Prevalence and Risk Factors for Weaning Failure From Venovenous Extracorporeal Membrane Oxygenation in Patients With Severe Acute Respiratory Insufficiency.

OBJECTIVE: Analysis of the prevalence and risk factors for weaning failure from venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with severe acute respiratory insufficiency. DESIGN: Single-center retrospective observational study. SETTING: Sixteen beds medical ICU at the University Hospital Regensburg. PATIENTS: Two hundred twenty-seven patients with severe acute respiratory insufficiency requiring VV-ECMO support between October 2011 and December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients meeting our ECMO weaning criteria (Sp o2 ≥ 90% with F io2 ≤ 0.4 or Pa o2 /F io2 > 150 mm Hg, pH = 7.35-7.45, positive end-expiratory pressure ≤ 10 cm H 2 O, driving pressure < 15 cm H 2 O, respiratory rate < 30/min, tidal volume > 5 mL/kg, ECMO bloodflow ≈ 1. 5 L/min, sweep gas flow ≈ 1 L/min, heart rate < 120/min, systolic blood pressure 90-160 mm Hg, norepinephrine < 0.2 µg/[kg*min]) underwent an ECMO weaning trial (EWT) with pausing sweep gas flow. Arterial blood gas analysis, respiratory and ventilator parameters were recorded prior, during, and after EWTs. Baseline data, including demographics, vitals, respiratory, ventilator, and laboratory parameters were recorded at the time of cannulation. One hundred seventy-nine of 227 (79%) patients were successfully decannulated. Ten patients (4%) underwent prolonged weaning of at least three failed EWTs before successful decannulation. The respiratory rate (19/min vs 16/min, p = 0.002) and Pa co2 (44 mm Hg vs 40 mm Hg, p = 0.003) were higher before failed than successful EWTs. Both parameters were risk factors for ECMO weaning failure (Pa co2 : odds ratio [OR] 1.05; 95% CI, 1.001-1.10; p = 0.045; respiratory rate: OR 1.10; 95% CI, 1.04-1.15; p < 0.001) in multivariable analysis. The rapid shallow breathing index [42 (1/L*min), vs 35 (1/L*min), p = 0.052) was higher before failed than successful EWTs. The decline of Sa o2 and Pa o2 /F io2 during EWTs was higher in failed than successful trials. CONCLUSIONS: Seventy-nine percent of patients were successfully decannulated with only 4% needing prolonged ECMO weaning. Before EWT only parameters of impaired ventilation (insufficient decarboxylation, higher respiratory rate) but not of oxygenation were predictive for weaning failure, whereas during EWT-impaired oxygenation was associated with weaning failure.

Clinical relevance of cell-free DNA during venovenous extracorporeal membrane oxygenation.

BACKGROUND: Thrombosis remains a critical complication during venovenous extracorporeal membrane oxygenation (VV ECMO). The involvement of neutrophil extracellular traps (NETs) in thrombogenesis has to be discussed. The aim was to verify NETs in the form of cell-free DNA (cfDNA) in the plasma of patients during ECMO. METHODS: A fluorescent DNA-binding dye (QuantifFluor®, Promega) was used to detect cell-free DNA in plasma samples. cfDNA concentrations from volunteers (n = 21) and patients (n = 9) were compared and correlated with clinical/technical data before/during support, ECMO end and time of a system exchange. RESULTS: Before ECMO, patients with a median (IQR) age of 59 (51/63) years, SOFA score of 11 (10/15), and ECMO run time of 9.0 (7.0/19.5) days presented significantly higher levels of cfDNA compared to volunteers (6.4 (5.8/7.9) ng/µL vs. 5.9 (5.4/6.3) ng/µL; p = 0.044). Within 2 days after ECMO start, cfDNA, inflammatory, and hemolysis parameters remained unchanged, while platelets decreased (p = 0.005). After ECMO removal at the end of therapy, cfDNA, inflammation, and coagulation data (except antithrombin III) remained unchanged. The renewal of a system resulted in known alterations in fibrinogen, d-dimers, and platelets, while cfDNA remained unchanged. CONCLUSION: Detection of cfDNA in plasma of ECMO patients was not an indicator of acute and circuit-induced thrombogenesis.

Intracranial hemorrhage in a large cohort of patients supported with veno-venous ECMO. A retrospective single-center analysis.

