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.

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.

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.

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.

Mortality on extracorporeal membrane oxygenation: Evaluation of independent risk factors and causes of death during venoarterial and venovenous support.

INTRODUCTION: Most patients on extracorporeal membrane oxygenation (ECMO) decease during therapy on the system. However, the actual causes of death have not been studied sufficiently. This study analyses the etiology, prevalence, and risk factors for the outcome variable death during ongoing ECMO for all patients and divided according to venoarterial (VA) or venovenous (VV) support. METHODS: We retrospectively analysed all patients receiving ECMO support at our institution between March 2006 to January 2021. Only the patients deceased during ongoing support were included. RESULTS: 2016 patients were placed on VA (n = 1168; 58%) or VV (n = 848; 42%) ECMO; 759 patients (37.7%) deceased on support. The causes of death differed between the support types: VA ECMO patients mostly died from cerebral ischemia (34%), low-cardiac output (LCO; 24.1%) and multi-organ failure (MOF; 21.6%), whereas in VV ECMO cases, refractory respiratory failure (28.2%), and sepsis (20.4%) dominated. Multivariate regression analysis revealed cardiopulmonary resuscitation (CPR) and acidosis prior to ECMO as risk factors for dying on VA ECMO, while high inotropic doses pre-ECMO, a high fraction of inspired oxygen on day 1, elevated lactate dehydrogenase, and international normalized ratio levels lead to an unfavourable outcome in VV ECMO patients. CONCLUSION: Even in highly experienced centers, ECMO mortality remains high and occurs mainly on support or 24 h after its termination. The causes of death differ between VV and VA ECMO, depending on the underlying diseases responsible for the need of extracorporeal support.

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.

Enabling the control of reperfusion parameters in out-of-hospital cardiac arrest: First applications of the CARL system.

INTRODUCTION: There is increasing evidence for extracorporeal cardiopulmonary resuscitation (ECPR) as a rescue therapy for selected patients in refractory cardiac arrest (CA). Besides patient selection, the control of reperfusion parameters is of eminent importance. Especially in out-of-hospital CA, monitoring and individualized, targeted reperfusion remains a great challenge for emergency personnel. The CARL® system is designed to enable an early control of a variety of reperfusion parameters and to pursue a targeted reperfusion strategy in ECPR. CASE PRESENTATION: We report the first 10 ECPR applications of the CARL® system in Regensburg, Germany. Early blood gas analysis, oxygen titration and pressure monitoring were feasible and enabled an individualized and targeted reperfusion strategy in all patients. After suffering from refractory CA and prolonged resuscitation attempts, five out of the first 10 patients survived and were successfully discharged from the hospital (CPC one on hospital discharge). CONCLUSION: Application of the CARL® system contributed to early monitoring and control of reperfusion parameters. Whether targeted ECPR may have the potential to improve outcomes in refractory OHCA remains the subject of future investigations.

Outcome after veno-venous extracorporeal membrane oxygenation in elderly compared to younger patients: A 14-year retrospective observational study.

BACKGROUND: The outcome after veno-venous extracorporeal membrane oxygenation in elderly patients is supposed to be unsatisfactory. Our primary aim was to determine the influence of advanced age on short- and long-term outcomes; the secondary aim was to analyze risk factors for impaired outcomes. METHODS: Between January 2006 and June 2020, 755 patients received V-V ECMO support at our department. Patients were grouped according to age (18-49.9, 50-59.9, 60-69.9, ≥70 years old), and then retrospectively analyzed for short- and long-term outcomes. Risk factors for in-hospital mortality and death during follow-up were assessed using multivariate regression analysis. RESULTS: Duration of V-V ECMO support was comparable between all groups median (8-10 days, p = 0.256). Likewise, the weaning rate was comparable in all age groups 68.2%-76.5%; (p = 0.354), but in-hospital mortality was significantly climbing with increasing age (<50 years 30.1%/n = 91 vs. 50-59.9 years 37.1%/n = 73, vs. 60-69.9 years 45.6%/n = 78 vs. ≥70 years 51.8%/n = 44; p < 0.001). Older age groups also showed significantly reduced cerebral performance category scores. The multivariate logistic analysis yielded age, acute and chronic hemodialysis, bilirubin on day 1 of support, malignancy, and primary lung disease as relevant risk factors for in-hospital mortality. Age, coronary artery disease, presence of another primary lung disease, malignancy, and immunosuppression were risk factors for death during follow-up. CONCLUSION: In V-V ECMO patients, advanced age is associated with more comorbidity, impaired short- and long-term outcome, and worse neurological outcome.

