PFA-100 System: A New Method for Assessment of Platelet Dysfunction.

This is a celebratory reprint of a historical paper published in STH in 1998. The original Abstract follows.The PFA-100 system is a platelet function analyzer designed to measure platelet-related primary hemostasis. The instrument uses two disposable cartridges: a collagen/epinephrine (CEPI) and a collagen/ADP (CADP) cartridge. Previous experience has shown that CEPI cartridges detect qualitative platelet defects, including acetylsalicylic acid (ASA)-induced abnormalities, while CADP cartridges detect only thrombocytopathies and not ASA use. In this seven-center trial, 206 healthy subjects and 176 persons with various platelet-related defects, including 127 ASA users, were studied. The platelet function status was determined by a platelet function test panel. Comparisons were made as to how well the defects were identified by the PFA-100 system and by platelet aggregometry. The reference intervals for both cartridges, testing the 206 healthy subjects, were similar to values described in smaller studies in the literature (mean closure time [CT] of 132 seconds for CEPI and 93 seconds for CADP). The use of different lot numbers of cartridges or duplicate versus singleton testing revealed no differences. Compared with the platelet function status, the PFA-100 system had a clinical sensitivity of 94.9% and a specificity of 88.8%. For aggregometry, a sensitivity of 94.3% and a specificity of 88.3% were obtained. These values are based on all 382 specimens. A separate analysis of sensitivity by type of platelet defect, ASA use versus congenital thrombocytopathies, revealed for the PFA-100 system a 94.5% sensitivity in identifying ASA users and a 95.9% sensitivity in identifying the other defects. For aggregometry, the values were 100% for ASA users and 79.6% for congenital defects. Analysis of concordance between the PFA-100 system and aggregometry revealed no difference in clinical sensitivity and specificity between the systems (p > 0.9999). The overall agreement was 87.5%, with a Kappa index of 0.751. The two tests are thus equivalent in their ability to identify normal and abnormal platelet defects. Testing 126 subjects who took 325 mg ASA revealed that the PFA-100 system (CEPI) was able to detect 71.7% of ASA-induced defects with a positive predictive value of 97.8%. The overall clinical accuracy of the system, calculated from the area under the receiver operating characteristic curve, was 0.977. The data suggest that the PFA-100 system is highly accurate in discriminating normal from abnormal platelet function. The ease of operation of the instrument makes it a useful tool to use in screening patients for platelet-related hemostasis defects.

Association of immature platelets with perioperative complications in neurosurgery.

Immature platelets are newly formed platelets with an increased prothrombotic potential. This study evaluates whether immature platelets are associated with relevant complications in neurosurgical patients. Data were obtained in the frame of a prospectively conducted observational study exploring the association between immature platelets and major cardiovascular events after surgery. Immature platelet fraction (IPF) and H-IPF (highly fluorescent immature platelet fraction) were measured preoperatively and postoperatively at the neurosurgical ward (24-72 hours after surgery). Therapy-relevant complications after surgery were stratified using the Clavien-Dindo Grade (CDG >2) as primary outcome. Data were analyzed in 391 neurosurgical patients. While preoperatively there were no differences in IPF or H-IPF, patients with higher therapy-complication grades had higher values post-op compared to patients with lower grade complications (≤2 CDG). Cut-off values identified by receiver operating characteristic curve analysis revealed that there were significantly more patients with H-IPF ≥0.95% in the group with serious complications (CDG >2) [odds ratio OR (95% confidence interval CI) = 2.06 (1.09-3.9), p = .025], whereas this association was not present for the IPF cutoff value. In a multivariate model, H-IPF≥0.95% was independently associated with serious complications after surgery [OR (95% CI) = 1.97 (1.03-3.78), p = .041]. These findings suggest that H-IPF is associated with surgical complications and may improve risk stratification of neurosurgical patients (clinicaltrials.gov: NCT02097602, registration date: 27/03/2014).