BACKGROUND: Intracranial bleeding (ICB) is a serious complication during veno-venous extracorporeal membrane oxygenation (V-V ECMO), with potentially fatal consequences. PURPOSE: This study aimed to evaluate the incidence, time of detection of ICB among patients treated with V-V ECMO and potential risk factors for developing ICB during V-V ECMO. METHODS: Five hundred fifty six patients were included in this retrospective single center analysis. RESULTS: Median time on V-V ECMO was 9 (IQR 6-15) days. Intracranial bleeding during V-V ECMO was detected in 10.9% of all patients (61 patients with ICB). Only 17 patients with ICB presented obvious clinical symptoms. Intracranial bleeding was detected on cerebral imaging in median after 5 days (IQR 1-14) after starting V-V ECMO. Overall survival to hospital discharge was 63.7% (ICB: 29.5%). Risk factors of ICB before starting V-V ECMO in univariable analysis were platelets <100/nl (OR: 3.82), creatinine >1.5mg/dl (OR: 1.98), norepinephrine >2.5mg/h (OR: 2.5), ASAT >80U/L (OR: 1.86), blood-urea >100mg/dl (OR: 1.81) and LDH >550u/L (OR: 2.07). Factors associated with cannulation were rapid decrease in paCO2 >35mmHg (OR: 2.56) and rapid decrease in norepinephrine >1mg/h (OR: 2.53). Multivariable analysis revealed low platelets, high paCO2 before ECMO, and rapid drop in paCO2 after V-V ECMO initiation as significant risk factors for ICB. CONCLUSION: The results emphasize that ICB is a frequent complication during V-V ECMO. Many bleedings were incidental findings, therefore screening for ICB is advisable. The univariate risk factors reflect the underlying disease severity, coagulation disorders and peri-cannulation factors, and may help to identify patients at risk.

A solution for global hygienic challenges regarding the application of heater-cooler systems in cardiac surgery.

71.759 surgical procedures were performed in 2019 with the aid of cardiopulmonary bypass in Germany. To adjust the patient's body temperature on extracorporeal circulation, the application of a heater-cooler unit (HCU) is mandatory. However, in case of insufficient sanitisation of HCU, life-threatening infections can be transmitted by the device to the patients, including Legionella bacteria, Mycobacterium chimaera, Pseudomonas aeruginosa. To avoid disease transmission, as a requirement for safe medical practice established by regulatory authorities, HCUs must be regularly disinfected by hazardous chemicals posing a danger for both handling humans and the environment. Therefore, to comply with regulations, HCU manufacturers have introduced both timely and financially extensive sanitisation procedures. Our paper describes a novel, effective and easy to handle disinfection method for the above problematics without utilising hazardous chemicals. The method's technical principle is electrolysis, resulting in drinking water quality regarding the analysed germs in the worldwide most commonly utilised heater-cooler device. The main aim of the study was to prove the efficacy and reliability of the device cleansing process. Furthermore, the economic impact of the novel method was evaluated. Therefore, we have undertaken 60 microbiological sampling series between December 2019 and November 2020 from a conventional HCU (3T LivaNova, Germany). During the total investigational period, no contamination with Pseudomonas aeruginosa or Legionellae could have been demonstrated in the HCU. The extreme slow-growing nontuberculous M. chimaera was detected only in one sample obtained from diamond electrode cleansed HCU water, and source of contamination was promptly eliminated by a simple technical modification of the device test-site. Additionally, the diamond electrode application is beneficial for eliminating potentially hazardous cleansing material from the process, which may affect otherwise both patients operated on cardiopulmonary bypass and the perfusionists.

Coagulation abnormalities in patients with COVID-19 on venovenous ECLS increased risk for technical complications and support times but had no impact on survival.

BACKGROUND: Patients with severe coronavirus disease-19 (COVID-19)-associated acute respiratory distress on venovenous extracorporeal lung support (V-V ECLS) showed a high incidence of vascular as well as ECLS-related thrombotic complications. The latter may influence the outcome of the patients. METHODS: This is a retrospective monocentric study on prospectively collected data of technical complications including 69 adult COVID-19 patients on V-V ECLS (ECLS Registry, March 2020 until April 2021) without and with system exchanges. Alterations in ECLS-specific data, hemolysis, coagulation, and hemostasis parameters were analyzed. RESULTS: Every second COVID-19 patient on V-V ECLS developed technical complications. Optimized ECLS management at our ECLS center reduced cases of acute clot formation (pump head thrombosis, acute oxygenator thrombosis) (17%), and allowed early identification of progressive clotting processes (worsened gas transfer, coagulation disorder) (14%, 54%) with a significant overhang of hyperfibrinolysis (37%). Although COVID-19 disease and technical complications caused the prolonged length of stay at the intensive care unit and ECLS support times, the proportion of successful weaning and survival rates were comparable with patients without system exchange. CONCLUSION: The survival of ECLS patients with COVID-19 was independent of the requirement for system exchange due to technical-induced coagulation disorders. Close monitoring for circuit clotting is mandatory in COVID-19 patients and is one prerequisite for successful organ support in these difficult patients.