Outcome after veno-arterial extracorporeal membrane oxygenation in elderly patients: A 14-year single-center experience.

BACKGROUND: Use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in elderly patients is controversial because of presumed poor outcome. Our primary aim was to determine the influence of advanced age on short- and long-term outcome; the secondary aim was to analyze risk factors for impaired outcome. METHODS: Between January 2006 and June 2020, 645 patients underwent VA-ECMO implantation in our department. The patients were categorized into four groups:<50, 50-59.9, 60-69.9 and ≥70 years old. Data were retrospectively analyzed for short- and long-term outcome. Risk factors for in-hospital mortality and mortality during follow-up were assessed using multivariate regression analysis. RESULTS: VA-ECMO support duration was comparable in all age groups (median 3 days). Weaning rates were 60.8%/n = 104 (<50 years), 51.4%/n = 90 (50-59.9 years), 58.8%/n = 107 (60-69.9), and 67.5%/n = 79 (≥70, p = 0.048). Hospital mortality was highest in the patients aged 50-59.9 years (68%/n = 119), but not in the elderly patients (60-69.9, ≥70:62.1%/n = 113, 58,1%/n = 68). At discharge, the cerebral performance category scores were superior in the patients <50 years. Multivariate logistic regression analysis revealed chronic kidney failure requiring hemodialysis, duration of cardiopulmonary resuscitation, and elevated blood lactate levels before VA-ECMO, but not age as predictors of in-hospital mortality. Cox's regression disclosed age as relevant risk factor for death during follow-up. The patients' physical ability was comparable in all age groups. CONCLUSION: VA-ECMO support should not be declined in patients only because of advanced age. Mortality and neurological status at hospital discharge and during follow-up were comparable in all age groups.

Major Bleeding and Thromboembolic Events in Veno-Venous Extracorporeal Membrane Oxygenation-Patients With Isolated Respiratory Failure.

Bleeding and thromboembolic events are common during veno-venous extracorporeal membrane oxygenation (vvECMO). It is unknown whether these complications are driven by the ECMO system itself, multiorgan-failure, or both. The aim of this study was to assess the prevalence of bleeding and thromboembolic events in patients with isolated respiratory failure. Patients with vvECMO were retrospectively included from March 2009 to October 2017. Exclusion included any organ failure other than respiratory. Major bleeding was defined as a decrease in hemoglobin ≥2 g/dl per 24 hours, the requirement for transfusion of ≥2 packed red blood cell concentrates per 24 hours, any retroperitoneal, pulmonary, central nervous system bleeding, or bleeding requiring surgery. Thromboembolic events were assessed by duplex sonography or CT scan. Of 601 patients, 123 patients with a mean age of 49 ± 15 years and a median Sepsis-related Organ Failure Assessment score of 8 (7-9) were eligible for the analysis. Major bleeding was observed in 73%; 35% of all bleedings occurred on the day of or after ECMO initiation. A more pronounced decrease of PaCO2 after ECMO initiation was seen in patients with intracranial bleeding (ICB) compared with those without. Thromboembolic events were noted in 30%. The levels of activated prothrombin time, fibrinogen, platelet count, or D-dimers affected neither bleeding nor the prevalence of thromboembolic events.

Corrigendum: Recirculation in single lumen cannula venovenous extracorporeal membrane oxygenation: A non-randomized bi-centric trial.

[This corrects the article DOI: 10.3389/fmed.2022.973240.].

Recirculation in single lumen cannula venovenous extracorporeal membrane oxygenation: A non-randomized bi-centric trial.

