Impact of major bleeding and thrombosis on 180-day survival in patients with severe COVID-19 supported with veno-venous extracorporeal membrane oxygenation in the United Kingdom: a multicentre observational study.

Bleeding and thrombosis are major complications in patients supported with extracorporeal membrane oxygenation (ECMO). In this multicentre observational study of 152 consecutive patients (≥18 years) with severe COVID-19 supported by veno-venous (VV) ECMO in four UK commissioned centres during the first wave of the COVID-19 pandemic (1 March to 31 May 2020), we assessed the incidence of major bleeding and thrombosis and their association with 180-day mortality. Median age (range) was 47 years (23-65) and 75% were male. Overall, the 180-day survival was 70·4% (107/152). The rate of major bleeding was 30·9% (47/152), of which intracranial bleeding (ICH) was 34% (16/47). There were 96 thrombotic events (63·1%) consisting of venous 44·7% [68/152 of which 66·2% were pulmonary embolism (PE)], arterial 18·6% (13/152) and ECMO circuit thrombosis 9·9% (15/152). In multivariate analysis, only raised lactate dehydrogenase (LDH) at the initiation of VV ECMO was associated with an increased risk of thrombosis [hazard ratio (HR) 1·92, 95% CI 1·21-3·03]. Major bleeding and ICH were associated with 3·87-fold (95% CI 2·10-7·23) and 5·97-fold [95% confidence interval (CI) 2·36-15·04] increased risk of mortality and PE with a 2·00-fold (95% CI1·09-3·56) risk of mortality. This highlights the difficult balancing act often encountered when managing coagulopathy in COVID-19 patients supported with ECMO.

Vascular Thrombosis in Severe COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Multicenter Study.

OBJECTIVES: Coronavirus disease 2019 has been reported to be a prothrombotic condition; however, multicenter data comparing this with other viral pneumonias in those requiring extracorporeal membrane oxygenation are lacking. We conducted a multicenter study using whole-body CT to examine the prevalence, severity, and nature of vascular complications in coronavirus disease 2019 in comparison with patients with other viral pneumonias. DESIGN: We analyzed whole-body CT scans for the presence of vascular thrombosis (defined as pulmonary artery thrombus, venous thrombus, systemic arterial thrombus, or end-organ infarct). The severity, distribution, and morphology of pulmonary artery thrombus were characterized. Competing risk cumulative incidence analysis was used to compare survival with discharge. SETTING: Three centers of the English national extracorporeal membrane oxygenation service. PATIENTS: Consecutive patients admitted with either coronavirus disease 2019 or noncoronavirus disease 2019 viral pneumonia admitted from January 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred thirty-six patients (45.2 ± 10.6 yr old, 39/146 [27%] female) requiring extracorporeal membrane oxygenation support underwent whole-body CT scans at admission. Of these, 86 had coronavirus disease 2019 pneumonia, and 50 had noncoronavirus disease 2019 viral pneumonia. Vascular thrombosis was seen more often in patients with coronavirus disease 2019 (odds ratio, 12.9 [95% CI 4.5-36.8]). In those with coronavirus disease 2019, 57 (73%) demonstrated pulmonary artery thrombus or pulmonary perfusion defects. Eighty-two percent of thrombus exhibited emboli-like morphology. The location of pulmonary artery thrombus and parenchymal perfusion defects was only concordant in 30% of cases. The risk of mortality was higher in those with coronavirus disease 2019 compared with noncoronavirus disease 2019 pneumonia (χ2 = 3.94; p = 0.047). Mortality was no different in coronavirus disease 2019 patients with or without vascular thrombosis (χ2 = 0.44; p = 0.51). CONCLUSIONS: In patients who received extracorporeal membrane oxygenation, coronavirus disease 2019 is associated with a higher prevalence of vascular thrombosis compared with noncoronavirus disease viral pneumonias. The pattern of pulmonary vascular changes suggests concurrent embolic disease and small vessel disease. Despite this, vascular thrombosis was not linked to poorer short-term prognosis in those with coronavirus disease 2019.

