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.

[Current status of teaching in lung ultrasound : Query of knowledge, utilization, need, and preferred teaching method]. / Zum Stand der Ausbildung im Lungenultraschall : Abfrage von Kenntnissen, Verwendung, Bedarf und bevorzugter Unterrichtsform.

BACKGROUND: Lung ultrasound (LUS) is a point-of-care technique which can quickly identify or rule out pathological findings. To date, it is unclear if knowledge about the use of LUS is readily available. OBJECTIVES: We aimed to identify how much knowledge about the use of LUS is present, if there is a need for teaching in LUS, as well as the preferred teaching method in LUS. MATERIALS AND METHODS: A total of 54 participants from two university departments of anesthesiology were randomized into the groups Online, Classroom, and Control. The Online group was taught by videos, the Classroom group by a traditional lecture with hands-on training, and the Control group was not taught at all. We conducted a pre- and posttest as well as a retention test 4 weeks after the end of the study by means of a survey (comparison with Mann-Whitney U test or t­test, respectively, with p < 0.05 considered to be significant). RESULTS: LUS is used "rarely" or "never", and mainly if there is a suspicion for pleural effusion (41.3%). There is a need for LUS (Online: 21.7%; Classroom: 60.9%; Control: 62.5%, p < 0.05). Hybrid teaching consisting of classroom-based and online-based teaching is preferred by the users (Online: 52.2%; Classroom: 56.5%; Control: 62.5%). At the end of the study, 32.6% of the participants of the intervention groups had used LUS in the diagnosis of a pneumothorax. Of the participants, 93.5% planned to use LUS more often in the future. CONCLUSIONS: LUS is rarely used. There is a considerable need for teaching of LUS. Internet-based teaching and traditional lectures are considered equal. Both teaching methods improve the knowledge about LUS and lead to increased use of LUS in daily practice. The participants prefer hybrid teaching incorporating both teaching methods.

Linear and non-linear heart rate metrics for the assessment of anaesthetists' workload during general anaesthesia.

BACKGROUND: Excessive workload may impact the anaesthetists' ability to adequately process information during clinical practice in the operation room and may result in inaccurate situational awareness and performance. This exploratory study investigated heart rate (HR), linear and non-linear heart rate variability (HRV) metrics and subjective ratings scales for the assessment of workload associated with the anaesthesia stages induction, maintenance and emergence. METHODS: HR and HRV metrics were calculated based on five min segments from each of the three anaesthesia stages. The area under the receiver operating characteristics curve (AUC) of the investigated metrics was calculated to assess their ability to discriminate between the stages of anaesthesia. Additionally, a multiparametric approach based on logistic regression models was performed to further evaluate whether linear or non-linear heart rate metrics are suitable for the assessment of workload. RESULTS: Mean HR and several linear and non-linear HRV metrics including subjective workload ratings differed significantly between stages of anaesthesia. Permutation Entropy (PeEn, AUC=0.828) and mean HR (AUC=0.826) discriminated best between the anaesthesia stages induction and maintenance. In the multiparametric approach using logistic regression models, the model based on non-linear heart rate metrics provided a higher AUC compared with the models based on linear metrics. CONCLUSIONS: In this exploratory study based on short ECG segment analysis, PeEn and HR seem to be promising to separate workload levels between different stages of anaesthesia. The multiparametric analysis of the regression models favours non-linear heart rate metrics over linear metrics.

[Pre-operative documentation of individual in-patient therapy goals : A medical staff questionnaire]. / Patientenorientierte Therapieziele im Krankenhaus : Eine Fragebogenerhebung an medizinischem Personal.

BACKGROUND: Perioperative care demands consideration of individual treatment goals. We evaluated the attitudes of medical staff towards a short standardized advance directive (SSAD) as a means of improving patient-orientated care at the transition from operating theater to general or intensive care wards. METHOD: Multicenter anonymized standardized multiple-choice questionnaire among physicians and nurses from various operative and anesthesiology departments. Questions addressing demographic parameters and attitudes towards advance directives in acute care settings (eleven 4­stepped Likert items). Univariate analysis of group comparisons using the chi-square and Kruskal-Wallis rank-sum test. Multivariable analysis of significant differences employing ordinal logistic regression. RESULTS: The overall return rate was 28.2 % (169 questionnaires). Of these, 19.5 % said that existing advance directives were regularly reassessed preoperatively. SSAD was expected to provide improved emergency care by 82.3 and 76.6 % thought that it would help to better focus intensive care resources according to patients' needs. DISCUSSION: Our study shows the dilemma of insufficiently structured directives for changing treatment goals as well as a high number of legal procedures to obtain proxy decisions due to missing out-patient advance health planning. From a medical staff perspective there is strong support for the concept of SSAD based on medical, ethical, economic and organizational reasons.

