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We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

Electrical impedance tomography (EIT) is a bedside monitoring tool that noninvasively visualizes local ventilation and arguably lung perfusion distribution. This article reviews and discusses both methodological and clinical aspects of thoracic EIT. Initially, investigators addressed the validation of EIT to measure regional ventilation. Current studies focus mainly on its clinical applications to quantify lung collapse, tidal recruitment, and lung overdistension to titrate positive end-expiratory pressure (PEEP) and tidal volume. In addition, EIT may help to detect pneumothorax. Recent studies evaluated EIT as a tool to measure regional lung perfusion. Indicator-free EIT measurements might be sufficient to continuously measure cardiac stroke volume. The use of a contrast agent such as saline might be required to assess regional lung perfusion. As a result, EIT-based monitoring of regional ventilation and lung perfusion may visualize local ventilation and perfusion matching, which can be helpful in the treatment of patients with acute respiratory distress syndrome (ARDS).

Introduction Percutaneous dilatational tracheostomy (PDT) is one of the most frequent procedures performed in the intensive care unit (ICU). PDT may add potential benefit to clinical management of critically ill patients. Despite this, no clinical guidelines are available. We sought to characterize current practice in this international survey. Methods An international survey, endorsed and peer reviewed by European Society of Intensive Care Medicine (ESICM), was carried out from May to October 2013. The questionnaire was accessible from the ESICM website in the ‘survey of the month’ section. Results 429 physicians from 59 countries responded to this survey. Single step dilatational tracheostomy was the most used PDT in ICU. Almost 75 % of PDT’s were performed by intensive care physicians. The main indication for PDT was prolonged mechanical ventilation. Tracheostomies were most frequently performed between 7–15 days after ICU admission. Volume control mechanical ventilation, and a combination of sedation, analgesia, neuromuscular blocking agents and fiberoptic bronchoscopy were used. Surgical tracheostomy was mainly performed in ICU by ENT specialists, and was generally chosen when for patients at increased risk for difficult PDT insertion. Bleeding controlled by compression and stoma infection/inflammation were the most common intra-procedural and late complications, respectively. Informed consent for PDT was obtained in only 60 % of cases. Conclusions This first international picture of current practices in regard to tracheostomy insertion demonstrates considerable geographic variation in practice, suggesting a need for greater standardization of approaches to tracheostomy insertion.

Objectives The objective of this preliminary study was to explore long-term changes in neurobehavioral parameters, brain morphology and electroencephalography of sepsis patients who received intensive care compared to non-septic intensive care unit (ICU) patients. Methods Two-centre follow-up study 6–24 months after discharge from hospital using published norms and existing databases of healthy controls for comparison. Patients included 25 septic and 19 non-septic ICU survivors who were recruited from two ICUs of a university and community hospital. Measurements used include brain morphology, standard electroencephalography, cognition and psychiatric health and health-related quality of life. Results Sepsis survivors showed cognitive deficits in verbal learning and memory and had a significant reduction of left hippocampal volume compared to healthy controls. Moreover, sepsis and to some extent non-septic ICU patients had more low-frequency activity in the EEG indicating unspecific brain dysfunction. No differences were found in health-related quality of life, psychological functioning or depressive symptoms, and depression could be ruled out as a confounding factor. Conclusions This study demonstrates permanent cognitive impairment in several domains in both septic and non-septic ICU survivors and unspecific brain dysfunction. In the sepsis group, left-sided hippocampal atrophy was found compared to healthy controls. Further study is needed to clarify what contribution sepsis and other factors at the ICU make to these outcomes. Specific neuroprotective therapies are warranted to prevent persisting brain changes in ICU patients.

Background Extracorporeal membrane oxygenation (ECMO) support in acute respiratory failure may be lifesaving, but bleeding and thromboembolic complications are common. The optimal anticoagulation strategy balancing these factors remains to be determined. This retrospective study compared two institutional anticoagulation management strategies focussing on oxygenator changes and both bleeding and thromboembolic events. Methods We conducted a retrospective observational cohort study between 04/2015 and 02/2020 in two ECMO referral centres in Germany in patients receiving veno-venous (VV)-ECMO support for acute respiratory failure for > 24 h. One centre routinely applied low-dose heparinization aiming for a partial thromboplastin time (PTT) of 35–40 s and the other routinely used a high-dose therapeutic heparinization strategy aiming for an activated clotting time (ACT) of 140–180 s. We assessed number of and time to ECMO oxygenator changes, 15-day freedom from oxygenator change, major bleeding events, thromboembolic events, 30-day ICU mortality, activated clotting time and partial thromboplastin time and administration of blood products. Primary outcome was the occurrence of oxygenator changes depending on heparinization strategy; main secondary outcomes were the occurrence of severe bleeding events and occurrence of thromboembolic events. The transfusion strategy was more liberal in the low-dose centre. Results Of 375 screened patients receiving VV-ECMO support, 218 were included in the analysis (117 high-dose group; 101 low-dose group). Disease severity measured by SAPS II score was 46 (IQR 36–57) versus 47 (IQR 37–55) and ECMO runtime was 8 (IQR 5–12) versus 11 (IQR 7–17) days ( P  = 0.003). There were 14 oxygenator changes in the high-dose group versus 48 in the low-dose group. Freedom from oxygenator change at 15 days was 73% versus 55% (adjusted HR 3.34 [95% confidence interval 1.2–9.4]; P  = 0.023). Severe bleeding events occurred in 23 (19.7%) versus 14 (13.9%) patients ( P  = 0.256) and thromboembolic events occurred in 8 (6.8%) versus 19 (19%) patients ( P  = 0.007). Mortality at 30 days was 33.3% versus 30.7% ( P  = 0.11). Conclusions In this retrospective study, ECMO management with high-dose heparinization was associated with lower rates of oxygenator changes and thromboembolic events when compared to a low-dose heparinization strategy. Prospective, randomized trials are needed to determine the optimal anticoagulation strategy in patients receiving ECMO support.

