Publications by authors named "Arthur S Slutsky"

319 Publications

Ventilator Weaning and Discontinuation Practices for Critically Ill Patients.

JAMA 2021 03;325(12):1173-1184

Departments of Medicine and Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.

Importance: Although most critically ill patients receive invasive mechanical ventilation (IMV), few studies have characterized how IMV is discontinued in practice.

Objective: To describe practice variation in IMV discontinuation internationally, associations between initial discontinuation events and outcomes, and factors associated with the use of select discontinuation strategies and failed initial spontaneous breathing trials (SBTs).

Design, Setting, And Participants: Prospective, multinational, observational study of critically ill adults who received IMV for at least 24 hours from 142 intensive care units (ICUs) in 19 countries within 6 regions (27 in Canada, 23 in India, 22 in the UK, 26 in Europe, 21 in Australia/New Zealand, and 23 in the US).

Exposures: Receiving IMV.

Main Outcomes And Measures: Primary analyses characterized types of initial IMV discontinuation events (extubation, SBT, or tracheostomy) and associations with clinical outcomes (including duration of ventilation, ICU and hospital mortality, and ICU and hospital length of stay). Secondary analyses examined the associations between SBT outcome and SBT timing and clinical outcomes.

Results: Among 1868 patients (median [interquartile range] age, 61.8 [48.9-73.1] years; 1173 [62.8%] men) 424 (22.7%) underwent direct extubation, 930 (49.8%) had an initial SBT (761 [81.8%] successful), 150 (8.0%) underwent direct tracheostomy, and 364 (19.5%) died before a weaning attempt. Across regions, there was variation in the use of written directives to guide care, daily screening, SBT techniques, ventilator modes, and the roles played by clinicians involved in weaning. Compared with initial direct extubation, patients who had an initial SBT had higher ICU mortality (20 [4.7%] vs 96 [10.3%]; absolute difference, 5.6% [95% CI, 2.6%-8.6%]), longer duration of ventilation (median of 2.9 vs 4.1 days; absolute difference, 1.2 days [95% CI, 0.7-1.6]), and longer ICU stay (median of 6.7 vs 8.1 days; absolute difference, 1.4 days [95% CI, 0.8-2.4]). Patients whose initial SBT failed (vs passed) had higher ICU mortality (29 [17.2%] vs 67 [8.8%]; absolute difference, 8.4% [95% CI, 2.0%-14.7%]), longer duration of ventilation (median of 6.1 vs 3.5 days; absolute difference, 2.6 days [95% CI, 1.6-3.6]), and longer ICU stay (median of 10.6 vs 7.7 days; absolute difference, 2.8 days [95% CI, 1.1-5.2]). Compared with patients who underwent early initial SBTs, patients who underwent late initial SBTs (>2.3 days after intubation) had longer duration of ventilation (median of 2.1 vs 6.1 days; absolute difference, 4.0 days [95% CI, 3.7-4.5]), longer ICU stay (median of 5.9 vs 10.8 days; absolute difference, 4.9 days [95% CI, 4.0-6.3]), and longer hospital stay (median of 14.3 vs 22.8 days; absolute difference, 8.5 days [95% CI, 6.0-11.0]).

Conclusions And Relevance: In this observational study of invasive mechanical ventilation discontinuation in 142 ICUs in Canada, India, the UK, Europe, Australia/New Zealand, and the US from 2013 to 2016, weaning practices varied internationally.

Trial Registration: ClinicalTrials.gov Identifier: NCT03955874.
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http://dx.doi.org/10.1001/jama.2021.2384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988370PMC
March 2021

Trends in COVID-19-related in-hospital mortality: lessons learned from nationwide samples.

Lancet Respir Med 2021 04 15;9(4):322-324. Epub 2021 Feb 15.

Division of Pulmonary, Allergy, and Critical Care, Columbia University Irving Medical Center and New York-Presbyterian Hospital, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/S2213-2600(21)00080-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906680PMC
April 2021

Enabling a learning healthcare system with automated computer protocols that produce replicable and personalized clinician actions.

J Am Med Inform Assoc 2021 Feb 16. Epub 2021 Feb 16.

Institute for Healthcare Improvement, Boston, Massachusetts, USA.

Clinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention-the starting point for delivery of "All the right care, but only the right care," an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.
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http://dx.doi.org/10.1093/jamia/ocaa294DOI Listing
February 2021

A simple nomogram for predicting failure of non-invasive respiratory strategies in adults with COVID-19: a retrospective multicentre study.

Lancet Digit Health 2021 03 8;3(3):e166-e174. Epub 2021 Feb 8.

Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Keenan Research Center, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada; Department of Medicine, Department of Surgery, and Department of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.

