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The clinical effectiveness of Oxiris®, particularly in reducing cytokines, remains uncertain due to the limited data provided. This study explored and analyzed the application value of Oxiris® endotoxin adsorption technology in a large animal model. Pigs received an intravenous LPS infusion. Six animals were treated 2 h after the infusion with an Oxiris® hemadsorption using a pumpless extracorporeal technique for 6 h. Five animals served as controls. Cardiocirculatory parameters, hyperspectral analysis, and a panel of cytokines were measured. The lipopolysaccharide infusion induced sepsis-like inflammation with tachycardia, elevated pulmonary pressure, elevated lactate level, as well as elevated pro-inflammatory cytokines like interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-12 and tumor necrosis factor alpha (TNF-α). In addition, increases of anti-inflammatory cytokines like IL-1ra and IL-10 were found. After 3 and 6 h in both groups, pro-inflammatory cytokines were significantly reduced. No differences between the intervention and the control group could be detected after 3 and 6 h for IL-1β, IL-2, IL-6, IL-8, IL-12 and TNF-α, suggesting no effect of the Oxiris® filter on the elimination of elevated cytokines with a pumpless extracorporeal hemadsorption technique. The presented large animal model may be a promising option for studying the effects of hemadsorption techniques. [ABSTRACT FROM AUTHOR]

Background and Objectives: Intra-abdominal hypertension (IAH) and acute respiratory distress syndrome (ARDS) are common concerns in intensive care unit patients with acute respiratory failure (ARF). Although both conditions lead to impairment of global respiratory parameters, their underlying mechanisms differ substantially. Therefore, a separate assessment of the different respiratory compartments should reveal differences in respiratory mechanics. Materials and Methods: We prospectively investigated alterations in lung and chest wall mechanics in 18 mechanically ventilated pigs exposed to varying levels of intra-abdominal pressures (IAP) and ARDS. The animals were divided into three groups: group A (IAP 10 mmHg, no ARDS), B (IAP 20 mmHg, no ARDS), and C (IAP 10 mmHg, with ARDS). Following induction of IAP (by inflating an intra-abdominal balloon) and ARDS (by saline lung lavage and injurious ventilation), respiratory mechanics were monitored for six hours. Statistical analysis was performed using one-way ANOVA to compare the alterations within each group. Results: After six hours of ventilation, end-expiratory lung volume (EELV) decreased across all groups, while airway and thoracic pressures increased. Significant differences were noted between group (B) and (C) regarding alterations in transpulmonary pressure (TPP) (2.7 ± 0.6 vs. 11.3 ± 2.1 cmH2O, p < 0.001), elastance of the lung (EL) (8.9 ± 1.9 vs. 29.9 ± 5.9 cmH2O/mL, p = 0.003), and elastance of the chest wall (ECW) (32.8 ± 3.2 vs. 4.4 ± 1.8 cmH2O/mL, p < 0.001). However, global respiratory parameters such as EELV/kg bodyweight (−6.1 ± 1.3 vs. −11.0 ± 2.5 mL/kg), driving pressure (12.5 ± 0.9 vs. 13.2 ± 2.3 cmH2O), and compliance of the respiratory system (−21.7 ± 2.8 vs. −19.5 ± 3.4 mL/cmH2O) did not show significant differences among the groups. Conclusions: Separate measurements of lung and chest wall mechanics in pigs with IAH or ARDS reveals significant differences in TPP, EL, and ECW, whereas global respiratory parameters do not differ significantly. Therefore, assessing the compartments of the respiratory system separately could aid in identifying the underlying cause of ARF. [ABSTRACT FROM AUTHOR]

Author(s): Armin Kalenka [sup.1] [sup.2] , Felix Gruner [sup.3] , Christel Weiß [sup.4] , Tim Viergutz [sup.3] Author Affiliations: (1) Department of Anaesthesiology and Intensive Care Medicine, Hospital Bergstraße, , [...]

Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb® and four Oxiris® hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45–85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb® blood flow [mL/min] = 4.226 × MAP [mmHg] − 3.496 (R-square 0.8133) and Oxiris® blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb® and Oxiris® devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes. [ABSTRACT FROM AUTHOR]

A study to examine the survival benefit of hydrocortisone therapy in patients suffering from septic shock is conducted. Results conclude that hydrocortisone did not increase survival or reversal of shock in patients with septic shock, but hastened reversal of shock in patients in whom shock was reversed.

