Relationship between D-dimers and dead-space on disease severity and mortality in COVID-19 acute respiratory distress syndrome: A retrospective observational cohort study

Background Despite its diagnostic and prognostic importance, physiologic dead space fraction is not included in the current ARDS definition or severity classification. ARDS caused by COVID-19 (C-ARDS) is characterized by increased physiologic dead space fraction and hypoxemia. Our aim was to investigate the relationship between dead space indices, markers of inflammation, immunothrombosis, severity and intensive care unit (ICU) mortality. Results Retrospective data including demographics, gas exchange, ventilatory parameters, and respiratory mechanics in the first 24 h of invasive ventilation. Plasma concentrations of D-dimers and ferritin were not significantly different across C-ARDS severity categories. Weak relationships were found between D-dimers and VR (r = 0.07, p = 0.13), PETCO2/PaCO2 (r = −0.1, p = 0.02), or estimated dead space fraction (r = 0.019, p = 0.68). Age, PaO2/FiO2, pH, PETCO2/PaCO2 and ferritin, were independently associated with ICU mortality. We found no association between D-dimers or ferritin and any dead-space indices adjusting for PaO2/FiO2, days of ventilation, tidal volume, and respiratory system compliance. Conclusions We report no association between dead space and inflammatory markers in mechanically ventilated patients with C-ARDS. Our results support theories suggesting that multiple mechanisms, in addition to immunothrombosis, play a role in the pathophysiology of respiratory failure and degree of dead space in C-ARDS.

Prone position: how understanding and clinical application of a technique progress with time

Historical background The prone position was first proposed on theoretical background in 1974 (more advantageous distribution of mechanical ventilation). The first clinical report on 5 ARDS patients in 1976 showed remarkable improvement of oxygenation after pronation. Pathophysiology The findings in CT scans enhanced the use of prone position in ARDS patients. The main mechanism of the improved gas exchange seen in the prone position is nowadays attributed to a dorsal ventilatory recruitment, with a substantially unchanged distribution of perfusion. Regardless of the gas exchange, the primary effect of the prone position is a more homogenous distribution of ventilation, stress and strain, with similar size of pulmonary units in dorsal and ventral regions. In contrast, in the supine position the ventral regions are more expanded compared with the dorsal regions, which leads to greater ventral stress and strain, induced by mechanical ventilation. Outcome in ARDS The number of clinical studies paralleled the evolution of the pathophysiological understanding. The first two clinical trials in 2001 and 2004 were based on the hypothesis that better oxygenation would lead to a better survival and the studies were more focused on gas exchange than on lung mechanics. The equations better oxygenation = better survival was disproved by these and other larger trials (ARMA trial). However, the first studies provided signals that some survival advantages were possible in a more severe ARDS, where both oxygenation and lung mechanics were impaired. The PROSEVA trial finally showed the benefits of prone position on mortality supporting the thesis that the clinical advantages of prone position, instead of improved gas exchange, were mainly due to a less harmful mechanical ventilation and better distribution of stress and strain. In less severe ARDS, in spite of a better gas exchange, reduced mechanical stress and strain, and improved oxygenation, prone position was ineffective on outcome. Prone position and COVID-19 The mechanisms of oxygenation impairment in early COVID-19 are different than in typical ARDS and relate more on perfusion alteration than on alveolar consolidation/collapse, which are minimal in the early phase. Bronchial shunt may also contribute to the early COVID-19 hypoxemia. Therefore, in this phase, the oxygenation improvement in prone position is due to a better matching of local ventilation and perfusion, primarily caused by the perfusion component. Unfortunately, the conditions for improved outcomes, i.e. a better distribution of stress and strain, are almost absent in this phase of COVID-19 disease, as the lung parenchyma is nearly fully inflated. Due to some contradictory results, further studies are needed to better investigate the effect of prone position on outcome in COVID-19 patients. Graphical

Differences in clinical characteristics and quantitative lung CT features between vaccinated and not vaccinated hospitalized COVID-19 patients in Italy.

