevoflurane, isoflurane, and propofol that induce the onset of electroencephalogram (EEG) suppression ('silent second'): MACBS and CP50BS. METHODS: Fifty-five unpremedicated patients (ASA physical status of I or II) undergoing elective surgery were randomly assigned to receive general anaesthesia with sevoflurane, isoflurane, or propofol. A two-channel EEG was continuously recorded to identify 'silent second'. Independent cross-over pairs were analysed using the 'Dixon's up-and-down' method, and MACBS/CP50BS values were calculated by logistic regression. RESULTS: CP50BS was 4.9 µg ml(-1) for propofol. MACBS was 2.9 vol% for sevoflurane and 1.5 vol% for isoflurane. CP50BS of propofol was less than one-third of CP50i, whereas MACBS of sevoflurane was >1.4-fold of MAC; MACBS of isoflurane was 1.3-fold of MAC. CONCLUSIONS: Immobility and cerebral effects reflect different entities of anaesthetic action. The median concentration of anaesthetic drug (volatile or i.v. agent) required to induce 'silent second' might be a more useful metric than the median concentration required to prevent movement in response to a surgical stimulus in order to compare relative potencies of anaesthetic agents on the brain. Advantage of the 'silent second' is an easy identification of this endpoint, while such a deep level is not required for clinical anaesthesia.

[Postoperative cognitive dysfunction. Possible neuronal mechanisms and practical consequences for clinical routine]. / Postoperative kognitive Dysfunktion. Mögliche neuronale Mechanismen und praktische Konsequenzen für den klinischen Alltag.

Postoperative cognitive dysfunction (POCD) presents as a long-lasting decline in cognitive function after a surgical procedure, predominantly occurring in elderly patients. The causes are most likely multifactorial with the exact mechanisms still unknown. Hypotheses of the causes of POCD are based on experimental evidence that anesthetics can impair mechanisms of learning and memory on a neuronal level and might lead to neurodegeneration. Additionally, surgery can result in neuroinflammation which could also underlie POCD. The most important strategy to avoid POCD is to maintain the patient's physiological homeostasis perioperatively. According to the presently available clinical studies recommendations in favor or against certain anesthesiological procedures cannot be given.

Monitors of the hypnotic component of anesthesia - correlation between bispectral index and cerebral state index.

BACKGROUND: The current study examines whether analysis of identical EEG data results in a high correlation coefficient of BIS and CSI values during all anesthetic levels and assesses the concordance of both EEG monitors for displaying the level of anesthesia as defined by the manufacturers. METHODS: EEG data of 40 patients undergoing elective surgery under general anesthesia with either sevoflurane/remifentanil or propofol/remifentanil were replayed to an EEG player and reanalysed by a BIS A-2000® monitor and a Cerebral State Monitor. Further, research into differences between CSI and BIS index values was performed, e.g., extraction of differences of ≥ 10 and ≥ 20 index points and of the EEG length with differing index values. RESULTS: The overall correlation coefficient was 0.68 without significant difference between propofol or sevoflurane group. In 51.8% of all recordings, both EEG monitors agreed in their classification of the anesthetic level. The number and length of differing index pairs was influenced by varying time delays of index calculation and different algorithms of index computation. CONCLUSION: In contrast to previous studies, our current approach combines the following conditions: analysis on basis of identical underlying EEG data from deep to light anesthesia, no guidance of anesthetic administration by one of the EEG-based monitors, avoidance of simultaneous EEG readings and the use of two different anesthetic regimens. Though the result of EEG analysis during anesthesia is similar with both monitors, CSI performance during propofol anesthesia was superior to sevoflurane anesthesia. Consequently, a lower agreement of classification of anesthetic levels between BIS and CSI was reached with the use of sevoflurane. Thus, CSI calculation seems not to be independent from anesthetic agent.

[Postoperative acute mitral regurgitation. Unexpected finding after minor non-cardiac surgery]. / Akute perioperative Mitralklappeninsuffizienz. Unerwarteter Befund nach nichtkardiochirurgischem Bagatelleingriff.

