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Abstract Background Ventilation management may differ between COVID–19 ARDS (COVID–ARDS) patients and patients with pre–COVID ARDS (CLASSIC–ARDS); it is uncertain whether associations of ventilation management with outcomes for CLASSIC–ARDS also exist in COVID–ARDS. Methods Individual patient data analysis of COVID–ARDS and CLASSIC–ARDS patients in six observational studies of ventilation, four in the COVID–19 pandemic and two pre–pandemic. Descriptive statistics were used to compare epidemiology and ventilation characteristics. The primary endpoint were key ventilation parameters; other outcomes included mortality and ventilator–free days and alive (VFD–60) at day 60. Results This analysis included 6702 COVID–ARDS patients and 1415 CLASSIC–ARDS patients. COVID–ARDS patients received lower median VT (6.6 [6.0 to 7.4] vs 7.3 [6.4 to 8.5] ml/kg PBW; p

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

OBJECTIVES:. We planned to synthesize evidence examining the potential efficacy and safety of performing physical rehabilitation and/or mobilization (PR&M) in adult patients receiving extracorporeal life support (ECLS). DATA SOURCES:. We included any study that compared PR&M to no PR&M or among different PR&M strategies in adult patients receiving any ECLS for any indication and any cannulation. We searched seven electronic databases with no language limitations. STUDY SELECTION AND DATA EXTRACTION:. Two reviewers, independently and in duplicate, screened all citations for eligibility. We used the Cochrane Risk of Bias 2 and Cochrane Risk Of Bias In Non-randomized Studies of Interventions tools to assess individual study risk of bias. Although we had planned for meta-analysis, this was not possible due to insufficient data, so we used narrative and tabular data summaries for presenting results. We assessed the overall certainty of the evidence for each outcome using the Grading of Recommendations Assessment, Development, and Evaluation framework. DATA SYNTHESIS:. We included 17 studies that enrolled 996 patients. Most studies examined venovenous extracorporeal membrane oxygenation (ECMO) and/or venoarterial ECMO as a bridge to recovery in the ICU. We found an uncertain effect of high-intensity/active PR&M on mortality, duration of mechanical ventilation, ICU length of stay, hospital length of stay, or quality of life compared with low-intensity/passive PR&M in patients receiving ECLS (very low certainty due to very serious imprecision). There was similarly an uncertain effect on safety events including clinically important bleeding, spontaneous intracerebral hemorrhage, limb ischemia, accidental decannulation, or ECLS circuit dysfunction (very low certainty due to very serious risk of bias and imprecision). CONCLUSIONS:. Based on the currently available summary of evidence, there is an uncertain effect of high-intensity/active PR&M on patient important outcomes or safety in patients receiving ECLS. Despite indirect data from other populations suggesting potential benefit of high-intensity PR&M in the ICU; further high-quality randomized trials evaluating the benefits and risks of physical therapy and/or mobilization in this population are needed.

BackgroundExtracorporeal membrane oxygenation (ECMO) represents an important but limited treatment for patients with severe COVID-19. We assessed the effects of an educational intervention on a person's ECMO care preference and examined whether patients and providers had similar ECMO preferences.MethodsIn the Video+Survey group, patients watched an educational video about ECMO's purpose, benefits, and risks followed by an assessment of ECMO knowledge and care preferences in seven scenarios varying by hypothetical patient age, function, and comorbidities. Patients in the Survey Only group and providers didn't watch the video. Logistic regression was used to estimate the probability of agreement for each ECMO scenario between the two patient groups and then between all patients and providers.ResultsVideo+Survey patients were more likely (64% vs. 17%; p = 0.02) to correctly answer all ECMO knowledge questions than Survey Only patients. Patients in both groups agreed that ECMO should be considered across all hypothetical scenarios, with predicted agreement above 65%. In adjusted analyses, patients and providers had similar predicted agreement for ECMO consideration across six of the seven scenarios, but patients showed greater preference (84% vs. 41%, p = 0.003) for the scenario of a functionally dependent 65-year-old with comorbidities than providers.Discussion and conclusionsAn educational video increased a person's ECMO knowledge but did not change their ECMO preferences. Clinicians were less likely than patients to recommend ECMO for older adults, so advanced care planning discussion between patients and providers about treatment options in critically ill patients with COVID-19 is critical.