What is the context?Immature platelets are newly formed platelets with a higher thrombotic potential and play an important role in atherothrombotic events.Higher levels of immature platelets were observed in patients with acute coronary syndrome or stroke.Lately, the focus in immature platelet research shifted from observation to outcomes. Immature platelets were identified as independent predictors of major cardiovascular events in cardiologic patients with coronary artery disease. Besides, an association between immature platelets and major cardiovascular events was described in surgical patients after non-cardiac surgery.What is new?This study builds on these findings and extends the focus to perioperative complications after neurosurgery.The data were obtained prospectively in the frame of an observational clinical trial exploring the association of immature platelets and major cardiovascular events in general. Data measured in the neurosurgical cohort of that study (391 neurosurgical patients) were analyzed in the present work.Within the limitations of our study, our analyses suggest that the postoperative IPF (immature platelet fraction) and H-IPF (highly fluorescent immature platelet fraction) values, which were measured at the neurosurgical ward after surgery are both associated with higher therapy-relevant complication grades (>2 according to Clavien-Dindo Grade), whereas preoperatively obtained values were not.What is the impact?This is the first study showing a relationship between immature platelets and therapy-relevant perioperative complications in neurosurgical patients. It could be a pilot trial for varied scientific questions including risk stratification of neurosurgical patients.

Ready for a "breakthrough" with ketamine? A look at recent pharmacological insights!

PURPOSE OF REVIEW: To update pharmacological insights on ketamine integrating information from different disciplines for developing steps to "breakthrough" approaches in clinical challenges. RECENT FINDINGS: Pharmacokinetic/pharmacodynamic (PK/PD) models have incorporated recirculation, ketamine metabolites, drug-drug interaction, and covariates such as age. Ketamine-induced relief from treatment-resistant depression has been explained by "disinhibition" of gamma-aminobutyric acid-ergic interneurons and synaptogenic mechanisms requiring neurotrophic signals. Neuroimaging/electroencephalographic investigations have shown an increase in gamma spectral power in healthy volunteers and patients with depression, but also opposite changes in functional network connectivity after subanesthetic ketamine. Volunteer data may not be transferable to clinical conditions. Altered states of consciousness induced by subanesthetic ketamine have been described by disruption of resisting-state functional networks and frontoparietal connectivity with preservation of multisensory and sensor-motor networks. This has been interpreted as a "disconnected consciousness". SUMMARY: More precise PK/PD models may improve the ketamine use regimen. The findings from research on depression are an important discovery because ketamine's impact on neuronal plasticity and synaptogenesis in human brain disease has directly been documented. Psychic adverse effects with subanesthetic ketamine are related to a "disconnected consciousness". Overall, progress has been made, but the "breakthrough" still has to come.

Drug-induced sleep endoscopy with target-controlled infusion using propofol and monitored depth of sedation to determine treatment strategies in obstructive sleep apnea.

BACKGROUND: Drug-induced sleep endoscopy (DISE) has become an important diagnostic examination tool in the treatment decision process for surgical therapies in the treatment of obstructive sleep apnea (OSA). Currently, there is a variety of regimes for the performance of DISE, which renders comparison and assessment across results difficult. It remains unclear how the different regimes influence the findings of the examination and the resulting conclusions and treatment recommendations. This study aimed to investigate the correlation between increasing levels of sedation (i.e., light, medium, and deep) induced by propofol using a target-controlled infusion (TCI) pump, with the obstruction patterns at the levels of the velum, oropharynx, tongue base, and epiglottis (i.e., VOTE classification). A second goal was the establishment of a sufficient sedation level to enable a reliable decision regarding treatment recommendations. MATERIAL AND METHODS: Forty-three patients with OSA underwent a DISE procedure using propofol TCI. Three levels of sedation were defined, depending on entropy levels and assessment of sedation: light sedation, medium sedation, and deep sedation. The evaluation of the upper airway at each level, with increasing sedation, was documented using the VOTE classification. The elapsed time at which each assessment was performed was recorded. RESULTS: Upper airway changes occurred and were measured throughout the DISE procedure. Clinically useful determinations of airway closure occurred at medium sedation; this level of sedation was most probably achieved with a blood propofol concentration of 3.2 µg/ml. In all 43 patients, definite treatment decisions could be made at medium sedation level. Increasing sedation did not result in changes in the treatment decision. CONCLUSIONS: Changes in upper airway collapse during DISE with propofol TCI occur at levels of medium sedation. Decisions regarding surgical treatment could be made at this level of sedation. CLINICAL TRIAL NAME: Upper Airway Collapse in Patients with Obstructive Sleep Apnea Syndrome by Drug Induced Sleep Endoscopy (URL: https://clinicaltrials.gov/ct2/results?term=NCT02588300&Search=Search ) REGISTRATION NUMBER: NCT02588300.