Introduction: Intra-abdominal hypertension (IAH) is a well-known phenomenon in critically ill patients. Effects of a moderately elevated intra-abdominal pressure (IAP) on lung mechanics are still not fully analyzed. Moreover, the optimal positive end-expiratory pressure (PEEP) in elevated IAP is unclear. Methods: We investigated changes in lung mechanics and transformation in histological lung patterns using three different PEEP levels in eighteen deeply anesthetized pigs with an IAP of 10 mmHg. After establishing the intra-abdominal pressure, we randomized the animals into 3 groups. Each of n = 6 (Group A = PEEP 5, B = PEEP 10 and C = PEEP 15 cmH2O). End-expiratory lung volume (EELV/kg body weight (bw)), pulmonary compliance (Cstat), driving pressure (ΔP) and transpulmonary pressure (ΔPL) were measured for 6 hours. Additionally, the histological lung injury score was calculated. Results: Comparing hours 0 and 6 in group A, there was a decrease of EELV/kg (27±2 vs. 16±1 ml/kg; p<0.05) and of Cstat (42±2 vs. 27±1 ml/cmH2O; p<0.05) and an increase of ΔP (11±0 vs. 17±1 cmH2O; p<0.05) and ΔPL (6±0 vs. 10±1 cmH2O; p<0.05). In group B, there was no significant change in EELV/kg (27±3 vs. 24±3 ml/kg), but a decrease in Cstat (42±3 vs. 32±1 ml/cmH20; p<0.05) and an increase in ΔP (11±1 vs. 15±1 cmH2O; p<0.05) and ΔPL (5±1 vs. 7±0 cmH2O; p<0.05). In group C, there were no significant changes in EELV/kg (27±2 vs. 29±3 ml/kg), ΔP (10±1 vs. 12±1 cmH2O) and ΔPL (5±1 vs. 7±1 cmH2O), but a significant decrease of Cstat (43±1 vs. 37±1 ml/cmH2O; p<0.05). Histological lung injury score was lowest in group B. Conclusions: A moderate elevated IAP of 10 mmHg leads to relevant changes in lung mechanics during mechanical ventilation. In our study, a PEEP of 10 cmH2O was associated with a lower lung injury score and was able to overcome the IAP induced alterations of EELV. [ABSTRACT FROM AUTHOR]

Background: The acute respiratory distress syndrome (ARDS) is characterized by pulmonary epithelial and endothelial barrier dysfunction and injury. In severe forms of ARDS, extracorporeal membrane oxygenation (ECMO) is often the last option for life support. Endothelial progenitor (EPC) and mesenchymal stem cells (MSC) can regenerate damaged endothelium and thereby improve pulmonary endothelial dysfunction. However, we still lack sufficient knowledge about how ECMO might affect EPC- and MSC-mediated regenerative pathways in ARDS. Therefore, we investigated if ECMO impacts EPC and MSC numbers in ARDS patients. Methods: Peripheral blood mononuclear cells from ARDS patients undergoing ECMO (n = 16) and without ECMO support (n = 12) and from healthy volunteers (n = 16) were isolated. The number and presence of circulating EPC and MSC was detected by flow cytometry. Serum concentrations of vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) were determined. Results: In the ECMO group, MSC subpopulations were higher by 71% compared to the non-ECMO group. Numbers of circulating EPC were not significantly altered. During ECMO, VEGF and Ang2 serum levels remained unchanged compared to the non-ECMO group (p = 0.16), but Ang2 serum levels in non-survivors of ARDS were significantly increased by 100% (p = 0.02) compared to survivors. Conclusions: ECMO support in ARDS is specifically associated with an increased number of circulating MSC, most likely due to enhanced mobilization, but not with a higher numbers of EPC or serum concentrations of VEGF and Ang2. [ABSTRACT FROM AUTHOR]

In recent years, extracorporeal hemadsorption (HA) techniques capable of adsorbing pro- and anti-inflammatory cytokines are increasingly used in various clinical situations. The therapeutic benefit of cytokine elimination likely depends on timing. Although treatment seems to be most effective when started within the first 24 h, therapy is often delayed as it must be combined with another extracorporeal circuit. Thus, using a pumpless extracorporeal HA technique might be a valuable option in order to expedite the commencement of cytokine elimination in critically ill patients. [ABSTRACT FROM AUTHOR]

Chronic stress is associated with hippocampal atrophy and cognitive dysfunction. This study investigates how long-lasting administration of corticosterone as a mimic of experimentally induced stress affects psychometric performance and the expression of the phosphatidylethanolamine binding protein (PEBP1) in the adult hippocampus of one-year-old male rats. Psychometric investigations were conducted in rats before and after corticosterone treatment using a holeboard test system. Rats were randomly attributed to 2 groups (n = 7) for daily subcutaneous injection of either 26.8 mg/kg body weight corticosterone or sesame oil (vehicle control). Treatment was continued for 60 days, followed by cognitive retesting in the holeboard system. For protein analysis, the hippocampal proteome was separated by 2D electrophoresis (2DE) followed by image processing, statistical analysis, protein identification via peptide mass fingerprinting and gel matching and subsequent functional network mapping and molecular pathway analysis. Differential expression of PEBP1 was additionally quantified by Western blot analysis. Results show that chronic corticosterone significantly decreased rat hippocampal PEBP1 expression and induced a working and reference memory dysfunction. From this, we derive the preliminary hypothesis that PEBP1 may be a novel molecular mediator influencing cognitive integrity during chronic corticosterone exposure in rat hippocampus. [ABSTRACT FROM AUTHOR]

Investigates the time course of possible alterations of both reflex and tonic control of heart rate (HR) in rats with myocardial infarction and only moderately impaired left ventricular function. Examination of whether the methods used to assess baroreflex sensitivity and heart rate variability in this study are suitable to estimate sympathetic and vagal tone.

Sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". One of the elements of dysregulated host response is an endocrine system disorder. Changes in its functioning in the course of sepsis affect almost all hormonal axes. In sepsis, a function disturbance of the hypothalamic–pituitary–adrenal axis has been described, in the range of which the most important seems to be hypercortisolemia in the acute phase. Imbalance in the hypothalamic–pituitary–thyroid axis is also described. The most typical manifestation is a triiodothyronine concentration decrease and reverse triiodothyronine concentration increase. In the somatotropic axis, a change in the secretion pattern of growth hormone and peripheral resistance to this hormone has been described. In the hypothalamic–pituitary–gonadal axis, the reduction in testosterone concentration in men and the stress-induced "hypothalamic amenorrhea" in women have been described. Catecholamine and β-adrenergic stimulation disorders have also been reported. Disorders in the endocrine system are part of the "dysregulated host response to infection". They may also affect other components of this dysregulated response, such as metabolism. Hormonal changes occurring in the course of sepsis require further research, not only in order to explore their potential significance in therapy, but also due to their promising prognostic value. [ABSTRACT FROM AUTHOR]

Infections with SARS-CoV-2 spread worldwide early in 2020. In previous winters, we had been treating patients with seasonal influenza. While creating a larger impact on the health care systems, comparisons regarding the intensive care unit (ICU) courses of both diseases are lacking. We compared patients with influenza and SARS-CoV-2 infections treated at a tertiary care facility offering treatment for acute respiratory distress syndrome (ARDS) and being a high-volume facility for extracorporeal membrane oxygenation (ECMO). Patients with COVID-19 during the first wave of the pandemic (n = 64) were compared to 64 patients with severe influenza from 2016 to 2020 at our ICU. All patients were treated using a standardized protocol. ECMO was used in cases of severe ARDS. Both groups had similar comorbidities. Time in ICU and mortality were not significantly different, yet mortality with ECMO was high amongst COVID-19 patients with approximately two-thirds not surviving. This is in contrast to a mortality of less than 40% in influenza patients with ECMO. Mortality was higher than estimated by SAPSII score on admission in both groups. Patients with COVID-19 were more likely to be male and non-smokers than those with influenza. The outcomes for patients with severe disease were similar. The study helps to understand similarities and differences between patients treated for severe influenza infections and COVID-19. [ABSTRACT FROM AUTHOR]

Vasoactive and inotropic medications are essential for sepsis management; however, the association between the maximum Vasoactive-Inotropic score (VISmax) and clinical outcomes is unknown in adult patients with sepsis. We investigated the VISmax as a predictor for mortality among such patients in the emergency department (ED) and compared its prognostic value with that of the sequential organ failure assessment (SOFA) score. This single-center retrospective study included 910 patients diagnosed with sepsis between January 2016 and March 2020. We calculated the VISmax using the highest doses of vasopressors and inotropes administered during the first 6 h on ED admission and categorized it as 0–5, 6–15, 16–30, 31–45, and >45 points. The primary outcome was 30-day mortality. VISmax for 30-day mortality was significantly higher in non-survivors than in survivors. The mortality rates in the five VISmax groups were 17.2%, 20.8%, 33.3%, 54.6%, and 70.0%, respectively. The optimal cut-off value of VISmax to predict 30-day mortality was 31. VISmax had better prognostic value than the cardiovascular component of the SOFA score and initial lactate levels. VISmax was comparable to the APACHE II score in predicting 30-day mortality. Multivariable analysis showed that VISmax 16–30, 31–45, and >45 were independent risk factors for 30-day mortality. VISmax in ED could help clinicians to identify sepsis patients with poor prognosis. [ABSTRACT FROM AUTHOR]