European Association of Cardiothoracic Anesthesiology and Intensive Care Pediatric Cardiac Anesthesia Fellowship Curriculum: First Edition.

Pediatric cardiac anesthesia is a subspecialty of cardiac and pediatric anesthesiology dedicated to the perioperative care of patients with congenital heart disease. Members of the Congenital and Education Subcommittees of the European Association of Cardiothoracic Anaesthesiology and Intensive Care (EACTAIC) agreed on the necessity to develop an EACTAIC pediatric cardiac anesthesia fellowship curriculum. This manuscript represents a consensus on the composition and the design of the EACTAIC Pediatric Cardiac Anesthesia Fellowship program. This curriculum provides a basis for the training of future pediatric cardiac anesthesiologists by clearly defining the theoretical and practical requirements for fellows and host centers.

Outcomes of the NHS England National Extracorporeal Membrane Oxygenation Service for adults with respiratory failure: a multicentre observational cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used to support adults with severe respiratory failure refractory to conventional measures. In 2011, NHS England commissioned a national service to provide ECMO to adults with refractory acute respiratory failure. Our aims were to characterise the patients admitted to the service, report their outcomes, and highlight characteristics potentially associated with survival. METHODS: An observational cohort study was conducted of all patients treated by the NHS England commissioned ECMO service between December 1, 2011 and December 31, 2017. Analysis was conducted according to a prespecified protocol (NCT: 03979222). Data are presented as median [inter-quartile range, IQR]. RESULTS: A total of 1205 patients were supported with ECMO during the study period; the majority (n=1150; 95%) had veno-venous ECMO alone. The survival rate at ECMO ICU discharge was 74% (n=887). Survivors had a lower median age (43 yr [32-52]), compared with non-survivors (49 y [39-60]). Increased severity of hypoxaemia at time of decision-to-cannulate was associated with a lower probability of survival: survivors had a median Sao2 of 90% (84-93%; median Pao2/Fio2, 9.4 kPa [7.7-12.6]), compared with non-survivors (Sao2 88% [80-92%]; Pao2/Fio2 ratio: 8.5 kPa [7.1-11.5]). Patients requiring ECMO because of asthma were more likely to survive (95% survival rate (95% CI, 91-99%), compared with a survival of 71% (95% CI, 69-74%) in patients with respiratory failure attributable to other diagnoses. CONCLUSION: A national ECMO service can achieve good short-term outcomes for patients with undifferentiated respiratory failure refractory to conventional management. CLINICAL TRIAL REGISTRATION: NCT03979222.

Mechanical Ventilation Management during Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome. An International Multicenter Prospective Cohort.

Rationale: Current practices regarding mechanical ventilation in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown.Objectives: To report current practices regarding mechanical ventilation in patients treated with ECMO for severe acute respiratory distress syndrome (ARDS) and their association with 6-month outcomes.Methods: This was an international, multicenter, prospective cohort study of patients undergoing ECMO for ARDS during a 1-year period in 23 international ICUs.Measurements and Main Results: We collected demographics, daily pre- and per-ECMO mechanical ventilation settings and use of adjunctive therapies, ICU, and 6-month outcome data for 350 patients (mean ± SD pre-ECMO PaO2/FiO2 71 ± 34 mm Hg). Pre-ECMO use of prone positioning and neuromuscular blockers were 26% and 62%, respectively. Vt (6.4 ± 2.0 vs. 3.7 ± 2.0 ml/kg), plateau pressure (32 ± 7 vs. 24 ± 7 cm H2O), driving pressure (20 ± 7 vs. 14 ± 4 cm H2O), respiratory rate (26 ± 8 vs. 14 ± 6 breaths/min), and mechanical power (26.1 ± 12.7 vs. 6.6 ± 4.8 J/min) were markedly reduced after ECMO initiation. Six-month survival was 61%. No association was found between ventilator settings during the first 2 days of ECMO and survival in multivariable analysis. A time-varying Cox model retained older age, higher fluid balance, higher lactate, and more need for renal-replacement therapy along the ECMO course as being independently associated with 6-month mortality. A higher Vt and lower driving pressure (likely markers of static compliance improvement) across the ECMO course were also associated with better outcomes.Conclusions: Ultraprotective lung ventilation on ECMO was largely adopted across medium- to high-case volume ECMO centers. In contrast with previous observations, mechanical ventilation settings during ECMO did not impact patients' prognosis in this context.