Self-confidence and knowledge of German ICU physicians in palliative care - a multicentre prospective study.

BACKGROUND: Little is known about ICU physicians' self-confidence and knowledge related to palliative care. Our objective was to investigate self-confidence and knowledge of German ICU physicians related to palliative care, and to assess the impact of work experience, gender, specialty and additional certifications in pain or palliative medicine. METHODS: In a multicentre prospective observational study ICU physicians of ten hospitals were asked to rate their self-confidence and to complete a multiple choice questionnaire for the assessment of knowledge. Beyond descriptive statistics and non-parametric tests for group comparisons, linear regression analysis was used to assess the impact of independent variable on self-confidence and knowledge. Spearman's rank test was calculated. RESULTS: 55% of answers in the knowledge test were correct and more than half of the participants rated themselves as "rather confident" or "confident". Linear regression analysis revealed that an additional certificate in either pain or palliative medicine significantly increased both knowledge and self-confidence, but only 15 out of 137 participants had at least one of those certificates. Relation between self-confidence and the results of the knowledge test was weak (r = 0.270 in female) and very weak (r = -0.007 in male). CONCLUSIONS: Although the questionnaire needs improvement according to the item analysis, it appears that, with respect to palliative care, ICU Physicians' self-confidence is not related to their knowledge. An additional certificate in either pain or palliative medicine was positively correlated to both self-confidence and knowledge. However, only a minority of the participants were qualified through such a certificate.

Neural Correlates of Sevoflurane-induced Unconsciousness Identified by Simultaneous Functional Magnetic Resonance Imaging and Electroencephalography.

BACKGROUND: The neural correlates of anesthetic-induced unconsciousness have yet to be fully elucidated. Sedative and anesthetic states induced by propofol have been studied extensively, consistently revealing a decrease of frontoparietal and thalamocortical connectivity. There is, however, less understanding of the effects of halogenated ethers on functional brain networks. METHODS: The authors recorded simultaneous resting-state functional magnetic resonance imaging and electroencephalography in 16 artificially ventilated volunteers during sevoflurane anesthesia at burst suppression and 3 and 2 vol% steady-state concentrations for 700 s each to assess functional connectivity changes compared to wakefulness. Electroencephalographic data were analyzed using symbolic transfer entropy (surrogate of information transfer) and permutation entropy (surrogate of cortical information processing). Functional magnetic resonance imaging data were analyzed by an independent component analysis and a region-of-interest-based analysis. RESULTS: Electroencephalographic analysis showed a significant reduction of anterior-to-posterior symbolic transfer entropy and global permutation entropy. At 2 vol% sevoflurane concentrations, frontal and thalamic networks identified by independent component analysis showed significantly reduced within-network connectivity. Primary sensory networks did not show a significant change. At burst suppression, all cortical networks showed significantly reduced functional connectivity. Region-of-interest-based thalamic connectivity at 2 vol% was significantly reduced to frontoparietal and posterior cingulate cortices but not to sensory areas. CONCLUSIONS: Sevoflurane decreased frontal and thalamocortical connectivity. The changes in blood oxygenation level dependent connectivity were consistent with reduced anterior-to-posterior directed connectivity and reduced cortical information processing. These data advance the understanding of sevoflurane-induced unconsciousness and contribute to a neural basis of electroencephalographic measures that hold promise for intraoperative anesthesia monitoring.

