Temporal changes in markers of coagulation and fibrinolysis in adults during extracorporeal membrane oxygenation.

INTRODUCTION: Bleeding and thrombotic events (BTE) are frequent during extracorporeal membrane oxygenation (ECMO). They occur at varying timepoints and may be affected by temporal changes in coagulation and fibrinolysis. We aimed to assess various coagulation and fibrinolytic markers over time and their relationship with BTE. METHODS: A single-centre prospective study was performed in 17 patients with severe respiratory failure receiving veno-venous ECMO. Blood samples were collected before and during ECMO, and around circuit decannulation. RESULTS: Prior to ECMO, D-Dimer, Plasmin-Antiplasmin complexes (PAP), Plasminogen-Activator Inhibitor-1 (PAI-1) and fibrinogen were elevated. There was an increase in D-Dimer and Prothrombin Fragments 1+2 (PF1+2) (729 to 1305pmol/L, p = .034) by day 1 and PAP increased by day 2 from baseline levels (median 1022 to 1797 µg/L, p = .023). There was a strong positive correlation in PAP, PF1+2 and thrombin-antithrombin complexes (TAT) to D-Dimer. BTE were frequent - 18% had major extracranial haemorrhage and 24% had intracranial haemorrhage. Over time, there was a progressive elevation PAP in patients developing subsequent extracranial haemorrhage, whereas D-Dimer, PAP and PF1+2 increased after intracranial haemorrhage. CONCLUSIONS: There were early changes in coagulation activity during ECMO by PF1+2 followed by subsequent fibrinolysis by PAP. Changes in PAP, PF1+2 and TAT were associated with major haemorrhage.

Extracorporeal Carbon Dioxide Removal With the Hemolung in Patients With Acute-on-Chronic Respiratory Failure: A Multicenter Retrospective Cohort Study.

Extracorporeal carbon dioxide removal (ECCO2R) devices are increasingly used in treating acute-on-chronic respiratory failure caused by chronic lung diseases. There are no large studies that investigated safety, efficacy, and the independent association of prognostic variables to survival that could define the role of ECCO2R devices in such patients. This multicenter, multinational, retrospective study investigated the efficacy, safety of a single ECCO2R device (Hemolung) in patients with acute on chronic respiratory failure and identified variables independently associated with intensive care unit (ICU) survival. The primary outcome was improvement in blood gasses with the use of Hemolung. Secondary outcomes included reduction in tidal volume, respiratory rate, minute ventilation, survival to ICU discharge, and complication profile. Multivariable regression analysis was used to identify variables that are independently associated with ICU survival. A total of 62 patients were included. There was a significant improvement in pH and partial pressure of carbon dioxide in arterial blood (PaCO2) along with a reduction in respiratory rate, tidal volume, and minute ventilation with Hemolung therapy. The complication profile did not differ between survivors and nonsurvivors. Multivariable analysis identified the duration of Hemolung therapy to be independently associated with survival to ICU discharge (adjusted odds ratio = 1.21; 95% confidence interval [CI] = 1.040-1.518; p = 0.01).

The intricate physiology of veno-venous extracorporeal membrane oxygenation: an overview for clinicians.

During veno-venous extracorporeal membrane oxygenation (V-V ECMO), blood is drained from the central venous circulation to be oxygenated and decarbonated by an artificial lung. It is then reinfused into the right heart and pulmonary circulation where further gas-exchange occurs. Each of these steps is characterized by a peculiar physiology that this manuscript analyses, with the aim of providing bedside tools for clinical care: we begin by describing the factors that affect the efficiency of blood drainage, such as patient and cannulae position, fluid status, cardiac output and ventilatory strategies. We then dig into the complexity of extracorporeal gas-exchange, with particular reference to the effects of extracorporeal blood-flow (ECBF), fraction of delivered oxygen (FdO2) and sweep gas-flow (SGF) on oxygenation and decarbonation. Subsequently, we focus on the reinfusion of arterialized blood into the right heart, highlighting the effects on recirculation and, more importantly, on right ventricular function. The importance and challenges of haemodynamic monitoring during V-V ECMO are also analysed. Finally, we detail the interdependence between extracorporeal circulation, native lung function and mechanical ventilation in providing adequate arterial blood gases while allowing lung rest. In the absence of evidence-based strategies to care for this particular group of patients, clinical practice is underpinned by a sound knowledge of the intricate physiology of V-V ECMO.

Left ventricular unloading in patients supported with veno-arterial extra corporeal membrane oxygenation; an international EuroELSO survey.

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) improves end-organ perfusion in cardiogenic shock but may increase afterload, which can limit cardiac recovery. Left ventricular (LV) unloading strategies may aid cardiac recovery and prevent complications of increased afterload. However, there is no consensus on when and which unloading strategy should be used. METHODS: An online survey was distributed worldwide via the EuroELSO newsletter mailing list to describe contemporary international practice and evaluate heterogeneity in strategies for LV unloading. RESULTS: Of 192 respondents from 43 countries, 53% routinely use mechanical LV unloading, to promote ventricular recovery and/or to prevent complications. Of those that do not routinely unload, 65% cited risk of complications as the reason. The most common indications for unplanned unloading were reduced arterial line pulsatility (68%), pulmonary edema (64%) and LV dilatation (50%). An intra-aortic balloon pump was the most frequently used device for unloading followed by percutaneous left ventricular assist devices. Echocardiography was the most frequently used method to monitor the response to unloading. CONCLUSIONS: Significant variation exists with respect to international practice of ventricular unloading. Further research is required that compares the efficacy of different unloading strategies and a randomized comparison of routine mechanical unloading versus unplanned unloading.

The Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal Compared With Conventional Lung Protective Ventilation on Cardiac Function.

OBJECTIVES: Lower tidal volume ventilation (targeting 3 mL/kg predicted body weight, PBW) facilitated by extracorporeal carbon dioxide removal (ECCO2R) has been investigated as a potential therapy for acute hypoxemic respiratory failure (AHRF) in the pRotective vEntilation with veno-venouS lung assisT in respiratory failure (REST) trial. We investigated the effect of this strategy on cardiac function, and in particular the right ventricle. DESIGN: Substudy of the REST trial. SETTING: Nine U.K. ICUs. PATIENTS: Patients with AHRF (Pao2/Fio2 < 150 mm Hg [20 kPa]). INTERVENTION: Transthoracic echocardiography and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements were collected at baseline and postrandomization in patients randomized to ECCO2R or usual care. MEASUREMENTS: The primary outcome measures were a difference in tricuspid annular plane systolic excursion (TAPSE) on postrandomization echocardiogram and difference in NT-proBNP postrandomization. RESULTS: There were 21 patients included in the echocardiography cohort (ECCO2R, n = 13; usual care, n = 8). Patient characteristics were similar in both groups at baseline. Median (interquartile range) tidal volumes were lower in the ECCO2R group compared with the usual care group postrandomization; 3.6 (3.1-4.2) mL/kg PBW versus 5.2 (4.9-5.7) mL/kg PBW, respectively (p = 0.01). There was no difference in the primary outcome measure of mean (sd) TAPSE in the ECCO2R and usual care groups postrandomization; 21.3 (5.4) mm versus 20.1 (3.2) mm, respectively (p = 0.60). There were 75 patients included in the NT-proBNP cohort (ECCO2R, n = 36; usual care, n = 39). Patient characteristics were similar in both groups at baseline. Median (interquartile range [IQR]) tidal volumes were lower in the ECCO2R group than the usual care group postrandomization; 3.8 (3.3-4.2) mL/kg PBW versus 6.7 (5.8-8.1) mL/kg PBW, respectively (p < 0.0001). There was no difference in median (IQR) NT-proBNP postrandomization; 1121 (241-5370) pg/mL versus 1393 (723-4332) pg/mL in the ECCO2R and usual care groups, respectively (p = 0.30). CONCLUSIONS: In patients with AHRF, a reduction in tidal volume facilitated by ECCO2R, did not modify cardiac function.

Extracorporeal Life Support Organization Registry International Report 2022: 100,000 Survivors.

The Extracorporeal Life Support Organization (ELSO) maintains the world's largest extracorporeal membrane oxygenation (ECMO) registry by volume, center participation, and international scope. This 2022 ELSO Registry Report describes the program characteristics of ECMO centers, processes of ECMO care, and reported outcomes. Neonates (0-28 days), children (29 days-17 years), and adults (≥18 years) supported with ECMO from 2009 through 2022 and reported to the ELSO Registry were included. This report describes adjunctive therapies, support modes, treatments, complications, and survival outcomes. Data are presented descriptively as counts and percent or median and interquartile range (IQR) by year, group, or level. Missing values were excluded before calculating descriptive statistics. Complications are reported per 1,000 ECMO hours. From 2009 to 2022, 154,568 ECMO runs were entered into the ELSO Registry. Seven hundred and eighty centers submitted data during this time (557 in 2022). Since 2009, the median annual number of adult ECMO runs per center per year increased from 4 to 15, whereas for pediatric and neonatal runs, the rate decreased from 12 to 7. Over 50% of patients were transferred to the reporting ECMO center; 20% of these patients were transported with ECMO. The use of prone positioning before respiratory ECMO increased from 15% (2019) to 44% (2021) for adults during the coronavirus disease-2019 (COVID-19) pandemic. Survival to hospital discharge was greatest at 68.5% for neonatal respiratory support and lowest at 29.5% for ECPR delivered to adults. By 2022, the Registry had enrolled its 200,000th ECMO patient and 100,000th patient discharged alive. Since its inception, the ELSO Registry has helped centers measure and compare outcomes across its member centers and strategies of care. Continued growth and development of the Registry will aim to bolster its utility to patients and centers.

Extracorporeal Carbon Dioxide Removal to Avoid Invasive Ventilation During Exacerbations of Chronic Obstructive Pulmonary Disease: VENT-AVOID Trial - A Randomized Clinical Trial.