Biased Agonism: The Future (and Present) of Inotropic Support.

Biased agonism, which is the concept that different ligands activate different downstream signalling partners in different ratios to cause different functional effects, is yet to gain appropriate appreciation in the field of inotropic pharmacology. Biased agonism has already proven to be a clinically translatable technology in analgesic pharmacology, but this development is yet to be translated into inotropes. A better appreciation of bias in clinically used inotropes and a focus on bias when developing novel inotropes has the potential to lead to more targeted, personalized, and cleaner inotropes.

The Effects of Escalation of Respiratory Support and Prolonged Invasive Ventilation on Outcomes of Cardiac Surgical Patients: A Retrospective Cohort Study.

OBJECTIVES: The aim of this study was to determine the effects of escalation of respiratory support and prolonged postoperative invasive ventilation on patient-centered outcomes, and identify perioperative factors associated with these 2 respiratory complications. DESIGN: A retrospective cohort analysis of cardiac surgical patients admitted to the cardiothoracic intensive care unit (ICU) between August 2015 and January 2018. Escalation of respiratory support was defined as "unplanned continuous positive airway pressure," "non-invasive ventilation," or "reintubation" after surgery; prolonged invasive ventilation was defined as "invasive ventilation beyond the first 12 hours following surgery." The primary endpoint was the composite of escalation of respiratory support and prolonged ventilation. SETTING: Tertiary cardiothoracic ICU. PARTICIPANTS: A total of 2,098 patients were included and analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The composite of escalation of support or prolonged ventilation occurred in 509 patients (24.3%). Patients who met the composite had higher mortality (2.9% v 0.1%; p < 0.001) and longer median [interquartile range] length of ICU (2.1 [1.0-4.9] v 0.9 [0.8-1.0] days; p < 0.0001) and hospital (10.6 [8.0-16.0] v 7.2 [6.2-10.0] days; p < 0.0001) stay. Hypoxemia and anemia on admission to ICU were the only 2 factors independently associated with the need for escalation of respiratory support or prolonged invasive ventilation. CONCLUSIONS: Escalation of respiratory support or prolonged invasive ventilation is frequently seen in cardiac surgery patients and is highly associated with increased mortality and morbidity. Hypoxemia and anemia on admission to the ICU are potentially modifiable factors associated with escalation of respiratory support or prolonged invasive ventilation.