This report describes the case of a 59-year-old man who was scheduled for general anesthesia with propofol, sufentanil and sevoflurane for removal of a metal implant. The patient was classified as American Society of Anesthesiologists (ASA) II status because of an asymptomatic mitral valve prolapse and medically treated arterial hypertension. During induction of narcosis a pulsoxymetrically measured inadequate increase in oxygen saturation after preoxygenation was noticed and a moderate respiratory obstruction occurred intraoperatively, but anesthesia was uneventfully completed and the patient was extubated. However, 3 h later the patient developed severe dyspnea, hypoxia, tachycardia and arterial hypotension. Physical examination revealed a new grade 4/6 systolic murmur radiating to the axilla and X-ray showed bilateral pulmonary edema. Neither electrocardiographic nor biochemical manifestations of acute myocardial infarction were identified but transthoracic echocardiography revealed fluttering of the posterior leaflet of the mitral valve with grade III regurgitation and dilation of the left atrium. Coronary angiography was normal and left ventriculography confirmed severe mitral regurgitation. Mitral valve repair was successfully performed 22 h after presentation of symptoms. Mitral regurgitation is a common finding on echocardiography, seen to some degree in over 75% of the population. The etiology of mitral valve insufficiency which can be caused by pathologic changes of one or more of the components of the mitral valve, including the leaflets, annulus, chordae tendineae, papillary muscles, or by abnormalities of the surrounding left ventricle and/or atrium are discussed. Rupture of mitral chordae tendineae is infrequent and causes acute hemodynamic deterioration and needs corrective surgery. Valve replacement should be performed only if mitral valve repair is not possible. Echocardiography is an invaluable tool in determining the severity of regurgitation, the integrity of the mitral valve apparatus, the extent of left ventricular enlargement, and the ejection fraction. Acute mitral valve regurgitation caused by a rupture of chordae tendineae should be considered in the differential diagnosis of perioperative acute pulmonary edema.

Teletherapeutic drug administration by long distance closed-loop control of propofol.

BACKGROUND: The objective of this pilot study was to investigate the feasibility of an EEG-controlled closed-loop administration of propofol over a long distance of about 200 km. METHODS: We performed a teletherapeutic propofol infusion during total intravenous anaesthesia with propofol in 11 patients undergoing general surgery. The teletherapeutic system consisted of a computer at the patient site in Munich and a computer at the control site in Erlangen, which were connected via the internet through a virtual private network. The patient's EEG signal was sent to the control site computer, where the median frequency (MEF) of the EEG power spectrum was calculated. The propofol infusion, determined by a model-based adaptive feedback algorithm to maintain a MEF of 1.5 to 2 Hz, was sent to the patient site computer connected to the infusion pump. The quality of the control was assessed by the performance error defined as the percentage deviation of the measured MEF from the set point and the necessity of interventions by the anaesthetist at the patient site. RESULTS: During closed-loop administration of propofol [83 (52) min] the median performance error of the system was - 4.6 (4.4)% and the median absolute performance error was 18.8 (5.7)%. From a total number of 10 905 transmitted EEG epochs, there were five epochs with transmission errors, without further consequences for drug control. In one patient, teletherapy was stopped because the internet connection was interrupted. CONCLUSIONS: Teletherapeutic drug administration could be realized over a longer distance. Further studies have to investigate the practicability and safety of teletherapeutic drug control in anaesthesia.

[Risks and complications of epidural neurolysis -- a review with case report]. / Schwerwiegende Risiken und Komplikationen der epiduralen Neurolyse nach Racz.

Racz's minimal invasive epidural catheter procedure, also known as "epidural neuroplasty" is not only utilized in patients suffering from failed spine surgery ("failed back surgery syndrome") but also increasingly applied to non-surgical back pain patients to prevent chronification or deterioration. Its hypothesized principle of action is local epidural lysis of adhesions, neurolysis of vertebral nerve roots and local lavage of proinflammatory mediators by repeated injection of local anesthetics, corticosteroids, hyaluronidase and hypertonic saline solution. However adverse events are well known to occur in epidural neuroplasty. Complications of epidural neuroplasty are due to the procedure itself or due to specific drugs-related side effects. Unintended dural puncture, administration of the drugs to the subarachnoid or subdural space, catheter shearing, infection and severe hemodynamic instability during application are most commonly observed adverse events. Complications related to the procedure itself occur immediately, while complications relating to drug administration show later onset. Within this context, we report a case of severe meningitis with neurologic sequelae in a patient who received Racz catheter-treatment for unspecific low-back pain and provide an overview of the literature on other potential severe complications. As a consequence, we recommend that the Racz catheter procedure as yet should be restricted to controlled clinical trials with rigorous inclusion- and exclusion criteria.