Abstract Background Percutaneous cannulation is now accepted as the first-line strategy for extracorporeal cardiopulmonary resuscitation (ECPR) in adults. However, previous studies comparing percutaneous cannulation to surgical cannulation have been limited by small sample size and single-center settings. This study aimed to compare in-hospital outcomes in cardiac arrest (CA) patients who received femoro-femoral ECPR with percutaneous vs surgical cannulation. Methods Adults with refractory CA treated with percutaneous (percutaneous group) or surgical (surgical group) femoro-femoral ECPR between January 2008 and December 2019 were extracted from the international Extracorporeal Life Support Organization registry. The primary outcome was severe neurological complication. Multivariable logistic regression analyses were performed to assess the association between percutaneous cannulation and in-hospital outcomes. Results Among 3575 patients meeting study inclusion, 2749 (77%) underwent percutaneous cannulation. The proportion of patients undergoing percutaneous cannulation increased from 18% to 89% over the study period (p

Introduction Extracorporeal membrane oxygenation (ECMO) is an intervention used in critically ill patients with severe cardiopulmonary failure that is expensive and resource intensive and requires specialised care. There remains a significant practice variation in its application. This systematic review will assess the evidence for key performance indicators (KPIs) in ECMO.Methods and analysis We will search Ovid MEDLINE, Ovid EMBASE, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library including the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials and databases from the National Information Center of Health Services Research and Health Care Technology, for studies involving KPIs in ECMO. We will rate methodological quality using the Newcastle-Ottawa Quality Assessment Scale. Randomized controlled trials (RCTs) will be evaluated with the Cochrane Risk of Bias tool, and qualitative studies will be evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN checklist). Grey literature sources will be searched for technical reports, practice guidelines and conference proceedings. We will identify relevant organisations, industry leaders and non-profit organisations that represent key opinion leads in the use of ECMO. We will search the Agency of Healthcare Research and Quality National Quality Measures Clearinghouse for ECMO-related KPIs. Studies will be included if they contain quality measures that occur in critically ill patients and are associated with ECMO. The analysis will be primarily descriptive. Each KPI will be evaluated for importance, scientific acceptability, utility and feasibility using the four criteria proposed by the US Strategic Framework Board for a National Quality Measurement and Reporting System. Finally, KPIs will be evaluated for their potential operational characteristics, their potential to be integrated into electronic medical records and their affordability, if applicable.Ethics and dissemination Ethical approval is not required as no primary data will be collected. Findings will be published in a peer-reviewed journal and presented at academic.PROSPERO registration number 9 August 2022. CRD42022349910.

IMPORTANCE:. Prone positioning is associated with improved mortality in patients with moderate/severe acute respiratory distress syndrome (ARDS) and has been increasingly used throughout the COVID-19 pandemic. In patients with refractory hypoxemia, transfer to an extracorporeal membrane oxygenation (ECMO) center may improve outcome but may be challenging due to severely compromised gas exchange. Transport of these patients in prone position may be advantageous; however, there is a paucity of data on their outcomes. OBJECTIVES:. The primary objective of this retrospective cohort study was to describe the early outcomes of ARDS patients transported in prone position for evaluation at a regional ECMO center. A secondary objective was to examine the safety of their transport in the prone position. DESIGN:. Retrospective cohort study. SETTING:. This study used patient charts from Ornge and Toronto General Hospital in Ontario, Canada, between February 1, 2020, and November 31, 2021. PARTICIPANTS:. Patient with ARDS transported in the prone position for ECMO evaluation to Toronto General Hospital. MAIN OUTCOMES AND MEASURES:. Descriptive analysis of patients transported in the prone position and their outcomes. RESULTS:. One hundred fifteen patients were included. Seventy-two received ECMO (63%) and 51 died (44%) with ARDS and sepsis as the most common listed causes of death. Patients were transported primarily for COVID-related indications (93%). Few patients required additional analgesia (8%), vasopressors (4%), or experienced clinically relevant desaturation during transport (2%). CONCLUSIONS AND RELEVANCE:. This cohort of patients with severe ARDS transported in prone position had outcomes ranging from similar to better compared with existing literature. Prone transport was performed safely with few complications or escalation in treatments. Prone transport to an ECMO center should be regarded as safe and potentially beneficial for patients with ARDS and refractory hypoxemia.