The effects of a moderately elevated intra-abdominal pressure (IAP) on lung mechanics in acute respiratory distress syndrome (ARDS) have still not been fully analyzed. Moreover, the optimal positive end-expiratory pressure (PEEP) in elevated IAP and ARDS is unclear. In this paper, 18 pigs under general anesthesia received a double hit lung injury. After saline lung lavage and 2 h of injurious mechanical ventilation to induce an acute lung injury (ALI), an intra-abdominal balloon was filled until an IAP of 10 mmHg was generated. Animals were randomly assigned to one of three groups (group A = PEEP 5, B = PEEP 10 and C = PEEP 15 cmH2O) and ventilated for 6 h. We measured end-expiratory lung volume (EELV) per kg bodyweight, driving pressure (ΔP), transpulmonary pressure (ΔPL), static lung compliance (Cstat), oxygenation (P/F ratio) and cardiac index (CI). In group A, we found increases in ΔP (22 ± 1 vs. 28 ± 2 cmH2O; p = 0.006) and ΔPL (16 ± 1 vs. 22 ± 2 cmH2O; p = 0.007), with no change in EELV/kg (15 ± 1 vs. 14 ± 1 mL/kg) when comparing hours 0 and 6. In group B, there was no change in ΔP (26 ± 2 vs. 25 ± 2 cmH2O), ΔPL (19 ± 2 vs. 18 ± 2 cmH2O), Cstat (21 ± 3 vs. 21 ± 2 cmH2O/mL) or EELV/kg (12 ± 2 vs. 13 ± 3 mL/kg). ΔP and ΔPL were significantly lower after 6 h when comparing between group C and A (21 ± 1 vs. 28 ± 2 cmH2O; p = 0.020) and (14 ± 1 vs. 22 ± 2 cmH2O; p = 0.013)). The EELV/kg increased over time in group C (13 ± 1 vs. 19 ± 2 mL/kg; p = 0.034). The P/F ratio increased in all groups over time. CI decreased in groups B and C. The global lung injury score did not significantly differ between groups (A: 0.25 ± 0.05, B: 0.21 ± 0.02, C: 0.22 ± 0.03). In this model of ALI, elevated IAP, ΔP and ΔPL increased further over time in the group with a PEEP of 5 cmH2O applied over 6 h. This was not the case in the groups with a PEEP of 10 and 15 cmH2O. Although ΔP and ΔPL were significantly lower after 6 hours in group C compared to group A, we could not show significant differences in histological lung injury score. [ABSTRACT FROM AUTHOR]

Background: The optimal level of positive end-expiratory pressure is still under debate. There are scare data examining the association of PEEP with transpulmonary pressure (TPP), end-expiratory lung volume (EELV) and intraabdominal pressure in ventilated patients with and without ARDS. Methods: We analyzed lung mechanics in 3 patient groups: group A, patients with ARDS; group B, obese patients (body mass index (BMI) > 30 kg/m2) and group C, a control group. Three levels of PEEP (5, 10, 15 cm H2O) were used to investigate the consequences for lung mechanics. Results: Fifty patients were included, 22 in group A, 18 in group B (BMI 38 ± 2 kg/m2) and 10 in group C. At baseline, oxygenation showed no differences between the groups. Driving pressure (ΔP) and transpulmonary pressure (ΔPL) was higher in group B than in groups A and C at a PEEP of 5 cm H2O (ΔP A: 15 ± 1, B: 18 ± 1, C: 14 ± 1 cm H2O; ΔPL A: 10 ± 1, B: 13 ± 1, C: 9 ± 0 cm H2O). Peak inspiratory pressure (Pinsp) rose in all groups as PEEP increased, but the resulting driving pressure and transpulmonary pressure were reduced, whereas EELV increased. Conclusion: Measuring EELV or TPP allows a personalized approach to lung-protective ventilation. [ABSTRACT FROM AUTHOR]

An automated system for pO2 analysis based upon phosphorescence quenching was tested. The system was calibrated in vitro with capillary samples of saline and blood. Results were compared to a conventional measuring procedure wherein pO2 was calculated off-line by computer fitting of phosphorescence decay signals. PO2 measurements obtained by the automated system were correlated (r2 = 0.98) with readings simultaneously generated by a blood gas analyzer, accuracy being highest in the low (0–20 mm Hg) and medium pO2 ranges (21–70 mm Hg). Measurements in in vivo studies in the hamster skin-fold preparation were similar to previously reported results. The automated system fits the phosphorescence decay data to a single exponential and allows repeated pO2 measurements in rapid sequence. [Copyright &y& Elsevier]

Objective: Mesenchymal stem cells (MSC) raise high hopes in clinical applications. However, the lack of common standards and a precise definition of MSC preparations remains a major obstacle in research and application of MSC. Whereas surface antigen markers have failed to precisely define this population, a combination of proteomic data and microarray data provides a new dimension for the definition of MSC preparations. Methods: In our continuing effort to characterize MSC, we have analyzed the differential transcriptome and proteome expression profiles of MSC preparations isolated from human bone marrow under two different expansion media (BM-MSC-M1 and BM-MSC-M2). Results: In proteomics, 136 protein spots were unambiguously identified by MALDI-TOF-MS and corresponding cDNA spots were selected on our “Human Transcriptome cDNA Microarray.” Combination of datasets revealed a correlation in differential gene expression and protein expression of BM-MSC-M1 vs BM-MSC-M2. Genes involved in metabolism were more highly expressed in BM-MSC-M1, whereas genes involved in development, morphogenesis, extracellular matrix, and differentiation were more highly expressed in BM-MSC-M2. Interchanging culture conditions for 8 days revealed that differential expression was retained in several genes whereas it was altered in others. Conclusion: Our results have provided evidence that homogeneous BM-MSC preparations can reproducibly be isolated under standardized conditions, whereas culture conditions exert a prominent impact on transcriptome, proteome, and cellular organization of BM-MSC. [Copyright &y& Elsevier]