Background: Recirculation is a common problem in venovenous (VV) extracorporeal membrane oxygenation (ECMO). The aims of this study were to compare recirculation fraction (Rf) between femoro-jugular and jugulo-femoral VV ECMO configurations, to identify risk factors for recirculation and to assess the impact on hemolysis. Methods: Patients in the medical intensive care unit (ICU) at the University Medical Center Regensburg, Germany receiving VV ECMO with femoro-jugular, and jugulo-femoral configuration at the ECMO Center Karolinska, Sweden, were included in this non-randomized prospective study. Total ECMO flow (Q EC ), recirculated flow (QREC), and recirculation fraction Rf = QREC/QEC were determined using ultrasound dilution technology. Effective ECMO flow (QEFF) was defined as QEFF = QEC * (1-Rf). Demographics, cannula specifics, and markers of hemolysis were assessed. Survival was evaluated at discharge from ICU. Results: Thirty-seven patients with femoro-jugular configuration underwent 595 single-point measurements and 18 patients with jugulo-femoral configuration 231 measurements. Rf was lower with femoro-jugular compared to jugulo-femoral configuration [5 (0, 11) vs. 19 (13, 28) %, respectively (p < 0.001)], resulting in similar QEFF [2.80 (2.21, 3.39) vs. 2.79 (2.39, 3.08) L/min (p = 0.225)] despite lower QEC with femoro-jugular configuration compared to jugulo-femoral [3.01 (2.40, 3.70) vs. 3.57 (3.05, 4.06) L/min, respectively (p < 0.001)]. In multivariate regression analysis, the type of configuration, distance between the two cannula tips, ECMO flow, and heart rate were significantly associated with Rf [B (95% CI): 25.8 (17.6, 33.8), p < 0.001; 960.4 (960.7, 960.1), p = 0.009; 4.2 (2.5, 5.9), p < 0.001; 960.1 (960.2, 0.0), p = 0.027]. Hemolysis was similar in subjects with Rf > 8 vs. ≤ 8%. Explorative data on survival showed comparable results in the femoro-jugular and the jugulo-femoral group (81 vs. 72%, p = 0.455). Conclusion: VV ECMO with femoro-jugular configuration caused less recirculation. Further risk factors for higher Rf were shorter distance between the two cannula tips, higher ECMO flow, and lower heart rate. Rf did not affect hemolysis.

Prevalence and outcomes of patients developing heparin-induced thrombocytopenia during extracorporeal membrane oxygenation.

OBJECTIVES: Unfractionated heparin (UFH) is the commonly used anticoagulant to prevent clotting of the ECMO circuit and thrombosis of the cannulated vessels. A side effect of UFH is heparin-induced thrombocytopenia (HIT). Little is known about HIT during ECMO and the impact of changing anticoagulation in ECMO patients with newly diagnosed HIT. The aim of the study was to determine the prevalence, complications, impact of switching anticoagulation to argatroban and outcomes of patients developing heparin-induced thrombocytopenia (HIT) during either veno-venous (VV) or veno-arterial (VA) ECMO. METHODS: Retrospective observational single centre study of prospectively collected data of consecutive patients receiving VV ECMO therapy for severe respiratory failure and VA ECMO for circulatory failure from January 2006 to December 2016 of the Medical intensive care unit (ICU) of the University Hospital of Regensburg. Treatment of HIT on ECMO was done with argatroban. RESULTS: 507 patients requiring ECMO were included. Further HIT-diagnostic was conducted if HIT-4T-score was ≥4. The HIT-confirmed group had positive HIT-enzyme-linked-immunosorbent-assay (ELISA) and positive heparin-induced-platelet-activation (HIPA) test, the HIT-suspicion group a positive HIT-ELISA and missing HIPA but remained on alternative anticoagulation until discharge and the HIT-excluded group a negative or positive HIT-ELISA, however negative HIPA. These were compared to group ECMO-control without any HIT suspicion. The prevalence of HIT-confirmed was 3.2%, of HIT-suspicion 2.0% and HIT-excluded 10.8%. Confirmed HIT was trendwise more frequent in VV than in VA (3.9 vs. 1.7% p = 0.173). Compared to the ECMO control group, patients with confirmed HIT were longer on ECMO (median 13 vs. 8 days, p = 0.002). Different types of complications were higher in the HIT-confirmed than in the ECMO-control group, but in-hospital mortality was not different (31% vs. 41%, p = 0.804). CONCLUSION: HIT is rare on ECMO, should be suspected, if platelets are decreasing, but seems not to increase mortality if treated promptly.

Arterial and venous vascular complications in patients requiring peripheral venoarterial extracorporeal membrane oxygenation.