[Perioperative pain therapy for knee endoprosthetics]. / Perioperative Schmerztherapie in der Kniegelenkendoprothetik.

Total knee arthroplasty (TKA) is associated with significant postoperative pain. Adequate analgesics and techniques are required for early mobilization, continuous passive motion and intensified physical therapy as well as for high-quality postoperative analgesia.However, in the immediate postoperative setting the excessive nociceptive input can be blocked by using doses which are most frequently associated with adverse effects like dizziness, nausea and vomiting, sedation and risk of respiratory depression. The use of peripheral nerve blocks is recommended after orthopaedic surgery. After TKA, the continuous "3 in 1 nerve block" has been proven to be more effective than conventional patient controlled intravenous opioid therapy as well as than epidural analgesia accompanied by side effects. Postoperative analgesic techniques influence surgical outcome, duration of hospitalization and re-convalescence. The use of regional analgesia after TKA may initially lead to higher costs but it is counterbalanced by a reduction in morbidity and mortality, decrease in hospitalization, improved re-convalescence and a better functional outcome.

Sevoflurane and propofol influence the expression of apoptosis-regulating proteins after cerebral ischaemia and reperfusion in rats.

BACKGROUND AND OBJECTIVE: Sevoflurane and propofol reduce the extent of necrosis and improve neurological outcome in rodent models of cerebral ischaemia and reperfusion. However, the effects of these anaesthetics on programmed cell death (apoptosis) are unclear. The present study investigates whether sevoflurane and propofol affect the expression of apoptosis-regulating proteins after cerebral ischaemia in rats. METHODS: Thirty-two fasted male Sprague-Dawley rats were tracheally intubated and the lungs were ventilated (isoflurane and N2O/O2 anaesthesia). After surgical preparation, the animals were randomly assigned to one of the following groups: control (n = 8): fentanyl intravenous (10 microg kg(-1) bolus and 25 microg kg(-1) h(-1) infusion) with N2O/O2; sevoflurane (n = 8): 2.0% sevoflurane (end-tidal concentration) and O2/air; propofol (n = 8): 0.8-1.0 mg kg(-1) min(-1) propofol intravenous and O2/air; sham-operated (n = 8): 25 microg kg(-1) h(-1) fentanyl intravenous and N2O/O2, no cerebral ischaemia. Ischaemia (30 min) was induced by unilateral common carotid artery occlusion plus haemorrhagic hypotension to a mean arterial pressure of 30-35 mmHg. Four hours after cerebral ischaemia the brains were removed and the expression of apoptosis-regulating proteins (Bax, Bcl-2, p53, Mdm-2) was determined using immunofluorescence and Western-blot analyses. RESULTS: The expression of the pro-apoptotic protein Bax was greater in control animals than in sevoflurane or propofol anaesthetized rats and than in sham-operated animals. The concentrations of Bcl-2, p53 and Mdm-2 were not changed 4 h after cerebral ischaemia. CONCLUSIONS: In addition to the anti-necrotic effects of sevoflurane and propofol, these anaesthetics also reduce the concentration of the apoptosis-inducing protein Bax as early as 4 h after ischaemia.

EEG-based indices of anaesthesia: correlation between bispectral index and patient state index?

BACKGROUND AND OBJECTIVE: Both the bispectral and the patient state indices are derived from the electroencephalogram and have been proposed as a measure of the same clinical target, the hypnotic component of anaesthesia. The present study evaluated whether there is concordance between the bispectral and the patient state indices with regard to end-points measured simultaneously in patients undergoing surgery under general anaesthesia. METHODS: Fifty-seven patients scheduled for elective abdominal, orthopaedic (Groups 1 and 2) or cardiac surgery (Group 3) under general anaesthesia were enrolled in the study. Anaesthesia was performed using remifentanil/ sevoflurane (Group 1, 19 patients), remifentanil/propofol (Group 2, 19 patients) or sufentanil/propofol/isoflurane (Group 3, 19 patients). The bispectral and the patient state indices were simultaneously recorded. Pearson's correlation between these two indices was calculated for the complete data and each group. The percentage of bispectral index values in the recommended range for general anaesthesia (45-60) that were confirmed by levels of patient state index (25-50) was calculated and vice versa. RESULTS: Overall correlation between the bispectral and the patient state indices was 0.667, 0.671 in Group 1, 0.650 in Group 2 and 0.675 in Group 3 (P < 0.01). For values of the bispectral index between 45 and 60, only 40% of corresponding patient state index values were between 25 and 50. For patient state index values of 25-50, only 50% of the corresponding bispectral index values were in the range of 45-60. CONCLUSIONS: Concordance between the bispectral and patient state indices is relatively weak, whereas both are thought to reflect the same clinical target, the hypnotic component of anaesthesia. As a consequence, further studies are required to compare reliability of both indices as indicators of different levels of hypnosis.

