Key characteristics impacting survival of COVID-19 extracorporeal membrane oxygenation

Background Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. Methods 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. Results Most patients were between 50 and 70 years of age. PaO2/FiO2 ratio prior to ECMO was 72 mmHg (IQR: 58–99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) (p = 0.0014, OR 0.64 (CI 0.41–0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28–1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. Conclusions Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival

Sedative Properties of Dexmedetomidine Are Mediated Independently from Native Thalamic Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Function at Clinically Relevant Concentrations

Dexmedetomidine is a selective α2-adrenoceptor agonist and appears to disinhibit endogenous sleep-promoting pathways, as well as to attenuate noradrenergic excitation. Recent evidence suggests that dexmedetomidine might also directly inhibit hyperpolarization-activated cyclic-nucleotide gated (HCN) channels. We analyzed the effects of dexmedetomidine on native HCN channel function in thalamocortical relay neurons of the ventrobasal complex of the thalamus from mice, performing whole-cell patch-clamp recordings. Over a clinically relevant range of concentrations (1–10 µM), the effects of dexmedetomidine were modest. At a concentration of 10 µM, dexmedetomidine significantly reduced maximal Ih amplitude (relative reduction: 0.86 [0.78–0.91], n = 10, and p = 0.021), yet changes to the half-maximal activation potential V1/2 occurred exclusively in the presence of the very high concentration of 100 µM (−4,7 [−7.5–−4.0] mV, n = 10, and p = 0.009). Coincidentally, only the very high concentration of 100 µM induced a significant deceleration of the fast component of the HCN activation time course (τfast: +135.1 [+64.7–+151.3] ms, n = 10, and p = 0.002). With the exception of significantly increasing the membrane input resistance (starting at 10 µM), dexmedetomidine did not affect biophysical membrane properties and HCN channel-mediated parameters of neuronal excitability. Hence, the sedative qualities of dexmedetomidine and its effect on the thalamocortical network are not decisively shaped by direct inhibition of HCN channel function

The xenon-mediated antagonism against the NMDA receptor is non-selective for receptors containing either NR2A or NR2B subunits in the mouse amygdala

In pharmacological studies using cultured neurones or heterologous expression systems, the N-methyl-Daspartate (NMDA) receptor has been found as a major target for the inhalational anaesthetic xenon (Xe). NMDA receptors play a crucial role in behavioural and cellular processes related to learning and memory, and NMDA receptor subunits type 2A (NR2A) and type 2B (NR2B) are critical determinants for synaptic plasticity. In the present study, we investigated in an acute mouse brain slice preparation of the basolateral amygdala whether the antagonism of Xe is subunit-selective against the NR2A or NR2B subunit. From principal neurones, pharmacologically isolated NMDA receptor-mediated currents (p-NMDA-Cs) were evoked upon focal photolysis of caged L-glutamate and recorded using the whole-cell patch-clamp technique. To test whether the Xe-induced inhibition of NMDA receptor-mediated currents is selective for NR2A or NR2B subunits, p-NMDA-Cs were recorded in the presence of the NR2A or NR2B subunit antagonists R-S-1-4-bromophenylethylamino-2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl-methylphosphonic acid (NVP-AAM077, 50 nM) or R-R*,S*-α-4-Hydroxyphenyl-β-methyl-4-phenylmethyl-1-piperidinepropanol hydrochloride (Ro 25-6981, 0.5 μM), respectively. The Xe-induced reduction under these conditions was not significantly different from that without NR2A or NR2B blockade. These results provide evidence, that the Xe-induced antagonism against NMDA receptors is non-selective against NR2A- or NR2B-containing receptors

Diurnal Dynamics of Wheat Evapotranspiration Derived from Ground-Based Thermal Imagery

The latent heat flux, one of the key components of the surface energy balance, can be inferred from remotely sensed thermal infrared data. However, discrepancies between modeled and observed evapotranspiration are large. Thermal cameras might provide a suitable tool for model evaluation under variable atmospheric conditions. Here, we evaluate the results from the Penman-Monteith, surface energy balance and Bowen ratio approaches, which estimate the diurnal course of latent heat fluxes at a ripe winter wheat stand using measured and modeled temperatures. Under overcast conditions, the models perform similarly, and radiometric image temperatures are linearly correlated with the inverted aerodynamic temperature. During clear sky conditions, the temperature of the wheat ear layer could be used to predict daytime turbulent fluxes (root mean squared error and mean absolute error: 20–35 W∙m−2, r2: 0.76–0.88), whereas spatially-averaged temperatures caused underestimation of pre-noon and overestimation of afternoon fluxes. Errors are dependent on the models’ ability to simulate diurnal hysteresis effects and are largest during intermittent clouds, due to the discrepancy between the timing of image capture and the time needed for the leaf-air-temperature gradient to adapt to changes in solar radiation. During such periods, we suggest using modeled surface temperatures for temporal upscaling and the validation of image data