Background: Prolonged invasive mechanical ventilation (IMV) influences patient outcome in multiple ways. In this regard the early weaning from IMV is a major goal to be achieved in the treatment of ICU patients. Adopting a weaning protocol that incorporates a Spontaneous Awakening Trial (SAT) and a Spontaneous Breathing Trial (SBT) seems to be essential to reach this goal. Most studies investigating the effectiveness of SAT/SBT protocols in ICU patients' outcomes have focused mainly on medical or mixed (medical and surgical), but not on exclusively surgical patient populations. Surgical patients usually experience more complications and often undergo revision surgeries, therefore needing longer sedation periods and adequate analgo-sedation therapy. Moreover, the longer IMV times make the weaning process more arduous., Methods: Our retrospective data analysis therefore investigates the effectiveness of a SAT/SBT protocol implementation in the surgical ICU of Heidelberg University Hospital, focusing exclusively on surgical patients and their outcome related to the weaning process. The SAT/SBT protocol was adopted in Heidelberg ICU starting from 05/2019. We therefore analyzed the time period before and after the implementation between 03/2018 and 08/2020. Adult patients who required invasive ventilation for at least 48 hours were screened for study entry. Demographic data, clinical data and SOFA Score on admission, were collected to define the baseline characteristics of the two groups. Only patients with full adherence to the protocol were included. The primary outcome was defined as the successful extubation, intended as an extubation not followed by successive re-intubations until discharge from the ICU. We performed an univariate analysis to evaluate the rate of successful extubations between the two groups., Results: In total, 199 patients were included in the analysis, 98 of which before the SAT/SBT protocol implementation (control group) and 101 after the SAT/SBT protocol implementation (intervention group). The successful extubation rate in the intervention group resulted in 82% (83/101 patients) compared to 64% (63/98 patients) in the control group (P<0.004)., Conclusions: We conclude that even for an exclusively surgical patient population, the implementation of a SAT/SBT protocol could result in a higher rate of successful extubation.

This correspondence argues that data presented previously cannot justify a novel approach for treating hypoxic patients with severe #COVID19 https://bit.ly/3dLaPlk., Competing Interests: Conflict of interest: A. Supady reports a research grant from CytoSorbents to his institution, and lecture fees from CytoSorbents and Abiomed, not related to this work. Conflict of interest: P.M. Lepper has nothing to disclose. Conflict of interest: H. Bracht has nothing to disclose. Conflict of interest: O. Moerer has nothing to disclose. Conflict of interest: R.M. Muellenbach has nothing to disclose. Conflict of interest: G. Michels has nothing to disclose. Conflict of interest: M.O. Fiedler reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from GE and Löwenstein; and support for attending meetings and/or travel from Löwenstein. Conflict of interest: A. Kalenka has nothing to disclose. Conflict of interest: M. Kochanek has nothing to disclose. Conflict of interest: H. Mutlak has nothing to disclose. Conflict of interest: G. Danziger has nothing to disclose. Conflict of interest: S. Muenz has nothing to disclose. Conflict of interest: D. Lunz has nothing to disclose. Conflict of interest: S. Hoersch has nothing to disclose. Conflict of interest: D. Staudacher has nothing to disclose. Conflict of interest: T. Wengenmayer has nothing to disclose. Conflict of interest: V. Zotzmann has nothing to disclose., (Copyright ©The authors 2021.)