Abstract Background Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality. Methods Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model. Results From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59–78], 40% female) were included. ICU and hospital mortality were 34% and 40%, respectively. ICU survivors were younger (67 [57–77] vs 74 [64–80] years, p

Abstract Background Insufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing − 3 to − 8 cm H2O; dynamic transpulmonary driving pressure ≤ 15 cm H2O) during AHRF. Methods In patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort. Results Of 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets. Conclusion Respiratory effort is frequently absent under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy. Trial registration: This trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583).

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 was 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, 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 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. Results Of 4522 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 48.8% (95% confidence interval 44.8–52.9%, high certainty). Mortality was higher among studies which enrolled patients later in the pandemic as opposed to earlier (1st half 2020: 41.2%, 2nd half 2020: 46.4%, 1st half 2021: 62.0%, 2nd half 2021: 46.5%, interaction p value = 0.0014). 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. Conclusions 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.

Abstract Background The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. Methods We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. Results Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0–25) and 25 (IQR 7–26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0–87) and 87 (IQR 0–88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). Conclusions In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

The COVID-19 pandemic has exposed the precarious demand-capacity balance in Canadian hospitals, including critical care where there is an urgent need for trained health care professionals to dramatically increase ICU capacity. The impact of the pandemic on ICUs varied significantly across the country with provinces that implemented public health measures later and relaxed them sooner being impacted more severely. Pediatric ICUs routinely admitted adult patients. Non-ICU areas were converted to ICUs and staff were redeployed from other essential service areas. Faced with a lack of critical care capacity, triage plans for ICU admission were developed and nearly implemented in some provinces. Twenty eight percent of patients in Canadian ICUs who required mechanical ventilation died. Surviving patients have required prolonged ICU admission, hospitalization and extensive ongoing rehabilitation. Family members of patients were not permitted to visit, resulting in additional psychological stresses to patients, families, and healthcare teams. ICU professionals also experienced extreme psychological stresses from caring for such large numbers of critically ill patients, often in sub-standard conditions. This resulted in large numbers of health workers leaving their professions. This pandemic is not yet over, and it is likely that new pandemics will follow. A review and recommendations for the future are provided.

Background. Primary graft dysfunction (PGD) is a form of acute respiratory failure that complicates 30% of bilateral lung transplants. Higher grades of PGD correlate with higher severity of respiratory failure and unfavorable outcomes. Immediate PGD determination posttransplant‚ however, is not always predictive of PGD over subsequent days or intensive care unit outcomes. We aimed to evaluate whether extravascular lung water index (ELWI) measured immediately post bilateral lung transplant was associated with higher severity of PGD at 72 h and duration of mechanical ventilation. Methods. We conducted a prospective, observational study of bilateral lung transplant patients admitted to the intensive care unit. ELWI measurements were performed at admission, 6, 12, 24, 36, 48, 60, and 72 h following transplant or until extubation. We evaluated the association between admission ELWI and 72-h PGD grade and duration of mechanical ventilation. Results. Across 56 patients enrolled, 268 transpulmonary thermodilution measurements were conducted. At admission, median ELWI increased with PGD grade (grade 1: 9 mL/kg [interquartile range (IQR), 8–11 mL/kg]‚ grade 2 [10 mL/kg (IQR, 8–12 mL/kg)]‚ and grade 3 [17 mL/kg (IQR, 14–19 mL/kg); P < 0.001]). Using multivariable Poisson regression analysis adjusting for confounders, admission ELWI elevation was associated with higher severity of PGD at 72 h (incidence rate ratio [IRR], 1.06; 95% confidence interval, 1.01-1.12) and duration of mechanical ventilation (IRR, 1.62; 95% confidence interval, 1.23-2.14). The combination of an ELWI of ≥13 mL/kg and partial pressure of oxygen/fraction of inspired oxygen ≤ 100 within 6 h of admission had high sensitivity (75%) and specificity (100%) for grade 3 PGD at 72 h (area under the curve, 0.95) and performed better than ELWI or partial pressure of oxygen/fraction of inspired oxygen alone. Conclusions. Our exploratory study demonstrates an association between admission ELWI and high grades of PGD at 72 h and longer duration of ventilation. These results provide the impetus to study whether goal-directed ELWI algorithms can improve transplant outcomes.

