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

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

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

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

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

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

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.

[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.

Contribution of High Viral Loads, Detection of Viral Antigen and Seroconversion to Severe Acute Respiratory Syndrome Coronavirus 2 Infectivity.

BACKGROUND: From a public health perspective, effective containment strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be balanced with individual liberties. METHODS: We collected 79 respiratory samples from 59 patients monitored in an outpatient center or in the intensive care unit of the University Hospital Regensburg. We analyzed viral load by quantitative real-time polymerase chain reaction, viral antigen by point-of-care assay, time since onset of symptoms, and the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies in the context of virus isolation from respiratory specimens. RESULTS: The odds ratio for virus isolation increased 1.9-fold for each log10 level of SARS-CoV-2 RNA and 7.4-fold with detection of viral antigen, while it decreased 6.3-fold beyond 10 days of symptoms and 20.0-fold with the presence of SARS-CoV-2 antibodies. The latter was confirmed for B.1.1.7 strains. The positive predictive value for virus isolation was 60.0% for viral loads >107 RNA copies/mL and 50.0% for the presence of viral antigen. Symptom onset before 10 days and seroconversion predicted lack of infectivity with negative predictive values of 93.8% and 96.0%. CONCLUSIONS: Our data support quarantining patients with high viral load and detection of viral antigen and lifting restrictive measures with increasing time to symptom onset and seroconversion. Delay of antibody formation may prolong infectivity.

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.

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.

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.

Measurement of Free Plasma Concentrations of Beta-Lactam Antibiotics: An Applicability Study in Intensive Care Unit Patients.

BACKGROUND: The antibacterial effect of antibiotics is linked to the free drug concentration. This study investigated the applicability of an ultrafiltration method to determine free plasma concentrations of beta-lactam antibiotics in ICU patients. METHODS: Eligible patients included adult ICU patients treated with ceftazidime (CAZ), meropenem (MEM), piperacillin (PIP)/tazobactam (TAZ), or flucloxacillin (FXN) by continuous infusion. Up to 2 arterial blood samples were drawn at steady state. Patients could be included more than once if they received another antibiotic. Free drug concentrations were determined by high-performance liquid chromatography with ultraviolet detection after ultrafiltration, using a method that maintained physiological conditions (pH 7.4/37°C). Total drug concentrations were determined to calculate the unbound fraction. In a post-hoc analysis, free concentrations were compared with the target value of 4× the epidemiological cut-off value (ECOFF) for Pseudomonas aeruginosa as a worst-case scenario for empirical therapy with CAZ, MEM or PIP/tazobactam and against methicillin-sensitive Staphylococcus aureus for targeted therapy with FXN. RESULTS: Fifty different antibiotic treatment periods in 38 patients were evaluated. The concentrations of the antibiotics showed a wide range because of the fixed dosing regimen in a mixed population with variable kidney function. The mean unbound fractions (fu) of CAZ, MEM, and PIP were 102.5%, 98.4%, and 95.7%, with interpatient variability of <6%. The mean fu of FXN was 11.6%, with interpatient variability of 39%. It was observed that 2 of 12 free concentrations of CAZ, 1 of 40 concentrations of MEM, and 11 of 23 concentrations of PIP were below the applied target concentration of 4 × ECOFF for P. aeruginosa. All concentrations of FXN (9 samples from 6 patients) were >8 × ECOFF for methicillin-sensitive Staphylococcus aureus. CONCLUSIONS: For therapeutic drug monitoring purposes, measuring total or free concentrations of CAZ, MEM, or PIP is seemingly adequate. For highly protein-bound beta-lactams such as FXN, free concentrations should be favored in ICU patients with prevalent hypoalbuminemia.

A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization.

