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.

[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.

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.

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.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

Secondary hemophagocytic lymphohistiocytosis and severe liver injury induced by hepatic SARS-CoV-2 infection unmasking Wilson's disease: Balancing immunosuppression.

A 21-year-old woman was hospitalized due to coronavirus disease 2019 (COVID-19)-associated respiratory and hepatic impairment concomitant with severe hemolytic anemia. Upon diagnosis of secondary hemophagocytic lymphohistiocytosis, immunosuppression with anakinra and steroids was started, leading to a hepatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and viremia. Subsequent liver biopsy revealed virus particles in hepatocytes by electron microscopy and SARS-CoV-2 virus could be isolated and cultured. Immunosuppression was stopped and convalescent donor plasma given. In the differential diagnosis, an acute crisis of Wilson's disease was raised by laboratory and genetic testing. This case highlights the complexity of balancing immunosuppression to control hyperinflammation versus systemic SARS-CoV-2 dissemination.

Coronavirus disease 2019 induces multi-lineage, morphologic changes in peripheral blood cells.

The clinical course of coronavirus disease 2019 (COVID-19) varies from mild symptoms to acute respiratory distress syndrome, hyperinflammation, and coagulation disorder. The hematopoietic system plays a critical role in the observed hyperinflammation, particularly in severely ill patients. We conducted a prospective diagnostic study performing a blood differential analyzing morphologic changes in peripheral blood of COVID-19 patients. COVID-19 associated morphologic changes were defined in a training cohort and subsequently validated in a second cohort (n = 45). Morphologic aberrations were further analyzed by electron microscopy (EM) and flow cytometry of lymphocytes was performed. We included 45 COVID-19 patients in our study (median age 58 years; 82% on intensive care unit). The blood differential showed a specific pattern of pronounced multi-lineage aberrations in lymphocytes (80%) and monocytes (91%) of patients. Overall, 84%, 98%, and 98% exhibited aberrations in granulopoiesis, erythropoiesis, and thrombopoiesis, respectively. Electron microscopy revealed the ultrastructural equivalents of the observed changes and confirmed the multi-lineage aberrations already seen by light microscopy. The morphologic pattern caused by COVID-19 is characteristic and underlines the serious perturbation of the hematopoietic system. We defined a hematologic COVID-19 pattern to facilitate further independent diagnostic analysis and to investigate the impact on the hematologic system during the clinical course of COVID-19 patients.

Incidence of early intra-cranial bleeding and ischaemia in adult veno-arterial extracorporeal membrane oxygenation and extracorporeal cardiopulmonary resuscitation patients: a retrospective analysis of risk factors.

BACKGROUND: Cerebral complications in veno-arterial extracorporeal membrane oxygenation are known to have a strong impact on mortality and morbidity. Aim of this study is to investigate the early incidence, risk factors and in-hospital mortality of intra-cranial ischaemia and haemorrhage in adults undergoing veno-arterial extracorporeal membrane oxygenation treatment. METHODS: This study is a single-centre retrospective analysis on adult patients undergoing veno-arterial extracorporeal membrane oxygenation for different indications. The inclusion criterion included patients with early routine cerebral computed tomography imaging during extracorporeal membrane oxygenation, with no clinical evidence of cerebral pathology prior to cannulation. Cerebral complications were grouped by aetiology and the territories of the brain's supplying arteries. RESULTS: One hundred eighty-seven adult patients with a total of 190 veno-arterial extracorporeal membrane oxygenation treatments were included. A total of 16.3% (n = 31) had evidence of either cerebral ischaemia (11.1%) or haemorrhage (5.8%); one patient suffered from both. Cerebral computed tomography scans were performed early in median on the first day after extracorporeal membrane oxygenation cannulation; in-hospital mortality of intra-cranial ischaemia and haemorrhage was 71.4% and 45.5%, respectively. Associated with an increased risk for ischaemic lesions were cannulation of the ascending aorta, higher age, presence of an autoimmune disease and cardiac surgery prior to veno-arterial extracorporeal membrane oxygenation. An association with haemorrhagic lesions was found for a lower blood PaCO2 at 2 hours, lower blood flow through the extracorporeal membrane oxygenation device at 2 hours, higher international normalized ratio and constantly higher activated partial thromboplastin time values as well as higher mean arterial pressures until haemorrhagic lesions were evident. CONCLUSION: Cerebral complications are frequent in patients on veno-arterial extracorporeal membrane oxygenation and may be clinically silent events. Careful monitoring with routine neuroimaging seems to be the most appropriate diagnostic approach at present. Intra-cranial ischaemia occurs more frequent than haemorrhage and is associated with cannulation of the aorta ascendens.