Background Recently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy. Methods In the original RCT, patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here, we report all clinical and biological endpoints of this study. Multivariate mixed-effects modeling of NE reduction was performed to investigate characteristics that could be associated with clinical response to TPE. Results A continuous effect of TPE on the reduction in NE doses over the initial 24 h was observed (SOC group: estimated NE dose reduction of 0.005 µg/kg/min per hour; TPE group: 0.018 µg/kg/min per hour, p  = 0.004). Similarly, under TPE, serum lactate levels, continuously decreased over the initial 24 h in the TPE group, whereas lactate levels increased under SOC ( p  = 0.001). A reduction in biomarkers and disease mediators (such as PCT ( p  = 0.037), vWF:Ag ( p  < 0.001), Angpt-2 ( p  = 0.009), sTie-2 ( p  = 0.005)) along with a repletion of exhausted protective factors (such as AT-III ( p  = 0.026), Protein C ( p  = 0.012), ADAMTS-13 ( p  = 0.008)) could be observed in the TPE but not in the SOC group. In a multivariate mixed effects model, increasing baseline lactate levels led to greater NE dose reduction effects with TPE as opposed to SOC ( p  = 0.004). Conclusions Adjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. We identified that baseline lactate concentration as a potential response predictor might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints. Trial registration  Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994 ).

Background Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. Methods A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. Results 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict “survival”. Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients’ age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. Conclusions Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration “ClinicalTrials” (clinicaltrials.gov) under NCT04455451.

Background Despite international guidelines for lung protective ventilation in neonatal or pediatric acute respiratory distress syndrome (nARDS/ pARDS), prospective data on bedside monitoring tools for regional ventilation distribution and lung mechanics are still rare. As a bedside and radiation-free procedure, electrical impedance tomography (EIT) offers a practical and safe approach for analyzing regional ventilation distributions. Recent trials in adults have shown the efficacy of an individualized EIT guided strategy for the improvement of ventilator induced lung injury (VILI). Methods We performed a single-center prospective feasibility study from November/2021 to December/2023 in the department of neonatal and pediatric intensive care medicine at the University Children´s Hospital in Bonn. All patients with diagnosis of nARDS (or history of perinatal lung disease-PLD)/ pARDS were screened for study inclusion. In all patients a decremental PEEP (positive end-expiratory pressure) trial was performed with a continuous EIT monitoring for an individual analysis of the EIT guided pixel compliance (C EIT ) and PEEP finding (EIT-PEEP). In the offline analysis, further EIT derived indices, such as global inhomogeneity index (GI), and center of ventilation (CoV), were calculated. Results Overall, 40 EIT measurements were performed in 26 neonatal and pediatric patients (nARDS/PLD, n  = 6; and pARDS, n  = 20) within a predefined decremental PEEP trial. Thirteen patients were classified as having severe nARDS (PLD)/ pARDS with an Oxygen Saturation Index (OSI) > 12 or Oxygenation Index (OI) > 16. In-hospital mortality rate was 27% in the overall cohort. The median EIT-PEEP (11mbar) was calculated as lowest, as compared to the clinically set PEEP (11.5mbar, p  < 0.001), and the ARDSnetwork PEEP table recommendation (ARDSnet-PEEP, 14mbar, p  = 0.018). In patients with nARDS/PLD, the EIT-PEEP was calculated 3mbar below the clinically set PEEP ( p  = 0.058) and 11 mbar below the ARDSnet-PEEP ( p  = 0.01). In the linear regression analysis, EIT-PEEP and the dynamic compliance (C DYN ) at -2mbar presented a significant correlation with a Cohen´s R 2 of 0.265 (β: 0.886, p  = 0.005). Conclusion EIT is feasible and can be performed safely in patients with diagnosis of nARDS/PLD and pARDS, even during ongoing extracorporeal membrane oxygenation (ECMO) support. An individualized PEEP finding strategy according to the EIT compliance might optimize regional ventilation distribution in these patients and can potentially decrease VILI. Clinical trial registration The study was registered at the German Clinical Trials Register (GCT; trial number: DRKS 00034905, Registration Date 15.08.2024). The registration was performed retrospectively after inclusion of the last patient.

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. PaO 2 /FiO 2 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. Trial registration Registered in the German Clinical Trials Register (study ID: DRKS00022964, retrospectively registered, September 7th 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022964 . Graphical abstract