BACKGROUND: To evaluate the differences in the clinical characteristics and severity of lung impairment, assessed by quantitative lung CT scan, between vaccinated and non-vaccinated hospitalized patients with COVID-19; and to identify the variables with best prognostic prediction according to SARS-CoV-2 vaccination status. We recorded clinical, laboratory and quantitative lung CT scan data in 684 consecutive patients [580 (84.8%) vaccinated, and 104 (15.2%) non-vaccinated], admitted between January and December 2021. RESULTS: Vaccinated patients were significantly older 78 [69-84] vs 67 [53-79] years and with more comorbidities. Vaccinated and non-vaccinated patients had similar PaO2/FiO2 (300 [252-342] vs 307 [247-357] mmHg; respiratory rate 22 [8-26] vs 19 [18-26] bpm); total lung weight (918 [780-1069] vs 954 [802-1149] g), lung gas volume (2579 [1801-3628] vs 2370 [1675-3289] mL) and non-aerated tissue fraction (10 [7.3-16.0] vs 8.5 [6.0-14.1] %). The overall crude hospital mortality was similar between the vaccinated and non-vaccinated group (23.1% vs 21.2%). However, Cox regression analysis, adjusted for age, ethnicity, age unadjusted Charlson Comorbidity Index and calendar month of admission, showed a 40% reduction in hospital mortality in the vaccinated patients (HRadj = 0.60, 95%CI 0.38-0.95). CONCLUSIONS: Hospitalized vaccinated patients with COVID-19, although older and with more comorbidities, presented a similar impairment in gas exchange and lung CT scan compared to non-vaccinated patients, but were at a lower risk of mortality.

In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation. METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing. FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms. INTERPRETATION: Patient's age, timing of cannulation (<4 days vs ≥4 days from intubation), and use of inotropes and vasopressors are essential factors to consider when analysing the outcomes of patients receiving ECMO for COVID-19. Despite post-discharge survival being favourable, persisting long-term symptoms suggest that dedicated post-ECMO follow-up programmes are required. FUNDING: None.

Steroid exposure and outcome in COVID-19 pneumonia.

Background: Corticosteroids are used to treat COVID-19 pneumonia. However, the optimal dose is unclear. This study describes the association between corticosteroid exposure with disease severity and outcome in COVID-19 pneumonia. Methods: This is a single-centre retrospective, observational study including adult ICU patients who received systemic corticosteroids for COVID-19 pneumonia between March 2020 and March 2021. We recorded patient characteristics, disease severity, total steroid exposure, respiratory support and gas exchange data, and 90-day mortality. Results: We included 362 patients. We allocated patients to groups with increasing disease severity according to the highest level of respiratory support that they received: high-flow nasal oxygen or continuous positive airway pressure (HFNO/CPAP) in 12.7%, invasive mechanical ventilation (IMV) in 61.6%, and extracorporeal membrane oxygenation (ECMO) in 25.7%. For these three groups, the median (inter-quartile range [IQR]) age was 61 (54-71) vs 58 (50-66) vs 46 (38-53) yr, respectively (P<0.001); median (IQR) APACHE (Acute Physiology and Chronic Health Evaluation) II scores were 12 (9-15) vs 14 (12-18) vs 15 (12-17), respectively (P=0.006); the median (IQR) lowest P a O 2 /FiO2 ratio was 15.1 (11.8-21.7) vs 15.1 (10.7-22.2) vs 9.5 (7.9-10.9) kPa, respectively (P<0.001). Ninety-day mortality was 9% vs 27% vs 37% (P=0.002). Median (IQR) dexamethasone-equivalent exposure was 37 (24-62) vs 174 (86-504) vs 535 (257-1213) mg (P<0.001). 'Pulsed' steroids were administered to 26% of the IMV group and 48% of the ECMO group. Patients with higher disease severity who received pulse steroids had a higher 90-day mortality. Conclusions: Corticosteroid exposure increased with the severity of COVID-19 pneumonia. Pulsed dose steroids were used more frequently in patients receiving greater respiratory support. Future studies should address patient selection and outcomes associated with pulsed dose steroids in patients with severe and deteriorating COVID-19 pneumonia.

