Publications by authors named "Gerhard Schneider"

95 Publications

Additive Manufacturing of Bulk Nanocrystalline FeNdB Based Permanent Magnets.

Micromachines (Basel) 2021 May 10;12(5). Epub 2021 May 10.

Materials Research Institute, Aalen University, 73430 Aalen, Germany.

Lab scale additive manufacturing of Fe-Nd-B based powders was performed to realize bulk nanocrystalline Fe-Nd-B based permanent magnets. For fabrication a special inert gas process chamber for laser powder bed fusion was used. Inspired by the nanocrystalline ribbon structures, well-known from melt-spinning, the concept was successfully transferred to the additive manufactured parts. For example, for Nd16.5-Pr1.5-Zr2.6-Ti2.5-Co2.2-Fe65.9-B8.8 (excess rare earth (RE) = Nd, Pr; the amount of additives was chosen following Magnequench (MQ) powder composition) a maximum coercivity of = 1.16 T, remanence = 0.58 T and maximum energy density of () = 62.3 kJ/m have been achieved. The most important prerequisite to develop nanocrystalline printed parts with good magnetic properties is to enable rapid solidification during selective laser melting. This is made possible by a shallow melt pool during laser melting. Melt pool depths as low as 20 to 40 µm have been achieved. The printed bulk nanocrystalline Fe-Nd-B based permanent magnets have the potential to realize magnets known so far as polymer bonded magnets without polymer.
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http://dx.doi.org/10.3390/mi12050538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150944PMC
May 2021

The influence of age on EEG-based anaesthesia indices.

J Clin Anesth 2021 May 8;73:110325. Epub 2021 May 8.

Department of Anesthesiology and Intensive Care Medicine, Technical University of Munich, School of Medicine, Munich, Germany. Electronic address:

Study Objective: In the upcoming years there will be a growing number of elderly patients requiring general anaesthesia. As age is an independent risk factor for postoperative delirium (POD) the incidence of POD will increase concordantly. One approach to reduce the risk of POD would be to avoid excessively high doses of anaesthetics by using neuromonitoring to guide anaesthesia titration. Therefore, we evaluated the influence of patient's age on various electroencephalogram (EEG)-based anaesthesia indices.

Design And Patients: We conducted an analysis of previously published data by replaying single electrode EEG episodes of maintenance of general anaesthesia from 180 patients (18-90 years; ASA I-IV) into the five different commercially available monitoring systems and evaluated their indices. We included the State/Response Entropy, Narcotrend, qCON/qNOX, bispectral index (BIS), and Treaton MGA-06. For a non-commercial comparison, we extracted the spectral edge frequency (SEF) from the BIS. To evaluate the influence of the age we generated linear regression models. We also assessed the correlation between the various indices.

Main Results: During anaesthetic maintenance the values of the SEF, State/Response Entropy, qCON/qNOX and BIS all significantly increased (0.05 Hz/0.19-0.26 index points per year) with the patient's age (p < 0.001); whereas the Narcotrend did not change significantly with age (0.06 index points per year; p = 0.28). The index values of the Treaton device significantly decreased with age (-0.09 index points per year; p < 0.001). These findings were independent of the administered dose of anaesthetics.

Conclusions: Almost all current neuromonitoring devices are influenced by age, with the potential to result in inappropriately high dosage of anaesthetics. Therefore, anaesthesiologists should be aware of this phenomenon, and the next generation of monitors should correct for these changes.
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http://dx.doi.org/10.1016/j.jclinane.2021.110325DOI Listing
May 2021

Rapid clinical evolution for COVID-19 translates into early hospital admission and unfavourable outcome: a preliminary report.

Multidiscip Respir Med 2021 Jan 2;16(1):744. Epub 2021 Apr 2.

Department of Anaesthesiology and Intensive Care Medicine, University hospital rechts der Isar, Technical University of Munich, School of Medicine, Munich.

Background: A wide range of mortality rates has been reported in COVID-19 patients on the intensive care unit. We wanted to describe the clinical course and determine the mortality rate in our institution's intensive care units.

Methods: To this end, we performed a retrospective cohort study of 50 COVID-19 patients admitted to the ICU at a large German tertiary university hospital. Clinical features are reported with a focus on ICU interventions, such as mechanical ventilation, prone positioning and extracorporeal organ support. Outcome is presented using a 7-point ordinal scale on day 28 and 60 following ICU admission.

Results: The median age was 64 years, 78% were male. LDH and D-Dimers were elevated, and patients were low on Vitamin D. ARDS incidence was 75%, and 43/50 patients needed invasive ventilation. 22/50 patients intermittently needed prone positioning, and 7/50 required ECMO. The interval from onset of the first symptoms to admission to the hospital and to the ICU was shorter in non-survivors than in survivors. By day 60 after ICU admission, 52% of the patients had been discharged. 60-day mortality rate was 32%; 37% for ventilated patients, and 42% for those requiring both: ventilation and renal replacement therapy.

Conclusions: Early deterioration might be seen as a warning signal for unfavourable outcome. Lung-protective ventilation including prone positioning remain the mainstay of the treatment.
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http://dx.doi.org/10.4081/mrm.2021.744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056325PMC
January 2021

Invasive pulmonary aspergillosis in critically ill patients with severe COVID-19 pneumonia: Results from the prospective AspCOVID-19 study.

PLoS One 2021 17;16(3):e0238825. Epub 2021 Mar 17.

Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.

Background: Superinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia.

Methods: We prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from nondirected bronchial lavage (NBL). We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls.

Findings: CAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia as compared to 8% in the control cohort. In the COVID-19 cohort, mean age, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p = 0.340) and days of mechanical ventilation (20 versus 15 days; p = 0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA.

Interpretation: CAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238825PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968651PMC
March 2021

Attenuation of Native Hyperpolarization-Activated, Cyclic Nucleotide-Gated Channel Function by the Volatile Anesthetic Sevoflurane in Mouse Thalamocortical Relay Neurons.

Front Cell Neurosci 2020 21;14:606687. Epub 2021 Jan 21.

Department of Anesthesiology and Intensive Care Medicine, Technical University of Munich School of Medicine, Munich, Germany.