Background: Non-invasive respiratory strategies (NIRS) including high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) have become widely used in patients with COVID-19 who develop acute respiratory failure. However, use of these therapies, if ineffective, might delay initiation of invasive mechanical ventilation (IMV) in some patients. We aimed to determine early predictors of NIRS failure and develop a simple nomogram and online calculator that can identify patients at risk of NIRS failure.

Methods: We did a retrospective, multicentre observational study in 23 hospitals designated for patients with COVID-19 in China. Adult patients (≥18 years) with severe acute respiratory syndrome coronavirus 2 infection and acute respiratory failure receiving NIRS were enrolled. A training cohort of 652 patients (21 hospitals) was used to identify early predictors of NIRS failure, defined as subsequent need for IMV or death within 28 days after intensive care unit admission. A nomogram was developed by multivariable logistic regression and concordance statistics (C-statistics) computed. C-statistics were validated internally by cross-validation in the training cohort, and externally in a validation cohort of 107 patients (two hospitals).

Findings: Patients were enrolled between Jan 1 and Feb 29, 2020. NIV failed in 211 (74%) of 286 patients and HFNC in 204 (56%) of 366 patients in the training cohort. NIV failed in 48 (81%) of 59 patients and HFNC in 26 (54%) of 48 patients in the external validation cohort. Age, number of comorbidities, respiratory rate-oxygenation index (ratio of pulse oximetry oxygen saturation/fraction of inspired oxygen to respiratory rate), Glasgow coma scale score, and use of vasopressors on the first day of NIRS in the training cohort were independent risk factors for NIRS failure. Based on the training dataset, the nomogram had a C-statistic of 0·80 (95% CI 0·74-0·85) for predicting NIV failure, and a C-statistic of 0·85 (0·82-0·89) for predicting HFNC failure. C-statistic values were stable in both internal validation (NIV group mean 0·79 [SD 0·10], HFNC group mean 0·85 [0·07]) and external validation (NIV group value 0·88 [95% CI 0·72-0·96], HFNC group value 0·86 [0·72-0·93]).

Interpretation: We have developed a nomogram and online calculator that can be used to identify patients with COVID-19 who are at risk of NIRS failure. These patients might benefit from early triage and more intensive monitoring.

Funding: Ministry of Science and Technology of the People's Republic of China, Key Research and Development Plan of Jiangsu Province, Chinese Academy of Medical Sciences.
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http://dx.doi.org/10.1016/S2589-7500(20)30316-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906717PMC
March 2021

Effect of Lowering Tidal Volume on Mortality in ARDS Varies with Respiratory System Elastance.

Am J Respir Crit Care Med 2021 Jan 13. Epub 2021 Jan 13.

Universidade de São Paulo Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, 67796, Laboratório de Pneumologia LIM-09, Disciplina de Pneumologia, Heart Institute (Incor), Ribeirao Preto, Brazil.

Rationale If the risk of ventilator-induced lung injury in acute respiratory distress syndrome is causally determined by driving pressure rather than tidal volume, then the effect of ventilation with lower tidal volumes on mortality would be predicted to vary according to respiratory system elastance. Objectives To determine whether the mortality benefit of ventilation with lower tidal volumes varies according to respiratory system elastance. Methods In a secondary analysis of patients from 5 randomized trials of lower vs. higher tidal volume ventilation strategies in ARDS and acute hypoxemic respiratory failure, the posterior probability of an interaction between randomized tidal volume strategy and respiratory system elastance on 60-day mortality was computed using Bayesian multivariable logistic regression. Measurements and Main Results Of 1,096 patients available for analysis, 416 (38%) died by day 60. The posterior probability that the mortality benefit from lower tidal volume ventilation strategies varied with respiratory system elastance was 93% (posterior median interaction odds ratio 0.80 per cmH2O/(ml/kg), 90% CrI 0.63-1.02). Respiratory system elastance was classified as low (<2 cmH2O/(ml/kg), n=321, 32%), intermediate (2-3 cmH2O/(ml/kg), n=475, 46%), and high (>3 cmH2O/(ml/kg), n=224, 22%). In these groups, the posterior probability of an absolute risk reduction (ARR) in mortality ≥1% was 55%, 82%, and 92%, respectively. The posterior probability of ARR≥5% was 29%, 58%, and 82%, respectively. Conclusions The mortality benefit of ventilation with lower tidal volumes in ARDS varies according to respiratory system elastance, suggesting that lung-protective ventilation strategies should primarily target driving pressure rather than tidal volume.
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http://dx.doi.org/10.1164/rccm.202009-3536OCDOI Listing
January 2021

Media Portrayals of Outcomes After Extracorporeal Membrane Oxygenation.

JAMA Intern Med 2021 Mar;181(3):391-394

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York.

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http://dx.doi.org/10.1001/jamainternmed.2020.6094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783587PMC
March 2021

Prévoir et gérer la coagulopathie et les manifestations thrombotiques de la COVID-19 sévère.

