Extracorporeal membrane oxygenation during pregnancy and peripartal. An international retrospective multicenter study

Introduction Extracorporeal Membrane Oxygenation (ECMO) may be used in the setting of pregnancy or the peripartal period, however its utility has not been well-characterized. This study aims to give an overview on the prevalence of peripartel ECMO cases and further assess the indications and outcomes of ECMO in this setting across multiple centers and countries. Methods A retrospective, multicenter, international cohort study of pregnant and peripartum ECMO cases was performed. Data were collected from six ECMO centers across three continents over a 10-year period. Results A total of 60 pregnany/peripartal ECMO cases have been identified. Most frequent indications are acute respiratory distress syndrome (n = 30) and pulmonary embolism (n = 5). Veno-venous ECMO mode was applied more often (77%). ECMO treatment during pregnancy was performed in 17 cases. Maternal and fetal survival was high with 87% (n = 52), respectively 73% (n = 44). Conclusions Various emergency scenarios during pregnancy and at time of delivery may require ECMO treatment. Peripartal mortality in a well-resourced setting is rare, however emergencies in the labor room occur and knowledge of available rescue therapy is essential to improve outcome. Obstetricians and obstetric anesthesiologists should be aware of the availability of ECMO resource at their hospital or region to ensure immediate contact when needed

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

Abstract 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

Recirculation in single lumen cannula venovenous extracorporeal membrane oxygenation: A non-randomized bi-centric trial

Background: Recirculation is a common problem in venovenous (VV) extracorporeal membrane oxygenation (ECMO). The aims of this study were to compare recirculation fraction (Rf) between femoro-jugular and jugulo-femoral VV ECMO configurations, to identify risk factors for recirculation and to assess the impact on hemolysis. Methods: Patients in the medical intensive care unit (ICU) at the University Medical Center Regensburg, Germany receiving VV ECMO with femoro-jugular, and jugulo-femoral configuration at the ECMO Center Karolinska, Sweden, were included in this non-randomized prospective study. Total ECMO flow (QEC), recirculated flow (QREC), and recirculation fraction Rf = QREC/QEC were determined using ultrasound dilution technology. Effective ECMO flow (QEFF) was defined as QEFF = QEC * (1–Rf). Demographics, cannula specifics, and markers of hemolysis were assessed. Survival was evaluated at discharge from ICU. Results: Thirty-seven patients with femoro-jugular configuration underwent 595 single-point measurements and 18 patients with jugulo-femoral configuration 231 measurements. Rf was lower with femoro-jugular compared to jugulo-femoral configuration [5 (0, 11) vs. 19 (13, 28) %, respectively (p 8 vs. ≤ 8%. Explorative data on survival showed comparable results in the femoro-jugular and the jugulo-femoral group (81 vs. 72%, p = 0.455). Conclusion: VV ECMO with femoro-jugular configuration caused less recirculation. Further risk factors for higher Rf were shorter distance between the two cannula tips, higher ECMO flow, and lower heart rate. Rf did not affect hemolysis

Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes

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.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

Major Bleeding and Thromboembolic Events in Veno-Venous Extracorporeal Membrane Oxygenation-Patients With Isolated Respiratory Failure

Bleeding and thromboembolic events are common during veno-venous extracorporeal membrane oxygenation (vvECMO). It is unknown whether these complications are driven by the ECMO system itself, multiorgan-failure, or both. The aim of this study was to assess the prevalence of bleeding and thromboembolic events in patients with isolated respiratory failure. Patients with vvECMO were retrospectively included from March 2009 to October 2017. Exclusion included any organ failure other than respiratory. Major bleeding was defined as a decrease in hemoglobin >= 2 g/dl per 24 hours, the requirement for transfusion of >= 2 packed red blood cell concentrates per 24 hours, any retroperitoneal, pulmonary, central nervous system bleeding, or bleeding requiring surgery. Thromboembolic events were assessed by duplex sonography or CT scan. Of 601 patients, 123 patients with a mean age of 49 +/- 15 years and a median Sepsis-related Organ Failure Assessment score of 8 (7-9) were eligible for the analysis. Major bleeding was observed in 73%; 35% of all bleedings occurred on the day of or after ECMO initiation. A more pronounced decrease of PaCO2 after ECMO initiation was seen in patients with intracranial bleeding (ICB) compared with those without. Thromboembolic events were noted in 30%. The levels of activated prothrombin time, fibrinogen, platelet count, or D-dimers affected neither bleeding nor the prevalence of thromboembolic events

Adaptive servo-ventilation and sleep quality in treatment emergent central sleep apnea and central sleep apnea in patients with heart disease and preserved ejection fraction

