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.

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.

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.

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.

Effects of Individualised High Positive End-Expiratory Pressure and Crystalloid Administration on Postoperative Pulmonary Function in Patients Undergoing Robotic-Assisted Radical Prostatectomy: A Prospective Randomised Single-Blinded Pilot Study.

OBJECTIVES: Robotic-assisted laparoscopic prostatectomy (RALP) is typically conducted in steep Trendelenburg position (STP). The aim of the study was to evaluate whether crystalloid administration and individual management of positive end-expiratory pressure (PEEP) improve peri- and post-operative pulmonary function in patients undergoing RALP. DESIGN: Prospective randomised single-centre single-blinded explorative study. SETTING: Patients were either allocated to a standard PEEP (5 cmH2O) group or an individualised high PEEP group. Furthermore, each group was divided into a liberal and a restrictive crystalloid group (8 vs. 4 mL/kg/h predicted body weight). Individualised PEEP levels were determined by means of preoperative recruitment manoeuvre and PEEP titration in STP. PARTICIPANTS: Informed consent was obtained from 98 patients scheduled for elective RALP. INTERVENTIONS: The following intraoperative parameters were analysed in each of the four study groups: ventilation setting (peak inspiratory pressure [PIP], plateau pressure, driving pressure [Pdriv], lung compliance [LC] and mechanical power [MP]) and postoperative pulmonary function (bed-side spirometry). The spirometric parameters Tiffeneau index (FEV1/FVC ratio) and mean forced expiratory flow (FEF25-75) were measured pre- and post-operatively. Data are shown as mean ± standard deviation (SD), and groups were compared with ANOVA. A p-value of <0.05 was considered significant. RESULTS: The two individualised high PEEP groups (mean PEEP 15.5 [±1.71 cmH2O]) showed intraoperative significantly higher PIP, plateau pressure and MP levels but significantly decreased Pdriv and increased LC. On the first and second postoperative day, patients with individualised high PEEP levels had a significantly higher mean Tiffeneau index and FEF25-75. Perioperative oxygenation and ventilation and postoperative spirometric parameters were not influenced by restrictive or liberal crystalloid infusion in either of the two respective PEEP groups. CONCLUSIONS: Individualised high PEEP levels (≥14 cmH2O) during RALP improved intraoperative blood oxygenation and resulted in more lung-protective ventilation. Furthermore, postoperative pulmonary function was improved for up to 48 h after surgery in the sum of the two individualised high PEEP groups. Restrictive crystalloid infusion during RALP seemed to have no effect on peri- and post-operative oxygenation and pulmonary function.

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%.

[Recommendations of the S3 Guideline "Use of Extracorporeal Circulation (ECLS/ ECMO) for Cardiac and Circulatory Failure" of the Association of Scientific Medical Societies in Germany]. / Empfehlungen der S3-Leitlinie (AWMF) "Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen".

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.

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.

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.

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.

Evaluation of models for prognosing mortality in critical care patients with COVID-19: First- and second-wave data from a German university hospital.

BACKGROUND: In a previous study, we had investigated the intensive care course of patients with coronavirus disease 2019 (COVID-19) in the first wave in Germany by calculating models for prognosticating in-hospital death with univariable and multivariable regression analysis. This study analyzed if these models were also applicable to patients with COVID-19 in the second wave. METHODS: This retrospective cohort study included 98 critical care patients with COVID-19, who had been treated at the University Medical Center Regensburg, Germany, between October 2020 and February 2021. Data collected for each patient included vital signs, dosage of catecholamines, analgosedation, anticoagulation, and antithrombotic medication, diagnostic blood tests, treatment with extracorporeal membrane oxygenation (ECMO), intensive care scores, ventilator therapy, and pulmonary gas exchange. Using these data, expected mortality was calculated by means of the originally developed mathematical models, thereby testing the models for their applicability to patients in the second wave. RESULTS: Mortality in the second-wave cohort did not significantly differ from that in the first-wave cohort (41.8% vs. 32.2%, p = 0.151). As in our previous study, individual parameters such as pH of blood or mean arterial pressure (MAP) differed significantly between survivors and non-survivors. In contrast to our previous study, however, survivors and non-survivors in this study showed significant or even highly significant differences in pulmonary gas exchange and ventilator therapy (e.g. mean and minimum values for oxygen saturation and partial pressure of oxygen, mean values for the fraction of inspired oxygen, positive expiratory pressure, tidal volume, and oxygenation ratio). ECMO therapy was more frequently administered than in the first-wave cohort. Calculations of expected mortality by means of the originally developed univariable and multivariable models showed that the use of simple cut-off values for pH, MAP, troponin, or combinations of these parameters resulted in correctly estimated outcome in approximately 75% of patients without ECMO therapy.

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.

Results from a national survey on COVID-19-associated mucormycosis in Germany: 13 patients from six tertiary hospitals.

BACKGROUND: Most COVID-19-associated mucormycosis (CAM) cases are reported from India and neighbouring countries. Anecdotally cases from Europe have been presented. OBJECTIVE: To estimate the disease burden and describe the clinical presentation of CAM in Germany. METHODS: We identified cases through German mycology networks and scientific societies, and collected anonymised clinical information via FungiScope®. RESULTS: We identified 13 CAM cases from six tertiary referral hospitals diagnosed between March 2020 and June 2021. Twelve patients had severe or critical COVID-19, eleven were mechanically ventilated for a median of 8 days (range 1-27 days) before diagnosis of CAM. Eleven patients received systemic corticosteroids. Additional underlying medical conditions were reported for all but one patient, five were immunocompromised because of malignancy or organ transplantation, three were diabetic. Eleven patients developed pneumonia. Mortality was 53.8% with a median time from diagnosis of mucormycosis to death of 9 days (range 0-214 days) despite treatment with liposomal amphotericin B and/or isavuconazole in 10 of 13 cases. CAM prevalence amongst hospitalised COVID-19 patients overall (0.67% and 0.58% in two centres) and those admitted to the intensive care unit (ICU) (1.47%, 1.78% and 0.15% in three centres) was significantly higher compared to non-COVID-19 patients (P < .001 for respective comparisons). CONCLUSION: COVID-19-associated mucormycosis is rare in Germany, mostly reported in patients with comorbidities and impaired immune system and severe COVID-19 treated in the ICU with high mortality compared to mainly rhino-orbito-cerebral CAM in patients with mild COVID-19 in India. Risk for CAM is higher in hospitalised COVID-19 patients than in other patients.