Mechanical Power Ratio and Respiratory Treatment Escalation in COVID-19 Pneumonia: A Secondary Analysis of a Prospectively Enrolled Cohort.

BACKGROUND: Under the hypothesis that mechanical power ratio could identify the spontaneously breathing patients with a higher risk of respiratory failure, this study assessed lung mechanics in nonintubated patients with COVID-19 pneumonia, aiming to (1) describe their characteristics; (2) compare lung mechanics between patients who received respiratory treatment escalation and those who did not; and (3) identify variables associated with the need for respiratory treatment escalation. METHODS: Secondary analysis of prospectively enrolled cohort involving 111 consecutive spontaneously breathing adults receiving continuous positive airway pressure, enrolled from September 2020 to December 2021. Lung mechanics and other previously reported predictive indices were calculated, as well as a novel variable: the mechanical power ratio (the ratio between the actual and the expected baseline mechanical power). Patients were grouped according to the outcome: (1) no-treatment escalation (patient supported in continuous positive airway pressure until improvement) and (2) treatment escalation (escalation of the respiratory support to noninvasive or invasive mechanical ventilation), and the association between lung mechanics/predictive scores and outcome was assessed. RESULTS: At day 1, patients undergoing treatment escalation had spontaneous tidal volume similar to those of patients who did not (7.1 ± 1.9 vs. 7.1 ± 1.4 ml/kgIBW; P = 0.990). In contrast, they showed higher respiratory rate (20 ± 5 vs. 18 ± 5 breaths/min; P = 0.028), minute ventilation (9.2 ± 3.0 vs. 7.9 ± 2.4 l/min; P = 0.011), tidal pleural pressure (8.1 ± 3.7 vs. 6.0 ± 3.1 cm H2O; P = 0.003), mechanical power ratio (2.4 ± 1.4 vs. 1.7 ± 1.5; P = 0.042), and lower partial pressure of alveolar oxygen/fractional inspired oxygen tension (174 ± 64 vs. 220 ± 95; P = 0.007). The mechanical power (area under the curve, 0.738; 95% CI, 0.636 to 0.839] P < 0.001), the mechanical power ratio (area under the curve, 0.734; 95% CI, 0.625 to 0.844; P < 0.001), and the pressure-rate index (area under the curve, 0.733; 95% CI, 0.631 to 0.835; P < 0.001) showed the highest areas under the curve. CONCLUSIONS: In this COVID-19 cohort, tidal volume was similar in patients undergoing treatment escalation and in patients who did not; mechanical power, its ratio, and pressure-rate index were the variables presenting the highest association with the clinical outcome.

Biochemical shunt: where and how?

G. Harutyunyan and co-workers, in their reply to our correspondence, introduce the fascinating concept of "biochemical shunt” to help explain some of the gas exchange abnormalities reported in patients with early coronavirus disease 2019 (COVID-19). In brief, they assert the plausibility that the oxyhaemoglobin dissociation curve (ODC), which may be normal in the arterial and venous blood, could be altered (i.e. reduced oxygen affinity) in the pulmonary blood flowing through diseased alveolar capillaries. It is not easy for us to understand which COVID-19-related factors, or metabolites, might alter the ODC specifically in the pulmonary circulation, and to what extent they involve the lung parenchyma (partially or totally, where and why). Let us suppose, for example, that the biochemical shunt occurs in the whole parenchyma (nearly fully ventilated in early COVID-19). Response to Harutyunyan et al. "Hypoxaemia in the early stage of COVID-19: prevalence of physical or biochemical factors?”https://bit.ly/3K1NSKu

Nutrition support practices across the care continuum in a single centre critical care unit during the first surge of the COVID-19 pandemic - A comparison of VV-ECMO and non-ECMO patients.