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study.

BACKGROUND: During venovenous extracorporeal membrane oxygenation (vvECMO), direct thrombin inhibitors are considered by some potentially advantageous over unfractionated heparin (UFH). We tested the hypothesis that Argatroban is non-inferior to UFH regarding thrombosis and bleeding during vvECMO. METHODS: We conducted a propensity-score matched observational non-inferiority study of consecutive patients without heparin-induced-thrombocytopenia (HIT) on vvECMO, treated between January 2006 and March 2019 in the medical intensive care unit at the University Hospital Regensburg. Anticoagulation was realized with UFH until August 2017 and with Argatroban from September 2017 onwards. Target activated partial thromboplastin time was 50 ± 5seconds in both groups. Primary composite endpoint was major thrombosis and/or major bleeding. Major bleeding was defined as a drop in hemoglobin of ≥ 2 g/dl/day or in transfusion of ≥ 2 packed red cells/24 h, or retroperitoneal, cerebral, or pulmonary bleeding. Major thrombosis was defined as obstruction of > 50% of the vessel lumen diameter by means of duplex sonography. We also assessed technical complications such as oxygenator defects or pump head thrombosis, the time-course of platelets, and the cost of anticoagulation (including HIT-testing). RESULTS: Out of 465 patients receiving UFH, 78 were matched to 39 patients receiving Argatroban. The primary endpoint occurred in 79% of patients in the Argatroban group and in 83% in the UFH group (non-inferiority for Argatroban, p = 0.026). The occurrence of technical complications was equally distributed (Argatroban 49% vs. UFH 42%, p = 0.511). The number of platelets was similar in both groups before ECMO therapy but lower in the UFH group after end of ECMO support (median [IQR]: 141 [104;198]/nl vs. 107 [54;171]/nl, p = 0.010). Anticoagulation costs per day of ECMO were higher in the Argatroban group (€26 [13.8;53.0] vs. €0.9 [0.5;1.5], p < 0.001) but not after accounting for blood products and HIT-testing (€63 [42;171) vs. €40 [17;158], p = 0.074). CONCLUSION: In patients without HIT on vvECMO, Argatroban was non-inferior to UFH regarding bleeding and thrombosis. The occurrence of technical complications was similarly distributed. Argatroban may have less impact on platelet decrease during ECMO, but this finding needs further evaluation. Direct drug costs were higher for Argatroban but comparable to UFH after accounting for HIT-testing and transfusions.

ECMO in COVID-19-prolonged therapy needed? A retrospective analysis of outcome and prognostic factors.

BACKGROUND: The role of venovenous extracorporeal membrane oxygenation (VV ECMO) in patients with COVID-19-induced acute respiratory distress syndrome (ARDS) still remains unclear. Our aim was to investigate the clinical course and outcome of those patients and to identify factors associated with the need for prolonged ECMO therapy. METHODS: A retrospective single-center study on patients with VV ECMO for COVID-19-associated ARDS was performed. Baseline characteristics, ventilatory and ECMO parameters, and laboratory and virological results were evaluated over time. Six months follow-up was assessed. RESULTS: Eleven of 16 patients (68.8%) survived to 6 months follow-up with four patients requiring short-term (<28 days) and seven requiring prolonged (⩾28 days) ECMO support. Lung compliance before ECMO was higher in the prolonged than in the short-term group (28.1 (28.8-32.1) ml/cmH2O vs 18.7 (17.7-25.0) ml/cmH2O, p = 0.030). Mechanical ventilation before ECMO was longer (19 (16-23) days vs 5 (5-9) days, p = 0.002) and SOFA score was higher (12.0 (10.5-17.0) vs 10.0 (9.0-10.0), p = 0.002) in non-survivors compared to survivors. Low viral load during the first days on ECMO tended to indicate worse outcomes. Seroconversion against SARS-CoV-2 occurred in all patients, but did not affect outcome. CONCLUSIONS: VV ECMO support for COVID-19-induced ARDS is justified if initiated early and at an experienced ECMO center. Prolonged ECMO therapy might be required in those patients. Although no relevant predictive factors for the duration of ECMO support were found, the decision to stop therapy should not be made dependent of the length of ECMO treatment.