The impact of interleukin serum levels on the prognosis of patients undergoing venoarterial extracorporeal membrane oxygenation.

Extracorporeal life support is increasingly used in the treatment of patients presenting with cardiogenic shock or in need of cardiopulmonary resuscitation. Identifying therapeutic targets and factors associated with the prognosis are highly desirable. The present study analyzed the impact of interleukin 6 and 8 on the outcome of patients undergoing venoarterial extracorporeal membrane oxygenation (VA ECMO). Interleukin 6 and 8 serum levels of 329 patients were analyzed prior to, on days 1 and 5 of VA ECMO therapy. Interleukin 6 and 8 serum levels of surviving and nonsurviving patients were compared. At time points with significant differences, receiver operating characteristics and cutoff levels were analyzed to determine the prognostic value of interleukin serum levels. Survival analysis was performed to compare patients above and below cutoff levels. Interleukin 6 serum levels were significantly elevated in nonsurviving patients prior to VA ECMO initiation. Interleukin 6 and 8 serum levels in nonsurviving patients were significantly elevated on day 1 of VA ECMO. Receiver operating characteristics analysis revealed significant prognostic impact of interleukin 6 and 8 on day 1 of VA ECMO (AUC 0.70 and 0.72). Survival analysis comparing patients above and below the cutoff showed a 1-year survival of 32.6% for IL6 and 20.8% for IL8 above, as well as 66.9% for IL6 and 61.9% for IL8 below the cutoff (P < .05). Interleukin 6 and 8 serum levels demonstrated prognostic value early in VA ECMO therapy. The technical applicability of interleukin reduction raises interest in interleukins 6 and 8 as therapeutic targets.

Factors associated with hemolysis during extracorporeal membrane oxygenation (ECMO)-Comparison of VA- versus VV ECMO.

Venovenous (VV) and venoarterial (VA) extracorporeal membrane oxygenation (ECMO) are effective support modalities to treat critically ill patients. ECMO-associated hemolysis remains a serious complication. The aim was to disclose similarities and differences in VA- and VV ECMO-associated hemolysis. This is a retrospective single-center analysis (January 2012 to September 2018) including 1,063 adult consecutive patients (VA, n = 606; VV, n = 457). Severe hemolysis (free plasma hemoglobin, fHb > 500 mg/l) during therapy occurred in 4% (VA) and 2% (VV) (p≤0.001). VV ECMO showed significantly more hemolysis by pump head thrombosis (PHT) compared to VA ECMO (9% vs. 2%; p≤0.001). Pretreatments (ECPR, cardiac surgery) of patients who required VA ECMO caused high fHb pre levels which aggravates the proof of ECMO-induced hemolysis (median (interquartile range), VA: fHb pre: 225.0 (89.3-458.0); VV: fHb pre: 72.0 (42.0-138.0); p≤0.001). The survival rate to discharge from hospital differed depending on ECMO type (40% (VA) vs. 63% (VV); p≤0.001). Hemolysis was dominant in VA ECMO patients, mainly caused by different indications and not by the ECMO support itself. PHT was the most severe form of ECMO-induced hemolysis that occurs in both therapies with low frequency, but more commonly in VV ECMO due to prolonged support time.