Abstract Background The acute respiratory distress syndrome (ARDS) has high morbidity and mortality. Positive end-expiratory pressure (PEEP) is commonly used in patients with ARDS but the best method to select the optimal PEEP level and reduce all-cause mortality is unclear. The primary objective of this network meta-analysis is to summarize the available evidence and to compare the effect of different PEEP selection strategies on all-cause mortality in adult patients with ARDS. Methods We will search MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and LILACS from inception onwards for randomized controlled trials assessing the effect of PEEP selection strategies in adult patients with moderate to severe ARDS. We will exclude studies that did not use a lung-protective ventilation approach as part of the comparator or intervention strategy. The primary outcome will be all-cause mortality (at the longest available follow-up and up to 90 days). Secondary outcomes will include barotrauma, ventilator-free days, intensive care unit and hospital length of stay, and changes in oxygenation. Two reviewers will independently screen all citations, full-text articles, and extract study-data. We will assess the risk of bias for each of the outcomes using version 2 of the Cochrane risk of bias tool for randomized controlled trials. If feasible, Bayesian network meta-analyses will be conducted to obtain pooled estimates of all potential head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and risk differences, together with the associated 95% credible intervals. We will assess certainty in effect estimates using GRADE methodology. Discussion The present study will inform clinical decision-making for adult patients with ARDS and will improve our understanding of the limitations of the available literature assessing PEEP selection strategies. Finally, this information may also inform the design of future randomized trials, including the selection of interventions, comparators, and predictive enrichment strategies. Trial registration PROSPERO 2020 CRD42020193302 .

Summary: Background: Cold static preservation (CSP) at higher temperatures (10°C) has been recently shown as an optimal strategy up to 24-36h of preservation. Here, we hypothesized that alternating 10°C static storage with cycles of normothermic ex vivo lung perfusion (EVLP) would provide conditions for cellular “recharge”, allowing for multi-day lung preservation. Methods: Donor lungs from male Yorkshire pigs were preserved using 10°C CSP with two cycles of 4h EVLP. After a total of 3 days of preservation, a left lung transplant was performed followed by 4h of graft evaluation. As controls, 2 lungs were preserved solely with continuous 10°C preservation for 3 days and transplanted. Findings: For animals receiving lungs preserved using a cyclic EVLP protocol, lung function and histological structures were stable and the recipient systemic partial pressure of oxygen/fraction of inspired oxygen (P/F Ratio) after excluding the contralateral lung was 422 ± 61 mmHg. In contrast, lungs preserved solely in continuous cold static storage at 10°C for 72h developed massive lung failure, resulting in recipient death. Metabolomic analysis revealed that EVLP plays a critical role in the re-vitalization of key central carbon energy metabolites (Glucose, Succinate, N-Acetyl Aspartate) and reducing the expression of the inflammasome activation marker CASP1. Interpretation: In conclusion, we demonstrate for the first time the feasibility of 3-day lung preservation leading to excellent early post-transplant outcomes. The thoughtful combination of cold storage (10°C) and intermittent EVLP can open new opportunities in organ transplantation. Funding: This work was supported by the UHN Foundation (Grant#1013612).

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 C RS—calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]—and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide. Results We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of C RS within the first seven days of MV. Median (IQR) age was 62 (52–71), patients were predominantly males (68%) and from Europe/North and South America (88%). C RS, within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV (p = 0.417) nor with PaO2/FiO2 (p = 0.100). Females presented lower C RS than males (95% CI of C RS difference between females-males: − 11.8 to − 7.4 mL/cmH2O p

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.