Is there really a benefit of using minimized cardiopulmonary bypass in CABG? A retrospective propensity score-matched study with 5000 cases.

The concept of minimized cardiopulmonary bypass targets at reduction of adverse effects triggered by extracorporeal circulation. In this study, benefits of minimized bypass in CABG were evaluated under particular consideration of patient body mass index and surgeon impact. From 2004 to 2014, 5164 patients underwent coronary bypass surgery (CABG). Conventional cardiopulmonary bypass (CCPB) was used in 2376 patients, minimized cardiopulmonary bypass (MCPB) in 2788 cases. Multivariate regression models were used in the entire cohort and in a propensity score-matched subgroup after expert CABG to figure out clinical differences such as mortality, postoperative renal function, and thromboembolic events. Overall mortality was 1.5% (n = 41) in the MCPB group and 3.5% (n = 82) in CCPB patients (p < 0.001). Postoperative renal failure and hemodialysis occurred in 2.6% (n = 72/MCPB) vs. 5.3% (n = 122/CCPB (p < 0.001). Multivariable regression revealed use of CCPB as risk factor for increased mortality (OR 2.01, p = 0.001), renal failure (OR 1.79, p < 0.001), and myocardial infarction (OR 1.98, p < 0.001) comparable to risk factors such as preoperative ventilation (OR 2.26, p = 0.048), diabetes mellitus (OR 1.68, p = 0.001), and cardiogenic shock (OR 3.81, p = 0.002). Body mass index had no effect on the analyzed outcome parameters (OR 0.92, p = 0.002). Propensity score-matching analysis of an expert CABG subgroup revealed CCPB as risk factor for mortality (OR 2.26, p = 0.004) and postoperative hemodialysis (OR 1.74, p = 0.017). Compared to conventional circuits, minimized bypass use in CABG is associated with lower mortality and less postoperative renal failure. A high body mass index is feasible and not a risk factor for MCPB surgery.

Incidence and Risk Factors for Cannula-Related Venous Thrombosis After Venovenous Extracorporeal Membrane Oxygenation in Adult Patients With Acute Respiratory Failure.

OBJECTIVES: Venovenous extracorporeal membrane oxygenation is indicated in patients with severe refractory acute respiratory failure. Venous thrombosis due to indwelling catheters is a frequent complication. The aim of this study was to analyze the incidence of cannula-related thrombosis and its risk factors after venovenous extracorporeal membrane oxygenation. DESIGN: Retrospective observational study. SETTING: A medical ICU at the University Hospital Regensburg. PATIENTS: We analyzed consecutive patients with severe respiratory failure (PaO2/FIO2 < 85 mm Hg and/or respiratory acidosis with pH < 7.25) who were successfully treated with venovenous extracorporeal membrane oxygenation in a medical ICU between 2010 and 2017. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: After extracorporeal membrane oxygenation weaning, duplex sonography or CT was conducted to detect cannula-related thrombosis. Thrombosis was classified as a large thrombosis by vein occlusion of greater than 50%. The incidence of thrombosis was correlated with risk factors such as coagulation variables (mean activated partial thromboplastin time ≤ 50 s, international normalized ratio antithrombin III, fibrinogen, plasma-free hemoglobin, platelets, and decline in D-dimer ≤ 50% the day after decannulation), cannula size, time on venovenous extracorporeal membrane oxygenation, renal failure, and underlying malignant disease. Data cut-off points were identified by receiver operating characteristic analysis. One-hundred seventy-two of 197 patients (87%) were screened. One-hundred six patients (62%) showed thrombosis that was considered large in 48 of 172 (28%). The incidence of thrombosis was higher in patients with a mean aPTT of less than or equal to 50 seconds (odds ratio, 1.02; p = 0.013) and in patients with a decline in D-dimer less than or equal to 50% (odds ratio, 2.76; p = 0.041) the day after decannulation following adjustment for risk factors. CONCLUSIONS: The incidence of cannula-related venous thrombosis after venovenous extracorporeal membrane oxygenation is high. Reduced systemic anticoagulation may enhance the risk of thrombosis. Sustained elevation of D-dimer after decannulation may indicate thrombosis. Patients should undergo routine duplex sonography after extracorporeal membrane oxygenation to detect thrombosis formation in the cannulated vessel.