Experiences of medical students and nursing trainees from unexpected death through simulation training

Abstract Background Dying in simulation training is controversially discussed. On the one hand, the danger of an emotional overload of the learners is pointed out. On the other hand, dying in simulation settings is addressed as an opportunity to prepare future health professionals to deal with patient death. The present study investigates how medical students and nursing trainees experience the sudden death of a simulated patient and how and under which conditions it can be valuable to simulate the patient’s death. Methods At the TUM School of Medicine in Munich, Germany, we developed an interprofessional, simulation-based course in which participants were unexpectedly confronted with a cardiac arrest scenario within which resuscitation had to be discontinued due to an advanced directive. After the course, focus groups were conducted with nine medical students and six nursing trainees. Data were analysed using Grounded Theory techniques. Results The participants reported low to high emotional involvement. The active renunciation of life-sustaining measures was felt to be particularly formative and caused a strange feeling and helplessness. Questions of what could have been done differently determined interviewees’ thoughts. The participants appreciated the opportunity to experience what it feels like to lose a patient. The course experience encouraged interviewees to reflect on dying and the interviewees explained that they feel better prepared to face death after the course. The unexpected character of the confrontation, presence of the advanced directive and debriefing positively affected the impact of the simulation. Conclusions The study recognises simulation training as a promising approach for preparing future health care professionals to encounter a patient’s death

Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: Evidence from In Vitro and In Vivo Experiments

Abstract Background: The thalamus is thought to be crucially involved in the anesthetic state. Here, we investigated the effect of the inhaled anesthetic xenon on stimulus-evoked thalamocortical network activity and on excitability of thalamocortical neurons. Because hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are key regulators of neuronal excitability in the thalamus, the effect of xenon on HCN channels was examined. Methods: The effects of xenon on thalamocortical network activity were investigated in acutely prepared brain slices from adult wild-type and HCN2 knockout mice by means of voltage-sensitive dye imaging. The influence of xenon on single-cell excitability in brain slices was investigated using the whole-cell patch-clamp technique. Effects of xenon on HCN channels were verified in human embryonic kidney cells expressing HCN2 channels. Results: Xenon concentration-dependently diminished thalamocortical signal propagation. In neurons, xenon reduced HCN channel-mediated Ih current amplitude by 33.4 ± 12.2% (at −133 mV; n = 7; P = 0.041) and caused a left-shift in the voltage of half-maximum activation (V1/2) from −98.8 ± 1.6 to −108.0 ± 4.2 mV (n = 8; P = 0.035). Similar effects were seen in human embryonic kidney cells. The impairment of HCN channel function was negligible when intracellular cyclic adenosine monophosphate level was increased. Using HCN2−/− mice, we could demonstrate that xenon did neither attenuate in vitro thalamocortical signal propagation nor did it show sedating effects in vivo. Conclusions: Here, we clearly showed that xenon impairs HCN2 channel function, and this impairment is dependent on intracellular cyclic adenosine monophosphate levels. We provide evidence that this effect reduces thalamocortical signal propagation and probably contributes to the hypnotic properties of xenon. </jats:sec

Propofol and Sevoflurane Differentially Modulate Cortical Depolarization following Electric Stimulation of the Ventrobasal Thalamus

The neuronal mechanisms how anesthetics lead to loss of consciousness are unclear. Thalamocortical interactions are crucially involved in conscious perception; hence the thalamocortical network might be a promising target for anesthetic modulation of neuronal information pertaining to arousal and waking behavior. General anesthetics affect the neurophysiology of the thalamus and the cortex but the exact mechanisms of how anesthetics interfere with processing thalamocortical information remain to be elucidated. Here we investigated the effect of the anesthetic agents sevoflurane and propofol on thalamocortical network activity in vitro. We used voltage-sensitive dye imaging techniques to analyze the cortical depolarization in response to stimulation of the thalamic ventrobasal nucleus in brain slices from mice. Exposure to sevoflurane globally decreased cortical depolarization in a dose-dependent manner. Sevoflurane reduced the intensity and extent of cortical depolarization and delayed thalamocortical signal propagation. In contrast, propofol neither affected area nor amplitude of cortical depolarization. However, propofol exposure resulted in regional changes in spatial distribution of maximum fluorescence intensity in deep regions of the cortex. In summary, our experiments revealed substance-specific effects on the thalamocortical network. Functional changes of the neuronal network are known to be pivotally involved in the anesthetic-induced loss of consciousness. Our findings provide further evidence that the mechanisms of anesthetic-mediated loss of consciousness are drug- and pathway-specific