CMAJ 2020 12;192(50):E1816-E1822

Centre de cardiologie Peter Munk (Godoy, Lawler), Université de Toronto, Toronto, Ont.; Instituto do Coracao (Godoy), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brésil; Division interdépartmentale de médecine de soins intensifs (Goligher, Lawler, Slutsky), Université de Toronto; Division de pneumologie (Goligher), Département de médecine, Réseau universitaire de santé; Institut de recherche de l'Hôpital général de Toronto (Goligher, Lawler); Centre de recherche Keenan (Slutsky), Institut du savoir Li Ka Shing, Hôpital St. Michael's, Toronto, Ont.; Faculté des sciences de la santé Max Rady, Faculté de médecine Max Rady (Zarychanski), Département de médecine interne, Université du Manitoba; Institut de recherche en oncohématologie (Zarychanski), CancerCare Manitoba, Winnipeg, Man.

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http://dx.doi.org/10.1503/cmaj.201240-fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759103PMC
December 2020

Gender-Based Differences in Outcomes Among Resuscitated Patients With Out-of-Hospital Cardiac Arrest.

Circulation 2021 Feb 15;143(7):641-649. Epub 2020 Dec 15.

Rescu at the Li Ka Shing Knowledge Institute, Emergency Medicine, St. Michael's Hospital, Division of Emergency Medicine, Department of Medicine, Faculty of Medicine, Institute for Health Policy and Management (L.M.), University of Toronto, Ontario, Canada.

Background: Studies examining gender-based differences in outcomes of patients experiencing out-of-hospital cardiac arrest have demonstrated that, despite a higher likelihood of return of spontaneous circulation, women do not have higher survival.

Methods: Patients successfully resuscitated from out-of-hospital cardiac arrest enrolled in the CCC trial (Trial of Continuous or Interrupted Chest Compressions during CPR) were included. Hierarchical multivariable logistic regression models were constructed to evaluate the association between gender and survival after adjustment for age, gender, cardiac arrest rhythm, witnessed status, bystander cardiopulmonary resuscitation, episode location, epinephrine dose, emergency medical services response time, and duration of resuscitation. Do not resuscitate (DNR) and withdrawal of life-sustaining therapy (WLST) order status were used to assess whether differences in postresuscitation outcomes were modified by baseline prognosis. The analysis was replicated among ALPS trial (Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest) participants.

Results: Among 4875 successfully resuscitated patients, 1825 (37.4%) were women and 3050 (62.6%) were men. Women were older (67.5 versus 65.3 years), received less bystander cardiopulmonary resuscitation (49.1% versus 54.9%), and had a lower proportion of cardiac arrests that were witnessed (55.1% versus 64.5%) or had shockable rhythm (24.3% versus 44.6%, <0.001 for all). A significantly higher proportion of women received DNR orders (35.7% versus 32.1%, =0.009) and had WLST (32.8% versus 29.8%, =0.03). Discharge survival was significantly lower in women (22.5% versus 36.3%, <0.001; adjusted odds ratio, 0.78 [95% CI, 0.66-0.93]; =0.005). The association between gender and survival to discharge was modified by DNR and WLST order status such that women had significantly reduced survival to discharge among patients who were not designated DNR (31.3% versus 49.9%, =0.005; adjusted odds ratio, 0.74 [95% CI, 0.60-0.91]) or did not have WLST (32.3% versus 50.7%, =0.002; adjusted odds ratio, 0.73 [95% CI, 0.60-0.89]). In contrast, no gender difference in survival was noted among patients receiving a DNR order (6.7% versus 7.4%, =0.90) or had WLST (2.8% versus 2.4%, =0.93). Consistent patterns of association between gender and postresuscitation outcomes were observed in the secondary cohort.

Conclusions: Among patients resuscitated after experiencing out-of-hospital cardiac arrest, discharge survival was significantly lower in women than in men, especially among patients considered to have a favorable prognosis.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050427DOI Listing
February 2021

Searching for the Optimal PEEP in Patients Without ARDS: High, Low, or in Between?

JAMA 2020 12;324(24):2490-2492

Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1001/jama.2020.23067DOI Listing
December 2020

Is severe COVID-19 pneumonia a typical or atypical form of ARDS? And does it matter?

Intensive Care Med 2021 01 25;47(1):83-85. Epub 2020 Nov 25.

Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.

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http://dx.doi.org/10.1007/s00134-020-06320-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686835PMC
January 2021

Clinical trials in critical care: can a Bayesian approach enhance clinical and scientific decision making?

Lancet Respir Med 2021 02 20;9(2):207-216. Epub 2020 Nov 20.

Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Medicine, Division of Respirology, University Health Network and Sinai Health System, Toronto, ON, Canada; Toronto General Hospital Research Institute, Toronto, ON, Canada.