BACKGROUND & AIMS: Critically ill patients with COVID-19 are at high nutrition risk. This study aimed to describe the nutrition support practices in a single centre critical care unit during the initial surge of the COVID-19 pandemic. Practices were explored from ICU admission to post-ICU follow-up clinic and patients who received veno-venous extra-corporeal membrane oxygenation (VV-ECMO) were compared to those who did not. METHODS: This retrospective observational study included COVID-19 positive, adult ICU patients who were mechanically ventilated for ≥72 h. Data were collected from ICU admission until the time of post-ICU clinic. For in-ICU data, results are compared between patients who did and did not receive VV-ECMO. RESULTS: 252 patients were included (VV-ECMO n = 58). Adequate energy and protein was delivered in 193 (76.6%) patients during their ICU admission with no differences between those who did and did not receive VV-ECMO (44 (75.9%) vs. 149 (76.8%)). Parenteral nutrition only being required in 12 (4.8%) patients. Following stepdown to the ward 77 (70%) patients required ongoing enteral nutrition support, and 74 (66.7%) required a texture modified diet or were NBM. Following hospital discharge, nearly a third of ICU survivors (28.4%) were referred for dietetic input. The most common referral reason was loss of weight. Breathlessness and fatigue were the most commonly reported nutrition impact symptoms experienced following hospital discharge. CONCLUSION: Results show it is possible to reach nutritional adequacy for most patients and that neither VV-ECMO nor proning were barriers to nutritional adequacy. Nutritional issues for patients who were critically ill with COVID-19 persist following stepdown to ward level and into the community and strategies to manage this require further investigation.

Nutrition support practices across the care continuum in a single centre critical care unit during the first surge of the COVID-19 pandemic – A comparison of VV-ECMO and non-ECMO patients

Background & aims Critically ill patients with COVID-19 are at high nutrition risk. This study aimed to describe the nutrition support practices in a single centre critical care unit during the initial surge of the COVID-19 pandemic. Practices were explored from ICU admission to post-ICU follow-up clinic and patients who received veno-venous extra-corporeal membrane oxygenation (VV-ECMO) were compared to those who did not. Methods This retrospective observational study included COVID-19 positive, adult ICU patients who were mechanically ventilated for ≥72 h. Data were collected from ICU admission until the time of post-ICU clinic. For in-ICU data, results are compared between patients who did and did not receive VV-ECMO. Results 252 patients were included (VV-ECMO n = 58). Adequate energy and protein was delivered in 193 (76.6%) patients during their ICU admission with no differences between those who did and did not receive VV-ECMO (44 (75.9%) vs. 149 (76.8%)). Parenteral nutrition only being required in 12 (4.8%) patients. Following stepdown to the ward 77 (70%) patients required ongoing enteral nutrition support, and 74 (66.7%) required a texture modified diet or were NBM. Following hospital discharge, nearly a third of ICU survivors (28.4%) were referred for dietetic input. The most common referral reason was loss of weight. Breathlessness and fatigue were the most commonly reported nutrition impact symptoms experienced following hospital discharge. Conclusion Results show it is possible to reach nutritional adequacy for most patients and that neither VV-ECMO nor proning were barriers to nutritional adequacy. Nutritional issues for patients who were critically ill with COVID-19 persist following stepdown to ward level and into the community and strategies to manage this require further investigation.

Myths and Misconceptions of Airway Pressure Release Ventilation: Getting Past the Noise and on to the Signal.

In the pursuit of science, competitive ideas and debate are necessary means to attain knowledge and expose our ignorance. To quote Murray Gell-Mann (1969 Nobel Prize laureate in Physics): "Scientific orthodoxy kills truth". In mechanical ventilation, the goal is to provide the best approach to support patients with respiratory failure until the underlying disease resolves, while minimizing iatrogenic damage. This compromise characterizes the philosophy behind the concept of "lung protective" ventilation. Unfortunately, inadequacies of the current conceptual model-that focuses exclusively on a nominal value of low tidal volume and promotes shrinking of the "baby lung" - is reflected in the high mortality rate of patients with moderate and severe acute respiratory distress syndrome. These data call for exploration and investigation of competitive models evaluated thoroughly through a scientific process. Airway Pressure Release Ventilation (APRV) is one of the most studied yet controversial modes of mechanical ventilation that shows promise in experimental and clinical data. Over the last 3 decades APRV has evolved from a rescue strategy to a preemptive lung injury prevention approach with potential to stabilize the lung and restore alveolar homogeneity. However, several obstacles have so far impeded the evaluation of APRV's clinical efficacy in large, randomized trials. For instance, there is no universally accepted standardized method of setting APRV and thus, it is not established whether its effects on clinical outcomes are due to the ventilator mode per se or the method applied. In addition, one distinctive issue that hinders proper scientific evaluation of APRV is the ubiquitous presence of myths and misconceptions repeatedly presented in the literature. In this review we discuss some of these misleading notions and present data to advance scientific discourse around the uses and misuses of APRV in the current literature.