Conventional or minimized cardiopulmonary bypass support during coronary artery bypass grafting? - An analysis by means of perfusion and body mass index.

The use of minimized cardiopulmonary bypass support to reduce the side effects of extracorporeal circulation is still contradictorily discussed. This study compares perfusion operated by conventional (CCPB) and minimized (MCPB) cardiopulmonary bypass support during coronary artery bypass grafting (CABG). This study includes the data of 5164 patients treated at our department between 2004 and 2014. Tissue perfusion during cardiopulmonary bypass support and cardiac arrest was assessed by means of body mass index, hemodilution, blood pressure with corresponding pump flow and venous oxygen saturation, serum lactate, and serum pH. Hemodilution was more pronounced after CCPB: hemoglobin had dropped to 4.47 ± 0.142 g/dL after CCPB and to 2.77 ± 0.148 g/dL after MCPB (P = 0.0022). Despite the higher pump flow in conventional circuits (4.86-4.95 L/min vs. 4.1-4.18 L/min), mean blood pressure was higher during minimized bypass support (53 ± 10 vs. 56 ± 13 mm Hg [aortic clamping], 57 ± 9 vs. 61 ± 12 mm Hg [34°C], 55 ± 9 vs.59 ± 11 mm Hg [aortic clamp removal], P < 0.0001) at all time points. Venous oxygen saturation remained on comparable levels of >70% during both conventional and minimized cardiopulmonary bypass support. The increase in serum lactate was more pronounced after CCPB (8.98 ± 1.28 vs. 3.66 ± 1.25 mg/dL, P = 0.0079), corresponding to a decrease in serum pH to acidotic levels (7.33 ± 0.06 vs. 7.35 ± 0.06, P < 0.0001). These effects were evident in all BMI ranges. Minimized cardiopulmonary bypass support provides efficient perfusion in all BMI ranges and is thus equivalent to conventional circuits.

Accumulations of von Willebrand factor within ECMO oxygenators: Potential indicator of coagulation abnormalities in critically ill patients?

Clot formation within membrane oxygenators (MOs) remains a critical problem during extracorporeal membrane oxygenation (ECMO). The composition of the clots-in particular, the presence of von Willebrand factor (vWF)-may be an indicator for prevalent nonphysiological flow conditions, foreign body reactions, or coagulation abnormalities in critically ill patients. Mats of interwoven gas exchange fibers from randomly collected MOs (PLS, Maquet, Rastatt, Germany) of 21 patients were stained with antibodies (anti-vWF and anti-P-selectin) and counterstained with 4',6-diamidino-2-phenylindole. The extent of vWF-loading was correlated with patient and technical data. While 12 MOs showed low vWF-loadings, 9 MOs showed high vWF-loading with highest accumulations close to crossing points of adjacent gas fibers. The presence and the extent of vWF-fibers/"cobwebs," leukocytes, platelet-leukocyte aggregates (PLAs), and P-selectin-positive platelet aggregates were independent of the extent of vWF-loading. However, the highly loaded MOs were obtained from patients with a significantly elevated SOFA score, severe thrombocytopenia, and persistent liver dysfunction. The coagulation abnormalities of these critically ill patients may cause an accumulation of the highly thrombogenic and elongated high-molecular-weight vWF multimers in the plasma which will be trapped in the MOs during the ECMO therapy.

Quantitative assessment of peripheral limb perfusion using a modified distal arterial cannula in venoarterial ECMO settings.

In cases of severe cardiopulmonary deterioration, quick establishment of venoarterial extracorporeal membrane oxygenation (ECMO) represents a support modality. After successful arterial peripheral cannulation, a certain grade of peripheral limb malperfusion is a fairly common phenomenon. Detection of peripheral malperfusion is vital, since it can result in compartment syndrome or even loss of the affected limb. To prevent or resolve emerging lower limb ischaemia, a newly designed perfusion catheter is placed into the superficial femoral artery, distal to the arterial cannula via ECMO. The aim of our study was to evaluate flow and haemodynamic characteristics of this novel distal limb perfusion cannula for ECMO therapy and present these important findings for the first time. The distal perfusion cannula blood flow increases in linear correlation with ECMO blood flow The variability of distal perfusion cannula blood flow with a 15 Fr cannula ranges between 160 ± 0.40 mL min-1 at 1.5 L min-1 ECMO flow rate and 480 ± 80 mL min-1 at 5.0 L min-1 ECMO blood flow, respectively. Comparatively, the 17-Fr-sized cannula performs on a scale of 140 ± 20 to 390 ± 60 mL distal perfusion cannula blood flow at 1.5-5.0 L min-1 ECMO blood flow, respectively. The quantitative assessment of the distal perfusion cannula blood flow has revealed that distal perfusion cannula blood flow can measure up to 10% of the ECMO blood flow. Furthermore, it has been also well demonstrated that the novel distal perfusion cannula is sufficient to compensate peripheral limb ischaemia.