Recent Bayesian reanalyses of prominent trials in critical illness have generated controversy by contradicting the initial conclusions based on conventional frequentist analyses. Many clinicians might be sceptical that Bayesian analysis, a philosophical and statistical approach that combines prior beliefs with data to generate probabilities, provides more useful information about clinical trials than the frequentist approach. In this Personal View, we introduce clinicians to the rationale, process, and interpretation of Bayesian analysis through a systematic review and reanalysis of interventional trials in critical illness. In the majority of cases, Bayesian and frequentist analyses agreed. In the remainder, Bayesian analysis identified interventions where benefit was probable despite the absence of statistical significance, where interpretation depended substantially on choice of prior distribution, and where benefit was improbable despite statistical significance. Bayesian analysis in critical care medicine can help to distinguish harm from uncertainty and establish the probability of clinically important benefit for clinicians, policy makers, and patients.
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http://dx.doi.org/10.1016/S2213-2600(20)30471-9DOI Listing
February 2021

The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline.

Intensive Care Med 2020 Dec 17;46(12):2226-2237. Epub 2020 Nov 17.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.

Purpose: High flow nasal cannula (HFNC) is a relatively recent respiratory support technique which delivers high flow, heated and humidified controlled concentration of oxygen via the nasal route. Recently, its use has increased for a variety of clinical indications. To guide clinical practice, we developed evidence-based recommendations regarding use of HFNC in various clinical settings.

Methods: We formed a guideline panel composed of clinicians, methodologists and experts in respiratory medicine. Using GRADE, the panel developed recommendations for four actionable questions.

Results: The guideline panel made a strong recommendation for HFNC in hypoxemic respiratory failure compared to conventional oxygen therapy (COT) (moderate certainty), a conditional recommendation for HFNC following extubation (moderate certainty), no recommendation regarding HFNC in the peri-intubation period (moderate certainty), and a conditional recommendation for postoperative HFNC in high risk and/or obese patients following cardiac or thoracic surgery (moderate certainty).

Conclusions: This clinical practice guideline synthesizes current best-evidence into four recommendations for HFNC use in patients with hypoxemic respiratory failure, following extubation, in the peri-intubation period, and postoperatively for bedside clinicians.
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http://dx.doi.org/10.1007/s00134-020-06312-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670292PMC
December 2020

Pathophysiology of COVID-19-associated acute respiratory distress syndrome - Authors' reply.

Lancet Respir Med 2021 01 13;9(1):e5-e6. Epub 2020 Nov 13.

Alma Mater Studiorum-Università di Bologna, Dipartimento di Scienze Mediche e Chirurgiche, Anesthesia and Intensive Care Medicine, Policlinico di Sant'Orsola, 40138 Bologna, Italy. Electronic address:

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http://dx.doi.org/10.1016/S2213-2600(20)30525-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832136PMC
January 2021

Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection.

EMBO Mol Med 2021 01 14;13(1):e13426. Epub 2020 Dec 14.

Department of Laboratory Medicine, Unit of Clinical Microbiology, Karolinska Institute, Stockholm, Sweden.

There is a critical need for safe and effective drugs for COVID-19. Only remdesivir has received authorization for COVID-19 and has been shown to improve outcomes but not decrease mortality. However, the dose of remdesivir is limited by hepatic and kidney toxicity. ACE2 is the critical cell surface receptor for SARS-CoV-2. Here, we investigated additive effect of combination therapy using remdesivir with recombinant soluble ACE2 (high/low dose) on Vero E6 and kidney organoids, targeting two different modalities of SARS-CoV-2 life cycle: cell entry via its receptor ACE2 and intracellular viral RNA replication. This combination treatment markedly improved their therapeutic windows against SARS-CoV-2 in both models. By using single amino-acid resolution screening in haploid ES cells, we report a singular critical pathway required for remdesivir toxicity, namely, Adenylate Kinase 2. The data provided here demonstrate that combining two therapeutic modalities with different targets, common strategy in HIV treatment, exhibit strong additive effects at sub-toxic concentrations. Our data lay the groundwork for the study of combinatorial regimens in future COVID-19 clinical trials.
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http://dx.doi.org/10.15252/emmm.202013426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799356PMC
January 2021

Current and evolving standards of care for patients with ARDS.

Intensive Care Med 2020 12 6;46(12):2157-2167. Epub 2020 Nov 6.

Interdepartmental Division of Critical Care Medicine, Departments of Medicine and Physiology, Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.