Respiratory indications for ECMO: focus on COVID-19.

Extracorporeal membrane oxygenation (ECMO) is increasingly being used for patients with severe respiratory failure and has received particular attention during the coronavirus disease 2019 (COVID-19) pandemic. Evidence from two key randomized controlled trials, a subsequent post hoc Bayesian analysis, and meta-analyses support the interpretation of a benefit of ECMO in combination with ultra-lung-protective ventilation for select patients with very severe forms of acute respiratory distress syndrome (ARDS). During the pandemic, new evidence has emerged helping to better define the role of ECMO for patients with COVID-19. Results from large cohorts suggest outcomes during the first wave of the pandemic were similar to those in non-COVID-19 cohorts. As the pandemic continued, mortality of patients supported with ECMO has increased. However, the precise reasons for this observation are unclear. Known risk factors for mortality in COVID-19 and non-COVID-19 patients are higher patient age, concomitant extra-pulmonary organ failures or malignancies, prolonged mechanical ventilation before ECMO, less experienced treatment teams and lower ECMO caseloads in the treating center. ECMO is a high resource-dependent support option; therefore, it should be used judiciously, and its availability may need to be constrained when resources are scarce. More evidence from high-quality research is required to better define the role and limitations of ECMO in patients with severe COVID-19.

End-Tidal to Arterial Pco2 Ratio as Guide to Weaning from Venovenous Extracorporeal Membrane Oxygenation.

Rationale: Weaning from venovenous extracorporeal membrane oxygenation (VV-ECMO) is based on oxygenation and not on carbon dioxide elimination. Objectives: To predict readiness to wean from VV-ECMO. Methods: In this multicenter study of mechanically ventilated adults with severe acute respiratory distress syndrome receiving VV-ECMO, we investigated a variable based on CO2 elimination. The study included a prospective interventional study of a physiological cohort (n = 26) and a retrospective clinical cohort (n = 638). Measurements and Main Results: Weaning failure in the clinical and physiological cohorts were 37% and 42%, respectively. The main cause of failure in the physiological cohort was high inspiratory effort or respiratory rate. All patients exhaled similar amounts of CO2, but in patients who failed the weaning trial, [Formula: see text]e was higher to maintain the PaCO2 unchanged. The effort to eliminate one unit-volume of CO2, was double in patients who failed (68.9 [42.4-123] vs. 39 [20.1-57] cm H2O/[L/min]; P = 0.007), owing to the higher physiological Vd (68 [58.73] % vs. 54 [41.64] %; P = 0.012). End-tidal partial carbon dioxide pressure (PetCO2)/PaCO2 ratio was a clinical variable strongly associated with weaning outcome at baseline, with area under the receiver operating characteristic curve of 0.87 (95% confidence interval [CI], 0.71-1). Similarly, the PetCO2/PaCO2 ratio was associated with weaning outcome in the clinical cohort both before the weaning trial (odds ratio, 4.14; 95% CI, 1.32-12.2; P = 0.015) and at a sweep gas flow of zero (odds ratio, 13.1; 95% CI, 4-44.4; P < 0.001). Conclusions: The primary reason for weaning failure from VV-ECMO is high effort to eliminate CO2. A higher PetCO2/PaCO2 ratio was associated with greater likelihood of weaning from VV-ECMO.

