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Background There are several reports of extracorporeal membrane oxygenation (ECMO) use in patients with coronavirus disease 2019 (COVID-19) who develop severe acute respiratory distress syndrome (ARDS). We conducted a systematic review and meta-analysis to guide clinical decision-making and future research. Methods We searched MEDLINE, Embase, Cochrane and Scopus databases from 1 December 2019 to 10 January 2021 for observational studies or randomised clinical trials examining ECMO in adults with COVID-19 ARDS. We performed random-effects meta-analyses and meta-regression, assessed risk of bias using the Joanna Briggs Institute checklist and rated the certainty of evidence using the GRADE approach. Survival outcomes were presented as pooled proportions while continuous outcomes were presented as pooled means, both with corresponding 95% confidence intervals [CIs]. The primary outcome was in-hospital mortality. Secondary outcomes were duration of ECMO therapy and mechanical ventilation, weaning rate from ECMO and complications during ECMO. Results We included twenty-two observational studies with 1896 patients in the meta-analysis. Venovenous ECMO was the predominant mode used (98.6%). The pooled in-hospital mortality in COVID-19 patients (22 studies, 1896 patients) supported with ECMO was 37.1% (95% CI 32.3–42.0%, high certainty). Pooled mortality in the venovenous ECMO group was 35.7% (95% CI 30.7–40.7%, high certainty). Meta-regression found that age and ECMO duration were associated with increased mortality. Duration of ECMO support (18 studies, 1844 patients) was 15.1 days (95% CI 13.4–18.7). Weaning from ECMO (17 studies, 1412 patients) was accomplished in 67.6% (95% CI 50.5–82.7%) of patients. There were a total of 1583 ECMO complications reported (18 studies, 1721 patients) and renal complications were the most common. Conclusion The majority of patients received venovenous ECMO support for COVID-19-related ARDS. In-hospital mortality in patients receiving ECMO support for COVID-19 was 37.1% during the first year of the pandemic, similar to those with non-COVID-19-related ARDS. Increasing age was a risk factor for death. Venovenous ECMO appears to be an effective intervention in selected patients with COVID-19-related ARDS. PROSPERO CRD42020192627 .

Over the course of the COVID-19 pandemic, the care of patients with COVID-19 has changed and the use of extracorporeal membrane oxygenation (ECMO) has increased. We aimed to examine patient selection, treatments, outcomes, and ECMO centre characteristics over the course of the pandemic to date. We retrospectively analysed the Extracorporeal Life Support Organization Registry and COVID-19 Addendum to compare three groups of ECMO-supported patients with COVID-19 (aged ≥16 years). At early-adopting centres—ie, those using ECMO support for COVID-19 throughout 2020—we compared patients who started ECMO on or before May 1, 2020 (group A1), and between May 2 and Dec 31, 2020 (group A2). Late-adopting centres were those that provided ECMO for COVID-19 only after May 1, 2020 (group B). The primary outcome was in-hospital mortality in a time-to-event analysis assessed 90 days after ECMO initiation. A Cox proportional hazards model was fit to compare the patient and centre-level adjusted relative risk of mortality among the groups. In 2020, 4812 patients with COVID-19 received ECMO across 349 centres within 41 countries. For early-adopting centres, the cumulative incidence of in-hospital mortality 90 days after ECMO initiation was 36·9% (95% CI 34·1–39·7) in patients who started ECMO on or before May 1 (group A1) versus 51·9% (50·0–53·8) after May 1 (group A2); at late-adopting centres (group B), it was 58·9% (55·4–62·3). Relative to patients in group A2, group A1 patients had a lower adjusted relative risk of in-hospital mortality 90 days after ECMO (hazard ratio 0·82 [0·70−0·96]), whereas group B patients had a higher adjusted relative risk (1·42 [1·17−1·73]). Mortality after ECMO for patients with COVID-19 worsened during 2020. These findings inform the role of ECMO in COVID-19 for patients, clinicians, and policy makers. None.