Care for patients with acute respiratory distress syndrome (ARDS) has changed considerably over the 50 years since its original description. Indeed, standards of care continue to evolve as does how this clinical entity is defined and how patients are grouped and treated in clinical practice. In this narrative review we discuss current standards - treatments that have a solid evidence base and are well established as targets for usual care - and also evolving standards - treatments that have promise and may become widely adopted in the future. We focus on three broad domains of ventilatory management, ventilation adjuncts, and pharmacotherapy. Current standards for ventilatory management include limitation of tidal volume and airway pressure and standard approaches to setting PEEP, while evolving standards might focus on limitation of driving pressure or mechanical power, individual titration of PEEP, and monitoring efforts during spontaneous breathing. Current standards in ventilation adjuncts include prone positioning in moderate-severe ARDS and veno-venous extracorporeal life support after prone positioning in patients with severe hypoxemia or who are difficult to ventilate. Pharmacotherapy current standards include corticosteroids for patients with ARDS due to COVID-19 and employing a conservative fluid strategy for patients not in shock; evolving standards may include steroids for ARDS not related to COVID-19, or specific biological agents being tested in appropriate sub-phenotypes of ARDS. While much progress has been made, certainly significant work remains to be done and we look forward to these future developments.
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http://dx.doi.org/10.1007/s00134-020-06299-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646492PMC
December 2020

Extracorporeal life support for adults with acute respiratory distress syndrome.

Intensive Care Med 2020 Dec 2;46(12):2464-2476. Epub 2020 Nov 2.

Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, NewYork-Presbyterian Hospital, New York, USA.

Extracorporeal life support (ECLS) can support gas exchange in patients with the acute respiratory distress syndrome (ARDS). During ECLS, venous blood is drained from a central vein via a cannula, pumped through a semipermeable membrane that permits diffusion of oxygen and carbon dioxide, and returned via a cannula to a central vein. Two related forms of ECLS are used. Venovenous extracorporeal membrane oxygenation (ECMO), which uses high blood flow rates to both oxygenate the blood and remove carbon dioxide, may be considered in patients with severe ARDS whose oxygenation or ventilation cannot be maintained adequately with best practice conventional mechanical ventilation and adjunctive therapies, including prone positioning. Extracorporeal carbon dioxide removal (ECCOR) uses lower blood flow rates through smaller cannulae and provides substantial CO elimination (~ 20-70% of total CO production), albeit with marginal improvement in oxygenation. The rationale for using ECCOR in ARDS is to facilitate lung-protective ventilation by allowing a reduction of tidal volume, respiratory rate, plateau pressure, driving pressure and mechanical power delivered by the mechanical ventilator. This narrative review summarizes physiological concepts related to ECLS, as well as the rationale and evidence supporting ECMO and ECCOR for the treatment of ARDS. It also reviews complications, limitations, and the ethical dilemmas that can arise in treating patients with ECLS. Finally, it discusses future key research questions and challenges for this technology.
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http://dx.doi.org/10.1007/s00134-020-06290-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605473PMC
December 2020

Effets du climat et des interventions de santé publique sur la pandémie de COVID-19 : une étude de cohorte prospective.

CMAJ 2020 11;192(44):E1374-E1382

Centre de recherche en santé appliquée (Jüni, Rothenbühler, Bobos, Thorpe, da Costa, Slutsky) Institut du savoir Li Ka Shing, Hôpital St. Michael; Département de médecine et Institut des politiques, de la gestion et de l'évaluation de la santé (Jüni), Université de Toronto, Toronto, Ont.; Ava AG (Rothenbühler), Zürich, Suisse; Département des sciences de la santé et de la réadaptation (Bobos), Université Western, London, Ont.; École Dalla Lana de santé publique (Thorpe, Fisman, Gesink), Université de Toronto, Toronto, Ont.; Institut des soins de santé primaires (da Costa), Université de Berne, Suisse; Division interdépartmentale de médecine de soins intensifs (Slutsky), Université de Toronto, Toronto, Ont.

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http://dx.doi.org/10.1503/cmaj.200920-fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647477PMC
November 2020

Human recombinant soluble ACE2 in severe COVID-19.

Lancet Respir Med 2020 11 24;8(11):1154-1158. Epub 2020 Sep 24.

Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.

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http://dx.doi.org/10.1016/S2213-2600(20)30418-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515587PMC
November 2020

Acute respiratory failure and mechanical ventilation in the context of the COVID-19 pandemic: why a special issue in ICM?

Intensive Care Med 2020 12 29;46(12):2131-2132. Epub 2020 Oct 29.

Keenan Research Center, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1007/s00134-020-06298-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594991PMC
December 2020

Validity of Empirical Estimates of the Ratio of Dead Space to Tidal Volume in ARDS.

Respir Care 2021 Apr 20;66(4):559-565. Epub 2020 Oct 20.

Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.

Background: The ratio of dead space to tidal volume (V/V) is a clinically relevant parameter in ARDS; it has been shown to predict mortality, and it determines the extent to which extracorporeal CO removal reduces tidal volume (V) and driving pressure (ΔP). V/V can be estimated with volumetric capnography, but empirical formulas using demographic and physiological information have been proposed to estimate V/V without the need of additional equipment. It is unknown whether estimated and measured V/V produce similar estimates of the predicted effect of extracorporeal CO removal on ΔP.