Quality of perioperative AEP--variability of expert ratings.

BACKGROUND: Previous studies suggest that auditory evoked potentials (AEP) may be used to monitor anaesthetic depth. However, during surgery and anaesthesia, the quality of AEP recordings may be reduced by artefacts. This can affect the interpretation of the data and complicate the use of the method. We assessed differences in expert ratings of the signal quality of perioperatively recorded AEPs. METHODS: Signal quality of 180 randomly selected AEP, recorded perioperatively during a European multicentre study, was rated independently by five experts as 'invalid' (0), 'poor' (1), or 'good' (2). Average (n=5) quality rating was calculated for each signal. Differences between quality ratings of the five experts were calculated for each AEP: inter-rater variability (IRV) was calculated as the difference between the worst and best classification of a signal. RESULTS: Average signal quality of 57% of the AEPs was rated as 'invalid', 39% as 'poor', and only 4% as 'good'. IRV was 0 in only 6%, 1 in 62%, and 2 in 32% of the AEP, that is in 32% one expert said signal quality was good, whereas a different expert thought the identical signal was invalid. CONCLUSIONS: There is poor agreement between experts regarding the signal quality of perioperatively recorded AEPs and, as a consequence, results obtained by one expert may not easily be reproduced by a different expert. This limits the use of visual AEP analysis to indicate anaesthetic depth and may affect the comparability of AEP studies, where waveforms were analysed by different experts. An objective automated method for AEP analysis could solve this problem.

Early recovery after remifentanil-pronounced compared with propofol-pronounced total intravenous anaesthesia for short painful procedures.

BACKGROUND: We compared recovery from high-dose propofol/low-dose remifentanil ('propofol-pronounced') compared with high-dose remifentanil/low-dose propofol ('remifentanil-pronounced') anaesthesia. METHODS: Adult patients having panendoscopy, microlaryngoscopy, or tonsillectomy were randomly assigned to receive either propofol-pronounced (propofol 100 microg x kg(-1) min(-1); remifentanil 0.15 microg x kg(-1) min(-1)) or remifentanil-pronounced (propofol 50 microg x kg(-1) min(-1); remifentanil 0.45 microg x kg(-1) min(-1)) anaesthesia. In both groups, the procedure was started with remifentanil 0.4 microg x kg(-1), propofol 2 mg x kg(-1), and mivacurium 0.2 mg x kg(-1). Cardiovascular measurements and EEG bispectral index (BIS) were recorded. To maintain comparable anaesthetic depth, additional propofol (0.5 mg x kg(-1)) was given if BIS values were greater than 55 and remifentanil (0.4 microg x kg(-1)) if heart rate or arterial pressure was greater than 110% of pre-anaesthetic values. RESULTS: Patient and surgical characteristics, cardiovascular measurements, and BIS values were similar in both groups. There were no differences in recovery times between the groups (time to extubation: 12.7 (4.5) vs 12.0 (3.6) min, readiness for transfer to the recovery ward: 14.4 (4.4) vs. 13.7 (3.6) min, mean (SD)). CONCLUSIONS: In patients having short painful surgery, less propofol does not give faster recovery as long as the same anaesthetic level (as indicated by BIS and clinical signs) is maintained by more remifentanil. However, recovery times were less variable following remifentanil-pronounced anaesthesia suggesting a more predictable recovery.

Detection of awareness in surgical patients with EEG-based indices--bispectral index and patient state index.