Summary: 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.

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used increasingly to support patients who are in cardiogenic shock. Due to the risk of complications, prediction models may aid in identifying patients who would benefit most from VA-ECMO. One such model is the Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score. Therefore, we wanted to validate the utility of the SAVE score in a contemporary cohort of adult patients. Methods: Retrospective data were extracted from electronic health records of 120 patients with cardiogenic shock supported with VA-ECMO between 2011 and 2018. The SAVE score was calculated for each patient to predict survival to hospital discharge. We assessed the SAVE score calibration by comparing predicted vs observed survival at discharge. We assessed discrimination with the area under the receiver operating curve using logistic regression. Results: A total of 45% of patients survived to hospital discharge. Survivors had a significantly higher mean SAVE score (–9.3 ± 4.1 in survivors vs –13.1 ± 4.4, respectively; P = 0.001). SAVE score discrimination was adequate (c = 0.77; 95% confidence interval 0.69-0.86; P < 0.001). SAVE score calibration was limited, as observed survival rates for risk classes II-V were higher in our cohort (II: 67% vs 58%; III: 78% vs 42%; IV: 61% vs 30%; and V: 29% vs 18%). Conclusions: The SAVE score underestimates survival in a contemporary North American cohort of adult patients with cardiogenic shock. Its inaccurate performance could lead to denying ECMO support to patients deemed to be too high risk. Further studies are needed to validate additional predictive models for patients requiring VA-ECMO. Résumé: Contexte: L’oxygénation extracorporelle veino-artérielle (ECMO-VA) est de plus en plus utilisée comme assistance pour les patients qui sont en choc cardiogène. En raison du risque de complications, des modèles de prédiction peuvent aider à déterminer quels patients bénéficieraient le plus d’une ECMO-VA. Le score SAVE (Survival After Veno-Arterial Extracorporeal Membrane Oxygenation) est un modèle de ce genre. Par conséquent, nous voulions valider l’utilité du score SAVE dans une cohorte contemporaine de patients adultes. Méthodologie: Des données rétrospectives ont été extraites de dossiers médicaux électroniques de 120 patients atteints d’un choc cardiogène ayant reçu une ECMO-VA entre 2011 et 2018. Le score SAVE a été calculé pour chaque patient afin de prédire la survie au congé de l’hôpital. Nous avons évalué la calibration du score SAVE en comparant la survie prédite au moment du congé et la survie observée. Nous avons évalué la discrimination par l’aire sous la courbe opérationnelle chez le receveur en faisant appel à la régression logistique. Résultats: Au total, 45 % des patients ont survécu au congé de l’hôpital. Les survivants affichaient un score SAVE moyen considérablement plus élevé (–9,3 ± 4,1 chez les survivants vs –13,1 ± 4,4; p = 0,001). La discrimination par le score SAVE était adéquate (c = 0,77; intervalle de confiance à 95 % : 0,69 à 0,86; p < 0,001). La calibration du score SAVE était limitée, car les taux pour les classes de risque II à V étaient plus élevés dans notre cohorte (II : 67 % vs 58 %; III : 78 % vs 42 %; IV : 61 % vs 30 %; et V : 29 % vs 18 %). Conclusions: Le score SAVE sous-estime la survie dans une cohorte nord-américaine contemporaine de patients adultes atteints d’un choc cardiogène. L’inexactitude de ses résultats pourrait faire en sorte qu’une assistance par ECMO serait refusée à des patients jugés comme présentant un risque élevé. D’autres études sont nécessaires pour valider d’autres modèles de prédiction pour les patients ayant besoin d’une ECMO-VA.

IMPORTANCE:. 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.

Abstract Introduction Prone position is known to improve mortality in patients with acute respiratory distress syndrome (ARDS). The impact of prone position in critically ill patients with coronavirus disease of 2019 (COVID-19) remains to be determined. In this review, we describe the mechanisms of action of prone position, systematically appraise the 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 16, 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 the hospital with COVID-19 disease who received respiratory support with high-flow nasal cannula, or noninvasive or mechanical ventilation and reported the use of prone position. The full text of eligible articles was reviewed, and data regarding study design, patient characteristics, interventions and outcomes were extracted. Results We found seven 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 and improvement in oxygenation and lung recruitment. Published studies lacked a 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.