As thalamocortical relay neurons are ascribed a crucial role in signal propagation and information processing, they have attracted considerable attention as potential targets for anesthetic modulation. In this study, we analyzed the effects of different concentrations of sevoflurane on the excitability of thalamocortical relay neurons and hyperpolarization-activated, cyclic-nucleotide gated (HCN) channels, which play a decisive role in regulating membrane properties and rhythmic oscillatory activity. The effects of sevoflurane on single-cell excitability and native HCN channels were investigated in acutely prepared brain slices from adult wild-type mice with the whole-cell patch-clamp technique, using voltage-clamp and current-clamp protocols. Sevoflurane dose-dependently depressed membrane biophysics and HCN-mediated parameters of neuronal excitability. Respective half-maximal inhibitory and effective concentrations ranged between 0.30 (95% CI, 0.18-0.50) mM and 0.88 (95% CI, 0.40-2.20) mM. We witnessed a pronounced reduction of HCN dependent I current amplitude starting at a concentration of 0.45 mM [relative change at -133 mV; 0.45 mM sevoflurane: 0.85 (interquartile range, 0.79-0.92), = 12, = 0.011; 1.47 mM sevoflurane: 0.37 (interquartile range, 0.34-0.62), = 5, < 0.001] with a half-maximal inhibitory concentration of 0.88 (95% CI, 0.40-2.20) mM. In contrast, effects on voltage-dependent channel gating were modest with significant changes only occurring at 1.47 mM [absolute change of half-maximal activation potential; 1.47 mM: -7.2 (interquartile range, -10.3 to -5.8) mV, = 5, = 0.020]. In this study, we demonstrate that sevoflurane inhibits the excitability of thalamocortical relay neurons in a concentration-dependent manner within a clinically relevant range. Especially concerning its effects on native HCN channel function, our findings indicate substance-specific differences in comparison to other anesthetic agents. Considering the importance of HCN channels, the observed effects might mechanistically contribute to the hypnotic properties of sevoflurane.
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http://dx.doi.org/10.3389/fncel.2020.606687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858256PMC
January 2021

Age-Related EEG Features of Bursting Activity During Anesthetic-Induced Burst Suppression.

Front Syst Neurosci 2020 3;14:599962. Epub 2020 Dec 3.

Department of Anesthesiology and Intensive Care Medicine, School of Medicine, Technical University Munich, Munich, Germany.

Electroencephalographic (EEG) Burst Suppression (BSUPP) is a discontinuous pattern characterized by episodes of low voltage disrupted by bursts of cortical synaptic activity. It can occur while delivering high-dose anesthesia. Current research suggests an association between BSUPP and the occurrence of postoperative delirium in the post-anesthesia care unit (PACU) and beyond. We investigated burst micro-architecture to further understand how age influences the neurophysiology of this pharmacologically-induced state. We analyzed a subset of EEG recordings ( = 102) taken from a larger data set previously published. We selected the initial burst that followed a visually identified "silent second," i.e., at least 1 s of iso-electricity of the EEG during propofol induction. We derived the (normalized) power spectral density [(n)PSD], the alpha band power, the maximum amplitude, the maximum slope of the EEG as well as the permutation entropy (PeEn) for the first 1.5 s of the initial burst of each patient. In the old patients >65 years, we observed significantly lower ( < 0.001) EEG power in the 1-15 Hz range. In general, their EEG contained a significantly higher amount of faster oscillations (>15 Hz). Alpha band power ( < 0.001), EEG amplitude ( = 0.001), and maximum EEG slope ( = 0.045) all significantly decreased with age, whereas PeEn increased ( = 0.008). Hence, we can describe an age-related change in features during EEG burst suppression. Sub-group analysis revealed no change in results based on pre-medication. These EEG changes add knowledge to the impact of age on cortical synaptic activity. In addition to a reduction in EEG amplitude, age-associated burst features can complicate the identification of excessive anesthetic administration in patients under general anesthesia. Knowledge of these neurophysiologic changes may not only improve anesthesia care through improved detection of burst suppression but might also provide insight into changes in neuronal network organization in patients at risk for age-related neurocognitive problems.
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http://dx.doi.org/10.3389/fnsys.2020.599962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744408PMC
December 2020

Rates of bacterial co-infections and antimicrobial use in COVID-19 patients: a retrospective cohort study in light of antibiotic stewardship.

Eur J Clin Microbiol Infect Dis 2021 Apr 2;40(4):859-869. Epub 2020 Nov 2.

Department of Internal Medicine II, Technical University of Munich, School of Medicine, Munich, Germany.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.
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http://dx.doi.org/10.1007/s10096-020-04063-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605734PMC
April 2021

Do private German health insurers invest their capital reserves of €353 billion according to environmental, social and governance criteria?

J Med Ethics 2020 Oct 13. Epub 2020 Oct 13.

Department of Anesthesiology and Intensive Care, TUM School of Medicine, Technical University of Munich, München, Germany.

Background: To prevent the planet from catastrophic global warming a reduction of greenhouse gas emissions to net zero is required. Thus, divestment from fossil fuels must be a strategic interest for health insurers. The aim of this study was to analyse the implementation of environmental, social and governance (ESG) criteria in German private health insurers' investments.

Methods: In 2019 a survey about ESG strategies was sent to German private health insurance companies. The survey evaluated investment strategies and thresholds for the exclusion of sectors and business practices, as well as company strategies for sustainable business development.

Findings: Given their business reports, German private health insurers manage assets of more than €350 billion. 11 of 40 insurance companies provided quantitative data, 10 refused to answer. According to quantitative data, €66 billion of assets is managed according to any ESG criteria; this equals an average of 76% of each company's bonds. None of these insurers excluded the production and sale of fossil fuels. All excluded coal mining but only at high thresholds. For €226 billion, no data were provided.

Interpretation: The findings are in contrast to the expected intrinsic economic interest of the insurers to stop global warming and improve public health. The majority of assets are managed in a highly problematic manner, especially the absence of capital allocated in fields contrary to medical ethics (eg, firearms, armour) cannot be presumed. Lack of transparency is a major problem that limits clients in choosing the insurer who has the most advanced ESG criteria.
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http://dx.doi.org/10.1136/medethics-2020-106381DOI Listing
October 2020

State entropy and burst suppression ratio can show contradictory information: A retrospective study.

Eur J Anaesthesiol 2020 Dec;37(12):1084-1092

From the Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Anaesthesiology and Intensive Care, Munich, Germany (M-G, S-P, G-S, M-K).

Background: Burst suppression is a characteristic electroencephalographic (EEG) pattern that reflects very deep levels of general anaesthesia and may correlate with increased risk of adverse outcomes such as postoperative delirium. EEG-based monitors such as the Entropy Module estimate the level of anaesthesia (state entropy) and provide another index reflecting the occurrence of burst suppression, that is the ratio of burst and suppression (BSR). In the Entropy Module, state entropy and BSR are not interconnected, as they are in the bispectral index (BIS). Hence, state entropy and BSR may provide contradicting information regarding the level of anaesthesia.

