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1.
BMJ (Clinical research ed.) ; 377:e068723-e068723, 2022.
Article in English | PMC | ID: covidwho-1822063

ABSTRACT

OBJECTIVE To estimate the effect of extracorporeal membrane oxygenation (ECMO) compared with conventional mechanical ventilation on outcomes of patients with covid-19 associated respiratory failure. DESIGN Observational study. SETTING 30 countries across five continents, 3 January 2020 to 29 August 2021. PARTICIPANTS 7345 adults admitted to the intensive care unit with clinically suspected or laboratory confirmed SARS-CoV-2 infection. INTERVENTIONS ECMO in patients with a partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio <80 mm Hg compared with conventional mechanical ventilation without ECMO. MAIN OUTCOME MEASURE The primary outcome was hospital mortality within 60 days of admission to the intensive care unit. Adherence adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for competing events and for baseline and time varying confounding. RESULTS 844 of 7345 eligible patients (11.5%) received ECMO at any time point during follow-up. Adherence adjusted mortality was 26.0% (95% confidence interval 24.5% to 27.5%) for a treatment strategy that included ECMO if the PaO2/FiO2 ratio decreased <80 mm Hg compared with 33.2% (31.8% to 34.6%) had patients received conventional treatment without ECMO (risk difference -7.1%, 95% confidence interval -8.2% to -6.1%;risk ratio 0.78, 95% confidence interval 0.75 to 0.82). In secondary analyses, ECMO was most effective in patients aged <65 years and with a PaO2/FiO2 <80 mm Hg or with driving pressures >15 cmH2O during the first 10 days of mechanical ventilation. CONCLUSIONS ECMO was associated with a reduction in mortality in selected adults with covid-19 associated respiratory failure. Age, severity of hypoxaemia, and duration and intensity of mechanical ventilation were found to be modifiers of treatment effectiveness and should be considered when deciding to initiate ECMO in patients with covid-19.

2.
Palliative Medicine ; : 02692163221087162, 2022.
Article in English | Sage | ID: covidwho-1794155

ABSTRACT

Background:Palliative care is well suited to support patients hospitalized with COVID-19, but integration into care has been variable and generally poor.Aim:To understand barriers and facilitators of palliative care integration for hospitalized patients with COVID-19.Methods:Internists, Intensivists and palliative care physicians completed semi-structured interviews about their experiences providing care to patients with COVID-19. Results were analysed using thematic analysis.Results:Twenty-three physicians (13 specialist palliative care, five intensivists, five general internists) were interviewed;mean?±?SD age was 42?±?11?years and 61% were female. Six thematic categories were described including: patient and family factors, palliative care knowledge, primary provider factors, COVID-19 specific factors, palliative care service factors, and leadership and culture factors. Patient and family factors included patient prognosis, characteristics that implied prognosis (i.e., age, etc.), and goals of care. Palliative care knowledge included confidence in primary palliative care skills, misperception that COVID-19 is not a ?palliative diagnosis?, and the need to choose quantity or quality of life in COVID-19 management. Primary provider factors included available time, attitude, and reimbursement. COVID-19 specific factors were COVID-19 as an impetus to act, uncertain illness trajectory, treatments and outcomes, and infection control measures. Palliative care service factors were accessibility, adaptability, and previous successful relationships. Leadership and culture factors included government-mandated support, presence at COVID planning tables, and institutional and unit culture.Conclusion:The study findings highlight the need for leadership support for formal integrated models of palliative care for patients with COVID-19, a palliative care role in pandemic planning, and educational initiatives with primary palliative care providers.