[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.

Sleep scoring made easy-Semi-automated sleep analysis software and manual rescoring tools for basic sleep research in mice.

Studying sleep behavior in animal models demands clear separation of vigilance states. Pure manual scoring is time-consuming and commercial scoring software is costly. We present a LabVIEW-based, semi-automated scoring routine using recorded EEG and EMG signals. This scoring routine is •designed to reliably assign the vigilance/sleep states wakefulness (WAKE), non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) to defined EEG/EMG episodes.•straightforward to use even for beginners in the field of sleep research.•freely available upon request. Chronic recordings from mice were used to design and evaluate the scoring routine consisting of an artifact-removal, a scoring- and a rescoring routine. The scoring routine processes EMG and different EEG frequency bands. Amplitude-based thresholds for EEG and EMG parameters trigger a decision tree assigning each EEG episode to a defined vigilance/sleep state automatically. Using the rescoring routine individual episodes or particular state transitions can be re-evaluated manually. High agreements between auto-scored and manual sleep scoring could be shown for experienced scorers and for beginners quickly and reliably. With small modifications to the software, it can be easily adapted for sleep analysis in other animal models.

[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.

Plasma oxytocin and vasopressin do not predict neuropeptide concentrations in human cerebrospinal fluid.

The involvement of the neuropeptides oxytocin (OXT) and vasopressin (AVP) in human socio-emotional behaviours is attracting increasing attention. There is ample evidence for elevated plasma levels upon a wide variety of social and emotional stimuli and scenarios, ranging from romantic love via marital distress up to psychopathology, with cause versus consequence being largely unclear. The present study examined whether plasma levels of both OXT and AVP are reflective of central neuropeptide levels, as assumed to impact upon socio-emotional behaviours. Concomitant plasma and cerebrospinal fluid (CSF) samples were taken from 41 non-neurological and nonpsychiatric patients under basal conditions. Although OXT and AVP levels in the CSF exceeded those in plasma, there was no correlation between both compartments, clearly suggesting that plasma OXT and AVP do not predict central neuropeptide concentrations. Thus, the validity of plasma OXT and AVP as potential biomarkers of human behaviour needs further clarification.

Cardiopulmonary resuscitation performance during simulator-based trainings: a comparative retrospective analysis of adherence to 2005 and 2010 guidelines.

BACKGROUND: New cardiopulmonary resuscitation (CPR) guidelines have been published in 2010 emphasizing the importance of minimizing interruptions during chest compression. The aim of our study was to compare the simulator-based CPR training performance of physicians not specialized in anaesthesia and intensive care nurses before and after implementation of new resuscitation guidelines. METHODS: In autumn 2010, a total of 74 scenarios during six 1.5 day simulation-based CPR trainings were performed. Four of them were conducted after the implementation of the 2010 guidelines. During each simulated scenario a programmed script standardized the conditions of the simulator and its reactions on the trainees' actions. CPR relevant parameters were extracted on the basis of the simulator's log files and no-flow-time fraction and median cardiac output of the simulator were calculated. Results before and after the guideline implementation were compared using the Wilcoxon Two Sample Test. RESULTS: Thirty-four out of 74 scenarios were included into the analysis. During training according to the 2010 guidelines, the no-flow-time fraction was lower (median: 21.8% [IQR: 16.1-27.1%] vs. 29.1 % [IQR: 25.0-30.9 %]; P=0.04). The median cardiac output increased from 1.60 L/min-1 [IQR: 1.50-1.65 L/min-1] to 1.90 L/min-1 [IQR: 1.80-2.10 L/min-1]; P<0.001) when the CPR training was conducted according to the 2010 resuscitation guidelines. CONCLUSION: Non-anesthesiological physicians and intensive care nurses training demonstrated an improved CPR performance in a high-fidelity human patient simulator with respect to the median cardiac output and duration of no-flow-time when 2010 CPR guidelines were applied.

Alterations in rotation thromboelastometry (ROTEM®) parameters: point-of-care testing vs analysis after pneumatic tube system transport.