A period of immobility after remifentanil administration protects from nausea: an experimental randomized cross-over study.

BACKGROUND: The opioid remifentanil induces a decrease of vestibulo-ocular reflex function, which has been associated with nausea and vomiting when the subjects are moved. The study investigates in healthy female volunteers if immobility after remifentanil administration protects from nausea and vomiting. METHODS: In volunteers, a standardized movement intervention (a manually applied head-trunk movement forward, backward and sideward) was started 5 min (session A), 35 min (session B) or 60 min (session C) after cessation of a remifentanil infusion (0.15 µg · kg-1 · min-1). In a cross-over design, 16 participants were randomized to the early (sessions A and B) or the late intervention group (sessions A and C). Nausea was assessed using a 11-point numerical rating scale before and after each movement intervention. Differences within and between groups were assessed with non-parametric tests for paired and unpaired data. RESULTS: Comparing sessions A, B and C, intensity of nausea was time-dependent after cessation of remifentanil administration (p = 0.015). In the early intervention group, nausea decreased from median 5.0 [IQR 1.5;6.0] in session A to 2.0 [1.0;3.0] in session B (p = 0.094); in the late intervention group nausea decreased from 3.5 [2.0;5.0] in session A to 0.5 [0.0;2.0] in session C (p = 0.031). CONCLUSIONS: In summary, in young healthy women, immobility after remifentanil administration protects from nausea and vomiting in a time-dependent manner. In analogy to motion sickness, opioid-induced nausea and vomiting in female volunteers can be triggered by movement. TRIAL REGISTRATION: German Clinical Trials Register DRKS00010667 . The trial was registered retrospectively on June, 20th 2016.

Situation awareness errors in anesthesia and critical care in 200 cases of a critical incident reporting system.

BACKGROUND: A loss of adequate Situation Awareness (SA) may play a major role in the genesis of critical incidents in anesthesia and critical care. This observational study aimed to determine the frequency of SA errors in cases of a critical incident reporting system (CIRS). METHODS: Two experts independently reviewed 200 cases from the German Anesthesia CIRS. For inclusion, reports had to be related to anesthesia or critical care for an individual patient and take place in an in-hospital setting. Based on the SA framework, the frequency of SA errors was determined. Representative cases were analyzed qualitatively to illustrate the role of SA for decision-making. RESULTS: SA errors were identified in 81.5%. Predominantly, errors occurred on the levels of perception (38.0%) and comprehension (31.5%). Errors on the level of projection played a minor role (12.0%). The qualitative analysis of selected cases illustrates the crucial role of SA for decision-making and performance. CONCLUSIONS: SA errors are very frequent in critical incidents reported in a CIRS. The SA taxonomy was suitable to provide mechanistic insights into the central role of SA for decision-making and thus, patient safety.

Differences between state entropy and bispectral index during analysis of identical electroencephalogram signals: a comparison with two randomised anaesthetic techniques.