Objectives: We aimed to describe the frequency and characteristics of contradicting state entropy and BSR and to present possible strategies of how to act in these situations.

Methods: We based our analyses on state entropy and BSR trend recordings from 2551 patients older than 59 years that showed BSR was > 0 throughout their intervention under general anaesthesia. We determined the maximum state entropy when BSR was > 0, the minimum state entropy with BSR = 0 and the duration of high state entropy with BSR > 0. Further, we selected four exemplar patients to present details of how state entropy and BSR can contradict each other during anaesthesia.

Results: We observed a wide range of state entropy values with BSR > 0. The median [IQR] of the maximum state entropy with BSR > 0 was 53 [45 to 61] and the median of the minimum state entropy without BSR was 21 [15 to 26]. Contradictory BSR and state entropy could persist over several minutes. The presented cases highlight these contradictory BSR and state entropy situations.

Conclusions: Our results illustrate contradictory state entropy and BSR indices that may be relevant for anaesthesia navigation. Longer-lasting episodes may lead to incorrect titration of the depth of the hypnotic component of anaesthesia. Hence, our results demonstrate the necessity to monitor and check the raw EEG or EEG parameters that are less processed than the commercially available indices to safely navigate anaesthesia.
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http://dx.doi.org/10.1097/EJA.0000000000001312DOI Listing
December 2020

Machine learning for a combined electroencephalographic anesthesia index to detect awareness under anesthesia.

PLoS One 2020 26;15(8):e0238249. Epub 2020 Aug 26.

Department of Anesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

Spontaneous electroencephalogram (EEG) and auditory evoked potentials (AEP) have been suggested to monitor the level of consciousness during anesthesia. As both signals reflect different neuronal pathways, a combination of parameters from both signals may provide broader information about the brain status during anesthesia. Appropriate parameter selection and combination to a single index is crucial to take advantage of this potential. The field of machine learning offers algorithms for both parameter selection and combination. In this study, several established machine learning approaches including a method for the selection of suitable signal parameters and classification algorithms are applied to construct an index which predicts responsiveness in anesthetized patients. The present analysis considers several classification algorithms, among those support vector machines, artificial neural networks and Bayesian learning algorithms. On the basis of data from the transition between consciousness and unconsciousness, a combination of EEG and AEP signal parameters developed with automated methods provides a maximum prediction probability of 0.935, which is higher than 0.916 (for EEG parameters) and 0.880 (for AEP parameters) using a cross-validation approach. This suggests that machine learning techniques can successfully be applied to develop an improved combined EEG and AEP parameter to separate consciousness from unconsciousness.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238249PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449480PMC
October 2020

Propofol Affects Cortico-Hippocampal Interactions via β3 Subunit-Containing GABA Receptors.

Int J Mol Sci 2020 Aug 14;21(16). Epub 2020 Aug 14.

Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhörnlestrasse 22, 72072 Tübingen, Germany.

Background: General anesthetics depress neuronal activity. The depression and uncoupling of cortico-hippocampal activity may contribute to anesthetic-induced amnesia. However, the molecular targets involved in this process are not fully characterized. GABA receptors, especially the type with β3 subunits, represent a main molecular target of propofol. We therefore hypothesized that GABA receptors with β3 subunits mediate the propofol-induced disturbance of cortico-hippocampal interactions.

Methods: We used local field potential (LFP) recordings from chronically implanted cortical and hippocampal electrodes in wild-type and β3(N265M) knock-in mice. In the β3(N265M) mice, the action of propofol via β3subunit containing GABA receptors is strongly attenuated. The analytical approach contained spectral power, phase locking, and mutual information analyses in the 2-16 Hz range to investigate propofol-induced effects on cortico-hippocampal interactions.

Results: Propofol caused a significant increase in spectral power between 14 and 16 Hz in the cortex and hippocampus of wild-type mice. This increase was absent in the β3(N265M) mutant. Propofol strongly decreased phase locking of 6-12 Hz oscillations in wild-type mice. This decrease was attenuated in the β3(N265M) mutant. Finally, propofol reduced the mutual information between 6-16 Hz in wild-type mice, but only between 6 and 8 Hz in the β3(N265M) mutant.

Conclusions: GABA receptors containing β3 subunits contribute to frequency-specific perturbation of cortico-hippocampal interactions. This likely explains some of the amnestic actions of propofol.
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http://dx.doi.org/10.3390/ijms21165844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461501PMC
August 2020

Technical considerations when using the EEG export of the SEDLine Root device.

J Clin Monit Comput 2020 Aug 19. Epub 2020 Aug 19.

Department of Anesthesiology and Intensive Care, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.

Electroencephalographic (EEG) patient monitoring during general anesthesia can help to assess the real-time neurophysiology of unconscious states. Some monitoring systems like the SEDLine Root allow export of the EEG to be used for retrospective analysis. We show that changes made to the SEDLine display during recording affected the recorded EEG. These changes can strongly impact retrospective analysis of EEG signals. Real-time changes of the feed speed in the SEDLine Root device display modifies the sampling rate of the exported EEG. We used a patient as well as a simulated EEG recording to highlight the effects of the display settings on the extracted EEG. Therefore, we changed EEG feed and amplitude resolution on the display in a systematic manner. To visualize the effects of these changes, we present raw EEG segments and the density spectral array of the recording. Changing the display's amplitude resolution affects the amplitudes. If the amplitude resolution is too fine, the exported EEG contains clipped amplitudes. If the resolution is too coarse, the EEG resolution becomes too low leading to a low-quality signal making frequency analysis impossible. The proportion of clipped or zero-line data caused by the amplitude setting was > 60% in our sedated patient. Changing the display settings results in undocumented changes in EEG amplitude, sampling rate, and signal quality. The occult nature of these changes could make the analysis of data sets difficult if not invalid. We strongly suggest researchers adequately define and keep the EEG display settings to export good quality EEG and to ensure comparability among patients.
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http://dx.doi.org/10.1007/s10877-020-00578-9DOI Listing
August 2020

Impact of Goal-Directed Therapy on Delayed Ischemia After Aneurysmal Subarachnoid Hemorrhage: Randomized Controlled Trial.

Stroke 2020 08 9;51(8):2287-2296. Epub 2020 Jul 9.

Department of Anesthesiology (A.A., M.B., R.B., M.H., G.S., S.S., J.S., J.M., M.E., B.J.), Klinikum rechts der Isar, Technical University Munich, Germany.

Background And Purpose: Delayed cerebral ischemia (DCI) is the most important cause for a poor clinical outcome after a subarachnoid hemorrhage. The aim of this study was to assess whether goal-directed hemodynamic therapy (GDHT), as compared to standard clinical care, reduces the rate of DCI after subarachnoid hemorrhage.