3.
EBioMedicine ; 78: 103982, 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1783293

ABSTRACT

BACKGROUND: Endothelial cell (EC) activation, endotheliitis, vascular permeability, and thrombosis have been observed in patients with severe coronavirus disease 2019 (COVID-19), indicating that the vasculature is affected during the acute stages of SARS-CoV-2 infection. It remains unknown whether circulating vascular markers are sufficient to predict clinical outcomes, are unique to COVID-19, and if vascular permeability can be therapeutically targeted. METHODS: Prospectively evaluating the prevalence of circulating inflammatory, cardiac, and EC activation markers as well as developing a microRNA atlas in 241 unvaccinated patients with suspected SARS-CoV-2 infection allowed for prognostic value assessment using a Random Forest model machine learning approach. Subsequent ex vivo experiments assessed EC permeability responses to patient plasma and were used to uncover modulated gene regulatory networks from which rational therapeutic design was inferred. FINDINGS: Multiple inflammatory and EC activation biomarkers were associated with mortality in COVID-19 patients and in severity-matched SARS-CoV-2-negative patients, while dysregulation of specific microRNAs at presentation was specific for poor COVID-19-related outcomes and revealed disease-relevant pathways. Integrating the datasets using a machine learning approach further enhanced clinical risk prediction for in-hospital mortality. Exposure of ECs to COVID-19 patient plasma resulted in severity-specific gene expression responses and EC barrier dysfunction, which was ameliorated using angiopoietin-1 mimetic or recombinant Slit2-N. INTERPRETATION: Integration of multi-omics data identified microRNA and vascular biomarkers prognostic of in-hospital mortality in COVID-19 patients and revealed that vascular stabilizing therapies should be explored as a treatment for endothelial dysfunction in COVID-19, and other severe diseases where endothelial dysfunction has a central role in pathogenesis. FUNDING INFORMATION: This work was directly supported by grant funding from the Ted Rogers Center for Heart Research, Toronto, Ontario, Canada and the Peter Munk Cardiac Center, Toronto, Ontario, Canada.

4.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327551

ABSTRACT

STRUCTURED ABSTRACT Background Endothelial cell (EC) activation, endotheliitis, vascular permeability, and thrombosis have been observed in patients with severe COVID-19, indicating that the vasculature is affected during the acute stages of SARS-CoV-2 infection. It remains unknown whether circulating vascular markers are sufficient to predict clinical outcomes, are unique to COVID-19, and if vascular permeability can be therapeutically targeted. Methods Evaluating the prevalence of circulating inflammatory, cardiac and EC activation markers, and the development of a microRNA atlas in 241 patients with suspected SARS-CoV-2 infection, allowed their prognostic value to be assessed by a Random Forest model machine learning approach. Subsequent ex vivo experiments assessed EC permeability responses to patient plasma and were used to uncover modulated gene regulatory networks from which rational therapeutic design was inferred. Findings Multiple inflammatory and EC activation biomarkers were associated with mortality in COVID-19 patients and in severity-matched SARS-CoV-2-negative patients, while dysregulation of specific microRNAs at presentation was specific for poor COVID-19-related outcomes and revealed disease-relevant pathways. Integrating the datasets using a machine learning approach further enhanced clinical risk prediction for in-hospital mortality. Exposure of ECs to COVID-19 patient plasma resulted in severity-specific gene expression responses and EC barrier dysfunction which was ameliorated using angiopoietin-1 mimetic or recombinant Slit2-N. Interpretation Integration of multi-omics data identified microRNA and vascular biomarkers prognostic of in-hospital mortality in COVID-19 patients and revealed that vascular stabilizing therapies should be explored as a treatment for endothelial dysfunction in COVID-19, and other severe diseases where endothelial dysfunction has a central role in pathogenesis. RESEARCH IN CONTEXT Evidence before this study While diagnostic testing has allowed for the rapid identification of COVID-19 cases, the lack of post-diagnosis risk assessment metrics, especially among the highest-risk subgroups, thereby undermined the cascade and allocation of care. To date, the integration of clinical data with broad omics technologies has opened up new avenues for efficiently delineating complex patient phenotypes and their associations with clinical outcomes, with circulating profiles of plasma microRNAs (miRNA), in particular, having been shown to be tightly associated with disease, and capable of providing not only detailed prognostic information but also mechanistic insight. Added value of this study Markers of endothelial dysfunction at presentation, while indicative of poor outcomes in COVID-19-positive patients, likely reflect systemic vascular dysfunction in critically ill patients and are not specific to SARS-CoV-2 infection. More so, the generation of a plasma microRNA atlas uncovers COVID-19-specific prognostic markers and multiple disease-specific pathways of interest, including endothelial barrier dysfunction. Furthermore, synthesis of electronic health record data with clinically relevant multi-omic datasets using a machine learning approach provides substantially better metrics by which mortality can be estimated in patients with severe COVID-19. Finally, targeted stabilization of the endothelial barrier with Q-Peptide and Slit2-N are novel therapeutic avenues that should be explored in COVID-19 patients. Implications of all the available evidence Together, our work provides biological insight into the role of the endothelium in SARS-CoV-2 infection, the importance of miRNA as disease- and pathway-specific biomarkers, and the exciting possibility that endothelial barrier stabilizing treatments might hold promise in COVID-19.