BACKGROUND: It is claimed that bispectral index (BIS) and state entropy reflect an identical clinical spectrum, the hypnotic component of anaesthesia. So far, it is not known to what extent different devices display similar index values while processing identical electroencephalogram (EEG) signals. OBJECTIVE: To compare BIS and state entropy during analysis of identical EEG data. Inspection of raw EEG input to detect potential causes of erroneous index calculation. DESIGN: Offline re-analysis of EEG data from a randomised, single-centre controlled trial using the Entropy Module and an Aspect A-2000 monitor. SETTING: Klinikum rechts der Isar, Technische Universität München, Munich. PATIENTS: Forty adult patients undergoing elective surgery under general anaesthesia. INTERVENTIONS: Blocked randomisation of 20 patients per anaesthetic group (sevoflurane/remifentanil or propofol/remifentanil). Isolated forearm technique for differentiation between consciousness and unconsciousness. MAIN OUTCOME MEASURES: Prediction probability (PK) of state entropy to discriminate consciousness from unconsciousness. Correlation and agreement between state entropy and BIS from deep to light hypnosis. Analysis of raw EEG compared with index values that are in conflict with clinical examination, with frequency measures (frequency bands/Spectral Edge Frequency 95) and visual inspection for physiological EEG patterns (e.g. beta or delta arousal), pathophysiological features such as high-frequency signals (electromyogram/high-frequency EEG or eye fluttering/saccades), different types of electro-oculogram or epileptiform EEG and technical artefacts. RESULTS: PK of state entropy was 0.80 and of BIS 0.84; correlation coefficient of state entropy with BIS 0.78. Nine percent BIS and 14% state entropy values disagreed with clinical examination. Highest incidence of disagreement occurred after state transitions, in particular for state entropy after loss of consciousness during sevoflurane anaesthesia. EEG sequences which led to false 'conscious' index values often showed high-frequency signals and eye blinks. High-frequency EEG/electromyogram signals were pooled because a separation into EEG and fast electro-oculogram, for example eye fluttering or saccades, on the basis of a single EEG channel may not be very reliable. These signals led to higher Spectral Edge Frequency 95 and ratio of relative beta and gamma band power than EEG signals, indicating adequate unconscious classification. The frequency of other artefacts that were assignable, for example technical artefacts, movement artefacts, was negligible and they were excluded from analysis. CONCLUSION: High-frequency signals and eye blinks may account for index values that falsely indicate consciousness. Compared with BIS, state entropy showed more false classifications of the clinical state at transition between consciousness and unconsciousness.

Monitoring depth of anesthesia utilizing a combination of electroencephalographic and standard measures.

BACKGROUND: For decades, monitoring depth of anesthesia was mainly based on unspecific effects of anesthetics, for example, blood pressure, heart rate, or drug concentrations. Today, electroencephalogram-based monitors promise a more specific assessment of the brain function. To date, most approaches were focused on a "head-to-head" comparison of either electroencephalogram- or standard parameter-based monitoring. In the current study, a multimodal indicator based on a combination of both electro encephalographic and standard anesthesia monitoring parameters is defined for quantification of "anesthesia depth." METHODS: Two hundred sixty-three adult patients from six European centers undergoing surgery with general anesthesia were assigned to 1 of 10 anesthetic combinations according to standards of the enrolling hospital. The anesthesia multimodal index of consciousness was developed using a data-driven approach, which maps standard monitoring and electroencephalographic parameters into an output indicator that separates different levels of anesthesia from awake to electroencephalographic burst suppression. Obtained results were compared with either a combination of standard monitoring parameters or the electroencephalogram-based bispectral index. RESULTS: The anesthesia multimodal index of consciousness showed prediction probability (P(K)) of 0.96 (95% CI, 0.95 to 0.97) to separate different levels of anesthesia (wakefulness to burst suppression), whereas the bispectral index had significantly lower PK of 0.80 (0.76 to 0.81) at corrected threshold P value of less than 0.05. At the transition between consciousness and unconsciousness, anesthesia multimodal index of consciousness yielded a PK of 0.88 (0.85 to 0.91). CONCLUSION: A multimodal integration of both standard monitoring and electroencephalographic parameters may more precisely reflect the level of anesthesia compared with monitoring based on one of these aspects alone.

Brain electrical activity obeys Benford's law.