Methods: We conducted a prospective randomized controlled trial. Patients >18 years of age with an aneurysmal subarachnoid hemorrhage were enrolled and randomly assigned to standard therapy or GDHT. Advanced hemodynamic monitoring and predefined GDHT algorithms were applied in the GDHT group. The primary end point was the occurrence of DCI. Functional outcome was assessed using the Glasgow Outcome Scale (GOS) 3 months after discharge.

Results: In total, 108 patients were randomized to the control (n=54) or GDHT group (n=54). The primary outcome (DCI) occurred in 13% of the GDHT group and in 32% of the control group patients (odds ratio, 0.324 [95% CI, 0.11-0.86]; =0.021). Even after adjustment for confounding parameters, GDHT was found to be superior to standard therapy (hazard ratio, 2.84 [95% CI, 1.18-6.86]; =0.02). The GOS was assessed 3 months after discharge in 107 patients; it showed more patients with a low disability (GOS 5, minor or no deficits) than patients with higher deficits (GOS 1-4) in the GDHT group compared with the control group (GOS 5, 66% versus 44%; GOS 1-4, 34% versus 56%; =0.025). There was no significant difference in mortality between the groups.

Conclusions: GDHT reduced the rate of DCI after subarachnoid hemorrhage with a better functional outcome (GOS=5) 3 months after discharge. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01832389.
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http://dx.doi.org/10.1161/STROKEAHA.120.029279DOI Listing
August 2020

Intensive Care Risk Estimation in COVID-19 Pneumonia Based on Clinical and Imaging Parameters: Experiences from the Munich Cohort.

J Clin Med 2020 May 18;9(5). Epub 2020 May 18.

Department of Diagnostic and Interventional Radiology, School of Medicine, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany.

The evolving dynamics of coronavirus disease 2019 (COVID-19) and the increasing infection numbers require diagnostic tools to identify patients at high risk for a severe disease course. Here we evaluate clinical and imaging parameters for estimating the need of intensive care unit (ICU) treatment. We collected clinical, laboratory and imaging data from 65 patients with confirmed COVID-19 infection based on polymerase chain reaction (PCR) testing. Two radiologists evaluated the severity of findings in computed tomography (CT) images on a scale from 1 (no characteristic signs of COVID-19) to 5 (confluent ground glass opacities in over 50% of the lung parenchyma). The volume of affected lung was quantified using commercially available software. Machine learning modelling was performed to estimate the risk for ICU treatment. Patients with a severe course of COVID-19 had significantly increased interleukin (IL)-6, C-reactive protein (CRP), and leukocyte counts and significantly decreased lymphocyte counts. The radiological severity grading was significantly increased in ICU patients. Multivariate random forest modelling showed a mean ± standard deviation sensitivity, specificity and accuracy of 0.72 ± 0.1, 0.86 ± 0.16 and 0.80 ± 0.1 and a receiver operating characteristic-area under curve (ROC-AUC) of 0.79 ± 0.1. The need for ICU treatment is independently associated with affected lung volume, radiological severity score, CRP, and IL-6.
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http://dx.doi.org/10.3390/jcm9051514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291055PMC
May 2020

The association of the anesthesiologist's academic and educational status with self-confidence, self-rated knowledge and objective knowledge in rational antibiotic application.

BMC Res Notes 2020 Mar 18;13(1):161. Epub 2020 Mar 18.

Department of Anaesthesiology and Intensive Care, Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Ismaninger Str. 22, 81675, Munich, Germany.

Objective: This study aimed to investigate the association of anesthetists' academic and educational status with self-confidence, self-rated knowledge and objective knowledge about rational antibiotic application. Therefore, anesthetists in Germany were asked about their self-confidence, self-rated knowledge and objective knowledge on antibiotic therapy via the Multiinstitutional Reconnaissance of practice with Multiresistant bacteria (MR2) survey. Other analysis from the survey have been published elsewhere, before.

Results: 361 (52.8%) questionnaires were completed by specialists and built the study group. In overall analysis the Certification in Intensive Care (CIC) was significantly associated with self-confidence (p < 0.001), self-rated knowledge (p < 0.001) and objective knowledge (p = 0.029) about antibiotic prescription. Senior consultant status was linked to self-confidence (p < 0.001) and self-rated knowledge (p = 0.005) but not objective knowledge. Likewise, working on Intensive Care Unit (ICU) during the last 12 months was significantly associated with self-rated knowledge and self-confidence (all p < 0.001). In a logistic regression model, senior consultant status was not associated with any tested influence factor. This analysis unveiled that CIC and working on ICU were more associated with anesthesiologists' self-confidence and self-rated knowledge than senior consultant status. However, neither of the characteristics was thoroughly associated with objective knowledge.
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http://dx.doi.org/10.1186/s13104-020-05010-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079461PMC
March 2020

Spectral and Entropic Features Are Altered by Age in the Electroencephalogram in Patients under Sevoflurane Anesthesia.

Anesthesiology 2020 05;132(5):1003-1016

From the Department of Anaesthesiology and Intensive Care, Klinikum rechts der Isar, Technical University Munich, Munich, Germany (M.K., S.B., G.S.) the Department of Anesthesiology (M.K., M.A.S., P.S.G.) the Medical Scientist Training Program (M.A.S.), Emory University School of Medicine, Atlanta, Georgia the Anesthesiology and Research Divisions, Atlanta Veterans Affairs Medical Center, (M.K., M.A.S., P.S.G.) Atlanta, Georgia the Department of Anaesthesia, Waikato Clinical School, University of Auckland, Hamilton, New Zealand (D.H., J.W.S.) the Waikato District Health Board, Hamilton, New Zealand (D.H., J.W.S.) the Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (D.H.) the Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York (P.S.G.).

Background: Preexisting factors such as age and cognitive performance can influence the electroencephalogram (EEG) during general anesthesia. Specifically, spectral EEG power is lower in elderly, compared to younger, subjects. Here, the authors investigate age-related changes in EEG architecture in patients undergoing general anesthesia through a detailed examination of spectral and entropic measures.

Methods: The authors retrospectively studied 180 frontal EEG recordings from patients undergoing general anesthesia, induced with propofol/fentanyl and maintained by sevoflurane at the Waikato Hospital in Hamilton, New Zealand. The authors calculated power spectral density and normalized power spectral density, the entropic measures approximate and permutation entropy, as well as the beta ratio and spectral entropy as exemplary parameters used in current monitoring systems from segments of EEG obtained before the onset of surgery (i.e., with no noxious stimulation).