Transfer of Patients With Cardiogenic Shock Using Veno-Arterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: The authors describe the experience of patient transfer on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) used as a salvage therapy for refractory cardiogenic shock, examining feasibility and long-term outcomes. DESIGN: A retrospective case series. SETTING: A tertiary referral cardiothoracic transplantation center. PARTICIPANTS AND INTERVENTIONS: Since 2012, the authors' multidisciplinary team has traveled to the referring center of 15 patients referred with refractory cardiogenic shock. Of these, 13 were instituted on VA ECMO support (8 peripheral and 5 central) and subsequently transferred to the authors' center. A further 11 patients were transferred to the authors' institution by the referring team, already having been placed on VA-ECMO (8 peripheral and 3 central). MEASUREMENTS AND MAIN RESULTS: All patients were safely transferred. The distance travelled ranged from 16 to 341 miles. The median duration of support on VA-ECMO was 4 days, ranging from 1 to 24 days. The VA-ECMO support was weaned, or the patient underwent a definitive surgical management (including 4 undergoing cardiac transplantation and 3 pulmonary endarterectomy) in 15 (62.5%) patients. The median intensive care unit stay was 15 days (range 1-109). Overall 30-day survival for this patient cohort was 69.6% with 1-year survival of 59.8%. For patients who were weaned from VA-ECMO, the 30-day survival was 100% and 1-year survival 92.9%. CONCLUSIONS: The authors' experience demonstrates the feasibility and survival benefit of a salvage VA-ECMO retrieval service for carefully selected patients with refractory cardiogenic shock. The authors suggest that a system based on the model of nationally commissioned severe respiratory failure services could be organized to support the transfer of these patients.

European Association of Cardiothoracic Anesthesiology (EACTA) Cardiothoracic and Vascular Anesthesia Fellowship Curriculum: First Edition.

This special article summarizes the design and certification process of the European Association of Cardiothoracic Anesthesiology (EACTA) Cardiothoracic and Vascular Anesthesia (CTVA) Fellowship Program. The CTVA fellowship training includes a two-year curriculum at an EACTA-accredited educational facility. Before fellows are accepted into the program, they must meet a number of requirements, including evidence of a valid license to practice medicine, a specialist degree examination in anesthesiology, and appropriate language skills as required in the host centers. The CVTA Fellowship Program has 2 sequential and complementary levels of training-both with a modular structure that allows for individual planning and also takes into account the differing national healthcare needs and requirements of the 36 countries represented in EACTA. The basic training period focuses on the anesthetic management of patients undergoing cardiac, thoracic, and vascular surgery and related procedures. The advanced training period is intended to deepen and to extend the clinical and nontechnical skills that fellows have acquired during the basic training. The goal of the EACTA fellowship is to produce highly trained and competent perioperative physicians who are able to care for patients undergoing cardiac, thoracic, and vascular anesthesia.

Permeability and diffusivity of nitric oxide in human plasma and red cells.

A simple diffusion cell was made to measure the permeability and diffusivity of Nitric Oxide in human plasma and red cells. Nitric oxide was passed through the cell containing plasma or nitrited red cells enclosed by silicone membranes. Steady state permeability (αNODNO ) was calculated from the cell dimensions and from the NO bulk flow entering and leaving the cell. The diffusion coefficient (DNO) was calculated in three ways: (i) by dividing the steady state permeability by published values for solubility (αNO ) in water at 26 °C and 37 °C (ii) by a numerical method and (iii) by an analytical method. Mean steady state permeability (95% confidence intervals) were plasma (26 °C) 5.57 × 10-11 (2.35 × 10-11-1.32 × 10-10) and (37 °C) 5.48 × 10-11 (2.13 × 10-11-1.41 × 10-10) mol cm-1 s-1 atm-1 and red cells (26 °C) 6.74 × 10-12 (1.29 × 10-12-3.53 × 10-11) and (37 °C) 3.93 × 10-11 (1.39 × 10-11-1.11.10-10) mol cm-1 s-1 atm-1. Median Diffusion Coefficients (DNO) for plasma at 37 °C ranged from 3-3.36 × 10-5 cm2 s-1 and red cells 2.41-2.94 × 10-5 cm2 s-1 depending on the method used. These values may be used for modelling NO transport in vivo in the human lung and capillary. Parameters used for modelling in vivo should be measured at 37 °C.

Bleeding Complications Associated With Percutaneous Tracheostomy Insertion in Patients Supported With Venovenous Extracorporeal Membrane Oxygen Support: A 10-Year Institutional Experience.