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.

The impact of obesity on pulmonary deterioration in patients undergoing robotic-assisted laparoscopic prostatectomy.

Obesity affects respiratory and hemodynamic function in anesthetized patients. The aim of this study was to evaluate the influence of the body mass index (BMI) on pulmonary changes in a permanent 45° steep Trendelenburg position (STP) during robotic-assisted laparoscopic prostatectomy (RALP). 51 patients undergoing RALP under standardized anesthesia were included. Perioperative pulmonary function and oxygenation were measured in awake patients (T0), 20 min after the induction of anesthesia (T1), after insufflation of the abdomen in supine position (T2), after 30 min in STP (T3), when controlling Santorini's plexus in STP (T4), before awakening while supine (T5), and after 45 min in the recovery room (T6). Patient-specific and time-dependent factor on ventilation and predicted peak inspiratory pressure (PIP), driving pressure (Pdriv) and lung compliance (LC) in a linear regression model were calculated. PIP and Pdriv increased significantly after induction of capnoperitoneum (T2-4) (p < 0.0001). In univariate mixed effects models, BMI was found to be a significant predictor for PIP and Pdriv increase and LC decrease. Obese patients a BMI > 31 kg/m2 reached critical PIP values ≥ 35 cmH2O. Postoperative oxygenation represented by the PaO2/FiO2 ratio was significantly decreased compared to T0 (p < 0.0001). Obesity in combination with STP and capnoperitoneum during RALP has a profound effect on pulmonary function. Increased PIP and Pdriv and decreased LC are directly correlated with a high BMI. Changes in PIP, Pdriv and LC during RALP may be predicted in relation to patient's BMI for consideration in the preoperative setting. Trial registration number Z-2014-0387-6. Registered on 8 July 2014.

[Non-Elective Thoracic Surgery in Patients with Respiratory Insufficiency During Support with Veno-Venous Extracorporeal Membrane Oxygenation]. / Nicht elektive thoraxchirurgische Operationen bei Patienten mit respiratorischer Insuffizienz und Einsatz einer venovenösen extrakorporalen Membranoxygenierung.

INTRODUCTION: Patients with severe respiratory failure and veno-venous extracorporeal membrane oxygenation (vv-ECMO) often require diagnostic or therapeutic thoracic surgery. METHODS: Retrospective analysis of prospectively collected data (Regensburg ECMO Registry) on all patients requiring vv-ECMO between December 2010 and December 2016 due to acute lung failure (ALF) with diagnostic or therapeutic thoracic surgery. Endpoints were the indications for thoracic surgery as well as postoperative morbidity and in-hospital mortality. RESULTS: A total of 418 patients (male n = 285, 68%, mean age 50.0 ± 16.5 years) with severe respiratory insufficiency refractory to conventional therapy required vv-ECMO. Indications for vv-ECMO were ALF due to pneumonia (59.8%), postoperative (18.7%), posttraumatic (9.8%), after chemotherapy (2.8%) and others (8.9%). Overall, in 24.4% (n = 102) of patients with vv-ECMO surgery was performed. Of these, 28.4% (n = 29) of patients required thoracic surgery. Primary indications for thoracic surgery were most frequently therapeutic due to hemothorax (n = 13; 44.8%), followed by carnifying pneumonia/pulmonary abscess (n = 5; 17.2%), pleural empyema (n = 3; 10.3%) and others (n = 3; 10.3%). In patients with interstitial lung disease of unknown origin (n = 5; 17.2%), diagnostic pulmonary biopsy was performed. For initial thoracic intervention thoracotomy was carried out in 93.1% (n = 27) of patients, whereas only two patients (6.9%) received thoracoscopy. At least one repeated thoracotomy was performed in 15 patients (51.7%) and nine patients (31.0%) underwent more than two surgeries. In-hospital mortality of patients with thoracic surgery (44.8%) was higher than in patients without thoracic surgery (35.7%; p = 0.326). CONCLUSION: Thoracic surgery in patients with vv-ECMO warrants strict indications, because postoperative complications are common and surgical revision (58,6%) is often required. Therefore, ECMO therapy should only be carried out in specialised centers with thoracic surgery.