Results: The oldest quartile of patients had significantly lower 1/f characteristics (P < 0.001; area under the receiver operating characteristics curve, 0.84 [0.76 0.92]), indicative of a more uniform distribution of spectral power. Analysis of the normalized power spectral density revealed no significant impact of age on relative alpha (P = 0.693; area under the receiver operating characteristics curve, 0.52 [0.41 0.63]) and a significant but weak effect on relative beta power (P = 0.041; area under the receiver operating characteristics curve, 0.62 [0.52 0.73]). Using entropic parameters, the authors found a significant age-related change toward a more irregular and unpredictable EEG (permutation entropy: P < 0.001, area under the receiver operating characteristics curve, 0.81 [0.71 0.90]; approximate entropy: P < 0.001; area under the receiver operating characteristics curve, 0.76 [0.66 0.85]). With approximate entropy, the authors could also detect an age-induced change in alpha-band activity (P = 0.002; area under the receiver operating characteristics curve, 0.69 [0.60 78]).

Conclusions: Like the sleep literature, spectral and entropic EEG features under general anesthesia change with age revealing a shift toward a faster, more irregular, oscillatory composition of the EEG in older patients. Age-related changes in neurophysiological activity may underlie these findings however the contribution of age-related changes in filtering properties or the signal to noise ratio must also be considered. Regardless, most current EEG technology used to guide anesthetic management focus on spectral features, and improvements to these devices might involve integration of entropic features of the raw EEG.
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http://dx.doi.org/10.1097/ALN.0000000000003182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159998PMC
May 2020

Time delay of the qCON monitor and its performance during state transitions.

J Clin Monit Comput 2021 Apr 10;35(2):379-386. Epub 2020 Feb 10.

Department of Anesthesiology and Intensive Care, Technical University of Munich School of Medicine, Ismaninger Str. 22, 81675, Munich, Germany.

We investigated the performance of the qCON index regarding its time delay for sudden changes in the anesthetic level as well as to separate responsiveness from unresponsiveness during loss and return of responsiveness (LOR and ROR). For evaluation of the time delay, we replayed relevant EEG episodes to the qCON to simulate sudden changes between the states (i) awake/sedation, (ii) adequate anesthesia, or (iii) suppression. We also replayed EEG from 40 patients during LOR and ROR to evaluate the qCON's ability to separate responsiveness from unresponsiveness. The time delays depended on the type of transition. The delays for the important transition between awake/sedation and adequate anesthesia were 21(5) s from awake/sedation to adequate anesthesia and 26(5) s in the other direction. The performance of the qCON to separate responsiveness from unresponsiveness depended on signal quality, the investigation window, i.e. ± 30 s or ± 60 s around LOR/ROR, and the specific transition being tested. AUC was 0.63-0.90 for LOR and 0.61-0.79 for ROR. Time delay and performance during state transitions of the qCON were similar to other monitoring systems such as bispectral index. The better performance of qCON during LOR than ROR probably reflects the sudden change in EEG activity during LOR and the more heterogeneous EEG during ROR.
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http://dx.doi.org/10.1007/s10877-020-00480-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943427PMC
April 2021

Identifying perioperative volume-related risk factors in head and neck surgeries with free flap reconstructions - An investigation with focus on the influence of red blood cell concentrates and noradrenaline use.

J Craniomaxillofac Surg 2020 Jan 16;48(1):67-74. Epub 2019 Dec 16.

Department of Anesthesiology, Technische Universität München, Germany.

Introduction: The amount of fluids administered intraoperatively seems to influence the postoperative outcome, and especially the transfusion of red blood cell concentrates (RBC) are known to have an increased risk of postoperative complications. This prospective study focuses on patients planned with microvascular free flap reconstruction and investigates the effect of various types and amounts of volumes given intraoperatively and on the intensive care unit with regard to overall postoperative complications.

Material And Methods: In this prospective study, 52 consecutive patients planned for reconstruction with microvascular free flaps were included. Intraoperatively administered volumes including blood products were documented by the anesthesiologists as well as volumes given during the intensive care unit stay. Postoperative complications were registered for the entire hospital stay. Statistical analysis was carried out correlating the amount and type of volumes with the incidence of postoperative complications.

Results: The intraoperative use of RBC showed a close to statistically significant increased risk of postoperative complications (mean/SD concentrates: 0.5/1.1 [no complications] vs. 1.0/1.4 [complications], p = 0.058). In a multivariate analysis with stepwise selection the use of human albumin, gelatin, or Ringer's acetate showed no correlation with complications. The overall blood loss, however, had no significant influence on the incidence of complications (mean/SD ml: 1187/761 [no complications] vs. 1004/600 [complications], p = 0.37). The use of noradrenalin during reconstructive surgeries with microvascular flaps bears statistically no increased risk of failure (mean/SD μg/kg/min: 36/23 [no flap loss] vs. 22/15 [flap loss], p = 0.289) or complications (mean/SD μg/kg/min: 34/22 [no complications] vs. 35/23 [complications], p = 0.807).

Conclusion: In our investigation, the use of crystalloids and colloids seems to have no influence on the postoperative outcome, but the use of RBC may have an increased overall incidence of postoperative complications. A careful hemostasis to limit the use of RBC remains essential despite available options of substitutions. The use of infusion-pump-administered noradrenaline seems valuable to sustain a stable circulation during surgeries with microvascular free flaps and may have no negative impact on postoperative complications.
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http://dx.doi.org/10.1016/j.jcms.2019.12.001DOI Listing
January 2020

Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures.

BMC Neurosci 2019 12 10;20(1):58. Epub 2019 Dec 10.

Dept. of Anesthesiology and Intensive Care, Experimental Anesthesiology Section, University Hospital Tübingen, Tübingen, Germany.

Background: The pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic and sedative-hypnotic effects. Although each of these molecules effectively reduce the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABA receptors containing a γ-subunit), while alcohol is less selective in its receptor bioactivity. Our investigation focuses on divergent actions of diazepam and ethanol on the firing patterns of cultured cortical neurons.

Method: We used electrophysiological recordings from organotypic slice cultures derived from Sprague-Dawley rat neocortex. We exposed these cultures to either diazepam (15 and 30 µM, n = 7) or ethanol (30 and 60 mM, n = 11) and recorded the electrical activity at baseline and experimental conditions. For analysis, we extracted the episodes of spontaneous activity, i.e., cortical up-states. After separation of action potential and local field potential (LFP) activity, we looked at differences in the number of action potentials, in the spectral power of the LFP, as well as in the coupling between action potential and LFP phase.