BACKGROUND: Monitoring and automated online analysis of brain electrical activity are frequently used for verifying brain diseases and for estimating anesthetic depth in subjects undergoing surgery. However, false diagnosis with potentially catastrophic consequences for patients such as intraoperative awareness may result from unnoticed irregularities in the process of signal analysis. Here we ask whether Benford's Law can be applied to detect accidental or intended modulation of neurophysiologic signals. This law states that the first digits of many datasets such as atomic weights or river lengths are distributed logarithmically and not equally. In particular, we tested whether data obtained from electrophysiological recordings of human patients representing global activity and organotypic slice cultures representing pure cortical activity follow the predictions of Benford's Law in the absence and in the presence of an anesthetic drug. METHODS: Electroencephalographic (EEG) recordings from human subjects and local field potential recordings from cultured cortical brain slices were obtained before and after administration of sevoflurane. The first digit distribution of the datasets was compared with the Benford distribution. RESULTS: All datasets showed a Benford-like distribution. Nevertheless, distributions belonging to different anesthetic levels could be distinguished in vitro and in human EEGs. With sevoflurane, the first digit distribution of the in vitro data becomes steeper, while it flattens for EEG data. In the presence of high frequency noise, the Benford distribution falls apart. CONCLUSIONS: In vitro and EEG data show a Benford-like distribution which is altered by sevoflurane or destroyed by noise used to simulate artefacts. These findings suggest that algorithms based on Benford's Law can be successfully used to detect sevoflurane-induced signal modulations in electrophysiological recordings.

Non-stationarity of EEG during wakefulness and anaesthesia: advantages of EEG permutation entropy monitoring.

Monitors evaluating the electroencephalogram (EEG) to determine depth of anaesthesia use spectral analysis approaches for analysis windows up to 61.5 s as well as additional smoothing algorithms. Stationary EEG is required to reliably apply the index algorithms. Because of rapid physiological changes, artefacts, etc., the EEG may not always fulfil this requirement. EEG analysis using permutation entropy (PeEn) may overcome this issue, since PeEn can also be applied to practically nonstationary EEG. One objective was to determine the duration of EEG sequences that can be considered stationary at different anaesthetic levels. The second, more important objective was to test the reliability of PeEn to reflect the anaesthetic levels for short EEG segments. EEG was recorded from 15 volunteers undergoing sevoflurane and propofol anaesthesia at different anaesthetic levels and for each group 10 data sets were included. EEG stationarity was evaluated for EEG sample lengths from 4 to 116 s for each level. PeEn was calculated for these sequences using different parameter settings and analysis windows from 2 to 60 s. During wakefulness EEG can only be considered stationary for sequences up to 12 s. With increasing anaesthetic level the probability and duration of stationary EEG increases. PeEn is able to reliably separate consciousness from unconsciousness for EEG segments as short as 2 s. Especially during wakefulness a conflict between stationary EEG sequence durations and methods used for monitoring may exist. PeEn does not require stationarity and functions for EEG sequences as short as 2 s. These promising results seem to support the application of non-linear parameters, such as PeEn, to depth of anaesthesia monitoring.

The influence of anaesthetists' experience on workload, performance and visual attention during simulated critical incidents.

Development of accurate Situation Awareness (SA) depends on experience and may be impaired during excessive workload. In order to gain adequate SA for decision making and performance, anaesthetists need to distribute visual attention effectively. Therefore, we hypothesized that in more experienced anaesthetists performance is better and increase of physiological workload is less during critical incidents. Additionally, we investigated the relation between physiological workload indicators and distribution of visual attention. In fifteen anaesthetists, the increase of pupil size and heart rate was assessed in course of a simulated critical incident. Simulator log files were used for performance assessment. An eye-tracking device (EyeSeeCam) provided data about the anaesthetists' distribution of visual attention. Performance was assessed as time until definitive treatment. T tests and multivariate generalized linear models (MANOVA) were used for retrospective statistical analysis. Mean pupil diameter increase was 8.1% (SD ± 4.3) in the less experienced and 15.8% (±10.4) in the more experienced subjects (p = 0.191). Mean heart rate increase was 10.2% (±6.7) and 10.5% (±8.3, p = 0.956), respectively. Performance did not depend on experience. Pupil diameter and heart rate increases were associated with a shift of visual attention from monitoring towards manual tasks (not significant). For the first time, the following four variables were assessed simultaneously: physiological workload indicators, performance, experience, and distribution of visual attention between "monitoring" and "manual" tasks. However, we were unable to detect significant interactions between these variables. This experimental model could prove valuable in the investigation of gaining and maintaining SA in the operation theatre.

High-fidelity human patient simulators compared with human actors in an unannounced mass-casualty exercise.

