Extracorporeal life support (ECLS) was developed more than 50 years ago, initially with venoarterial and subsequently with venovenous configurations. As the technique of ECLS significantly improved ...and newer skills developed, complexity in terminology and advances in cannula design led to some misunderstanding of and inconsistency in definitions, both in clinical practice and in scientific research. This document is a consensus of multispecialty international representatives of the Extracorporeal Life Support Organization, including the North America, Latin America, EuroELSO, South West Asia and Africa, and Asia-Pacific chapters, imparting a global perspective on ECLS. The goal is to provide a consistent and unambiguous nomenclature for ECLS and to overcome the inconsistent use of abbreviations for ECLS cannulation. Secondary benefits are ease of multicenter collaboration in research, improved registry data quality, and clear communication among practitioners and researchers in the field.
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.
Analysis of the prevalence and risk factors for weaning failure from venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with severe acute respiratory insufficiency.
Single-center ...retrospective observational study.
Sixteen beds medical ICU at the University Hospital Regensburg.
Two hundred twenty-seven patients with severe acute respiratory insufficiency requiring VV-ECMO support between October 2011 and December 2017.
None.
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.
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.
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 systemsthe 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.
Symptoms of gastro-esophageal reflux disease (GERD) in pregnancy are reported with a prevalence of 30-80%. The aim of this study was to assess the prevalence and severity of GERD symptoms during the ...course of pregnancy. Furthermore current practice in medical care for GERD during pregnancy was assessed.
We performed a prospective longitudinal cohort study on 510 pregnant women (mean age 28.12, SD 5.3). Investigations for reflux symptoms where based on the use of validated reflux-disease questionnaire (RDQ). Additional information was collected about the therapy. A group of non-pregnant women (mean age 24.56, SD 5.7) was included as controls. Frequency and severity of reflux symptoms were recorded in each trimester of pregnancy.
The prevalence of GERD symptoms in pregnant women increased from the first trimester with 26.1 to 36.1% in the second trimester and to 51.2% in the third trimester of pregnancy. The prevalence of GERD symptoms in the control group was 9.3%.Pregnant women received medication for their GERD symptoms in 12.8% during the first, 9.1% during the second and 15.7% during the third trimester. Medications used >90% antacids, 0% PPI.
GERD symptoms occur more often in pregnant women than in non-pregnant and the frequency rises in the course of pregnancy. Medical therapy is used in a minority of cases and often with no adequate symptom relief.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intracranial bleeding (ICB) is a serious complication during veno-venous extracorporeal membrane oxygenation (V-V ECMO), with potentially fatal consequences.
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.
Five hundred fifty six patients were included in this retrospective single center analysis.
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 paCO
>35mmHg (OR: 2.56) and rapid decrease in norepinephrine >1mg/h (OR: 2.53). Multivariable analysis revealed low platelets, high paCO
before ECMO, and rapid drop in paCO
after V-V ECMO initiation as significant risk factors for ICB.
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.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Extracorporeal life support (ECLS) has extensive applications in managing patients with acute cardiac and pulmonary failure. Two primary modalities of ECLS, cardiopulmonary bypass (CPB) and ...extracorporeal membrane oxygenation (ECMO), include several similarities in their composition, complications, and patient outcomes. Both CPB and ECMO pose a high risk of thrombus formation and platelet activation due to the large surface area of the devices and bleeding due to system anticoagulation. Therefore, novel methods of anticoagulation are needed to reduce the morbidity and mortality associated with extracorporeal support. Nitric oxide has potent antiplatelet properties and presents a promising alternative or addition to anticoagulation with heparin during extracorporeal support.
We developed two ex-vivo models of CPB and ECMO to investigate nitric oxide (NO) effects on anticoagulation and inflammation in these systems.
Sole addition of NO as an anticoagulant was not successful in preventing thrombus formation in the ex vivo setups, therefore a combination of low level heparin with NO was used. Antiplatelet effects were observed in the ex vivo ECMO model when nitric oxide was delivered at 80 PPM. Platelet count was preserved after 480 minutes when nitric oxide was delivered at 30 PPM.