OBJECTIVES: To evaluate the bleeding complications associated with percutaneous tracheostomy while a patient is receiving venovenous extracorporeal membrane oxygen (VV ECMO) support. DESIGN: Retrospective, observational analysis. SETTING: Single-center, tertiary, academic institution. PARTICIPANTS: All consecutive patients on VV ECMO over a 10 year-period undergoing percutaneous tracheostomy. INTERVENTIONS: Percutaneous tracheostomy. MEASUREMENTS AND MAIN RESULTS: Fifty percutaneous tracheostomies were performed in patients requiring VV ECMO support over the 10-year period. The authors observed a 40% incidence of bleeding, with 32% of these incidences characterized as minor (self-limiting, localized stomal ooze) and 8% characterized as significant (necessitating surgical control and frequent packing or accompanied by a decrease in hemoglobin >20%). CONCLUSIONS: Bleeding is associated with percutaneous tracheostomy and is self-limiting in the majority of patients.

Usefulness of the STOP-Bang Questionnaire in a Cardiac Surgical Population.

OBJECTIVE: The aim of this study was to assess the predictive accuracy of the STOP-Bang questionnaire in relation to obstructive sleep apnea (OSA) detected by nocturnal oximetry, as well as postoperative outcomes, in a population undergoing cardiac surgery. DESIGN: A prospective observational cohort study. SETTING: The specialist cardiothoracic center at the Royal Papworth Hospital, Cambridge University Health Partners, United Kingdom. PARTICIPANTS: All adult patients, undergoing elective coronary artery bypass grafting with or without cardiac valve surgery between March 2013 and July 2014 were included. The authors excluded patients participating in other interventional studies, those who had a tracheostomy before surgery, and those who required emergency surgery or were due to be admitted on the day of surgery. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Cardiac surgical patients were screened for the risk of OSA with the use of STOP-Bang questionnaire. The presence of OSA prior to surgery was assessed with overnight oximetry. The predictive performance of the STOP-Bang questionnaire was assessed by calculating sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve (AUC)-receiver operating characteristic curve (ROC). Multiple-logistic regression models were used to assess for associations between the STOP-Bang scores and postoperative outcomes. The STOP-Bang questionnaire discriminated poorly between mild OSA (AUC-ROC 0.57 [95% confidence interval (CI) 0.47-0.67]) and moderate/severe OSA (AUC-ROC 0.82 (95% CI 0.69-0.95)]. Accuracy was increased by modifying the cut-off value to 6 or greater, with sensitivity and specificity of 75% and 77%, respectively. A STOP-Bang score indicating the possibility of OSA was not significantly associated with prolonged intensive care unit lengths of stay (hazard ratio [HR] 1.1; 95% CI 0.99-1.19; p = 0.08) or postoperative complications (odds ratio [OR] 1.0; 95% CI 0.59-1.72; p = 0.98). CONCLUSIONS: In the study population, a STOP-Bang questionnaire score of 3 or greater had limited predictive value for identifying cardiac surgical patients at high risk of OSA. STOP-Bang scores were not significantly associated with worse postoperative outcomes. A STOP-Bang score of 6 or greater could help identify patients in need of a sleep study to confirm the presence of OSA as such patients may be at increased risk of postoperative complications.

Prediction of Patient Length of Stay on the Intensive Care Unit Following Cardiac Surgery: A Logistic Regression Analysis Based on the Cardiac Operative Mortality Risk Calculator, EuroSCORE.

