Pumpless Extracorporeal Hemadsorption Technique (pEHAT) : A Proof-of-Concept Animal Study

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

Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion

IL-1β requires processing by caspase-1 to generate the active, pro-inflammatory cytokine. Acute IL-1β secretion from inflammasome-activated macrophages requires caspase-1-dependent GSDMD cleavage, which also induces pyroptosis. Mechanisms of IL-1β secretion by pyroptotic and non-pyroptotic cells, and the precise functions of caspase-1 and GSDMD therein, are unresolved. Here, we show that, while efficient early secretion of endogenous IL-1β from primary non-pyroptotic myeloid cells in vitro requires GSDMD, later IL-1β release in vitro and in vivo proceeds independently of GSDMD. IL-1β maturation is sufficient for slow, caspase-1/GSDMD-independent secretion of ectopic IL-1β from resting, non-pyroptotic macrophages, but the speed of IL-1β release is boosted by inflammasome activation, via caspase-1 and GSDMD. IL-1β cleavage induces IL-1β enrichment at PIP2-enriched plasma membrane ruffles, and this is a prerequisite for IL-1β secretion and is mediated by a polybasic motif within the cytokine. We thus reveal a mechanism in which maturation-induced IL-1β trafficking facilitates its unconventional secretion

Characteristics and provision of care of patients with the acute respiratory distress syndrome: descriptive findings from the DACAPO cohort baseline and comparison with international findings: a cross-sectional study

Background: Little is known about the characteristics and real world life circumstances of ARDS (acute respiratory distress syndrome) patient populations. This knowledge is essential for transferring evidence-based therapy into routine healthcare. The aim of this study was to report socio-demographic and clinical characteristics in an unselected population of ARDS patients and to compare these results to findings from other large ARDS cohorts. Methods: A German based cross-sectional observational study was carried out. A total of 700 ARDS patients were recruited in 59 study sites between September 2014 and January 2016. Socio-demographic, disease and care related variables were recorded. Additionally, characteristics of other large ARDS cohorts identified by a systematic literature search were extracted into evidence tables. Results: Median age of ARDS patients was 58 years, 69% were male. Sixty percent had no employment, predominantly due to retirement. Seventy-one percent lived with a partner. The main cause of ARDS was a pulmonary 'direct' origin (79%). The distribution of severity was as follows: mild (14%), moderate (48%), severe (38%). Overall ICU mortality was calculated to be 34%. The observed prevalence of critical events (hypoxemia, hypoglycemia, re-intubation) was 47%. Supportive measures during ICU-treatment were applied to 60% of the patients. Other ARDS cohorts revealed a high heterogeneity in reported concomitant diseases, but sepsis and pneumonia were most frequently reported. Mean age ranged from 54 to 71 years and most patients were male. Other socio-demographic factors have been almost neglected. Conclusions: The proportion of patients suffering of mild ARDS was lower compared to the only study identified, which also applied the Berlin definition. The frequency of critical events during ICU treatment was high and the implementation of evidence-based therapy (prone positioning, neuro-muscular blockers) was limited. More evidence on socio-demographic characteristics and further studies applying the current diagnostic criteria are desirable

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

Der Stellenwert von Midazolam als Komponente in einem modernen Sedierungskonzept von postoperativ nachbeatmeten, allgemeinchirurgischen Patienten

Hintergrund. Die in der Intensivmedizin häufig angewendete analgetische und sedative Therapie ist assoziiert mit einer Immobilisation des Patienten, einer erhöhten Morbidität, einer verlängerten Beatmungszeit, einer verlängerten Krankenhausverweildauer und erhöhten Krankheitskosten. Die meisten Sedierungsprotokolle basieren auf der Verwendung von Benzodiazepinen mit einer mittleren oder langen Halbwertszeit, welche ein zügiges Weaning verhindern. Das Ziel unserer Studie ist, ein alternatives, Benzodiazepin-freies Sedierungsprotokoll zu entwerfen. Material und Methoden. Im Jahr 2008 wurden 134 Patienten mittels eines konventionellen Sedierungsprotokolls unter Verwendung von Benzodiazepinen und Propofol behandelt (Kohorte2008>72+). Im Jahr 2009 haben wir eine neue Sedierungsstrategie eingeführt, welche auf der Verwendung von Sufentanil, nichtsteroidalen Antirheumatika, Neuroleptika und Antidepressiva beruht. Diese wurde an 140 Patienten angewandt (Kohorte2009>72-). Die Phase in tiefer Sedierung, die Dauer der maschinellen Beatmung, sowie die Verweildauer auf Intensivstation und im Krankenhaus wurden retrospektiv analysiert. Die statistischen Berechnungen wurden unter Anwendung des Log-Rank-Tests und des Wald-Chi-Quadrat-Tests auf Signifikanz überprüft. Ergebnisse. Kohorte2008>72+ zeigt im Vergleich zur Kohorte2009>72- sowohl eine längere Phase in tiefer Sedierung (18,7±2,5 Tage vs 12,6±1,85 Tage, p=0,031) als auch eine längere, kontrollierte Beatmungsdauer (311,35±32,69 vs 143,96±20,76 Stunden, p<0,0001). Des Weiteren tendiert Kohorte2008 auch zu einer längeren, insgesamten Beatmungsphase als Kohorte2009 (653,66±98,37 Stunden vs 478,89±68,92 Stunden, p=0,128). Die mittlere Verweildauer auf Intensivstation lag im Jahr 2008 bei 35,30±4,26 Tagen und im Jahr 2009 bei 33,24±2,93 Tagen (n.s.). Die mittlere Krankenhausverweildauer betrug in Kohorte2008 57,0±9,8 Tage und in Kohorte2009 64,3±8,1 Tage (n.s.). Schlussfolgerung. Ein Benzodiazepin-freies Sedierungsprotokoll verkürzt sowohl die Phase der tiefen Sedierung als auch die Dauer der kontrollierten Beatmung. Es werden jedoch größer angelegte Studien benötigt, um zu untersuchen, ob dieses neue Protokoll auch die Beatmungstage insgesamt signifikant reduzieren kann