Background Reduced sleep quality is associated with impaired quality of life and increased mortality in patients with heart failure. The aim of this study was to observe changes in sleep fragmentation and sleep quality in patients with heart disease and preserved left ventricular ejection fraction (pEF) treated with adaptive servo-ventilation (ASV) therapy for treatment of emergent central sleep apnea (TECSA) or central sleep apnea (CSA). Methods 114 patients with structural heart disease and pEF introduced to ASV therapy between 2010 and 2015 were retrospectively analyzed. Patients were stratified into two groups; TECSA (n = 60) or CSA (n = 54). Changes of sleep fragmentation and sleep quality from baseline to ASV initiation were compared. Results ASV therapy leads to a significant reduction of apnea-hypopnea index (AHI) and arousal index in patients with TECSA and CSA (Delta AHI: -43 +/- 21 vs. -47 +/- 22/h; Delta arousal index -11 +/- 15, vs. -11 +/- 21/h). ASV treatment leads to a significant increase in sleep efficiency in TECSA compared to CSA (Delta SE: 10 +/- 19 vs. 1 +/- 18%, p = 0.019). Both groups had significantly longer stage N3 (N3) and rapid eye movement sleep (REM) on ASV (Delta N3: 8 +/- 11 vs. 9 +/- 13%; Delta REM 7 +/- 9 vs. 3 +/- 8%; p < 0.05 for all comparisons baseline vs. ASV). Conclusions In patients with heart disease and pEF, whose TECSA and CSA were treated with ASV, a significant reduction of AHI and arousal index as well as an increase of N3 and REM sleep was observed. Increase of sleep efficiency was significantly greater in TECSA compared to CSA. Hence, improvements of sleep quality were modestly greater in patients with TECSA compared to those with CSA

Predictors of poor outcome after extra-corporeal membrane oxygenation for refractory cardiac arrest (ECPR): A post hoc analysis of a multicenter database

Background: The objective was to assess predictors for unfavorable neurological outcome (UO) in out-of-hospital (OHCA) and in-hospital (IHCA) cardiac arrest patients treated with Extracorporeal cardiopulmonary resuscitation (ECPR). Methods: A post hoc analysis of retrospective data from five European ECPR centers (January 2012-December 2016) was performed. The primary composite endpoint was 3-month UO defined as survival with a cerebral performance category (CPC) of 3-4 or death (CPC 5). Results: A total of 413 patients treated with ECPR were included (median age was 57 [48-65] years, male gender 78%): 61% of patients (n = 250) suffered OHCA. The median time from collapse to ECMO placement was 63 [45-82] minutes. Overall, 81% patients (n = 333) showed unfavorable UO, which was higher in OHCA patients (90% vs 66%), as compared to IHCA. In OHCA, prolonged time from collapse to ECMO initiation (OR 1.02, p < 0.01) and higher ECMO blood flow (OR 1.99, p = 0.01) were associated with UO while initial shockable rhythm (OR 0.04, p < 0.01), previous heart disease (OR 0.20, p < 0.01) and pre-hospital hypothermia (OR 0.08, p < 0.01) had a protective role. In IHCA, prolonged time from arrest to ECMO implantation (OR 1.02, p = 0.03), high lactate level on admission (OR 1.15, p < 0.01) and higher body weight (OR 1.03, p < 0.01) were independently associated with UO. Conclusions: IHCA and OHCA patients receiving ECPR have different predictors of UO at presentation, suggesting that selection criteria for ECPR should be decided according to the location of CA. After ECMO initiation, ECMO blood flow management and mean arterial pressure targets might also impact neurological recovery

Early Findings after Implementation of Veno-Arteriovenous ECMO: A Multicenter European Experience

Extracorporeal membrane oxygenation (ECMO) is increasingly used to treat cardiopulmonary failure in critically ill patients. Peripheral cannulation may be complicated by a persistent low cardiac output in case of veno-venous cannulation (VV-ECMO) or by differential hypoxia (e.g., lower PaO2 in the upper than in the lower body) in case of veno-arterial cannulation (VA-ECMO) and severe impairment of pulmonary function associated with cardiac recovery. The treatment of such complications remains challenging. We report the early effects of the use of veno-arterial-venous (V-AV) ECMO in this setting. Methods: Retrospective analysis including patients from five different European ECMO centers (January 2013 to December 2016) who required V-AV ECMO. We collected demographic data as well as comorbidities and ECMO characteristics, hemodynamics, and arterial blood gas values before and immediately after (i.e., within 2 h) V-AV implementation. Results: A total of 32 patients (age 53 (interquartiles, IQRs: 31-59) years) were identified: 16 were initially supported with VA-ECMO and 16 with VV-ECMO. The median time to V-AV conversion was 2 (1-5) days. After V-AV implantation, heart rate and norepinephrine dose significantly decreased, while PaO2 and SaO(2) significantly increased compared to baseline values. Lactate levels significantly decreased from 3.9 (2.3-7.1) to 2.8 (1.4-4.4) mmol/L (p = 0.048). A significant increase in the overall ECMO blood flow (from 4.5 (3.8-5.0) to 4.9 (4.3-5.9) L/min; p < 0.01) was observed, with 3.0 (2.5-3.2) L/min for the arterial and 2.8 (2.1-3.6) L/min for the venous return flows. Conclusions: In ECMO patients with differential hypoxia or persistently low cardiac output syndrome, V-AV conversion was associated with improvement in some hemodynamic and respiratory parameters. A significant increase in the overall ECMO blood flow was also observed, with similar flow distributed into the arterial and venous return cannulas

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 PaCO 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