OBJECTIVE: The aim of this study was to develop a statistical model based on patient parameters to predict the length of stay (LOS) in the intensive care unit (ICU) following cardiac surgery in a single center. DESIGN: Data were collected from patients admitted to the ICU following cardiac surgery over a 10-year period (2006-2016). Both the additive and logistic EuroSCORE were calculated, and logistic regression analysis was carried out to formulate a model relating the predicted LOS to the EuroSCORE. This model was used to stratify patients into short stay (less than 48 hours) or long stay (more than 48 hours). SETTING: ICU at Papworth Hospital, Cambridgeshire. PARTICIPANTS: A total of 18,377 consecutive patients who had been in ICU following cardiac surgery (coronary graft bypass surgery, valve surgery, or a combination of both). INTERVENTIONS: This was an observational study. MEASUREMENTS AND MAIN RESULTS: The authors have shown that both the additive and logistic EuroSCORE can be used to stratify cardiac surgical patients in various predicted LOS in ICU. Further adjustments can be made to increase the number of patients correctly identified as either short stay or long stay. Comparison of the model predictions to the data demonstrated a high overall accuracy of 79.77%, and receiver operating characteristic curve analysis showed the area under the curve to be 0.7296. CONCLUSION: This analysis of an extensive data set shows that patient LOS in ICU after cardiac surgery in a single center can be predicted accurately using the simple cardiac operative risk scoring tool EuroSCORE. Using such predictions has the potential to improve ICU resource management.

Central Veno-Arterial Extracorporeal Membrane Oxygenation (C-VA-ECMO) After Cardiothoracic Surgery: A Single-Center Experience.

OBJECTIVES: Central veno-arterial extracorporeal membrane oxygenation (C-VA-ECMO) provides temporary cardiorespiratory support for patients in heart failure who cannot be weaned from cardiopulmonary bypass successfully. Outcomes are influenced by the reversibility of the initial insult and complications of the technique. METHODS: The authors reviewed their single-center experience over the last 8 years to inform future practice. The study included all patients supported with C-VA-ECMO after cardiothoracic surgery between January 2008 and July 2016. The authors identified mortality risk factors using logistic regression analysis and chi-square tests. RESULTS: One hundred and one patients were supported with C-VA-ECMO during the studied period. Weaning from ECMO was successful in 57.4% of patients, whereas 7.9% were bridged to veno-venous ECMO, 2% to peripheral veno-arterial ECMO, and 2% to biventricular ventricular assist devices. In-hospital and 1-year survival for all patients was 33.7% and 27.7%, respectively. Survival was considerably higher in transplantation patients (n = 11), at 63.6% and 54.5%, respectively. Risk factors linked to in-hospital mortality were age older than 70 years, lactate level greater than 4 mmol/L after 48 hours, and hepatic and kidney failure during ECMO support. CONCLUSIONS: Overall one-third of patients in the cohort who the authors believe would otherwise have died from postcardiotomy cardiogenic shock survived because C-VA-ECMO was commenced after cardiac surgery. Survival is greater in transplantation patients necessitating this form of support during or immediately after surgery.

Patients Discharged From the Intensive Care Unit on a Dopamine Infusion-A Retrospective, Observational Study.

OBJECTIVE: To assess the safety of discharging cardiac surgical patients from the intensive care unit (ICU) to wards while the patients are still receiving a dopamine infusion. DESIGN: Retrospective, observational study. SETTING: Cardiothoracic ICU of a tertiary academic hospital in the United Kingdom. PARTICIPANTS: The study comprised all cardiac surgical patients older than 18 years and admitted between September 1, 2015 and September 16, 2016 to the ICU and subsequently discharged to a surgical ward. Patients were divided in the following 2 groups: a dopamine group with patients discharged with a dopamine infusion and a control group with patients discharged without any dopamine infusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The hospital mortality rate was comparable in both groups (0.7% in the dopamine group v 0.2% in the control group [p = 0.11]), despite that the median logistic EuroSCORE was significantly higher in the dopamine group (7.0 v 3.8 [p < 0.01]). The ICU readmission rate was higher in the dopamine group (6.6% v 2.4%; p < 0.01). ICU and hospital lengths of stay were longer in the dopamine group (1.7 v 0.9 days [p < 0.01] and 11.4 v 8.0 days [p < 0.01], respectively). CONCLUSIONS: Despite a higher ICU readmission rate, ICU discharge of patients on dopamine infusion was not associated with increased mortality.