BACKGROUND: Patient state index (PSI) and bispectral index (BIS) are values derived from the EEG, which can measure the hypnotic component of anaesthesia. We measured the ability of PSI and BIS to distinguish consciousness from unconsciousness during induction and emergence from anaesthesia and a period of awareness in surgical patients. METHODS: Forty unpremedicated patients were randomized to receive: (1) sevoflurane/remifentanil (< or =0.1 microg kg(-1) min(-1)), (2) sevoflurane/remifentanil (> or = 0.2 microg kg(-1) min(-1)), (3) propofol/remifentanil (< or =0.1 microg kg(-1) min(-1)), (4) propofol/remifentanil (> or = 0.2 microg kg(-1) min(-1)). Every 30 s after the start of the remifentanil, patients were asked to squeeze the investigator's hand. Sevoflurane or propofol were given until loss of consciousness (LOC1). Tunstall's isolated forearm technique was used during neuromuscular block with succinylcholine. After tracheal intubation, propofol or sevoflurane were stopped until return of consciousness (ROC1). Propofol or sevoflurane were re-started to induce LOC2. After surgery, drugs were discontinued and recovery (ROC2) was observed. PSI and BIS at LOC (LOC1 and LOC2) were compared with those at ROC (ROC1 and ROC2) (t-test). Prediction probability (P(k)) was calculated from values at the last command before and at LOC and ROC. Values are mean (SD). RESULTS: At non-responsiveness, BIS (66 (17)) and PSI (55 (23)) were significantly less than at responsiveness (BIS, 79 (14); PSI, 77 (18); P<0.05). The wide variation with both BIS and PSI measurements of the 80 'awareness' values led to an erroneous classification as unconscious in some cases (BIS, six patients; PSI, nine patients). P(k) was 0.68 (0.03) (BIS) and 0.69 (0.03) (PSI). CONCLUSIONS: Despite significant differences between mean values at responsiveness and non-responsiveness for BIS and PSI, neither measure may be sufficient to detect awareness in an individual patient, reflected by a P(k) less than below 70%.

Prediction of movement following noxious stimulation during 1 minimum alveolar anesthetic concentration isoflurane/nitrous oxide anesthesia by means of middle latency auditory evoked responses.

This paper investigates the applicability of generalized dynamic neural networks for the design of a two-valued anesthetic depth indicator during isoflurane/nitrous oxide anesthesia. The indicator construction is based on the processing of middle latency auditory evoked responses (MLAER) in combination with the observation of the patient's movement reaction to skin incision. The framework of generalized dynamic neural networks does not require any data preprocessing, visual data inspection or subjective feature extraction. The study is based on a data set of 106 patients scheduled for elective surgery under isoflurane/nitrous oxide anesthesia. The processing of the measured MLAER is performed by a recurrent neural network that transforms the MLAER signals into signals having a very uncomplex structure. The evaluation of these signals is self-evident, and yields to a simple threshold classifier. Using only evoked potentials before the pain stimulus, the patient's reaction could be predicted with a probability of 81.5%. The MLAER is closely associated to the patient's reaction to skin incision following noxious stimulation during 1 minimum alveolar anesthetic concentration isoflurane/nitrous oxide anesthesia. In combination with other parameters, MLAER could contribute to an objective and trustworthy movement prediction to noxious stimulation.

Capillary leak syndrome after cardiopulmonary bypass in elective, uncomplicated coronary artery bypass grafting operations: does it exist?

OBJECTIVE: Operations coupled with cardiopulmonary bypass may provoke a systemic inflammatory response, and it has been suggested that this responses causes capillary leakage of proteins, edema formation, and even organ failure. However, capillary leak syndrome is mainly a clinical diagnosis and has not been verified as yet by actual demonstration of protein leakage from the circulation. We have therefore measured the disappearance of labeled plasma protein before and after cardiopulmonary bypass. METHODS: Sixteen patients scheduled for elective coronary artery bypass grafting were enrolled in a prospective controlled study. The cardiopulmonary bypass circuit was primed with crystalloids only. Tumor necrosis factor alpha, interleukin 6, interleukin 8, anaphylatoxin C3a, and terminal complement complex C5b9 levels were determined before, during, and 3 hours after cardiopulmonary bypass. The transvascular escape rate of plasma protein from the intravascular compartment was assessed by measuring the disappearance of intravenously injected Evans blue dye before and during the third hour after cardiopulmonary bypass. RESULTS: A significant inflammatory response could be demonstrated by means of the 5 measured mediators after bypass. The maximal increase, as compared with the baseline value, was found for interleukin 6 (36-fold). The transvascular escape rate of Evans blue dye was similar before and after bypass (7.6 +/- 0.6%/h vs 7.3 +/- 0.6%/h). CONCLUSIONS: The above data confirm the systemic inflammatory response induced by cardiopulmonary bypass. Contrary to expectations, the transvascular escape rate of Evans blue dye did not change when comparing values before and after bypass. The data do not support the concept of increased protein leakage in the exchange vessels after bypass. We were unable to demonstrate a capillary leak syndrome.