Central cannulation by Seldinger technique: a reliable method in ascending aorta and aortic arch replacement.

BACKGROUND: Extensive type A aortic dissections that involve peripheral great vessels can complicate the choice of a cannulation site for cardiopulmonary bypass. We started to employ direct cannulation of the true lumen on the concavity of the aortic arch by Seldinger technique and evaluated the efficacy of this access technique as an alternative arterial inflow target in aortic surgery. MATERIAL/METHODS: Twenty-four consecutive patients (mean age: 59±14 years) underwent type A aortic dissection repair using selective antegrade cerebral perfusion. Direct aortic cannulation was used in 14 cases, subclavian access in 6 patients, and femoral entry in 4 patients. Perioperative factors were evaluated to identify the reliability and eventual benefits of direct cannulation method at the aortic arch. RESULTS: There were no operative deaths and cumulative 30-day mortality rate was 25% (6). Permanent neurological deficits were not observed; in 1 patient transient changes occurred (4%). Time to reach circulatory arrest was the shortest in the direct access group, with mean 27±11 (CI: 20.6-33.3) min vs. 43±22 (28.0-78.0) min (p=0.058) and 32±8 (23.6-40.4) min (p=0.34) by femoral cannulation and subclavian entry, respectively. Direct arch cannulation resulted in the best renal function in the first 72 h after surgery and similar characteristics were observed in lactic acid levels. CONCLUSIONS: Ultrasound-guided direct cannulation on the concavity of the aortic arch using a Seldinger technique is a reliable method in dissection repairs. Prompt antegrade perfusion provides not only cerebral but also peripheral organ and tissue protection, which is an advantage in this high-risk group of patients.

Computer based visualization of clot structures in extracorporeal membrane oxygenation and histological clot investigations for understanding thrombosis in membrane lungs.

Extracorporeal membrane oxygenation (ECMO) was established as a treatment for severe cardiac or respiratory disease. Intra-device clot formation is a common risk. This is based on complex coagulation phenomena which are not yet sufficiently understood. The objective was the development and validation of a methodology to capture the key properties of clots deposed in membrane lungs (MLs), such as clot size, distribution, burden, and composition. One end-of-therapy PLS ML was examined. Clot detection was performed using multidetector computed tomography (MDCT), microcomputed tomography (µCT), and photography of fiber mats (fiber mat imaging, FMI). Histological staining was conducted for von Willebrand factor (vWF), platelets (CD42b, CD62P), fibrin, and nucleated cells (4', 6-diamidino-2-phenylindole, DAPI). The three imaging methods showed similar clot distribution inside the ML. Independent of the imaging method, clot loading was detected predominantly in the inlet chamber of the ML. The µCT had the highest accuracy. However, it was more expensive and time consuming than MDCT or FMI. The MDCT detected the clots with low scanning time. Due to its lower resolution, it only showed clotted areas but not the exact shape of clot structures. FMI represented the simplest variant, requiring little effort and resources. FMI allowed clot localization and calculation of clot volume. Histological evaluation indicated omnipresent immunological deposits throughout the ML. Visually clot-free areas were covered with leukocytes and platelets forming platelet-leukocyte aggregates (PLAs). Cells were embedded in vWF cobwebs, while vWF fibers were negligible. In conclusion, the presented methodology allowed adequate clot identification and histological classification of possible thrombosis markers such as PLAs.

Neutrophil extracellular traps - a potential trigger for the development of thrombocytopenia during extracorporeal membrane oxygenation.