Thoracic Bleeding Complications in Patients With Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: Patients with respiratory failure are treated more frequently with venovenous extracorporeal membrane oxygenation (vv-ECMO). These patients are at risk for bleeding due to complex multifactorial coagulation disorders resulting from the extracorporeal circulation. METHODS: A retrospective analysis was conducted of prospectively collected data on all patients requiring vv-ECMO between December 2010 and December 2016. End points were the incidence, consequence, and in-hospital mortality of patients with thoracic bleeding complications. RESULTS: The study included 418 patients (aged 50 ± 16.5 years) requiring vv-ECMO. In 23.2% (n = 97) of patients, relevant hemorrhage was documented. Thoracic bleeding developed in 40 patients (41.2%), followed by diffuse (21.6%), cerebral (14.4%), gastrointestinal (6.2%), cannulation site (6.2%), and other bleeding locations. Thoracic bleeding complications occurred spontaneously (40%), postoperatively (37.5%), after interventions (20%), and after trauma (2.5%). A thoracic operation was performed in 60% (n = 24) of these patients, and a repeated operation due to bleeding was necessary in 45.8%. Mean ECMO duration (18.6 ± 16.8 days; p = 0.035) and hospital length of stay (58 ± 50 days; p = 0.002) were significantly longer than that in patients without bleeding. In-hospital mortality was significantly higher in patients with thoracic bleeding complications (52.5%) than in patients without bleeding complications (32.7%; p = 0.013). CONCLUSIONS: Thoracic bleeding complications were observed in 9.6% of patients and represented the most frequent bleeding complication during vv-ECMO treatment. Almost 60% of patients required surgical revision, and nearly half of these patients underwent a repeated operation. Because mortality is high in these patients, vv-ECMO should be performed in only centers experienced with thoracic surgery.

Accumulation of Multipotent Progenitor Cells on Polymethylpentene Membranes During Extracorporeal Membrane Oxygenation.

Multipotent progenitor cells were mobilized during pediatric extracorporeal membrane oxygenation (ECMO). We hypothesize that these cells also adhered onto polymethylpentene (PMP) fibers within the membrane oxygenator (MO) during adult ECMO support. Mononuclear cells were removed from the surface of explanted PMP-MOs (n = 16). Endothelial-like outgrowth and mesenchymal-like cells were characterized by flow cytometric analysis using different surface markers. Spindle-shaped attaching cells were identified early, but without proliferative activity. After long-term cultivation palisading type or cobblestone-type outgrowth cells with high proliferative activity appeared and were characterized as (i) leukocytoid CD45+/CD31+ (CD133+/VEGFR-II+/CD90+/CD14+/CD146dim/CD105dim); (ii) endothelial-like CD45-/CD31+ (VEGF-RII+/CD146+/CD105+/CD133-/CD14-/CD90-); and (iii) mesenchymal-like cells CD45-/CD31- (CD105+/CD90+/CD133dim/VEGFR-II-/CD146-/CD14-). The distribution of the cell populations depended on the MO and cultivation time. Endothelial-like cells formed capillary-like structures and did uptake Dil-acetylated low-density lipoprotein. Endothelial- and mesenchymal-like cells adhered on the surface of PMP-MOs. Further research is needed to identify the clinical relevance of these cells.

Hemostatic Changes During Extracorporeal Membrane Oxygenation: A Prospective Randomized Clinical Trial Comparing Three Different Extracorporeal Membrane Oxygenation Systems.