Abstract Background Extracorporeal membrane oxygenation (ECMO) is used to provide temporary cardiorespiratory support to critically ill children. While short-term outcomes and costs have been evaluated in this population, less is known regarding long-term survival and costs. Methods Population-based cohort study from Ontario, Canada (October 1, 2009 to March 31, 2017), of pediatric patients (

Abstract Background Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2

Abstract 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 (ΔP 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 (ΔP L,dyn, the difference between peak and end-expiratory transpulmonary pressure), and ΔP occ were measured daily in mechanically ventilated patients in two ICUs in Toronto, Canada. A conversion factor to predict ΔP L,dyn and P mus from ΔP 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 ΔP L were frequently excessively high: P mus exceeded 10 cm H2O on 84% of study days and ΔP L,dyn exceeded 15 cm H2O on 53% of study days. ΔP occ measurements accurately detected P mus > 10 cm H2O (AUROC 0.92, 95% CI 0.83–0.97) and ΔP L,dyn > 15 cm H2O (AUROC 0.93, 95% CI 0.86–0.99). In the external validation cohort (n = 12), estimating P mus and ΔP L,dyn from ΔP occ measurements detected excessively high P mus and ΔP L,dyn with similar accuracy (AUROC ≥ 0.94). Conclusions Measuring ΔP 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.

Abstract Background Routine application of chlorhexidine oral rinse is recommended to reduce risk of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Recent reappraisal of the evidence from two meta-analyses suggests chlorhexidine may cause excess mortality in non-cardiac surgery patients and does not reduce VAP. Mechanisms for possible excess mortality are unclear. The CHORAL study will evaluate the impact of de-adopting chlorhexidine and implementing an oral care bundle (excluding chlorhexidine) on mortality, infection-related ventilator-associated complications (IVACs), and oral health status. Methods The CHORAL study is a stepped wedge, cluster randomized controlled trial in six academic intensive care units (ICUs) in Toronto, Canada. Clusters (ICU) will be randomly allocated to six sequential steps over a 14-month period to de-adopt oral chlorhexidine and implement a standardized oral care bundle (oral assessment, tooth brushing, moisturization, and secretion removal). On study commencement, all clusters begin with a control period in which the standard of care is oral chlorhexidine. Clusters then begin crossover from control to intervention every 2 months according to the randomization schedule. Participants include all mechanically ventilated adults eligible to receive the standardized oral care bundle. The primary outcome is ICU mortality; secondary outcomes are IVACs and oral health status. We will determine demographics, antibiotic usage, mortality, and IVAC rates from a validated local ICU clinical registry. With six clusters and 50 ventilated patients on average each month per cluster, we estimate that 4200 patients provide 80% power after accounting for intracluster correlation to detect an absolute reduction in mortality of 5.5%. We will analyze our primary outcome of mortality using a generalized linear mixed model adjusting for time to account for secular trends. We will conduct a process evaluation to determine intervention fidelity and to inform interpretation of the trial results. Discussion The CHORAL study will inform understanding of the effectiveness of de-adoption of oral chlorhexidine and implementation of a standardized oral care bundle for decreasing ICU mortality and IVAC rates while improving oral health status. Our process evaluation will inform clinicians and decision makers about intervention delivery to support future de-adoption if justified by trial results. Trial registration ClinicalTrials.gov, NCT03382730. Registered on December 26, 2017.