The application of prone positioning for acute respiratory distress syndrome (ARDS) has evolved, with recent trials focusing on patients with more severe ARDS, and applying prone ventilation for more prolonged periods. This review evaluates the effect of prone positioning on 28-day mortality (primary outcome) compared with conventional mechanical ventilation in the supine position for adults with ARDS. We updated the literature search from a systematic review published in 2010, searching MEDLINE, EMBASE, and CENTRAL (through to August 2016). We included randomized, controlled trials (RCTs) comparing prone to supine positioning in mechanically ventilated adults with ARDS, and conducted sensitivity analyses to explore the effects of duration of prone ventilation, concurrent lung-protective ventilation and ARDS severity. Secondary outcomes included Pa /Fi ratio on Day 4 and an evaluation of adverse events. Meta-analyses used random effects models. Methodologic quality of the RCTs was evaluated using the Cochrane risk of bias instrument, and methodologic quality of the overall body of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) guidelines. Eight RCTs fulfilled entry criteria, and included 2,129 patients (1,093 [51%] proned). Meta-analysis revealed no difference in mortality (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.68-1.04), but subgroup analyses found lower mortality with 12 hours or greater duration prone (five trials; RR, 0.74; 95% CI, 0.56-0.99) and for patients with moderate to severe ARDS (five trials; RR, 0.74; 95% CI, 0.56-0.99). Pa /Fi ratio on Day 4 for all patients was significantly higher in the prone positioning group (mean difference, 23.5; 95% CI, 12.4-34.5). Prone positioning was associated with higher rates of endotracheal tube obstruction and pressure sores. Risk of bias was low across the trials. Prone positioning is likely to reduce mortality among patients with severe ARDS when applied for at least 12 hours daily.

Background Prediction scoring systems for coronary artery bypass grafting (CABG) patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) have not yet been reported. This study was designed to develop a predictive score for in-hospital mortality for cardiogenic shock patients who received VA-ECMO after isolated CABG. Methods Retrospective cohort study of consecutive CABG patients supported with VA-ECMO ( n  = 166) at the Beijing Anzhen Hospital between February 2004 and March 2017. Results One hundred and six patients (64%) could be weaned from VA-ECMO, and 74 patients (45%) survived to hospital discharge. On the basis of multivariable logistic regression analyses, the pRedicting mortality in patients undergoing veno-arterial Extracorporeal MEMBrane oxygenation after coronary artEry bypass gRafting (REMEMBER) score was created with six pre-ECMO parameters: older age, left main coronary artery disease, inotropic score > 75, CK-MB > 130 IU/L, serum creatinine > 150 umol/L, and platelet count < 100 × 10 9 /L. Four risk classes, namely class I (REMEMBER score 0–13), class II (14–19), class III (20–25), and class IV (> 25) with their corresponding mortality (13%, 55%, 70%, and 94%, respectively), were identified. The area under the receiver operating characteristic curve 0.85(95% CI 0.79–0.91) for the REMEMBER score was better than those for the SOFA, SAVE, EuroSCORE, and ENCOURAGE scores in this population. Conclusions The REMEMBER score might help clinicians at bedside to predict in-hospital mortality for patients receiving VA-ECMO after isolated CABG for refractory cardiogenic shock. Prospective studies are needed to externally validate this scoring system.

Abstract Rationale Diaphragm dysfunction worsens outcomes in mechanically ventilated patients, but the clinical impact of potentially preventable changes in diaphragm structure and function caused by mechanical ventilation is unknown. Objectives To determine whether diaphragm atrophy developing during mechanical ventilation leads to prolonged ventilation. Methods Diaphragm thickness was measured daily by ultrasound in adults requiring invasive mechanical ventilation; inspiratory effort was assessed by thickening fraction. The primary outcome was time to liberation from ventilation. Secondary outcomes included complications (reintubation, tracheostomy, prolonged ventilation, or death). Associations were adjusted for age, severity of illness, sepsis, sedation, neuromuscular blockade, and comorbidity. Measurements and Main Results Of 211 patients enrolled, 191 had two or more diaphragm thickness measurements. Thickness decreased more than 10% in 78 patients (41%) by median Day 4 (interquartile range, 3–5). Development of decreased thickness was associated with a lower daily probability of liberation from ventilation (adjusted hazard ratio, 0.69; 95% confidence interval [CI], 0.54–0.87; per 10% decrease), prolonged ICU admission (adjusted duration ratio, 1.71; 95% CI, 1.29–2.27), and a higher risk of complications (adjusted odds ratio, 3.00; 95% CI, 1.34–6.72). Development of increased thickness (n = 47; 24%) also predicted prolonged ventilation (adjusted duration ratio, 1.38; 95% CI, 1.00–1.90). Decreasing thickness was related to abnormally low inspiratory effort; increasing thickness was related to excessive effort. Patients with thickening fraction between 15% and 30% (similar to breathing at rest) during the first 3 days had the shortest duration of ventilation. Conclusions Diaphragm atrophy developing during mechanical ventilation strongly impacts clinical outcomes. Targeting an inspiratory effort level similar to that of healthy subjects at rest might accelerate liberation from ventilation.