Extracorporeal life support (ECLS) is a means to support patients with acute respiratory failure. Initially, recommendations to treat severe cases of pandemic coronavirus disease 2019 (COVID-19) with ECLS have been restrained. In the meantime, ECLS has been shown to produce similar outcomes in patients with severe COVID-19 compared to existing data on ARDS mortality. We performed an international email survey to assess how ECLS providers worldwide have previously used ECLS during the treatment of critically ill patients with COVID-19. A questionnaire with 45 questions (covering, e.g., indication, technical aspects, benefit, and reasons for treatment discontinuation), mostly multiple choice, was distributed by email to ECLS centers. The survey was approved by the European branch of the Extracorporeal Life Support Organization (ELSO); 276 ECMO professionals from 98 centers in 30 different countries on four continents reported that they employed ECMO for very severe COVID-19 cases, mostly in veno-venous configuration (87%). The most common reason to establish ECLS was isolated hypoxemic respiratory failure (50%), followed by a combination of hypoxemia and hypercapnia (39%). Only a small fraction of patients required veno-arterial cannulation due to heart failure (3%). Time on ECLS varied between less than 2 and more than 4 weeks. The main reason to discontinue ECLS treatment prior to patient's recovery was lack of clinical improvement (53%), followed by major bleeding, mostly intracranially (13%). Only 4% of respondents reported that triage situations, lack of staff or lack of oxygenators, were responsible for discontinuation of ECLS support. Most ECLS physicians (51%, IQR 30%) agreed that patients with COVID-19-induced ARDS (CARDS) benefitted from ECLS. Overall mortality of COVID-19 patients on ECLS was estimated to be about 55%. ECLS has been utilized successfully during the COVID-19 pandemic to stabilize CARDS patients in hypoxemic or hypercapnic lung failure. Age and multimorbidity limited the use of ECLS. Triage situations were rarely a concern. ECLS providers stated that patients with severe COVID-19 benefitted from ECLS., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Background and objectives: The laryngeal mask is the method of choice for airway management in children during minor surgical procedures. There is a paucity of data regarding optimal management of mechanical ventilation in these patients. The Supreme™ airway laryngeal mask offers the option to insert a gastric tube to empty the stomach contents of air and/or gastric juice. The aim of this investigation was to evaluate the impact of positive end-expiratory positive pressure (PEEP) levels on ventilation parameters and gastric air insufflation during general anesthesia in children using pressure-controlled ventilation with laryngeal mask. Materials and Methods: An observational trial was carried out in 67 children aged between 1 and 11 years. PEEP levels of 0, 3 and 5 mbar were tested for 5 min in each patient during surgery and compared with ventilation parameters (dynamic compliance (mL/cmH 2 O), etCO 2 (mmHg), peak pressure (mbar), tidal volume (mL), respiratory rate (per minute), FiO 2 and gastric air (mL)) were measured at each PEEP. Air was aspirated from the stomach at the start of the sequence of measurements and at the end. Results : Significant differences were observed for the ventilation parameters: dynamic compliance (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001), peak pressure (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001) and tidal volume (PEEP 5 vs. PEEP 3: p = 0.0048, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001). All parameters increased significantly with higher PEEP, with the exception of etCO 2 (significant decrease) and respiratory rate (no significant difference). We also showed different values for air quantity in the comparisons between the different PEEP levels (PEEP 5: 2.8 ± 3.9 mL, PEEP 3: 1.8 ± 3.0 mL; PEEP 0: 1.6 ± 2.3 mL) with significant differences between PEEP 5 and PEEP 3 ( p = 0.0269) and PEEP 5 and PEEP 0 ( p = 0.0209). Conclusions : Our data suggest that ventilation with a PEEP of 5 mbar might be more lung protective in children using the Supreme™ airway laryngeal mask, although gastric air insufflation increased with higher PEEP. We recommend the use of a laryngeal mask with the option of inserting a gastric tube to evacuate potential gastric air.

Background: During the H1N1 pandemic of 2009 and 2010, the large number of patients with severe respiratory failure due to H1N1 infection strained the capacities of treatment facilities for extracorporeal membrane oxygenation (ECMO) around the world. No data on this topic have yet been published for Germany., Methods: During the pandemic, the German ARDS Network (a task force of the DIVI's respiratory failure section) kept track of the availability of ECMO treatment facilities with a day-to-day, Internet-based capacity assessment. In cooperation with the Robert Koch Institute, epidemiological and clinical data were obtained on all patients treated for influenza in intensive care units., Results: 116 patients were identified who had H1N1 disease and were treated in the intensive care units of 9 university hospitals and 3 other maximum medical care hospitals. 61 of them received ECMO. The overall mortality was 38% (44 of 116 patients); among patients receiving ECMO, the mortality was 54% (33 of 61 patients). The mortality was higher among patients who had an accompanying malignancy or immune deficiency (72.2%)., Conclusion: Even persons without any other accompanying disease developed life-threatening respiratory failure as a result of H1N1 infection, and many of these patients needed ECMO. This study reveals for the first time that the mortality of H1N1 infection in Germany is comparable to that in other countries. H1N1 patients with acute respiratory failure had a worse outcome if they also had serious accompanying diseases.

Background: A certain correlation between unfavorable clinical outcome, incidence of vasospasm, and impaired pressure autoregulation in patients following aneurysmal subarachnoid hemorrhage (aSAH) has been suggested. However, determination of vasospasm is inaccurate and the measurement technique of cerebral vasoreactivity seems not to have been sufficiently validated. Therefore, a correlation of clinical outcome and the extent of angiographic VS was performed using an established autoregulation test., Material and Methods: Proximal and global angiographic vasospasm (pVS, gVS) were determined in bilateral M1 segments. Dynamic tests of pressure autoregulation were performed 1 day before and after, and on the day of angiography using Aaslid's thigh leg cuff test. Patient outcome was assessed using the Extended Glasgow Outcome Scale (GOSE)., Key Results: Complete datasets were available for 22 patients. Mean autoregulatory indices (ARI) around the day of angiography were 3.9 ± 2.3. Proximal mean reduction of vessel diameter was -23.3% ± 9.1%. Global vasospasm was not present in 10 hemispheres, mild in 15, moderate in 15, and severe in 4. Hemispheric ARI values and angiographic data showed a significant correlation (pVS -0.382, p = 0.015; gVS -0.477, p = 0.002). The degree of angiographic vasospasm and low ARI values correlated significantly with an unfavorable outcome (0.677, p = 0.001)., Conclusion: Incidence of angiographic vasospasm and impaired clinical outcome seems to be related to impaired pressure autoregulation following aSAH.