Small-dose S(+)-ketamine reduces postoperative pain when applied with ropivacaine in epidural anesthesia for total knee arthroplasty.

UNLABELLED: Reduction of nociceptive input through blockade of N-methyl-D-aspartate (NMDA) receptors has been reported. We compared the effects of epidural S(+)-ketamine versus placebo on postoperative pain in a randomized, double-blinded study in 37 patients undergoing unilateral knee arthroplasty. After lumbar epidural anesthesia with ropivacaine (10 mg/mL, 10-20 mL), 19 patients received 0.9% epidural saline, and 18 patients received 0.25 mg/kg epidural S(+)-ketamine 10 min before surgical incision. After surgery, patient-controlled epidural analgesia with ropivacaine was provided. During the first 8 h after surgery, visual analog scale pain rating was similar between groups. Twenty-four and 48 h after surgery, patients anesthetized with ropivacaine had higher visual analog scale ratings at rest and during movement (P < 0.05) than patients anesthetized with S(+)-ketamine and ropivacaine. Forty-eight hours after surgery, patients anesthetized with ropivacaine also consumed more ropivacaine (558 +/- 210 mg) (P < 0.01) than those anesthetized with S(+)-ketamine and ropivacaine (319 +/- 204 mg). Adverse events were similar between groups. Patients who received S(+)-ketamine and ropivacaine rated the quality of their pain therapy better than those who received ropivacaine alone (P < 0.05). We conclude that the combination of S(+)-ketamine and ropivacaine in epidural anesthesia increases postoperative pain relief when compared with ropivacaine. IMPLICATIONS: Epidural S(+)-ketamine applied with ropivacaine before surgery is a rational approach to decrease injury-induced pain sensitization. Epidural blockade with an N-methyl-D-aspartate receptor antagonist and a local anesthetic may provide better analgesia in the postoperative period than a local anesthetic alone.

Cerebral histopathology following portal venous infusion of bacteria in a chronic porcine model.

BACKGROUND: The aim of this study was to histologically investigate brain damage after prolonged periods of bacteremia in pigs. METHODS: Twenty-one pathogen-free Göttingen minipigs were anesthetized and instrumented with a femoral arterial, a pulmonary arterial, and through midline abdominal incision with a portal venous catheter. After craniotomy the superior sagittal sinus was cannulated. A lumbosacral spinal catheter was inserted for sampling of cerebrospinal fluid. Twelve hours after instrumentation, the animals were randomized in two groups: septic and control animals. The septic group received an infusion of 107 colony-forming units per kilogram of living Escherichia coli over 0.5 h through portal venous catheter each day. The control group received saline. Postoperative intensive care treatment included 4 days of controlled mechanical ventilation, sedation, and intravenous nutrition. The brains then were removed, fixed, and processed for histology. Each pathologic alteration found in the samples was assessed and given a severity code (0-3). RESULTS: Sham-operated animals showed no alterations caused by the instrumentation and the intensive care treatment. The septic group showed typical clinical signs of sepsis. Vasopressor support and mechanical ventilation prevented systemic hypotension and hypoxemia. High serum and cerebrospinal fluid levels of interleukin-6 and tumor necrosis factor-alpha were detected. The septic group showed severe histologic abnormalities of the brain including perivascular edema, spongiform degeneration, hyperemia, and purpura. Damage of neurons was seen including eosinophilic cytoplasm, shrunken nuclei, and disintegration of the nuclear membrane. CONCLUSIONS: Abdominal sepsis induced severe brain damage that was not related to systemic hypoxia or ischemia. High cerebrospinal fluid levels of tumor necrosis factor-alpha and interleukin-6 were related to an inflammatory process in the brain resulting in cerebral edema and death of neurons.