5.
SSRN;
Preprint in English | SSRN | ID: ppcovidwho-326151

ABSTRACT

Background: Extracorporeal membrane oxygenation (ECMO) has been used extensively for coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). Reports early in the pandemic suggested that mortality in patients with COVID-19 receiving ECMO were comparable to non-COVID-19-related ARDS. However, subsequent reports suggested that mortality appeared to be increasing over time. Therefore, we conducted an updated systematic review and meta-analysis, in order to characterise changes in mortality over time, and elucidate risk factors for poor outcomes. Methods: We conducted a meta-analysis (CRD42021271202), searching MEDLINE, Embase, Cochrane, and Scopus databases, from 1 December 2019 to 26 January 2022, for studies reporting on mortality among adults with COVID-19 receiving ECMO. We also captured hospital and intensive care unit (ICU) lengths of stay, duration of mechanical ventilation and ECMO, as well as complications of ECMO. We conducted random-effects meta-analyses, assessed risk of bias of included studies using the Joanna Briggs Institute checklist and evaluated certainty of pooled estimates using GRADE methodology. Findings: Of 4,522 citations, we included 52 studies comprising 18,211 patients in the meta-analysis. The pooled mortality rate among patients with COVID-19 requiring ECMO was 48·5% (95% confidence interval (CI): 44·4%-52·6%, high certainty). Mortality was higher among studies which enrolled patients later in the pandemic as opposed to earlier (1st half 2020: 40·8%, 2nd half 2020: 46·4%, 1st half 2021: 61·2%, 2nd half 2021: 46·5%, interaction p-value = 0·016). Predictors of increased mortality included age, the time of final patient enrolment from 1 January 2020, and the proportion of patients receiving corticosteroids, and reduced duration of ECMO run. Interpretation: The mortality rate for patients receiving ECMO for COVID-19-related ARDS has increased as the pandemic has progressed. The reasons for this are likely multifactorial, however as outcomes for these patients evolve, the decision to initiate ECMO should include the best contextual estimate of mortality at the time of ECMO initiation.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306446

ABSTRACT

Background: Risk factors associated with mortality in patients with coronavirus disease 2019 (COVID-19) on mechanical ventilation are still not fully elucidated. Thus, we aimed to identify patient-level factors, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation (28-day IMV mortality) in patients with COVID-19. Methods: Prospective observational cohort study in 148 intensive care units in the global COVID-19 Critical Care Consortium . Patients with clinically suspected or laboratory confirmed COVID-19 infection admitted to the intensive care unit (ICU) from February 2 nd through December 29th, 2020, requiring IMV. No study-specific interventions were performed. Patient characteristics and clinical data were assessed upon ICU admission, the commencement of IMV and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day IMV mortality. Results: : A total of 1713 patients were included in the survival analysis, 588 patients died in hospital within 28 days of commencing IMV (34.3%). Cox-regression analysis identified associations between the hazard of 28-day IMV mortality with age (HR 1.27 per 10-year increase in age, 95% CI 1.17 to 1.37, P<0.001), PEEP upon commencement of IMV (HR 0.78 per 5-cmH 2 O increase, 95% CI 0.66-0.93, P=0.005). Time-dependent parameters associated with 28-day IMV mortality were serum creatinine (HR 1.30 per doubling, 95% CI 1.19-1.42, P<0.001), lactate (HR 1.16 per doubling, 95% CI 1.06-1.27 P=0.001), PaCO 2 (HR 1.31 per doubling, 95% CI 1.05-1.64, P=0.015), pH (HR 0.82 per 0.1 increase, 95% CI 0.74-0.91, P<0.001), PaO 2 /FiO 2 (HR 0.56 per doubling, 95% CI 0.50-0.62, P<0.001) and mean arterial pressure (HR 0.92 per 10 mmHg increase, 95% CI 0.88-0.97, P=0.002). Conclusions: : This international study establishes that in mechanically ventilated patients with COVID-19, older age and clinically relevant variables monitored at the bedside are risk factors for 28-day IMV mortality. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-306445