OBJECTIVE: Extracorporeal membrane oxygenation is a rescue therapy for patients with severe lung failure. Major complications caused by extracorporeal membrane oxygenation are bleeding, thrombosis, and hemolysis. The aim of this study was to compare the impact of different extracorporeal membrane oxygenation systems on blood hemostasis in adults during veno-venous extracorporeal membrane oxygenation therapy. DESIGN: Single center prospective randomized study. SETTING: University Hospital Regensburg, Germany. PATIENTS: Adult patients with severe acute respiratory distress syndrome requiring veno-venous extracorporeal membrane oxygenation therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three different extracorporeal membrane oxygenation systems: the Cardiohelp system (Maquet Cardiopulmonary AG), the Dideco ECC.O5 (Sorin Group), and the Deltastream system with Hilite 7000 LT + DP3 pumphead (Medos Medizintechnik AG) were compared. Therefore hemostasis, anticoagulation, hemolysis, and inflammatory parameters were monitored. Of the 54 patients included in the study, 18 patients each were randomly assigned to the three different extracorporeal membrane oxygenation systems. Exclusion criteria were acute renal failure, trauma, and surgery within 2 days. The median time on veno-venous extracorporeal membrane oxygenation support was 13.5 days (4-70 d). Median platelet count had dropped from 220.5 G/L before extracorporeal membrane oxygenation therapy to a minimum of 133 G/L by the last day of extracorporeal membrane oxygenation support. During the first 5 days of extracorporeal membrane oxygenation therapy, prothrombin fragment 1.2 (F1.2) (1.36-2.4 µM), thrombin-antithrombin complex (14.5-50 µg/L), and D-dimers (6.00-27.0 mg/L) increased, whereas fibrinogen values dropped from 5.8 to 4.1 g/L. The three different extracorporeal membrane oxygenation systems did not show any differences with regard to hemostasis, anticoagulation, hemolysis, and inflammatory parameters within the first 5 days of extracorporeal membrane oxygenation therapy. CONCLUSIONS: Over time, miniaturized veno-venous extracorporeal membrane oxygenation therapy increasingly activates coagulation. The different types of membrane oxygenators and pumps did not significantly alter hemostasis.

Efficiency of gas transfer in venovenous extracorporeal membrane oxygenation: analysis of 317 cases with four different ECMO systems.

PURPOSE: Polymethylpentene membrane oxygenators used in venovenous extracorporeal membrane oxygenation (vvECMO) differ in their physical characteristics. The aim of the study was to analyze the gas transfer capability of different ECMO systems in clinical practice, as the choice of the appropriate system may be influenced by the needs of the patient. METHODS: Retrospective study on prospectively collected data of adults with severe respiratory failure requiring vvECMO support (Regensburg ECMO Registry, 2009-2013). Oxygen (O2) transfer and carbon dioxide (CO2) elimination of four different ECMO systems (PLS system, n = 163; Cardiohelp system (CH), n = 59, Maquet Cardiopulmonary, Rastatt, Germany; Hilite 7000 LT system, n = 56, Medos Medizintechnik, Stolberg, Germany; ECC.05 system, n = 39, Sorin Group, Mirandola (MO), Italy) were analyzed. RESULTS: Gas transfer depended on type of ECMO system, blood flow, and gas flow (p ≤ 0.05, each). CO2 removal is dependent on sweep gas flow and blood flow, with higher blood flow and/or gas flow eliminating more CO2 (p ≤ 0.001). CO2 elimination capacity was highest with the PLS system (p ≤ 0.001). O2 transfer at blood flow rates below 3 l/min depended on blood flow, at higher blood flow rates on blood flow and gas flow. The system with the smallest gas exchange surface (ECC.05 system) was least effective in O2 transfer, but in terms of the gas exchange surface was the most effective. CONCLUSION: Our analysis suggests that patients with severe hypoxemia and need for high flow ECMO benefit more from the PLS/CH or Hilite 7000 LT system. The ECC.05 system is advisable for patients with moderate hypoxemia and/or hypercapnia.