Critically ill survivors may have functional impairments even five years after hospital discharge. To date there are four systematic reviews suggesting a beneficial impact for mobilisation in mechanically ventilated and intensive care unit (ICU) patients, however there is limited information about the influence of timing, frequency and duration of sessions. Earlier mobilisation during ICU stay may lead to greater benefits. This study aims to determine the effect of early rehabilitation for functional status in ICU/high-dependency unit (HDU) patients. Systematic review and meta-analysis. MEDLINE, EMBASE, CINALH, PEDro, Cochrane Library, AMED, ISI web of science, Scielo, LILACS and several clinical trial registries were searched for randomised and non-randomised clinical trials of rehabilitation compared to usual care in adult patients admitted to an ICU/HDU. Results were screened by two independent reviewers. Primary outcome was functional status. Secondary outcomes were walking ability, muscle strength, quality of life, and healthcare utilisation. Data extraction and methodological quality assessment using the PEDro scale was performed by primary reviewer and checked by two other reviewers. The authors of relevant studies were contacted to obtain missing data. 5733 records were screened. Seven articles were included in the narrative synthesis and six in the meta-analysis. Early rehabilitation had no significant effect on functional status, muscle strength, quality of life, or healthcare utilisation. However, early rehabilitation led to significantly more patients walking without assistance at hospital discharge (risk ratio 1.42; 95% CI 1.17-1.72). There was a non-significant effect favouring intervention for walking distance and incidence of ICU-acquired weakness. Early rehabilitation during ICU stay was not associated with improvements in functional status, muscle strength, quality of life or healthcare utilisation outcomes, although it seems to improve walking ability compared to usual care. Results from ongoing studies may provide more data on the potential benefits of early rehabilitation in critically ill patients.

Diaphragm atrophy and dysfunction have been reported in humans during mechanical ventilation, but the prevalence, causes, and functional impact of changes in diaphragm thickness during routine mechanical ventilation for critically ill patients are unknown. To describe the evolution of diaphragm thickness over time during mechanical ventilation, its impact on diaphragm function, and the influence of inspiratory effort on this phenomenon. In three academic intensive care units, 107 patients were enrolled shortly after initiating ventilation along with 10 nonventilated intensive care unit patients (control subjects). Diaphragm thickness and contractile activity (quantified by the inspiratory thickening fraction) were measured daily by ultrasound. Over the first week of ventilation, diaphragm thickness decreased by more than 10% in 47 (44%), was unchanged in 47 (44%), and increased by more than 10% in 13 (12%). Thickness did not vary over time following extubation or in nonventilated patients. Low diaphragm contractile activity was associated with rapid decreases in diaphragm thickness, whereas high contractile activity was associated with increases in diaphragm thickness (P = 0.002). Contractile activity decreased with increasing ventilator driving pressure (P = 0.01) and controlled ventilator modes (P = 0.02). Maximal thickening fraction (a measure of diaphragm function) was lower in patients with decreased or increased diaphragm thickness (n = 10) compared with patients with unchanged thickness (n = 10; P = 0.05 for comparison). Changes in diaphragm thickness are common during mechanical ventilation and may be associated with diaphragmatic weakness. Titrating ventilatory support to maintain normal levels of inspiratory effort may prevent changes in diaphragm configuration associated with mechanical ventilation.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Background Excessive respiratory muscle effort during mechanical ventilation may cause patient self-inflicted lung injury and load-induced diaphragm myotrauma, but there are no non-invasive methods to reliably detect elevated transpulmonary driving pressure and elevated respiratory muscle effort during assisted ventilation. We hypothesized that the swing in airway pressure generated by respiratory muscle effort under assisted ventilation when the airway is briefly occluded (Δ P occ ) could be used as a highly feasible non-invasive technique to screen for these conditions. Methods Respiratory muscle pressure ( P mus ), dynamic transpulmonary driving pressure (Δ P L,dyn , the difference between peak and end-expiratory transpulmonary pressure), and Δ P occ were measured daily in mechanically ventilated patients in two ICUs in Toronto, Canada. A conversion factor to predict Δ P L,dyn and P mus from Δ P occ was derived and validated using cross-validation. External validity was assessed in an independent cohort (Nanjing, China). Results Fifty-two daily recordings were collected in 16 patients. In this sample, P mus and Δ P L were frequently excessively high: P mus exceeded 10 cm H 2 O on 84% of study days and Δ P L,dyn exceeded 15 cm H 2 O on 53% of study days. Δ P occ measurements accurately detected P mus > 10 cm H 2 O (AUROC 0.92, 95% CI 0.83–0.97) and Δ P L,dyn  > 15 cm H 2 O (AUROC 0.93, 95% CI 0.86–0.99). In the external validation cohort ( n  = 12), estimating P mus and Δ P L,dyn from Δ P occ measurements detected excessively high P mus and Δ P L,dyn with similar accuracy (AUROC ≥ 0.94). Conclusions Measuring Δ P occ enables accurate non-invasive detection of elevated respiratory muscle pressure and transpulmonary driving pressure. Excessive respiratory effort and transpulmonary driving pressure may be frequent in spontaneously breathing ventilated patients.