ABSTRACT

Background: Heterogeneous respiratory system static compliance (C RS ) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level. Methods We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe the impact of C RS on the ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide. Results We enrolled 318 COVID-19 patients enrolled into the study from January 14th through September 31th, 2020 in 19 countries and stratified into two C RS groups. C RS was calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)] and available within 48 h from commencement of MV in 318 patients. Patients were mean ± SD of 58.0 ± 12.2, predominantly from Europe (54%) and males (68%). Median C RS (IQR) was 34.1 mL/cmH 2 O (26.5–45.5) and PaO 2 /FiO 2 was 119 mmHg (87.1–164) and was not correlated with C RS . Female sex presented lower C RS than in males (95% CI: -13.8 to -8.5 P < 0.001) and higher body mass index (34.7 ± 10.9 vs 29.1 ± 6.0, p < 0.001). Median (IQR) PEEP was 12 cmH 2 O (10–15), throughout the range of C RS , while median (IQR) driving pressure was 12.3 (10–15) cmH 2 O and significantly decreased as C RS improved (p < 0.001). No differences were found in comorbidities and clinical management between C RS strata. In addition, 28-day ICU mortality and hospital mortality did not differ between C RS groups. Conclusions This multicentre report provides a comprehensive account of C RS in COVID-19 patients on MV – predominantly males or overweight females, in their late 50 s – admitted to ICU during the first international outbreaks. Phenotypes associated with different C RS upon commencement of MV could not be identified. Trial documentation: Available at https://www.covid-critical.com/study. Trial registration ACTRN12620000421932.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-319745

ABSTRACT

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 st December 2019 to 10 th January 2021 for observational studies or randomized clinical trials examining ECMO in adults with COVID-19 ARDS. We performed random-effects meta-analyses and metaregression, 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). 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: Majority of patients received ECMO support for COVID-19-related ARDS. In-hospital mortality in patients receiving ECMO support for COVID-19 was 37.1%, 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

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319460

ABSTRACT

Introduction: Prone position improves mortality in patients with acute respiratory distress syndrome (ARDS). The impact of prone position in critically ill COVID-19 patients remains to be determined. In this review, we describe mechanisms of action of prone position, systematically appraise current experience of prone position in COVID-19 patients and highlight unique considerations for prone position practices during this pandemic. Methods: : For our systematic review, we searched PubMed, Scopus and EMBASE from January 1, 2020 to April 16th 2020. After completion of our search, we became aware of four relevant publications during article preparation that were published in May and June 2020 and these studies were reviewed for eligibility and inclusion. We included all studies reporting clinical characteristics of patients admitted to hospital with COVID-19 disease who received respiratory support with high flow nasal cannula, non-invasive or MV and reported the use of prone position. Full text of eligible articles was reviewed and data regarding study design patient characteristics, interventions and outcomes were extracted. Results: : We found 7 studies (total 1899 patients) describing prone position in COVID-19. Prone position has been increasingly used in non-intubated patients with COVID-19;studies show high tolerance, improvement in oxygenation and lung recruitment. Published studies lacked description of important clinical outcomes (e.g., mortality, duration of mechanical ventilation). Conclusions: : Based on the findings of our review, we recommend prone position in patients with moderate to severe COVID-19 ARDS as per existing guidelines. A trial of prone position should be considered for non-intubated COVID-19 patients with hypoxemic respiratory failure, as long as this does not result in a delay in intubation.