Methods: We performed a secondary analysis of data from a previous clinical trial including subjects with ARDS in whom V/V and CO production ([Formula: see text]) were measured with volumetric capnography. The estimated ratio of dead space to tidal volume (V/V) was calculated using standard empiric formulas. Agreement between measured and estimated values was evaluated with Bland-Altman analysis. Agreement between the predicted change in ΔP with extracorporeal CO removal as computed using the measured ratio of alveolar dead space to tidal volume (V/V) or estimated V/V (V/V) was also evaluated.

Results: V/V was higher than measured V/V, and agreement between them was low (bias 0.05, limits of agreement -0.21 to 0.31). Differences between measured and estimated [Formula: see text] accounted for 57% of the error in V/V. The predicted reduction in ΔP with extracorporeal CO removal computed using V/V was in reasonable agreement with the expected reduction using V/V (bias -0.7 cm HO, limits of agreement -1.87 to 0.47 cm HO). In multivariable regression, measured V/V was associated with mortality (odds ratio 1.9, 95% CI 1.2-3.1, = .01), but V/V was not (odds ratio 1.2, 95% CI 0.8-1.8, = .3).

Conclusions: V/V and V/V showed low levels of agreement and cannot be used interchangeably in clinical practice. Nevertheless, the predicted decrease in ΔP due to extracorporeal CO removal was similar when computed from either estimated or measured V/V.
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http://dx.doi.org/10.4187/respcare.08246DOI Listing
April 2021

Evaluation of PEEP and prone positioning in early COVID-19 ARDS.

EClinicalMedicine 2020 Nov 11;28:100579. Epub 2020 Oct 11.

Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Background: In face of the Coronavirus Disease (COVID)-19 pandemic, best practice for mechanical ventilation in COVID-19 associated Acute Respiratory Distress Syndrome (ARDS) is intensely debated. Specifically, the rationale for high positive end-expiratory pressure (PEEP) and prone positioning in early COVID-19 ARDS has been questioned.

Methods: The first 23 consecutive patients with COVID-19 associated respiratory failure transferred to a single ICU were assessed. Eight were excluded: five were not invasively ventilated and three received veno-venous ECMO support. The remaining 15 were assessed over the first 15 days of mechanical ventilation. Best PEEP was defined by maximal oxygenation and was determined by structured decremental PEEP trials comprising the monitoring of oxygenation, airway pressures and trans-pulmonary pressures. In nine patients the impact of prone positioning on oxygenation was investigated. Additionally, the effects of high PEEP and prone positioning on pulmonary opacities in serial chest x-rays were determined by applying a semiquantitative scoring-system. This investigation is part of the prospective observational PA-COVID-19 study.

Findings: Patients responded to initiation of invasive high PEEP ventilation with markedly improved oxygenation, which was accompanied by reduced pulmonary opacities within 6 h of mechanical ventilation. Decremental PEEP trials confirmed the need for high PEEP (17.9 (SD ± 3.9) mbar) for optimal oxygenation, while driving pressures remained low. Prone positioning substantially increased oxygenation (<0.01).

Interpretation: In early COVID-19 ARDS, substantial PEEP values were required for optimizing oxygenation. Pulmonary opacities resolved during mechanical ventilation with high PEEP suggesting recruitment of lung volume.

Funding: German Research Foundation, German Federal Ministry of Education and Research.
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http://dx.doi.org/10.1016/j.eclinm.2020.100579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547915PMC
November 2020

We've never seen a patient with ARDS!

Intensive Care Med 2020 Dec 13;46(12):2133-2135. Epub 2020 Oct 13.

Keenan Research Center, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1007/s00134-020-06255-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553366PMC
December 2020

What have we learned ventilating COVID-19 patients?

Intensive Care Med 2020 12 12;46(12):2458-2460. Epub 2020 Oct 12.

Keenan Research Center for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1007/s00134-020-06275-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549087PMC
December 2020

Effect of Driving Pressure Change During Extracorporeal Membrane Oxygenation in Adults With Acute Respiratory Distress Syndrome: A Randomized Crossover Physiologic Study.

Crit Care Med 2020 Dec;48(12):1771-1778

1Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada. 2Latner Thoracic Surgery Research Laboratories, University Health Network, University of Toronto, Toronto, ON, Canada. 3Extracorporeal Life Support Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. 4Department of Medicine, Division of Respirology, University Health Network and Sinai Health System, Toronto, ON, Canada. 5Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada. 6Department of Medicine, University Health Network and Sinai Health System, Toronto, ON, Canada. 7Division of Thoracic Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada. 8Keenan Research Center at the Li-Ka-Shing Knowledge Institute of St. Michael´s Hospital, Toronto, ON, Canada. 9Toronto General Hospital Research Institute, Toronto, ON, Canada.