BACKGROUND: Thromboelastometry as point-of-care (POC) testing enables the analysis of the clotting process at the bedside, providing rapid results to guide haemostatic therapy. However, POC testing utilizes medical staff who are managing critically ill patients, as non-laboratory personnel may not be sufficiently trained to run the devices. To resolve these problems, thromboelastometry can be performed in the central laboratory and rapid transport of samples can be accomplished via a pneumatic tube system (PTS). This study compares thromboelastometry parameters of blood samples analysed immediately with those analysed after PTS transport. METHODS: In patients with normal haemostasis, two arterial blood samples were collected from each patient (n=92) in citrated plastic tubes to investigate the assays INTEM (n=35), EXTEM (n=27), and FIBTEM (n=30). One blood sample was analysed immediately, the other sample after PTS transport. Thromboelastometry was performed using a single ROTEM(®) device. RESULTS: The mean clot firmness values were significantly lower for PTS samples in both the INTEM (-0.7 mm cf. -1.1 mm) and EXTEM (-1.4 cf. -1.7 mm) assays. INTEM coagulation time (CT) was significantly lower in PTS samples with a mean difference of -13 s. EXTEM CT was significantly higher in PTS samples with a mean difference of +3.9 s. CONCLUSIONS: Thromboelastometry parameters of blood samples analysed after PTS transport are significantly altered compared with those analysed immediately. However, in patients with normal haemostasis, the alterations were small and without clinical consequence, implying that analysis after PTS transport is an acceptable alternative to prompt analysis at the bedside. Further studies should focus on patients with impaired haemostasis.

[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.

Visual attention of anaesthetists during simulated critical incidents.

BACKGROUND: Situation awareness (SA) is considered to be an important non-technical skill for delivering safe anaesthesia. The spatial distribution of visual attention (VA) is an underlying process for attaining adequate SA. In the present study, a novel technology was used to assess the distribution of VA in anaesthetists delivering anaesthesia. The impact of a critical incident on VA in relation to individual experience is analysed in a descriptive and exploratory manner. METHODS: Fifteen anaesthetists induced general anaesthesia in a full-scale simulator while wearing a head-mounted eye-tracking camera system. After an uneventful session, workload was increased in a randomized order by simulation of a critical incident in the second or third session. Eye tracking was used for the assessment of individual's distribution of VA to monitors, patient, and environment. A post hoc video analysis revealed information about the spatial distribution of VA. Descriptive statistics and exploratory analysis were used. RESULTS: Twenty per cent of VA was directed to the patient monitor (30% during critical incident scenarios, P=0.003). The more experienced anaesthetists (more than 2 yr of work experience) increased the amount of time dedicated to manual tasks from 21% to 25% during critical incidents, whereas the less experienced decreased from 20% to 14% (P=0.061). CONCLUSIONS: Distribution of attention is different during anaesthesia induction with critical incidents compared with uneventful anaesthesia induction. Less experienced anaesthesia providers spend more time on monitoring tasks. Further investigation in confirmatory designs is needed.

Eye tracking for assessment of workload: a pilot study in an anaesthesia simulator environment.

BACKGROUND: Workload assessment is an important tool for improving patient safety in anaesthesia. We tested the hypothesis that heart rate, pupil size, and duration of fixation increase, whereas saccade amplitude decreases with increased workload during simulated critical incidents. METHODS: Fifteen trainee anaesthetists participated in this randomized cross-over trial. Each participant used a head-mounted eye-tracking device (EyeSeeCam) during induction of general anaesthesia in a full-scale simulation during three different sessions. No critical incident was simulated in the first session. In a randomized order, workload was increased by simulation of a critical incident in the second or third session. Pupil size, duration of fixations, saccadic amplitude, and heart rate of each participant and the simulator conditions were recorded continuously and synchronized. The data were analysed by paired sample t-tests and mixed-effects regression analysis. RESULTS: The findings of the second and third sessions of 11 participants were analysed. Pupil diameter and heart rate increased simultaneously as the severity of the simulated critical incident increased. Allowing for individual effects, the simulator conditions explained 92.6% of the variance in pupil diameter and 93.6% of the variance in heart rate (both P<0.001). The duration of fixation decreased with increased workload. The saccadic amplitude remained unaffected by workload changes. CONCLUSIONS: Pupil size and heart rate reflect workload increase within simulator sessions, but they do not permit overall workload comparisons between individuals or sessions. Contrary to our assumption, the duration of fixation decreased with increased workload. Saccade amplitude did not reflect workload fluctuations.

The mu-opioid receptor agonist remifentanil induces acute dysphoria irrespective of its analgesic properties.