Introduction: The aim of this study was to investigate the prevalence of arterial and venous complications in patients requiring peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO) and its risk factors at the time of cannulation and during extracorporeal membrane oxygenation (ECMO) support and to assess vascular complications in association with decannulation. Material and methods: Between January 2010 to January 2020, out of 1,030 eligible patients requiring VA-ECMO, 427 with analyzable vascular screening were included. Duplex sonography and/or CT scan after decannulation were used to screen for thrombosis and pulmonary embolism as well as arterial complications. Near-infrared spectrometry (NIRS) was established at the time of cannulation and was continuously monitored during the ECMO therapy. Results: The prevalence of venous complications was 27%. Thrombosis and pulmonary embolism were observed in 21 and 7% of patients, respectively. Pulmonary embolism was more frequently diagnosed in patients with thrombosis (22 vs. 3%, p < 0.001). In multivariate analysis, cannulation in the jugular vein was determined as a risk factor for venous thrombosis in contrast to the extent of anticoagulation. The prevalence of arterial complications was 37%, mainly ischemia followed by bleeding, dissection, and compartment syndrome. Vascular surgery was necessary for 19% of the patients, of whome 1% required major amputations. A distal perfusion cannula (DPC) was implanted at cannulation in 24% of patients and secondarily in 16% of patients after cannulation as required during ECMO support. In the multivariate analysis, risk factors for leg ischemia at the time of cannulation were elevated D-dimers, lower NIRS on the cannulated leg, and lack of a DPC. The best discriminative parameter was the difference in NIRS between the non-cannulated leg and the cannulated leg. In contrast, during ECMO support, only the lack of a DPC was associated with leg ischemia. A similar rate of complications associated with decannulation, mainly arterial thrombosis, ischemia, or bleeding, was seen with percutaneous and surgical approaches (18 vs. 17%, p = 0.295). Conclusion: Patients requiring VA ECMO should be routinely screened for vascular complications. The decision to insert a DPC should be evaluated individually. However, NIRS monitoring of the cannulated leg and the non-cannulated leg is essential to identify the legs at risk for critical ischemia. As complications associated with decannulation were equally distributed between percutaneous and surgical approaches, the applied method may be chosen according to local experience.

Multi-organ dysfunction syndrome in patients undergoing extracorporeal life support.

BACKGROUND: Multiple organ failure is a common complication in patients undergoing ECLS significantly affecting patient outcomes. Gaining knowledge about the mechanisms of onset, clinical course, risk factors, and potential therapeutic targets is highly desirable. METHODS: Data of 354 patients undergoing ECLS with one-, two, three-, and four organ failures were retrospectively analyzed. Incidence of multiple organ dysfunction (MODS), its impact on survival, risk factors for its occurrence, and the impact of proinflammatory mediators on the occurrence of MODS in patients undergoing ECLS were investigated. RESULTS: The median follow-up was 66 (IQR 6; 820) days. 245 (69.2%) patients could be weaned from ECLS, 30-day survival and 1-year survival were 194 (54.1%) and 157 (44.4%), respectively. The duration of mechanical support was 4 (IQR 2; 7) days in the median. Increasing severity of MODS resulted in significant prolongation of mechanical circulatory support and worsening of the outcome. Liver dysfunction had the strongest impact on patient mortality (OR = 2.5) and survival time (19 vs 367 days). The serum concentration of analyzed interleukins rose significantly with each, additional organ affected by dysfunction (p < 0.001). All analyzed proinflammatory cytokines showed significant predictivity relative to the occurrence of MODS with interleukin 8 serum level prior to ECLS showing the strongest predictive potential for the occurrence of MODS (AUC 0.78). CONCLUSION: MODS represents a frequent complication in patients undergoing ECLS with a significant impact on survival. Proinflammatory cytokines show prognostic capacity regarding the occurrence and severity of multi-organ dysfunction.

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.

A patient with pulmonary hypertension waiting for donor lungs during the pandemic: 194 days on extracorporeal life support including 143 days on pulmonary artery to left atrium shunt.

Patients with pulmonary hypertension and end-stage lung disease are fraught with high mortality while on a waiting list for lung transplant. With sometimes rapid deterioration they may require veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as an immediate life-saving technique, which is a time-limited solution. The technique of pulmonary artery to left atrium (PA-LA) shunt fitted with an oxygenator enables bridging the patient to transplant for a longer time period. This low-resistance paracorporeal pumpless lung assist device allows for de-adaptation of the right ventricle back to lower afterload before the lung transplantation is carried out. The PA-LA shunt with an oxygenator also conveys a risk of multiple complications with reported median of 10-26 days until transplant. We report a case of pulmonary capillary hemangiomatosis in a 35-year-old female who had to wait for donor lungs during the pandemic of SARS-CoV-2 for 143 days on PA-LA shunt with oxygenator following 51 days on VA-ECMO. The extremely long course associated with multiple complications including three cerebral embolisms, episodes of sepsis and ingrowth of the return cannula into the left ventricular wall gives insight into the limits of this bridging technique.