Combined delivery of nitric oxide and heparin did not improve haemocompatibility in either ex vivo model of CPB and ECMO. Anti-inflammatory effects of NO in ECMO systems have to be evaluated further.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Coronavirus disease 2019 (COVID-19) can lead to pneumonia and hyperinflammation. Here we show a sensitive method to measure polyclonal T cell activation by downstream effects on responder ...cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood. We report a clear T cell hyporeactivity in hospitalized COVID-19 patients that is pronounced in ventilated patients, associated with prolonged virus persistence and reversible with clinical recovery. COVID-19-induced T cell hyporeactivity is T cell extrinsic and caused by plasma components, independent of occasional immunosuppressive medication of the patients. Monocytes respond stronger in males than females and IL-2 partially restores T cell activation. Downstream markers of T cell hyporeactivity are also visible in fresh blood samples of ventilated patients. Based on our data we developed a score to predict fatal outcomes and identify patients that may benefit from strategies to overcome T cell hyporeactivity.
Background
Extracorporeal membrane oxygenation (ECMO) is a life-saving modality used to manage cardiopulmonary failure refractory to conventional medical and surgical therapies. Despite advances in ...ECMO equipment, bleeding and thrombosis remain significant complications. While the flow rate for ECMO support is well recognized, less is known about the minimum-rate requirements and haemostasis. We investigated the relationship between different ECMO flow rates, and their effect on haemolysis and coagulation.
Methods
Ten ex-vivo ECMO circuits were tested using donated, < 24-h-old human whole blood, with two flow rates: high-flow at 4 L/min (normal adult cardiac output;
n
= 5) and low-flow at 1.5 L/min (weaning;
n
= 5). Serial blood samples were taken for analysis of haemolysis, von Willebrand factor (vWF) multimers by immunoblotting, rotational thromboelastometry, platelet aggregometry, flow cytometry and routine coagulation laboratory tests.
Results
Low-flow rates increased haemolysis after 2 h (
p
= 0.02), 4 h (
p
= 0.02) and 6 h (
p
= 0.02) and the loss of high-molecular-weight vWF multimers (
p
= 0.01), while reducing ristocetin-induced platelet aggregation (
p
= 0.0002). Additionally, clot formation times were prolonged (
p
= 0.006), with a corresponding decrease in maximum clot firmness (
p
= 0.006).
Conclusions
In an ex-vivo model of ECMO, low-flow rate (1.5 L/min) altered haemostatic parameters compared to high-flow (4 L/min). Observed differences in haemolysis, ristocetin-induced platelet aggregation, high-molecular-weight vWF multimers and clot formation time suggest an increased risk of bleeding complications. Since patients are often on ECMO for protracted periods, extended-duration studies are required to characterise long-term ECMO-induced haemostatic changes.
Veno-venous extracorporeal membrane oxygenation (VV ECMO) is a rescue treatment for acute respiratory distress syndrome (ARDS) failing protective mechanical ventilation. It temporarily provides ...proper gas exchange: hypoxia is treated by adjusting the blood flow rate and fraction in spired oxygen over the ventilator (FiO
) on the extracorporeal membrane oxygenation (ECMO) circuit while CO
removal is regulated by the ECMO fresh gas flow. Therefore, ventilator settings can be gradually reduced allowing the lungs to rest and recover. Nowadays, indications for ECMO referral and implantation are clearly formulated; on the contrary, little evidence currently exists to guide the process of weaning from ECMO support, especially concerning the timing during the course of lung healing. Therefore, indications to stop ECMO are less well standardized so that in clinical trials extracorporeal assistance is generally continued until lung recovery, with neither specific nor homogenous criteria for withdrawal. Notably, in almost all papers dealing with data on VV ECMO support, the management of weaning and the weaning procedure itself are not described. The aim of this paper is to make a picture of VV ECMO weaning, as it is performed in three European large volume intensive care units (ICUs) which represent referral centers for VV ECMO treatment. We focused on data concerning the timing of VV ECMO weaning and parameters at the time of weaning, in order to assess adequacy and safety of VV ECMO removal.
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