Neutrophil extracellular traps (NETs) have recently emerged as a potential link between inflammation, immunity, and thrombosis, as well as other coagulation disorders which present a major challenge in the context of extracorporeal membrane oxygenation (ECMO). By examining blood from ECMO patients for NETs and their precursors and correlating them with clinical and laboratory biomarkers of coagulation and inflammation, this study aims to evaluate the association between the presence of NETs in the bloodstream of ECMO patients and the development of potentially severe coagulation disorders during ECMO therapy. Therefore, blood samples were collected from healthy volunteers (n=13) and patients receiving veno-venous (VV) ECMO therapy (n=10). To identify NETs and their precursors, DNA and myeloperoxidase as well as granulocyte marker CD66b were visualized simultaneously by immunofluorescence staining in serial blood smears. Differentiation of DNA-containing objects and identification of NETs and their precursors was performed semiautomatically by a specific algorithm using the shape and size of DNA staining and the intensity of MPO and CD66b signal. Neutrophil extracellular traps and their precursors could be detected in blood smears from patients requiring VV ECMO. Compared to volunteers, ECMO patients presented significantly higher rates of NETs and NET precursors as well as an increased proportion of neutrophil granulocytes in all detected nucleated cells. A high NET rate prior to the initiation of ECMO therapy was associated with both increased IL-6 and TNF-α levels as an expression of a high cytokine burden. These patients with increased NET release also presented an earlier and significantly more pronounced decrease in platelet counts and ATIII activity following initiation of therapy compared with patients with less elevated NETs. These findings provide further indications for the development of immune-mediated acquired thrombocytopenia in ECMO patients.

COVID-19 infection triggered idiopathic capillary leak syndrome treated with ECMELLA.

Background: Idiopathic systemic capillary leak syndrome (ISCLS) is characterized by recurrent systemic capillary leakage and hypovolemic shock. Case presentation: We report a 59-year-old Caucasian man with ISCLS and persistent hypovolemic and cardiogenic shock after COVID-19 infection. Mechanical circulatory support was provided with veno-arterial extracorporeal membrane oxygenation and a microaxial pump. Massive fluid resuscitation was needed. Subsequent complications prolonged the intensive care treatment. Mechanical circulatory support was needed for 22 days. Cardiac function eventually fully recovered, and the patient survived without neurologic compromise. Conclusions: This case of severe ISCLS triggered by COVID-19 highlights that even the most severe hypovolemic and cardiogenic shock may be reversible in ISCLS.

Refractory circulatory failure in COVID-19 patients treated with veno-arterial ECMO a retrospective single-center experience.

OBJECTIVE: In this retrospective case series, survival rates in different indications for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and differential diagnoses of COVID-19 associated refractory circulatory failure are investigated. METHODS: Retrospective analysis of 28 consecutive COVID-19 patients requiring VA-ECMO. All VA-ECMO's were cannulated peripherally, using a femoro-femoral cannulation. RESULTS: At VA-ECMO initiation, median age was 57 years (IQR: 51-62), SOFA score 16 (IQR: 13-17) and norepinephrine dosing 0.53µg/kg/min (IQR: 0.35-0.87). Virus-variants were: 61% wild-type, 14% Alpha, 18% Delta and 7% Omicron. Indications for VA-ECMO support were pulmonary embolism (PE) (n = 5, survival 80%), right heart failure due to secondary pulmonary hypertension (n = 5, survival 20%), cardiac arrest (n = 4, survival 25%), acute heart failure (AHF) (n = 10, survival 40%) and refractory vasoplegia (n = 4, survival 0%). Among the patients with AHF, 4 patients suffered from COVID-19 associated heart failure (CovHF) (survival 100%) and 6 patients from sepsis associated heart failure (SHF) (survival 0%). Main Complications were acute kidney injury (AKI) 93%, renal replacement therapy was needed in 79%, intracranial hemorrhage occurred in 18%. Overall survival to hospital discharge was 39%. CONCLUSION: Survival on VA-ECMO in COVID-19 depends on VA-ECMO indication, which should be considered in further studies and clinical decision making. A subgroup of patients suffers from acute heart failure due to inflammation, which has to be differentiated into septic or COVID-19 associated. Novel biomarkers are required to ensure reliable differentiation between these entities; a candidate might be soluble interleukin 2 receptor.

Extended Cellular Deposits on Gas Exchange Capillaries Are Not an Indicator of Clot Formation: Analysis of Different Membrane Oxygenators.