Rationale: It is unclear whether extracorporeal CO2 removal (ECCO2R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives: To determine whether ECCO2R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV. Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018-2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO2R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33). Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P = 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0-0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO2R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00-1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO2R arm (22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P = 0.73). Conclusions: In subjects with exacerbation of COPD, the use of ECCO2R compared with standard care did not improve VFD-5. Clinical trial registered with www.clinicaltrials.gov (NCT03255057).

State of the art: Monitoring of the respiratory system during veno-venous extracorporeal membrane oxygenation.

Monitoring the patient receiving veno-venous extracorporeal membrane oxygenation (VV ECMO) is challenging due to the complex physiological interplay between native and membrane lung. Understanding these interactions is essential to understand the utility and limitations of different approaches to respiratory monitoring during ECMO. We present a summary of the underlying physiology of native and membrane lung gas exchange and describe different tools for titrating and monitoring gas exchange during ECMO. However, the most important role of VV ECMO in severe respiratory failure is as a means of avoiding further ergotrauma. Although optimal respiratory management during ECMO has not been defined, over the last decade there have been advances in multimodal respiratory assessment which have the potential to guide care. We describe a combination of imaging, ventilator-derived or invasive lung mechanic assessments as a means to individualise management during ECMO.

Bilateral Femoral Cannulation Is Associated With Reduced Severe Limb Ischemia-Related Complications Compared With Unilateral Femoral Cannulation in Adult Peripheral Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Registry.

OBJECTIVES: Peripheral venoarterial extracorporeal membrane oxygenation (ECMO) with femoral access is obtained through unilateral or bilateral groin cannulation. Whether one cannulation strategy is associated with a lower risk for limb ischemia remains unknown. We aim to assess if one strategy is preferable. DESIGN: A retrospective cohort study based on the Extracorporeal Life Support Organization registry. SETTING: ECMO centers worldwide included in the Extracorporeal Life Support Organization registry. PATIENTS: All adult patients (≥ 18 yr) who received peripheral venoarterial ECMO with femoral access and were included from 2014 to 2020. INTERVENTIONS: Unilateral or bilateral femoral cannulation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of limb ischemia defined as a composite endpoint including the need for a distal perfusion cannula (DPC) after 6 hours from implantation, compartment syndrome/fasciotomy, amputation, revascularization, and thrombectomy. Secondary endpoints included bleeding at the peripheral cannulation site, need for vessel repair, vessel repair after decannulation, and in-hospital death. Propensity score matching was performed to account for confounders. Overall, 19,093 patients underwent peripheral venoarterial ECMO through unilateral ( n = 11,965) or bilateral ( n = 7,128) femoral cannulation. Limb ischemia requiring any intervention was not different between both groups (bilateral vs unilateral: odds ratio [OR], 0.92; 95% CI, 0.82-1.02). However, there was a lower rate of compartment syndrome/fasciotomy in the bilateral group (bilateral vs unilateral: OR, 0.80; 95% CI, 0.66-0.97). Bilateral cannulation was also associated with lower odds of cannulation site bleeding (bilateral vs unilateral: OR, 0.87; 95% CI, 0.76-0.99), vessel repair (bilateral vs unilateral: OR, 0.55; 95% CI, 0.38-0.79), and in-hospital mortality (bilateral vs unilateral: OR, 0.85; 95% CI, 0.81-0.91) compared with unilateral cannulation. These findings were unchanged after propensity matching. CONCLUSIONS: This study showed no risk reduction for overall limb ischemia-related events requiring DPC after 6 hours when comparing bilateral to unilateral femoral cannulation in peripheral venoarterial ECMO. However, bilateral cannulation was associated with a reduced risk for compartment syndrome/fasciotomy, lower rates of bleeding and vessel repair during ECMO, and lower in-hospital mortality.

Behavioural and physiological impacts of low salinity on the sea urchin Echinus esculentus.

Reduced seawater salinity as a result of freshwater input can exert a major influence on the ecophysiology of benthic marine invertebrates, such as echinoderms. While numerous experimental studies have explored the physiological and behavioural effects of short-term, acute exposure to low salinity in echinoids, surprisingly few have investigated the consequences of chronic exposure, or compared the two. In this study, the European sea urchin, Echinus esculentus, was exposed to low salinity over the short term (11‰, 16‰, 21‰, 26‰ and 31‰ for 24 h) and longer term (21, 26 and 31‰ for 25 days). Over the short term, oxygen consumption, activity coefficient and coelomic fluid osmolality were directly correlated with reduced salinity, with 100% survival at ≥21‰ and 0% at ≤16‰. Over the longer term at 21‰ (25 days), oxygen consumption was significantly higher, feeding was significantly reduced and activity coefficient values were significantly lower than at control salinity (31‰). At 26‰, all metrics were comparable to the control by the end of the experiment, suggesting acclimation. Furthermore, beneficial functional resistance (righting ability and metabolic capacity) to acute low salinity was observed at 26‰. Osmolality values were slightly hyperosmotic to the external seawater at all acclimation salinities, while coelomocyte composition and concentration were unaffected by chronic low salinity. Overall, E. esculentus demonstrate phenotypic plasticity that enables acclimation to reduced salinity around 26‰; however, 21‰ represents a lower acclimation threshold, potentially limiting its distribution in coastal areas prone to high freshwater input.