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.

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

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

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

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

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

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

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.

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

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

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.

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.

Extracorporeal Life Support in Postcardiotomy Cardiogenic Shock: A View on Scenario, Outcome, and Risk Factors in 261 Patients.

BACKGROUND: Weaning failure from cardiopulmonary bypass, postoperative low cardiac output (LCO), and cardiopulmonary resuscitation (CPR) are common scenarios preceding extracorporeal life support (ECLS) implantation after cardiac surgery. The impact of these scenarios on short- and long-term outcome are not well described. METHODS: Between March 2006 and December 2018, 261 patients received ECLS support after cardiac surgery. Data of patients with weaning failure (NW), postoperative LCO, and CPR leading to ECLS implantation were retrospectively analyzed regarding outcome. Risk factors for outcome after postcardiotomy ECLS were assessed by uni- or multivariate regression analysis. RESULTS: Median duration of extracorporeal support was 5.5 ± 8.5 days. Overall mortality on ECLS was 39.1%. Scenario analysis revealed weaning failure from cardiopulmonary bypass in 40.6%, postoperative LCO in 24.5%, and postoperative CPR in 34.9% leading to initiation of ECLS. Most common cause of death was refractory LCO (25.3%). Overall follow-up survival was 23.7%. Survival after weaning and during follow-up in all subgroups was 9.2% (CPR), 5.0% (LCO), and 9.6% (NW), respectively. Uni- or multivariate regression analysis revealed age, aortic surgery, and vasopressor medication level on day 1 as risk for death on support, as well as postoperative renal failure, and body mass index (BMI) as risk factors for death during follow-up. CONCLUSION: Mortality after postcardiotomy ECLS is high. Overall, outcome after CPR, NW, weaning failure and LCO is comparable. Postoperative resuscitation does not negatively affect outcome after postcardiotomy ECLS. Neurological status of ECLS survivors is good.

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.

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.

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

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

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.

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

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

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

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

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

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