Diagnosis and management of covid-19 in pregnancy.

Pregnant women with covid-19 are at greater risk of severe disease than their non-pregnant peers, and yet they are frequently denied investigations or treatments because of unfounded concerns about risk to the fetus. The basic principles of diagnosing and managing covid-19 are the same as for non-pregnant patients, and a multidisciplinary, expert team approach is essential to ensure optimal care. During pregnancy, treatment with corticosteroids should be modified to use non-fluorinated glucocorticoids. Il-6 inhibitors and monoclonal antibodies, together with specific antiviral therapies, may also be considered. Prophylaxis against venous thromboembolism is important. Women may require respiratory support with oxygen, non-invasive ventilation, ventilation in a prone position (either awake or during invasive ventilation), intubation and ventilation, and extracorporeal membrane oxygenation (ECMO). Pregnancy is not a contraindication for any of these supportive therapies, and the criteria for providing them are the same as in the general population. Decisions regarding timing, place, and mode of delivery should be taken with a multidisciplinary team including obstetricians, physicians, anesthetists, and intensivists experienced in the care of covid-19 in pregnancy. Ideally these decisions should take place in consultation with centers that have experience and expertise in all these specialties.

Validation of at-the-bedside formulae for estimating ventilator driving pressure during airway pressure release ventilation using computer simulation.

BACKGROUND: Airway pressure release ventilation (APRV) is widely available on mechanical ventilators and has been proposed as an early intervention to prevent lung injury or as a rescue therapy in the management of refractory hypoxemia. Driving pressure ([Formula: see text]) has been identified in numerous studies as a key indicator of ventilator-induced-lung-injury that needs to be carefully controlled. [Formula: see text] delivered by the ventilator in APRV is not directly measurable in dynamic conditions, and there is no "gold standard" method for its estimation. METHODS: We used a computational simulator matched to data from 90 patients with acute respiratory distress syndrome (ARDS) to evaluate the accuracy of three "at-the-bedside" methods for estimating ventilator [Formula: see text] during APRV. RESULTS: Levels of [Formula: see text] delivered by the ventilator in APRV were generally within safe limits, but in some cases exceeded levels specified by protective ventilation strategies. A formula based on estimating the intrinsic positive end expiratory pressure present at the end of the APRV release provided the most accurate estimates of [Formula: see text]. A second formula based on assuming that expiratory flow, volume and pressure decay mono-exponentially, and a third method that requires temporarily switching to volume-controlled ventilation, also provided accurate estimates of true [Formula: see text]. CONCLUSIONS: Levels of [Formula: see text] delivered by the ventilator during APRV can potentially exceed levels specified by standard protective ventilation strategies, highlighting the need for careful monitoring. Our results show that [Formula: see text] delivered by the ventilator during APRV can be accurately estimated at the bedside using simple formulae that are based on readily available measurements.

Survival benefit of extracorporeal membrane oxygenation in severe COVID-19: a multi-centre-matched cohort study.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) has become an established therapy for severe respiratory failure in coronavirus disease 2019 (COVID-19). The added benefit of receiving ECMO in COVID-19 remains uncertain. The aim of this study is to analyse the impact of receiving ECMO at specialist centres on hospital mortality. METHODS: A multi-centre retrospective study was conducted in COVID-19 patients from 111 hospitals, referred to two specialist ECMO centres in the United Kingdom (UK) (March 2020 to February 2021). Detailed covariate data were contemporaneously curated from electronic referral systems. We analysed added benefit of ECMO treatment in specialist centres using propensity score matching techniques. RESULTS: 1363 patients, 243 receiving ECMO, were analysed. The best matching technique generated 209 matches, with a marginal odds ratio (OR) for mortality of 0.44 (95% CI 0.29-0.68, p < 0.001) and absolute mortality reduction of 18.2% (44% vs 25.8%, p < 0.001) for treatment with ECMO in a specialist centre. CONCLUSION: We found ECMO provided at specialist centres conferred significant survival benefit. Where resources and specialism allow, ECMO should be widely offered.