Long-term follow-up and quality of life in patients receiving extracorporeal membrane oxygenation for pulmonary embolism and cardiogenic shock.

BACKGROUND: Since 2019, European guidelines recommend considering extracorporeal life support as salvage strategy for the treatment of acute high-risk pulmonary embolism (PE) with circulatory collapse or cardiac arrest. However, data on long-term survival, quality of life (QoL) and cardiopulmonary function after extracorporeal membrane oxygenation (ECMO) are lacking. METHODS: One hundred and nineteen patients with acute PE and severe cardiogenic shock or in need of mechanical resuscitation (CPR) received venoarterial or venovenous ECMO from 2007 to 2020. Long-term data were obtained from survivors by phone contact and personal interviews. Follow-up included a QoL analysis using the EQ-5D-5L questionnaire, echocardiography, pulmonary function testing and cardiopulmonary exercise testing. RESULTS: The majority of patients (n = 80, 67%) were placed on ECMO during or after CPR with returned spontaneous circulation. Overall survival to hospital discharge was 45.4% (54/119). Nine patients died during follow-up. At a median follow-up of 54.5 months (25-73; 56 ± 38 months), 34 patients answered the QoL questionnaire. QoL differed largely and was slightly reduced compared to a German reference population (EQ5D5L index 0.7 ± 0.3 vs. 0.9 ± 0.04; p < 0.01). 25 patients (73.5%) had no mobility limitations, 22 patients (65%) could handle their activities, while anxiety and depression were expressed by 10 patients (29.4%). Return-to-work status was 33.3% (average working hours: 36.2 ± 12.5 h/per week), 15 (45.4%) had retired from work early. 12 patients (35.3%) expressed limited exercise tolerance and dyspnea. 59% (20/34) received echocardiography and pulmonary function testing, 50% (17/34) cardiopulmonary exercise testing. No relevant impairment of right ventricular function and an only slightly reduced mean peak oxygen uptake (76.3% predicted) were noted. CONCLUSIONS: Survivors from severe intractable PE in cardiogenic shock or even under CPR with ECMO seem to recover well with acceptable QoL and only minor cardiopulmonary limitations in the long term. To underline these results, further research with larger study cohorts must be obtained.

Reliability of prognostic biomarkers after prehospital extracorporeal cardiopulmonary resuscitation with target temperature management.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) performed at the emergency scene in out-of-hospital cardiac arrest (OHCA) can minimize low-flow time. Target temperature management (TTM) after cardiac arrest can improve neurological outcome. A combination of ECPR and TTM, both implemented as soon as possible on scene, appears to have promising results in OHCA. To date, it is still unknown whether the implementation of TTM and ECPR on scene affects the time course and value of neurological biomarkers. METHODS: 69 ECPR patients were examined in this study. Blood samples were collected between 1 and 72 h after ECPR and analyzed for S100, neuron-specific enolase (NSE), lactate, D-dimers and interleukin 6 (IL6). Cerebral performance category (CPC) scores were used to assess neurological outcome after ECPR upon hospital discharge. Resuscitation data were extracted from the Regensburg extracorporeal membrane oxygenation database and all data were analyzed by a statistician. The data were analyzed using non-parametric methods. Diagnostic accuracy of biomarkers was determined by area under the curve (AUC) analysis. Results were compared to the relevant literature. RESULTS: Non-hypoxic origin of cardiac arrest, manual chest compression until ECPR, a short low-flow time until ECPR initiation, low body mass index (BMI) and only a minimal need of extra-corporeal membrane oxygenation support were associated with a good neurological outcome after ECPR. Survivors with good neurological outcome had significantly lower lactate, IL6, D-dimer, and NSE values and demonstrated a rapid decrease in the initial S100 value compared to non-survivors. CONCLUSIONS: A short low-flow time until ECPR initiation is important for a good neurological outcome. Hypoxia-induced cardiac arrest has a high mortality rate even when ECPR and TTM are performed at the emergency scene. ECPR patients with a higher BMI had a worse neurological outcome than patients with a normal BMI. The prognostic biomarkers S100, NSE, lactate, D-dimers and IL6 were reliable indicators of neurological outcome when ECPR and TTM were performed at the emergency scene.