Postoperative cognitive dysfunction (POCD) is a known phenomenon occurring after anesthesia with volatile anesthetics (VA), such as isoflurane. Recent reports suggest that VA interact with neurodegenerative disease-associated proteins including compounds with pathogenic relevance in Alzheimer disease (AD) and induce processes that may be linked to AD neuropathology. Unfortunately, our present understanding of the exact anesthetics' molecular mechanisms of action, their side effects on the brain, and their catenation with AD pathology is still limited. The present study analyzes the differential proteome of the hippocampus immediately after and 3 days after a 3-hour 1 minimal alveolar concentration isoflurane anesthesia in rats. Differential 2-dimensional electrophoresis, mass spectrometry, and functional network mapping were used to identify and functionally classify 12 different hippocampal proteins, which were significantly regulated after isoflurane anesthesia (6 up-regulated, 11 down-regulated with P<0.01). Induction of differential expression ranged from 0.05 (25-fold down-regulation) to 4.4 (4.4-fold up-regulation). Ten proteins were regulated immediately after and 7 proteins 3 days after isoflurane exposure. The proteome displays isoflurane-responsive protein candidates, which have also been shown to play a role in AD. They were grouped according to their key biologic activities, which showed that isoflurane affects selected biologic processes including synaptic plasticity, stress response, detoxification, and cytoskeleton in early and late recovery phases after anesthesia. These processes are also affected in AD. Results are discussed in view of AD, the toxicity mechanisms of isoflurane as well as the implications for our present understanding and conduction of clinical anesthesia.

During the course of sepsis, heart and liver dysfunction occurs in 20-30 % of patients. Both septic cardiomyopathy and septic liver dysfunction have a high mortality and the underlying molecular pathophysiology remains unclear. The present study investigated changes in both cardiac and liver protein expression after cecal ligature and puncture (CLP) in a model of rat sepsis during a post-induction time course of 12, 24, and 48 hours. After approval by the local institutional review board, 62 male Wistar rats were investigated and assigned to three sham groups (n=16) and three sepsis groups (n=46). Rats of the sepsis groups and control groups were analyzed at specific time points after sepsis induction. Sepsis was induced by CLP and both heart and liver were removed after decapitation and prepared for proteomics. 2D-gel electrophoresis (2D-GE) and mass spectrometry (MS) as well as bioinformatic network pathway analysis (Ingenuity Pathways Analysis, IPA) were used to identify changes in protein expression between septic and non-septic samples. N=27 rats of the sepsis group died (mortality 59 %) and no rat of the sham group died. More than 1,100 proteins could be discriminated with the proteomic method in both organs, of which 12 and 13 proteins were significantly regulated in heart and liver, respectively. 82 % of the cardiac proteins could be associated with mitochondrial function. Both heart and liver proteins were primarily down-regulated in the course of sepsis. IPA associated the sets of differentially regulated proteins with proteins of heart and liver with compromised energy production. Sepsis induced significant alterations in the cardiac and liver proteome at 12, 24, and 48 hours after sepsis induction. Differentially regulated proteins of both organs mainly play a role in energy production. The diverse protein regulation indicates metabolic derangement and severely compromised cellular energy production following sepsis. Here, protein alterations may reflect septic organ dysfunction.

Objectives: Despite a decreased mortality from sepsis, the absolute number of sepsis-related deaths has actually increased during the last years. At present, there are no biological markers available that can reliably assist early clinical diagnosis and the prompt initiation of therapy. This study investigated the changes in serum protein expression in a coecal ligature and puncture model of rat sepsis at 12, 24, and 48 hours after the induction of sepsis using differential proteomics., Methods: Sixty-two male Wistar rats were randomly assigned to a sepsis group (coecal ligature and puncture; n = 46) or a sham group (n = 16). Surviving rats were killed 12 hour (n = 6), 24 hour (n = 9), or 48 hour (n = 4) after operation, and their serum lysates were subjected to two-dimensional gel electrophoresis and peptide mass fingerprinting. A systematic functional network mapping and molecular pathway analysis were performed using Ingenuity Pathways Analysis., Results: Septic mortality was 58.7%, but no rat of the sham group was lost. Per gel, an average of 1,082 +/- 10 spots could be discriminated, of which 40 different protein spots were differentially expressed (p < 0.01). From the total of 40, the number of regulated protein spots was 13 (12 hour group) versus 10 (24 hour group) versus 18 (48 hour group). Ingenuity pathways analysis identified 10 of the differential proteins and allocated them to a pathway of tissue inflammation., Conclusions: The present study quantitatively detected several proteins differentially expressed in acute sepsis. Since a longer time-period was investigated and compared with previous studies, the results may offer new insights into septic organ dysfunction and altered protein pathways. The horizontal analysis of protein expression arrays and systematic biochemical pathways may represent an important new tool for the clinical assessment of septic conditions and support the development of early sepsis markers.