High-fidelity simulators (HFSs) have been shown to prompt critical actions at a level equal to that of trained human actors (HAs) and increase perceived realism in intrahospital mass-casualty incident (MCI) exercises. For unannounced prehospital MCI exercises, however, no data are available about the feasibility of incorporating HFSs. This case report describes the integration of HFSs in such an unannounced prehospital MCI drill with HAs and provides data about the differences concerning triage, treatment, and transport of HFSs and HAs with identical injury patterns. For this purpose, 75 actors and four high-fidelity simulators were subdivided into nine groups defined by a specific injury pattern. Four HFSs and six HAs comprised a group suffering from traumatic brain injury and blunt abdominal trauma. Triage results, times for transport, and number of diagnostic and therapeutic tasks were recorded. Means were compared by t test or one-way ANOVA. Triage times and results did not differ between actors and simulators. The number of diagnostic (1.25, SD = 0.5 in simulators vs 3.5, SD = 1.05 in HAs; P = .010) and therapeutic tasks (2.0, SD = 1.6 in simulators vs 4.8, SD = 0.4 in HAs; P = .019) were significantly lower in simulators. Due to difficulties in treating and evacuating the casualties from the site of the accident in a timely manner, all simulators died. Possible causal factors and strategies are discussed, with the aim of increasing the utility of simulators in emergency medicine training.

Spatiotemporal reconfiguration of large-scale brain functional networks during propofol-induced loss of consciousness.

Applying graph theoretical analysis of spontaneous BOLD fluctuations in functional magnetic resonance imaging (fMRI), we investigated whole-brain functional connectivity of 11 healthy volunteers during wakefulness and propofol-induced loss of consciousness (PI-LOC). After extraction of regional fMRI time series from 110 cortical and subcortical regions, we applied a maximum overlap discrete wavelet transformation and investigated changes in the brain's intrinsic spatiotemporal organization. During PI-LOC, we observed a breakdown of subcortico-cortical and corticocortical connectivity. Decrease of connectivity was pronounced in thalamocortical connections, whereas no changes were found for connectivity within primary sensory cortices. Graph theoretical analyses revealed significant changes in the degree distribution and local organization metrics of brain functional networks during PI-LOC: compared with a random network, normalized clustering was significantly increased, as was small-worldness. Furthermore we observed a profound decline in long-range connections and a reduction in whole-brain spatiotemporal integration, supporting a topological reconfiguration during PI-LOC. Our findings shed light on the functional significance of intrinsic brain activity as measured by spontaneous BOLD signal fluctuations and help to understand propofol-induced loss of consciousness.

Situation awareness in anesthesia: concept and research.

Accurate situation awareness (SA) of medical staff is integral for providing optimal performance during the treatment of patients. An understanding of SA and how it affects treatment of patients is therefore crucial for patient safety and an essential element for research on human factors in anesthesia. This review describes the concept of SA in the anesthesia environment, including the interaction with associated medical teams. Different approaches for its assessment in the work environment of anesthesia are provided. Factors contributing to expertise in SA are described and approaches for the training of SA in anesthesia are discussed, as are types of errors that occur during the development of SA. Finally, the authors briefly present strategies to improve SA during daily anesthesia practice through altered designs of monitor displays.

Simultaneous electroencephalographic and functional magnetic resonance imaging indicate impaired cortical top-down processing in association with anesthetic-induced unconsciousness.