OBJECTIVE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges national health systems and the global economy. Monitoring of infection rates and seroprevalence can guide public health measures to combat the pandemic. This depends on reliable tests on active and former infections. Here, we set out to develop and validate a specific and sensitive enzyme linked immunosorbent assay (ELISA) for detection of anti-SARS-CoV-2 antibody levels. METHODS: In our ELISA, we used SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike (S) ectodomain as antigens. We assessed sera from patients infected with seasonal coronaviruses, SARS-CoV-2 and controls. We determined and monitored IgM-, IgA- and IgG-antibody responses towards these antigens. In addition, for a panel of 22 sera, virus neutralization and ELISA parameters were measured and correlated. RESULTS: The RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R2 = 0.89). Seroconversion started at 5 days after symptom onset and led to robust antibody levels at 10 days after symptom onset. We demonstrate high specificity (99.3%; N = 1000) and sensitivity (92% for IgA, 96% for IgG and 98% for IgM; > 10 days after PCR-proven infection; N = 53) in serum. CONCLUSIONS: With the described RBD-based ELISA protocol, we provide a reliable test for seroepidemiological surveys. Due to high specificity and strong correlation with virus neutralization, the RBD ELISA holds great potential to become a preferred tool to assess thresholds of protective immunity after infection and vaccination.

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

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

Tracheostomy management in patients with severe acute respiratory distress syndrome receiving extracorporeal membrane oxygenation: an International Multicenter Retrospective Study.

BACKGROUND: Current practices regarding tracheostomy in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown. Our objectives were to assess the prevalence and the association between the timing of tracheostomy (during or after ECMO weaning) and related complications, sedative, and analgesic use. METHODS: International, multicenter, retrospective study in four large volume ECMO centers during a 9-year period. RESULTS: Of the 1,168 patients treated with ECMO for severe ARDS (age 48 ± 16 years, 76% male, SAPS II score 51 ± 18) during the enrollment period, 353 (30%) and 177 (15%) underwent tracheostomy placement during or after ECMO, respectively. Severe complications were uncommon in both groups. Local bleeding within 24 h of tracheostomy was four times more frequent during ECMO (25 vs 7% after ECMO, p < 0.01). Cumulative sedative consumption decreased more rapidly after the procedure with sedative doses almost negligible 48-72 h later, when tracheostomy was performed after ECMO decannulation (p < 0.01). A significantly increased level of consciousness was observed within 72 h after tracheostomy in the "after ECMO" group, whereas it was unchanged in the "during-ECMO" group. CONCLUSION: In contrast to patients undergoing tracheostomy after ECMO decannulation, tracheostomy during ECMO was neither associated with a decrease in sedation and analgesia levels nor with an increase in the level of consciousness. This finding together with a higher risk of local bleeding in the days following the procedure reinforces the need for a case-by-case discussion on the balance between risks and benefits of tracheotomy when performed during ECMO.

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

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

[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.

Percutaneous Cannulation for Extracorporeal Life Support in Severely and Morbidly Obese Patients.

BACKGROUND: Extracorporeal life support systems are well-established devices for treating patients with acute cardiopulmonary failure. Severe or morbid obesity may result in complications such as limb ischemia, bleeding, unsuccessful cannulation, or infection at the cannulation sites. This article reports on our experience with cannulation and associated complications in severely and morbidly obese patients. METHODS: Between January 2006 and September 2016, 153 severely or morbidly obese patients with a body mass index >35 kg/m2 were cannulated percutaneously for extracorporeal life support at our center. Among those, 115 patients were treated with venovenous extracorporeal membrane oxygenation (VV ECMO) for acute lung failure and 38 patients with venoarterial extracorporeal membrane oxygenation (VA ECMO) for cardiogenic shock. Complications related to percutaneous access and long-term follow-up were analyzed retrospectively. Primary focus was on the success of cannulation, outcome, thrombosis, bleeding, limb ischemia, and infection at the cannulation site. Normal-weight patients receiving extracorporeal life support served as control. RESULTS: Percutaneous cannulation was successfully performed in all patients. Eighty-five (74%) patients were weaned from VV ECMO and 20 (52%) patients were weaned from VA ECMO. Limb ischemia requiring surgical intervention occurred in 5 (3%) patients, bleeding in 7 (5%) patients, and wound infection in 3 (2%) patients. In all other patients, decannulation was uneventful. These data as well as the long-term survival rates were comparable to those of normal-weight patients (P > .05). CONCLUSION: Percutaneous vessel cannulation for extracorporeal life support systems is generally feasible. Therefore, percutaneous cannulation may well be performed in severely and morbidly obese patients. Patient outcome rather depends on appropriate support than on anatomy.

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.

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.

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.