Results: While both substances seem to decrease neocortical action potential firing in a not significantly different (p = 0.659, Mann-Whitney U) fashion, diazepam increases the spectral power of the up-state without significantly impacting the spectral composition, whereas ethanol does not significantly change the spectral power but the oscillatory architecture of the up-state as revealed by the Friedman test with Bonferroni correction (p < 0.05). Further, the action potential to LFP-phase coupling reveals a synchronizing effect of diazepam for a wide frequency range and a narrow-band de-synchronizing effect for ethanol (p < 0.05, Kolmogorov-Smirnov test).

Conclusion: Diazepam and ethanol, induce specific patterns of network depressant actions. Diazepam induces cortical network inhibition and increased synchronicity via gamma subunit containing GABA receptors. Ethanol also induces cortical network inhibition, but without an increase in synchronicity via a wider span of molecular targets.
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http://dx.doi.org/10.1186/s12868-019-0540-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902402PMC
December 2019

Trauma as a monstrous quasi-object.

Int J Psychoanal 2019 Dec 3;100(6):1184-1198. Epub 2020 Jan 3.

German Psychoanalytic Association (DPV), Mannheim, Germany.

It is characteristic of a trauma that the subject cannot process and symbolically represent the traumatic experience. With Lacan's theory of 'the real', the traumatic experience is understood as one of being overwhelmed by a . In developmental terms, I refer to a (birth) and the subject's . It manifests itself during childhood in transitions from one ontological constitution to another that are necessitated by internal or external changes. Such transitions involve the child's on his primary objects, and they require from them. This also applies to the child's , as his primary objects must react appropriately to his constitution , so that he can feel existentially affirmed by them in his being. The adult, also, is reliant on knowing that he is affirmed as a human being in his existence, which can be experienced in the of the other. Metaphorically speaking, this also applies to the gaze and behaviour of the natural and technological environment, which can transform, like a personal object, into a traumatic monstrous quasi-object. The paper concludes with a clinical vignette in which the emergence and transformation of a monstrous quasi-object is illustrated in the treatment of a female patient suffering from severe early traumata.
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http://dx.doi.org/10.1080/00207578.2019.1703341DOI Listing
December 2019

["Please take over the patient with M1 occlusion in the angio suite"].

Anaesthesist 2019 11;68(11):731-732

Fakultät für Medizin, Klinikum rechts der Isar, Klinik für Anästhesiologie und Intensivmedizin, Technische Universität München, Ismaninger Str. 22, 81675, München, Deutschland.

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http://dx.doi.org/10.1007/s00101-019-00649-wDOI Listing
November 2019

Medical ethics in the Anthropocene: how are €100 billion of German physicians' pension funds invested?

Lancet Planet Health 2019 10;3(10):e405-e406

Faculty of Economics and Management, Technical University Berlin, Berlin, Germany.

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http://dx.doi.org/10.1016/S2542-5196(19)30189-5DOI Listing
October 2019

Continuous chest compressions with a simultaneous triggered ventilator in the Munich Emergency Medical Services: a case series.

Ger Med Sci 2019 26;17:Doc06. Epub 2019 Jun 26.

Board of Directors, Emergency Medical Services, Munich, Germany.

Mechanical chest compression devices are commonly used providing a constant force and frequency of chest compression during cardiopulmonary resuscitation. However, there are currently no recommendations on ventilation during cardiopulmonary resuscitation with a mechanical chest compression device using continuous mode. An effective method for ventilation in such scenarios might be a triggered oxygen-powered resuscitator. We report seven cardiopulmonary resuscitation cases from the Munich Emergency Medical Service where mechanical chest compression devices in continuous mode were used with an oxygen-powered resuscitator. In each case, the resuscitator (Oxylator) was running in automatic mode delivering a breath during the decompression phase of the chest compressions at a frequency of 100 per minute. End-tidal carbon dioxide and pulse oximetry were measured. Additional data was collected from the resuscitation protocol of each patient. End-tidal carbon dioxide was available in all cases while oxygen saturation only in four. Five patients had a return of spontaneous circulation. Based on the end-tidal carbon dioxide values of each of the cases, the resuscitator did not seem to cause hyperventilation and suggests that good-quality cardiopulmonary resuscitation was delivered. Continuous chest compressions using a mechanical chest compression device and simultaneous synchronized ventilation using an oxygen-powered resuscitator in an automatic triggering mode might be feasible during cardiopulmonary resuscitation.
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http://dx.doi.org/10.3205/000272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637291PMC
April 2020

Impact of PReOperative Midazolam on OuTcome of Elderly patients (I-PROMOTE): study protocol for a multicentre randomised controlled trial.

Trials 2019 Jul 15;20(1):430. Epub 2019 Jul 15.

Department of Anaesthesiology, Medical Faculty RWTH Aachen University, Aachen, Germany.

Introduction: Premedication of surgical patients with benzodiazepines has become questionable regarding risk-benefit ratio and lack of evidence. Though preoperative benzodiazepines might alleviate preoperative anxiety, a higher risk for adverse events is described, particularly for elderly patients (≥ 65 years). Several German hospitals already withhold benzodiazepine premedication from elderly patients, though evidence for this approach is lacking. The patient-centred outcome known as global postoperative patient satisfaction is recognised as a substantial quality indicator of anaesthesia care incorporated by the American Society of Anesthesiologists. Therefore, we aim to assess whether the postoperative patient satisfaction after premedication with placebo compared to the preoperative administration of 3.75 mg midazolam in elderly patients differs.

Methods: This study is a multicentre, randomised, placebo-controlled, double-blinded, two-arm parallel, interventional trial, conducted in nine German hospitals. In total 614 patients (≥ 65-80 years of age) undergoing elective surgery with general anaesthesia will be randomised to receive either 3.75 mg midazolam or placebo. The primary outcome (global patient satisfaction) will be assessed with the validated EVAN-G questionnaire on the first postoperative day. Secondary outcomes will be assessed until the first postoperative day and then 30 days after surgery. They comprise among other things: functional and cognitive recovery, postoperative delirium, health-related quality of life assessment, and mortality or new onset of serious cardiac or pulmonary complications, acute stroke, or acute kidney injury. Analysis will adhere to the intention-to-treat principle. The primary outcome will be analysed with the use of mixed linear models including treatment effect and study centre as factors and random effects for blocks. Exploratory adjusted and subgroup analyses of the primary and secondary outcomes with regard to gender effects, frailty, pre-operative anxiety level, patient demographics, and surgery experience will also be performed.

Discussion: This is, to the best of our knowledge, the first study analysing patient satisfaction after premedication with midazolam in elderly patients. In conclusion, this study will provide high-quality data for the decision-making process regarding premedication in elderly surgical patients.