10.
Critical care clinics ; 2022.
Article in English | EuropePMC | ID: covidwho-1615400

ABSTRACT

Synopsis Extracorporeal membrane oxygenation (ECMO) is an intervention for severe acute respiratory distress syndrome (ARDS). Despite COVID-19 related ARDS might have some distinct features, its overall clinical presentation resembles ARDS from other etiologies. Thus, similar evidence-based practices for its management should be applied. These include lung-protective ventilation, prone positioning, and adjuvant strategies such as ECMO, when appropriate. Current evidence suggests that ECMO in COVID-19 related ARDS has similar efficacy and safety profile as for non-COVID-19 ARDS. The high number of severe COVID-19 cases and demand for therapies such as ECMO poses a unique opportunity to increase our understanding on how to optimize this intervention.

13.
Chest ; 160(5): 1729-1738, 2021 11.
Article in English | MEDLINE | ID: covidwho-1517092

ABSTRACT

ARDS is a clinically heterogeneous syndrome, rather than a distinct disease. This heterogeneity at least partially explains the difficulty in studying treatments for these patients and contributes to the numerous trials of therapies for the syndrome that have not shown benefit. Recent studies have identified different subphenotypes within the heterogeneous patient population. These different subphenotypes likely have variable clinical responses to specific therapies, a concept known as heterogeneity of treatment effect. Recognizing different subphenotypes and heterogeneity of treatment effect has important implications for the clinical management of patients with ARDS. This review presents studies that have identified different subphenotypes and discusses how they can modify the effects of therapies evaluated in trials that are commonly considered to have shown no overall benefit in patients with ARDS.


Subject(s)
Genetic Heterogeneity , Respiratory Distress Syndrome , Biological Variation, Population , Humans , Precision Medicine/methods , Respiratory Distress Syndrome/genetics , Respiratory Distress Syndrome/therapy , Treatment Outcome
14.
Crit Care Explor ; 3(11): e0567, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1515112

ABSTRACT

Factors associated with mortality in coronavirus disease 2019 patients on invasive mechanical ventilation are still not fully elucidated. OBJECTIVES: To identify patient-level parameters, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation or coronavirus disease 2019. DESIGN SETTING AND PARTICIPANTS: Prospective observational cohort study by the global Coronavirus Disease 2019 Critical Care Consortium. Patients with laboratory-confirmed coronavirus disease 2019 requiring invasive mechanical ventilation from February 2, 2020, to May 15, 2021. MAIN OUTCOMES AND MEASURES: Patient characteristics and clinical data were assessed upon ICU admission, the commencement of invasive mechanical ventilation and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day invasive mechanical ventilation mortality. RESULTS: One-thousand five-hundred eighty-seven patients were included in the survival analysis; 588 patients died in hospital within 28 days of commencing invasive mechanical ventilation (37%). Cox-regression analysis identified associations between the hazard of 28-day invasive mechanical ventilation mortality with age (hazard ratio, 1.26 per 10-yr increase in age; 95% CI, 1.16-1.37; p < 0.001), positive end-expiratory pressure upon commencement of invasive mechanical ventilation (hazard ratio, 0.81 per 5 cm H2O increase; 95% CI, 0.67-0.97; p = 0.02). Time-dependent parameters associated with 28-day invasive mechanical ventilation mortality were serum creatinine (hazard ratio, 1.28 per doubling; 95% CI, 1.15-1.41; p < 0.001), lactate (hazard ratio, 1.22 per doubling; 95% CI, 1.11-1.34; p < 0.001), Paco2 (hazard ratio, 1.63 per doubling; 95% CI, 1.19-2.25; p < 0.001), pH (hazard ratio, 0.89 per 0.1 increase; 95% CI, 0.8-14; p = 0.041), Pao2/Fio2 (hazard ratio, 0.58 per doubling; 95% CI, 0.52-0.66; p < 0.001), and mean arterial pressure (hazard ratio, 0.92 per 10 mm Hg increase; 95% CI, 0.88-0.97; p = 0.003). CONCLUSIONS AND RELEVANCE: This international study suggests that in patients with coronavirus disease 2019 on invasive mechanical ventilation, older age and clinically relevant variables monitored at baseline or sequentially during the course of invasive mechanical ventilation are associated with 28-day invasive mechanical ventilation mortality hazard. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes.