Mu-opioidergic agonists are believed to induce euphoria, whereas kappa-agonists are thought to lead to dysphoria. Our study investigated mood effects of remifentanil, a mu-receptor opioid agonist, in healthy male volunteers. Moreover, we examined interactions between mood and pain. Three conditions were investigated in 21 volunteers: saline, 0.05 and 0.15 microg kg(-1) min(- 1) remifentanil. Each condition was investigated during non-painful heat and during painful heat stimulation. Mood was measured with the von Zerssen's mood scale (Bf-S score) and pain intensity using a Visual Analogue Scale (VAS). High Bf-S scores are reflecting discontent and dysphoria. Changes were tested for significance using a linear mixed model approach. Remifentanil significantly increased Bf-S scores during painful heat (+91.4%), indicating a negative mood effect, although it reduced VAS scores of painful heat intensity (-49.0%). The type of sensory stimulation (non-painful versus painful) had no effect on mood. There was no interaction between remifentanil dose and type of stimulation. Our results provide evidence for negative mood effects of remifentanil. These effects occur with and without pain. Taken into account that remifentanil reduces pain, one could have expected analgesia-related amelioration of mood instead. In clinical practice, these remifentanil effects should be considered and a comedication might be advisable.

Time delay of electroencephalogram index calculation: analysis of cerebral state, bispectral, and Narcotrend indices using perioperatively recorded electroencephalographic signals.

BACKGROUND: Monitoring of anaesthetic depth with EEG-derived indices may detect EEG changes associated with awareness and thereby help to decrease the incidence of intraoperative awareness with postoperative recall. All currently available monitors need varying time periods to calculate a new index when reacting to changes in anaesthetic depth. The exact time delay for calculation of new index values is unknown. In a previous study, we used simulated EEG signals and found considerable time lags for the cerebral state index (Danmeter, Odense, Denmark), the bispectral index (Aspect Medical Systems Inc., Newton, MA, USA), and the Narcotrend index (MonitorTechnik, Bad Bramstedt, Germany). The aim of this study was to investigate whether the time delays observed with simulated EEG signals also applied to real EEG data. METHODS: We used perioperatively recorded EEG data from a database corresponding to the awake state, general anaesthesia, and suppression of cortical activity, respectively. After a switch from one state of consciousness to another, the time necessary for all indices to adjust the index value to the underlying input signal was measured. RESULTS: We found time delays for all indices between 24 (7) and 122 (23) s before the new state was indicated. In accordance with our previous results, these time delays were not constant and depended on the particular starting and target index value. Results were different for decreasing and increasing values. CONCLUSIONS: Our results may show a limitation of the value of electronic EEG indices in prevention of awareness with recall. Furthermore, due to different time delays for ascending and descending values, the results of pharmacodynamic studies may be influenced by this phenomenon.

Dose-dependent effect of S(+) ketamine on post-ischemic endogenous neurogenesis in rats.

BACKGROUND: Ketamine is a non-competitive antagonist at N-methyl-D-aspartate (NMDA) receptors and reduces neuronal injury after cerebral ischemia by blocking the excitotoxic effects of glutamate. However, cerebral regeneration by means of endogenous neurogenesis may be impaired with blockade of NMDA receptors. The effects of S(+) ketamine on post-ischemic neurogenesis are unknown and investigated in this study. METHODS: Thirty-two male Sprague-Dawley rats were randomly assigned to the following treatment groups with intravenous S(+) ketamine anesthesia: S(+) ketamine 0.75 mg/kg/min with or without cerebral ischemia and S(+) ketamine 1.0 mg/kg/min with or without cerebral ischemia. Eight non-anesthetized, non-ischemic animals were investigated as naïve controls. Forebrain ischemia was induced by bilateral common carotid artery occlusion in combination with hemorrhagic hypotension. 5-bromo-2-deoxyuridine (BrdU) was injected intraperitoneally for seven consecutive post-operative days. BrdU-positive neurons in the dentate gyrus and histopathological damage of the hippocampus were analyzed after 28 days. RESULTS: The number of new neurons was not affected by S(+) ketamine in the absence of cerebral ischemia. The ischemia-induced increase in neurogenesis was reduced by high-dose S(+) ketamine. Cell death of ischemic animals did not vary between low- and high-dose S(+) ketamine. CONCLUSION: While low concentrations of S(+) ketamine allow an ischemia-induced increase in the number of new neurons, high S(+) ketamine concentrations block the post-ischemic increase in newly generated neurons. This effect is irrespective of the extent of other histopathological damage and in line with studies showing that NMDA receptor antagonists like MK-801 inhibit neurogenesis after cerebral ischemia.