Objectives: Venovenous extracorporeal membrane oxygenation is an effective intervention to improve gas exchange in patients with severe acute respiratory distress syndrome. However, the mortality of patients with severe acute respiratory distress syndrome supported with venovenous extracorporeal membrane oxygenation remains high, and this may be due in part to a lack of standardized mechanical ventilation strategies aimed at further minimizing ventilator-induced lung injury. We tested whether a continuous positive airway pressure ventilation strategy mitigates ventilator-induced lung injury in patients with severe acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation, compared with current ventilation practice that employs tidal ventilation with limited driving pressure. We used plasma biomarkers as a surrogate outcome for ventilator-induced lung injury.

Design: Randomized crossover physiologic study.

Setting: Single-center ICU.

Patients: Ten patients with severe acute respiratory distress syndrome supported on venovenous extracorporeal membrane oxygenation.

Interventions: The study included four phases. After receiving pressure-controlled ventilation with driving pressure of 10 cm H2O for 1 hour (phase 1), patients were randomly assigned to receive first either pressure-controlled ventilation 20 cm H2O for 2 hours (phase 2) or continuous positive airway pressure for 2 hours (phase 3), and then crossover to the other phase for 2 hours; during phase 4 ventilation settings returned to baseline (pressure-controlled ventilation 10 cm H2O) for 4 hours.

Measurements And Main Results: There was a linear relationship between the change in driving pressure and the plasma concentration of interleukin-6, soluble receptor for advanced glycation end products, interleukin-1ra, tumor necrosis factor alpha, surfactant protein D, and interleukin-10.

Conclusions: Ventilator-induced lung injury may occur in acute respiratory distress syndrome patients on venovenous extracorporeal membrane oxygenation despite the delivery of volume- and pressure-limited mechanical ventilation. Reducing driving pressure to zero may provide more protective mechanical ventilation in acute respiratory distress syndrome patients supported with venovenous extracorporeal membrane oxygenation. However, the risks versus benefits of such an approach need to be confirmed in studies that are designed to test patient centered outcomes.
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http://dx.doi.org/10.1097/CCM.0000000000004637DOI Listing
December 2020

Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry.

Lancet 2020 10 25;396(10257):1071-1078. Epub 2020 Sep 25.

Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, and Center for Acute Respiratory Failure, New York-Presbyterian Hospital, New York, NY, USA.

Background: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date.

Methods: We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality.

Findings: Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4-40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20-2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6-41·5).

Interpretation: In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(20)32008-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518880PMC
October 2020

Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis.

JAMA 2020 10;324(13):1330-1341

Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Importance: Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support.

Objective: To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality.

Design, Setting, And Participants: Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance-weighted fixed-effect analysis using risk ratios.

Exposures: Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients).

Main Outcomes And Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events.

Results: A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as "low" for 6 of the 7 mortality results and as "some concerns" in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82]; P < .001 based on a fixed-effect meta-analysis). There was little inconsistency between the trial results (I2 = 15.6%; P = .31 for heterogeneity) and the summary OR was 0.70 (95% CI, 0.48-1.01; P = .053) based on the random-effects meta-analysis. The fixed-effect summary OR for the association with mortality was 0.64 (95% CI, 0.50-0.82; P < .001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths), the OR was 0.69 (95% CI, 0.43-1.12; P = .13) for hydrocortisone (3 trials, 374 patients, and 94 deaths), and the OR was 0.91 (95% CI, 0.29-2.87; P = .87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Among the 6 trials that reported serious adverse events, 64 events occurred among 354 patients randomized to corticosteroids and 80 events occurred among 342 patients randomized to usual care or placebo.

Conclusions And Relevance: In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.
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http://dx.doi.org/10.1001/jama.2020.17023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489434PMC
October 2020

Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study.

Lancet Respir Med 2020 12 27;8(12):1201-1208. Epub 2020 Aug 27.

Dipartimento di Scienze Mediche e Chirurgiche, Anesthesia and Intensive Care Medicine, Policlinico di Sant'Orsola, Alma Mater Studiorum-Università di Bologna, Bologna, Italy. Electronic address:

Background: Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19.

Methods: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed.

Findings: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm HO (33-52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm HO [25-43]; p<0·0001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1·66 [1·32-1·95] vs 1·90 [1·50-2·33]; p=0·0001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0·0001).

Interpretation: Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rates.

Funding: None.
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http://dx.doi.org/10.1016/S2213-2600(20)30370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834127PMC
December 2020

Corticosteroid therapy for critically ill patients with COVID-19: A structured summary of a study protocol for a prospective meta-analysis of randomized trials.

Trials 2020 Aug 24;21(1):734. Epub 2020 Aug 24.

Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Canada.

Objectives: Primary objective: To estimate the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization. Secondary objectives: To examine whether the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization varies between subgroups related to treatment characteristics, disease severity at the time of randomization, patient characteristics, or risk of bias. To examine the effect of corticosteroids compared with usual care or placebo on serious adverse events.