Chronic stress is associated with hippocampal atrophy and cognitive dysfunction. This study investigates how long-lasting administration of corticosterone as a mimic of experimentally induced stress affects psychometric performance and the expression of the phosphatidylethanolamine binding protein (PEBP1) in the adult hippocampus of one-year-old male rats. Psychometric investigations were conducted in rats before and after corticosterone treatment using a holeboard test system. Rats were randomly attributed to 2 groups (n = 7) for daily subcutaneous injection of either 26.8 mg/kg body weight corticosterone or sesame oil (vehicle control). Treatment was continued for 60 days, followed by cognitive retesting in the holeboard system. For protein analysis, the hippocampal proteome was separated by 2D electrophoresis (2DE) followed by image processing, statistical analysis, protein identification via peptide mass fingerprinting and gel matching and subsequent functional network mapping and molecular pathway analysis. Differential expression of PEBP1 was additionally quantified by Western blot analysis. Results show that chronic corticosterone significantly decreased rat hippocampal PEBP1 expression and induced a working and reference memory dysfunction. From this, we derive the preliminary hypothesis that PEBP1 may be a novel molecular mediator influencing cognitive integrity during chronic corticosterone exposure in rat hippocampus.

Background: Recent studies showed changes in cerebral protein expression up to 3 days after desflurane anesthesia in rats. In the present study, we investigated the existence of persisting changes on the proteome level after sevoflurane anesthesia that persisted for as long as 28 days after anesthesia., Methods: Rats were anesthetized by spontaneous inhalation of 2.4% sevoflurane in air for 3 h. Animals (n = 6 for each group) were killed either directly, 72 h, or 28 days after anesthesia. Brains were removed and subjected to global protein expression profiling based on two-dimensional gel electrophoresis and mass spectrometry. Expression factors were compared to results from untreated conscious animals at each time point. Data were statistically analyzed by ANOVA (P < 0.01) and a cut of more than two-fold change in the expression factor., Results: We found 11 protein spots differentially regulated directly after anesthesia. Seventeen proteins were differentially expressed 72 h after the anesthesia. Only one spot was differentially regulated 28 days after anesthesia. The plausible targets of these differentially regulated proteins can be attributed to synaptic vesicle handling and cell-cell communication., Conclusions: Sevoflurane induced relevant changes in protein expression profiles directly and 72 h after an anesthesia with 1 MAC. Twenty-eight days after the anesthesia, all proteins except one had returned to baseline levels of abundance.

Background: Sepsis is still the leading cause of death in the intensive care unit. Our goal was to elucidate potential early differences in serum between survivors (SURV) and non-survivors (NON-SURV) on day 28., Methods: We applied proteomic technology to serum samples of patients with sepsis and septic shock. Serum samples from 18 patients with sepsis and septic shock were obtained during the first 12 h after diagnosis of septic shock. Patients were grouped into SURV and NON-SURV on day 28., Results: Seven patients survived and 11 patients died. Using proteome analysis, two-dimensional gel electrophoresis detected more than 200 spots per gel. A differential protein expression was discovered between SURV and NON-SURV, whereby protein alterations not yet described in sepsis were revealed., Conclusions: Our results show that proteomic profiling is a useful approach for detecting protein expression dynamics in septic patients, and may bring us closer to achieving a comprehensive molecular profiling compared with genetic studies alone.

Multipotent mesenchymal stem cells (MSCs) derived from human umbilical cord blood (UCB) represent promising candidates for the development of future strategies in cellular therapy. To create a comprehensive protein expression profile for UCB-MSCs, one UCB unit from a full-term delivery was isolated from the unborn placenta, transferred into culture, and their whole-cell protein fraction was subjected to two-dimensional electrophoresis (2-DE). Unambiguous protein identification was achieved with peptide mass fingerprinting matrix-assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS), peptide sequencing (MALDI LIFT-TOF/TOF MS), as well as gel-matching with previously identified databases. In overall five replicate 2-DE runs, a total of 2037 +/- 437 protein spots were detected of which 205 were identified representing 145 different proteins and 60 isoforms or post-translational modifications. The identified proteins could be grouped into several functional categories, such as metabolism, folding, cytoskeleton, transcription, signal transduction, protein degradation, detoxification, vesicle/protein transport, cell cycle regulation, apoptosis, and calcium homeostasis. The acquired proteome map of nondifferentiated UCB-MSCs is a useful inventory which facilitates the identification of the normal proteomic pattern as well as its changes due to activated or suppressed pathways of cytosolic signal transduction which occur during proliferation, differentiation, or other experimental conditions.