Trial Registration: ClinicalTrials.gov, NCT03052660 . Registered on 14 February 2017. EudraCT 2016-004555-79 .
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http://dx.doi.org/10.1186/s13063-019-3512-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6632125PMC
July 2019

Changes in Whole Brain Dynamics and Connectivity Patterns during Sevoflurane- and Propofol-induced Unconsciousness Identified by Functional Magnetic Resonance Imaging.

Anesthesiology 2019 06;130(6):898-911

From the Department of Neurology (D.G., R.I.) Department of Anesthesiology (A.R., G.S., D.J.), Klinikum rechts der Isar, Technical University Munich, München, Germany GIGA-Consciousness, Coma Science Group (S.K.L., C.D.P., S.L.) GIGA-Consciousness, Sensation and Perception Research Group (A.V., V.B.) GIGA Research, University, and Department of Algology and Palliative Care, Department of Neurology (S.L.) Department of Anesthesia and Intensive Care Medicine (V.B.) CHU University Hospital of Liège (C.D.P.), Liège, Belgium GIGA-Cyclotron Research Center: In Vivo Imaging, University of Liège, Liège, Belgium (A.P.) University Department of Anesthesia and Intensive Care Medicine, CHR Citadelle, Liège, Belgium (V.B.) Department of Neurology, University of Wisconsin, Madison, Wisconsin (M.B.) Asklepios Clinic, Department of Neurology, Bad Tölz, Germany (R.I.).

Background: A key feature of the human brain is its capability to adapt flexibly to changing external stimuli. This capability can be eliminated by general anesthesia, a state characterized by unresponsiveness, amnesia, and (most likely) unconsciousness. Previous studies demonstrated decreased connectivity within the thalamus, frontoparietal, and default mode networks during general anesthesia. We hypothesized that these alterations within specific brain networks lead to a change of communication between networks and their temporal dynamics.

Methods: We conducted a pooled spatial independent component analysis of resting-state functional magnetic resonance imaging data obtained from 16 volunteers during propofol and 14 volunteers during sevoflurane general anesthesia that have been previously published. Similar to previous studies, mean z-scores of the resulting spatial maps served as a measure of the activity within a network. Additionally, correlations of associated time courses served as a measure of the connectivity between networks. To analyze the temporal dynamics of between-network connectivity, we computed the correlation matrices during sliding windows of 1 min and applied k-means clustering to the matrices during both general anesthesia and wakefulness.

Results: Within-network activity was decreased in the default mode, attentional, and salience networks during general anesthesia (P < 0.001, range of median changes: -0.34, -0.13). Average between-network connectivity was reduced during general anesthesia (P < 0.001, median change: -0.031). Distinct between-network connectivity patterns for both wakefulness and general anesthesia were observed irrespective of the anesthetic agent (P < 0.001), and there were fewer transitions in between-network connectivity patterns during general anesthesia (P < 0.001, median number of transitions during wakefulness: 4 and during general anesthesia: 0).

Conclusions: These results suggest that (1) higher-order brain regions play a crucial role in the generation of specific between-network connectivity patterns and their dynamics, and (2) the capability to interact with external stimuli is represented by complex between-network connectivity patterns.
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http://dx.doi.org/10.1097/ALN.0000000000002704DOI Listing
June 2019

Assessment of Regional Perfusion and Organ Function: Less and Non-invasive Techniques.

Front Med (Lausanne) 2019 22;6:50. Epub 2019 Mar 22.

Medizinische Klinik und Poliklinik II, Klinikum rechts der Isar, Technische Universität München, München, Germany.

Sufficient organ perfusion essentially depends on preserved macro- and micro-circulation. The last two decades brought substantial progress in the development of less and non-invasive monitoring of macro-hemodynamics. However, several recent studies suggest a frequent incoherence of macro- and micro-circulation. Therefore, this review reports on interactions of macro- and micro-circulation as well as on specific regional and micro-circulation. Regarding global micro-circulation the last two decades brought advances in a more systematic approach of clinical examination including capillary refill time, a graded assessment of mottling of the skin and accurate measurement of body surface temperatures. As a kind of link between macro- and microcirculation, a number of biochemical markers can easily be obtained. Among those are central-venous oxygen saturation (SO), plasma lactate and the difference between central-venous and arterial CO (cv-a-pCO-gap). These inexpensive markers have become part of clinical routine and guideline recommendations. While their potential to replace parameters of macro-circulation such as cardiac output (CO) is limited, they facilitate the interpretation of the adequacy of CO and other macro-circulatory markers. Furthermore, they give additional hints on micro-circulatory impairment. In addition, a number of more sophisticated technical approaches to quantify and visualize micro-circulation including video-microscopy, laser flowmetry, near-infrared spectroscopy (NIRS), and partial oxygen pressure measurement have been introduced within the last 20 years. These technologies have been extensively used for scientific purposes. Moreover, they have been successfully used for educational purposes and to visualize micro-circulatory disturbances during sepsis and other causes of shock. Despite several studies demonstrating the association of these techniques and parameters with outcome, their practical application still is limited. However, future improvements in automated and "online" diagnosis will help to make these technologies more applicable in clinical routine. This approach is promising with regard to several studies which demonstrated the potential to guide therapy in different types of shock. Finally several organs have specific patterns of circulation related to their special anatomy (liver) or their auto-regulatory capacities (brain, kidney). Therefore, this review also discusses specific issues of monitoring liver, brain, and kidney circulation and function.
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http://dx.doi.org/10.3389/fmed.2019.00050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438879PMC
March 2019

Modulation of frontal EEG alpha oscillations during maintenance and emergence phases of general anaesthesia to improve early neurocognitive recovery in older patients: protocol for a randomised controlled trial.

Trials 2019 Feb 22;20(1):146. Epub 2019 Feb 22.

Department of Anaesthesiology, Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand.

Background: Postoperative delirium may manifest in the immediate post-anaesthesia care period. Such episodes appear to be predictive of further episodes of inpatient delirium and associated adverse outcomes. Frontal electroencephalogram (EEG) findings of suppression patterns and low proprietary index values have been associated with postoperative delirium and poor outcomes. However, the efficacy of titrating anaesthesia to proprietary index targets for preventing delirium remains contentious. We aim to assess the efficacy of two strategies which we hypothesise could prevent post-anaesthesia care unit (PACU) delirium by maximising the alpha oscillation observed in frontal EEG channels during the maintenance and emergence phases of anaesthesia.