16.
Crit Care Med ; 49(10): e1001-e1014, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1475867

ABSTRACT

OBJECTIVES: Several studies have reported prone positioning of nonintubated patients with coronavirus diseases 2019-related hypoxemic respiratory failure. This systematic review and meta-analysis evaluated the impact of prone positioning on oxygenation and clinical outcomes. DESIGN AND SETTING: We searched PubMed, Embase, and the coronavirus diseases 2019 living systematic review from December 1, 2019, to November 9, 2020. SUBJECTS AND INTERVENTION: Studies reporting prone positioning in hypoxemic, nonintubated adult patients with coronavirus diseases 2019 were included. MEASUREMENTS AND MAIN RESULTS: Data on prone positioning location (ICU vs non-ICU), prone positioning dose (total minutes/d), frequency (sessions/d), respiratory supports during prone positioning, relative changes in oxygenation variables (peripheral oxygen saturation, Pao2, and ratio of Pao2 to the Fio2), respiratory rate pre and post prone positioning, intubation rate, and mortality were extracted. Twenty-five observational studies reporting prone positioning in 758 patients were included. There was substantial heterogeneity in prone positioning location, dose and frequency, and respiratory supports provided. Significant improvements were seen in ratio of Pao2 to the Fio2 (mean difference, 39; 95% CI, 25-54), Pao2 (mean difference, 20 mm Hg; 95% CI, 14-25), and peripheral oxygen saturation (mean difference, 4.74%; 95% CI, 3-6%). Respiratory rate decreased post prone positioning (mean difference, -3.2 breaths/min; 95% CI, -4.6 to -1.9). Intubation and mortality rates were 24% (95% CI, 17-32%) and 13% (95% CI, 6-19%), respectively. There was no difference in intubation rate in those receiving prone positioning within and outside ICU (32% [69/214] vs 33% [107/320]; p = 0.84). No major adverse events were recorded in small subset of studies that reported them. CONCLUSIONS: Despite the significant variability in frequency and duration of prone positioning and respiratory supports applied, prone positioning was associated with improvement in oxygenation variables without any reported serious adverse events. The results are limited by a lack of controls and adjustments for confounders. Whether this improvement in oxygenation results in meaningful patient-centered outcomes such as reduced intubation or mortality rates requires testing in well-designed randomized clinical trials.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Prone Position/physiology , COVID-19/mortality , Humans , Patient Positioning , Respiratory Insufficiency/etiology , Respiratory Insufficiency/physiopathology
17.
Lancet ; 398(10307): 1230-1238, 2021 10 02.
Article in English | MEDLINE | ID: covidwho-1440421

ABSTRACT

BACKGROUND: 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. METHODS: 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. FINDINGS: 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]). INTERPRETATION: 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. FUNDING: None.


Subject(s)
COVID-19/therapy , Extracorporeal Membrane Oxygenation/methods , Hospital Mortality/trends , Respiratory Distress Syndrome/therapy , Adult , COVID-19/mortality , Duration of Therapy , Extracorporeal Membrane Oxygenation/trends , Female , Humans , Male , Middle Aged , Patient Selection , Practice Guidelines as Topic , Registries , Respiratory Distress Syndrome/mortality , SARS-CoV-2
19.
Intensive Care Med ; 47(9): 1054-1056, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1401012

Subject(s)
Medicine , Humans
20.
Crit Care ; 25(1): 211, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1352668

ABSTRACT

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.


Subject(s)
COVID-19/therapy , Critical Illness/therapy , Extracorporeal Membrane Oxygenation/methods , Respiratory Distress Syndrome/therapy , Adult , Age Factors , Aged , COVID-19/complications , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Positive-Pressure Respiration/methods , Respiratory Distress Syndrome/etiology , Risk Assessment
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