BACKGROUND: In imaging functional connectivity (FC) analyses of the resting brain, alterations of FC during unconsciousness have been reported. These results are in accordance with recent electroencephalographic studies observing impaired top-down processing during anesthesia. In this study, simultaneous records of functional magnetic resonance imaging (fMRI) and electroencephalogram were performed to investigate the causality of neural mechanisms during propofol-induced loss of consciousness by correlating FC in fMRI and directional connectivity (DC) in electroencephalogram. METHODS: Resting-state 63-channel electroencephalogram and blood oxygen level-dependent 3-Tesla fMRI of 15 healthy subjects were simultaneously registered during consciousness and propofol-induced loss of consciousness. To indicate DC, electroencephalographic symbolic transfer entropy was applied as a nonlinear measure of mutual interdependencies between underlying physiological processes. The relationship between FC of resting-state networks of the brain (z values) and DC was analyzed by a partial correlation. RESULTS: Independent component analyses of resting-state fMRI showed decreased FC in frontoparietal default networks during unconsciousness, whereas FC in primary sensory networks increased. DC indicated a decline in frontal-parietal (area under the receiver characteristic curve, 0.92; 95% CI, 0.68-1.00) and frontooccipital (0.82; 0.53-1.00) feedback DC (P<0.05 corrected). The changes of FC in the anterior default network correlated with the changes of DC in frontal-parietal (rpartial=+0.62; P=0.030) and frontal-occipital (+0.63; 0.048) electroencephalographic electrodes (P<0.05 corrected). CONCLUSION: The simultaneous propofol-induced suppression of frontal feedback connectivity in the electroencephalogram and of frontoparietal FC in the fMRI indicates a fundamental role of top-down processing for consciousness.

Functional outcome in female rats after 45 minutes of deep hypothermic circulatory arrest: gender matters.

BACKGROUND: After adjusting for cofactors, female gender remains an independent risk factor. The aim of our study was to investigate the role of gender on functional outcome 14 days after 45 minutes of deep hypothermic circulatory arrest (DHCA) in rats. METHODS: After institutional animal care committee Institutional Review Board approval, 40 male and 40 female rats were randomly divided into two groups (40 DHCA, 40 controls). The rats were neutered or sham-neutered and 40 of them were subjected to DHCA with 40 controls remaining naïve. Postoperative functional performance was assessed with modified hole-board test. Brain morphology was assessed using hematoxylin and eosin (HE) staining and cerebral inflammation/apoptosis determined immunohistochemically. Data were analyzed using general linear models (post hoc analysis of variance [ANOVA] and Bonferroni t tests) and Kruskal-Wallis (post hoc Mann-Whitney U test) (p < 0.05). RESULTS: Cognition and behavior after 45 minutes of DHCA were comparable to that of four naïve rats in all four DHCA groups. Motor function and morphologic outcome were better in females. Nuclear factor kappa B (NFκB) was upregulated in the female normal group. Activated caspase-3 was higher in females whereas poly(ADP-ribose) polymerase was in males. Of note is the secondary finding of a high drop-out rate during the early postoperative phase in the female groups (16 out of 37). CONCLUSIONS: Postoperative motor skills were better in females, with less neuronal damage, more neuronal NFκB, and activated caspase-3. However, the chance finding of a high mortality rate in females warrants investigation with mortality as the principal aim, focusing on heart, liver, lung, kidney, and intestine with regard to its rate.

Time delay of monitors of the hypnotic component of anesthesia: analysis of state entropy and index of consciousness.

Monitors evaluating the hypnotic component of anesthesia by analyzing the electroencephalogram (EEG) may help to decrease the incidence of intraoperative awareness with recall. To calculate an index representing the anesthetic level, these monitors have different time delays until the correct index is displayed. In previous studies, intraoperatively recorded real and simulated EEG signals were used to determine time delays of cerebral state and Narcotrend and Bispectral indices. In the present study, we determined time delays of state entropy and index of consciousness. For this purpose, recorded real and simulated EEG sequences representing different anesthetic levels were played back to the tested monitors. Simulated and real perioperatively recorded EEG signals indicating stable states "awake," "general anesthesia," and "cortical suppression" were used to evaluate the time delays. Time delays were measured when switching from one state to another and were defined as the required time span of the monitor to reach the stable target index. Comparable results were obtained using simulated and real EEG sequences. Time delays were not constant and ranged from 18 to 152 seconds. They were also different for increasing and decreasing values. Time delays were dependent on starting and target index values. Time delays of index calculation may limit the investigated monitor's ability to prevent interoperative awareness with recall. Different time delays for increasing and decreasing transitions could be a problem if the monitors are used for pharmacodynamic studies.