Antithrombogenic coatings of artificial surfaces within extracorporeal membrane oxygenation (ECMO) circuits improved its bio- and hemocompatibility. However, there is still a risk of thrombus formation in particular within the membrane oxygenator (MO). Since inflammatory cells are essential components within clots, the aim was to identify the extent of cellular accumulations on gas exchange capillaries from different ECMO systems. Thirty-four MOs (PLS, n = 27, Getinge; Hilite 7000 LT, n = 7, Fresenius Medical Care, Germany) were collected from adult patients. The extent of cellular deposits on gas exchange capillaries was classified using nuclear 4',6-diamidino-2-phenylindole staining and fluorescence microscopy. All Hilite oxygenators exhibited small cellular deposits. In contrast, the cellular distribution was heterogeneous on capillaries from PLS oxygenators: small deposits (34%), clusters (44%) and membrane-spanning cell structures (pseudomembranes) (22%). Overall, the median fluorescence intensity was significantly higher in the PLS group. Nevertheless, within 3 days before MO removal, there was no alteration in critical parameters ( d -dimer and fibrinogen levels, platelet counts, and pressure drop across the MO). In conclusion, despite the histological differences on the gas capillaries from different types of oxygenators, there was no further evidence of increased inflammation and coagulation parameters that indicate clot formation within oxygenators.

Prognostic factors for favorable outcomes after veno-venous extracorporeal membrane oxygenation in critical care patients with COVID-19.

BACKGROUND: Patients with COVID-19 and severe acute respiratory failure may require veno-venous extracorporeal membrane oxygenation (VV ECMO). Yet, this procedure is resource-intensive and high mortality rates have been reported. Thus, predictors for identifying patients who will benefit from VV ECMO would be helpful. METHODS: This retrospective study included 129 patients with COVID-19 and severe acute respiratory failure, who had received VV ECMO at the University Medical Center Regensburg, Germany, between 1 March 2020 and 31 December 2021. Patient-specific factors and relevant intensive-care parameters at the time of the decision to start VV ECMO were investigated regarding their value as predictors of patient survival. In addition, the intensive-care course of the first 10 days of VV ECMO was compared between survivors and patients who had died in the intensive care unit. RESULTS: The most important parameters for predicting outcome were patient age and platelet count, which differed significantly between survivors and non-survivors (age: 52.6±8.1 vs. 57.4±10.1 years, p<0.001; platelet count before VV ECMO: 321.3±132.2 vs. 262.0±121.0 /nL, p = 0.006; average on day 10: 199.2±88.0 vs. 147.1±57.9 /nL, p = 0.002). A linear regression model derived from parameters collected before the start of VV ECMO only included age and platelet count. Patients were divided into two groups by using receiver operating characteristics (ROC) analysis: group 1: 78% of patients, mortality 26%; group 2: 22% of patients, mortality 75%. A second linear regression model included average blood pH, minimum paO2, and average pump flow on day 10 of VV ECMO in addition to age and platelet count. The ROC curve resulted in two cut-off values and thus in three groups: group 1: 25% of patients, mortality 93%; group 2: 45% of patients, mortality 31%; group 3: 30% of patients, mortality 0%.

Impact of fluid balance and blood transfusion during extracorporeal circulation on outcome for acute type A aortic dissection surgery.

BACKGROUND: In thoracic aortic surgery, fluid replacement and blood transfusion during extracorporeal circulation (ECC) are associated with increased coagulopathy, elevated inflammatory response, and end-organ dysfunction. The optimal strategy has not been established in this regard. The aim of this study was to evaluate the effect of the fluid balance during ECC in thoracic aortic dissection surgery on outcome. METHODS: Between 2009 and 2020, 358 patients suffering from acute type A aortic dissection (ATAAD) underwent aortic surgery at our heart center. In-hospital mortality, major complications (postoperative stroke, respiratory failure, heart failure, acute renal failure), and follow-up mortality were assessed. Logistic regression analysis was used to identify whether fluid balance and blood transfusion during ECC were risk factors for occurring adverse events. RESULTS: The in-hospital mortality amounted to 20.4%. Major complications included temporary neurologic deficit in 13.4%, permanent neurologic deficit in 6.1%, acute renal failure in 32.7%, prolonged ventilation for respiratory failure in 17.9%, and acute heart failure in 10.9% of cases. At a mean of 42 months after discharge of 285 survivors, follow-up mortality was 13.3%. Multivariate analysis revealed major complications as well as the risk of in-hospital and follow-up mortality to increase with fluid balance and blood transfusion during ECC. CONCLUSIONS: Fluid balance and blood transfusion during ECC present with predictive potential concerning the risk of postoperative adverse events.