Study Design: Prospective meta-analysis of randomized controlled trials. Both placebo-controlled and open-label trials are eligible.

Participants: Hospitalised, critically ill patients with suspected or confirmed COVID-19.

Intervention And Comparator: Intervention groups will have received therapeutic doses of a steroid (dexamethasone, hydrocortisone or methylprednisolone) with IV or oral administration immediately after randomization. The comparator groups will have received standard of care or usual care or placebo.

Main Outcome: All-cause mortality up to 28 days after randomization.

Search Methods: Systematic searching of clinicaltrials.gov , EudraCT, the WHO ISRCTN registry, and the Chinese clinical trials registry. Additionally, research and WHO networks will be asked for relevant trials.

Risk Of Bias Assessments: These will be based on the Cochrane RoB 2 tool, and will use structured information provided by the trial investigators on a form designed for this prospective meta-analysis. We will use GRADE to assess the certainty of the evidence.

Statistical Analyses: Trial investigators will provide data on the numbers of participants who did and did not experience each outcome according to intervention group, overall and in specified subgroups. We will conduct fixed-effect (primary analysis) and random-effects (Paule-Mandel estimate of heterogeneity and Hartung-Knapp adjustment) meta-analyses. We will quantify inconsistency in effects between trials using I statistics. Evidence for subgroup effects will be quantified by ratios of odds ratios comparing effects in the subgroups, and corresponding interaction p-values. Comparisons between subgroups defined by trial characteristics will be made using random-effects meta-regression. Comparisons between subgroups defined by patient characteristics will be made by estimating trial-specific ratios of odds ratios comparing intervention effects between subgroups then combining these using random-effects meta-analysis. Steroid interventions will be classified as high or low dose according to whether the dose is greater or less than or equal to 400 mg hydrocortisone per day or equivalent. We will use network meta-analysis methods to make comparisons between the effects of high and low dose steroid interventions (because one trial randomized participants to both low and high dose steroid arms).

Prospero Registration Number: CRD42020197242 FULL PROTOCOL: The full protocol for this prospective meta-analysis is attached as an additional file, accessible from the Trials website (Additional file 1). To expedite dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol for the systematic review.
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http://dx.doi.org/10.1186/s13063-020-04641-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443535PMC
August 2020

Venoarterial extracorporeal membrane oxygenation to rescue sepsis-induced cardiogenic shock: a retrospective, multicentre, international cohort study.

Lancet 2020 08;396(10250):545-552

Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Université INSERM-UMRS 1166, Institute of Cardiometabolism and Nutrition, Paris, France.

Background: Patients with sepsis-induced cardiomyopathy with cardiogenic shock have a high mortality. This study assessed venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for sepsis-induced cardiogenic shock refractory to conventional treatments.

Methods: In this retrospective, multicentre, international cohort study, we compared outcomes of 82 patients (aged ≥18 years) with septic shock who received VA-ECMO at five academic ECMO centres, with 130 controls (not receiving ECMO) obtained from three large databases of septic shock. All patients had severe myocardial dysfunction (cardiac index 3 L/min per m or less or left ventricular ejection fraction [LVEF] 35% or less) and severe haemodynamic compromise (inotrope score at least 75 μg/kg per min or lactic acidaemia at least 4 mmol/L) at time of inclusion. The primary endpoint was survival at 90 days. A propensity score-weighted analysis was done to control for confounders.

Findings: At baseline, patients treated with VA-ECMO had more severe myocardial dysfunction (mean cardiac index 1·5 L/min per mvs 2·2 L/min per m, LVEF 17% vs 27%), more severe haemodynamic impairment (inotrope score 279 μg/kg per min vs 145 μg/kg per min, lactataemia 8·9 mmol/L vs 6·5 mmol/L), and more severe organ failure (Sequential Organ Failure Assessment score 17 vs 13) than did controls, with p<0·0001 for each comparison. Survival at 90 days for patients treated with VA-ECMO was significantly higher than for controls (60% vs 25%, risk ratio [RR] for mortality 0·54, 95% CI [0·40-0·70]; p<0·0001). After propensity score weighting, ECMO remained associated with improved survival (51% vs 14%, adjusted RR for mortality 0·57, 95% CI [0·35-0·93]; p=0·0029). Lactate and catecholamine clearance were also significantly enhanced in patients treated with ECMO. Among the 49 survivors treated with ECMO, 32 who had been treated at the largest centre reported satisfactory Short Form-36 evaluated health-related quality of life at 1-year follow-up.

Interpretation: Patients with severe sepsis-induced cardiogenic shock treated with VA-ECMO had a large and significant improvement in survival compared with controls not receiving ECMO. However, despite the careful propensity-weighted analysis, we cannot rule out unmeasured confounders.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(20)30733-9DOI Listing
August 2020