Methods: This is a 2 × 2 factorial, double-blind, stratified, randomised control trial of 600 patients. Eligible patients are those aged 60 years or over who are undergoing non-cardiac, non-intracranial, volatile-based anaesthesia of expected duration of more than 2 h. Patients will be stratified by pre-operative cognitive status, surgery type and site. For the maintenance phase of anaesthesia, patients will be randomised (1:1) to an alpha power-maximisation anaesthesia titration strategy versus standard care avoiding suppression patterns in the EEG. For the emergence phase of anaesthesia, patients will be randomised (1:1) to early cessation of volatile anaesthesia and emergence from an intravenous infusion of propofol versus standard emergence from volatile anaesthesia only. The primary study outcomes are the power of the frontal alpha oscillation during the maintenance and emergence phases of anaesthesia. Our main clinical outcome of interest is PACU delirium.

Discussion: This is a largely exploratory study; the extent to which EEG signatures can be modified by titration of pharmacological agents is not known. The underlying concept is maximisation of anaesthetic efficacy by individualised drug titration to a clearly defined EEG feature. The interventions are already clinically used strategies in anaesthetic practice, but have not been formally evaluated. The addition of propofol during the emergence phase of volatile-based general anaesthesia is known to reduce emergence delirium in children; however, the efficacy of this strategy in older patients is not known.

Trial Registration: Australian and New Zealand Clinical Trial Registry, ID: 12617001354370 . Registered on 27/09/2017.
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http://dx.doi.org/10.1186/s13063-019-3178-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387545PMC
February 2019

Differences in pain treatment between surgeons and anaesthesiologists in a physician staffed prehospital emergency medical service: a retrospective cohort analysis.

BMC Anesthesiol 2019 01 31;19(1):18. Epub 2019 Jan 31.

Klinik für Unfallchirurgie, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Bavaria, Germany.

Background: Although pain treatment is an important objective in prehospital emergency medicine the incidence of oligoanalgesia is still high in prehospital patients. Given that prehospital emergency medicine in Germany is open for physicians of any speciality, the prehospital pain treatment may differ depending on the primary medical education. Aim of this study was to explore the difference in pain treatment between surgeons and anaesthesiologists in a physician staffed emergency medical service.

Methods: Retrospective single centre cohort analysis in a physician staffed ground based emergency medical service from January 2014 until December 2016. A total of 8882 consecutive emergency missions were screened. Primary outcome measure was the difference in application frequency of prehospital analgesics by anaesthesiologist or surgeon. Univariate and multivariate logistic regression analysis was used for statistical analysis including subgroup analysis for trauma and acute coronary syndrome.

Results: A total of 8238 patients were included in the analysis. There was a significant difference in the application frequency of analgesics between surgeons and anaesthesiologists especially for opioids (p < 0.001, OR 0.68 [0.56-0.82]). Fentanyl was the most common administered analgesic in the trauma subgroup, but significantly less common used by surgeons (p = 0.005, OR 0.63 [0.46-0.87]). In acute coronary syndrome cases there was no significant difference in morphine administration between anaesthesiologists and surgeons (p = 0.49, OR 0.88 [0.61-1.27]).

Conclusions: Increased training for prehospital pain treatment should be implemented, since opioids were administered notably less frequent by surgeons than by anaesthesiologists.
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http://dx.doi.org/10.1186/s12871-019-0683-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357417PMC
January 2019

Cognitive decline in Tg2576 mice shows sex-specific differences and correlates with cerebral amyloid-beta.

Behav Brain Res 2019 02 17;359:408-417. Epub 2018 Nov 17.

Department of Anaesthesiology and Intensive Care Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany.

Patients suffering from Alzheimer's disease show a sex-dependent decline of cognitive function. The aim of this investigation was to show these differences in an animal model for Alzheimer's disease and to determine whether this effect is correlated to amyloid-beta-induced pathophysiological changes. Therefore, we assessed cognitive performance with the modified hole-board test in female and male Tg2576 and wild type mice at the age of 6, 8, 10, 12, 14, and 16 months and correlated these findings to the total amount of soluble amyloid-beta and insoluble amyloid deposits in the brain. Tg2576 mice perform worse than wild types. Female Tg2576 mice develop an accentuated cognitive impairment (wrong choice total) beginning at the age of 12 months compared to their male littermates. Alterations in the mice's behaviour do not show interference with these deficits. Cognitive impairment is correlated to the amount of soluble amyloid-beta and insoluble amyloid deposits in the brain in a sex-dependent manner.
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http://dx.doi.org/10.1016/j.bbr.2018.11.022DOI Listing
February 2019

Substance-Specific Differences in Human Electroencephalographic Burst Suppression Patterns.

Front Hum Neurosci 2018 21;12:368. Epub 2018 Sep 21.

Department of Anesthesiology and Intensive Care, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.

Different anesthetic agents induce burst suppression in the electroencephalogram (EEG) at very deep levels of general anesthesia. EEG burst suppression has been identified to be a risk factor for postoperative delirium (POD). EEG based automated detection algorithms are used to detect burst suppression patterns during general anesthesia and a burst suppression ratio (BSR) is calculated. Unfortunately, applied algorithms do not give information as precisely as suggested, often resulting in an underestimation of the patients' burst suppression level. Additional knowledge of substance-specific burst suppression patterns could be of great importance to improve the ability of EEG based monitors to detect burst suppression. In a re-analysis of EEG recordings obtained from a previous study, we analyzed EEG data of 45 patients undergoing elective surgery under general anesthesia. The patients were anesthetized with sevoflurane, isoflurane or propofol ( = 15, for each group). After skin incision, the used agent was titrated to a level when burst suppression occurred. In a visual analysis of the EEG, blinded to the used anesthetic agent, we included the first distinct burst in our analysis. To avoid bias through changing EEG dynamics throughout the burst, we only focused on the first 2 s of the burst. These episodes were analyzed using the power spectral density (PSD) and normalized PSD, the absolute burst amplitude and absolute burst slope, as well as permutation entropy (PeEn). Our results show significant substance-specific differences in the architecture of the burst. Volatile-induced bursts showed higher burst amplitudes and higher burst power. Propofol-induced bursts had significantly higher relative power in the EEG alpha-range. Further, isoflurane-induced bursts had the steepest burst slopes. We can present the first systematic comparison of substance-specific burst characteristics during anesthesia. Previous observations, mostly derived from animal studies, pointing out the substance-specific differences in bursting behavior, concur with our findings. Our findings of substance-specific EEG characteristics can provide information to help improve automated burst suppression detection in monitoring devices. More specific detection of burst suppression may be helpful to reduce excessive EEG effects of anesthesia and therefore the incidence of adverse outcomes such as POD.
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http://dx.doi.org/10.3389/fnhum.2018.00368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160564PMC
September 2018