Objectives:. To assess differences in cognitive outcomes and sleep in adult survivors of critical illness, managed with venovenous extracorporeal membrane oxygenation as compared to conventional mechanical ventilation only. Design:. Retrospective cohort study linked with data from the COGnitive outcomes and WELLness study. Setting:. A multisite study from five adult medical/surgical ICUs in Toronto. Patients:. Thirty-three ICU survivors including adult patients who received venovenous extracorporeal membrane oxygenation (n = 11) matched with patients who received mechanical ventilation only (n = 22) using specified covariates (e.g., age). Interventions:. None. Measurements and Main Results:. Baseline demographics and admission diagnoses were collected at enrollment. Cognitive outcome was evaluated using the Repeatable Battery for the Assessment of Neuropsychologic Status (global cognitive function) and Trail Making Test B (executive function), and sleep variables were estimated using actigraphy. Assessments occurred at 7 days post ICU discharge and again at 6- and 12-month follow-up. No statistically significant difference was seen between patients treated with or without venovenous extracorporeal membrane oxygenation in the mean daily Riker Sedation Agitation Score; however, patients in the venovenous extracorporeal membrane oxygenation group received greater amounts of fentanyl over their ICU stay as compared to patients receiving conventional mechanical ventilation only (p < 0.001). No significant differences were found in performance on either of the cognitive assessment tools, between survivors treated or not with venovenous extracorporeal membrane oxygenation at any of the time points assessed. Total sleep time estimated by actigraphy increased from approximately 6.5 hours in hospital to 7.5 hours at 6-month follow-up in all patients, regardless of treatment type. Total sleep time remained consistent in both groups from 6 to 12 months post ICU discharge. Conclusions:. In this small retrospective case series, no significant differences were found in sleep or cognitive outcomes between extracorporeal life support and non–extracorporeal life support survivors. Further, in this hypothesis-generating study, differences in administered sedative doses during the ICU stay seen between the two groups did not impact 6- or 12-month cognitive performance or actigraphy-estimated sleep time.

Abstract Background Veno-venous extracorporeal CO2 removal (vv-ECCO2R) and non-invasive neurally adjusted ventilator assist (NIV-NAVA) are two promising techniques which may prevent complications related to prolonged invasive mechanical ventilation in patients with acute exacerbation of COPD. Methods A physiological study of the electrical activity of the diaphragm (Edi) response was conducted with varying degrees of extracorporeal CO2 removal to control the respiratory drive in patients with severe acute exacerbation of COPD breathing on NIV-NAVA. Results Twenty COPD patients (SAPS II 37 ± 5.6, age 57 ± 9 years) treated with vv-ECCO2R and supported by NIV-NAVA were studied during stepwise weaning of vv-ECCO2R. Based on dyspnea, tolerance, and blood gases, weaning from vv-ECCO2R was successful in 12 and failed in eight patients. Respiratory drive (measured via the Edi) increased to 19 ± 10 μV vs. 56 ± 20 μV in the successful and unsuccessful weaning groups, respectively, resulting in all patients keeping their CO2 and pH values stable. Edi was the best predictor for vv-ECCO2R weaning failure (ROC analysis AUC 0.95), whereas respiratory rate, rapid shallow breathing index, and tidal volume had lower predictive values. Eventually, 19 patients were discharged home, while one patient died. Mortality at 90 days and 180 days was 15 and 25%, respectively. Conclusions This study demonstrates for the first time the usefulness of the Edi signal to monitor and guide patients with severe acute exacerbation of COPD on vv-ECCO2R and NIV-NAVA. The Edi during vv-ECCO2R weaning was found to be the best predictor of tolerance to removing vv-ECCO2R.

Abstract 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.

Abstract Background The Extracorporeal Life Support Organization (ELSO) Maastricht Treaty for Nomenclature in Extracorporeal Life Support (ECLS) established consensus nomenclature and abbreviations for ECLS to ensure accurate, concise communication. Methods We build on this consensus nomenclature by layering a framework of precise and efficient abbreviations for cannula configuration that describe flow direction, number of cannulae used, any additional ECLS-related catheters, and cannulation sites. This work is a consensus of international representatives of the ELSO, including those from the North American, Latin American, European, South and West Asian, and Asian-Pacific chapters of ELSO. Results The classification increases in descriptive capability by introducing a third (cannula tip position) and fourth (cannula dimension) level to those provided in the previous consensus on ECLS cannulation configuration nomenclature. This expansion offers the simplest level needed to convey cannulation information yet allows for more details when required. Conclusions A complete nomenclature for ECLS cannulation configurations accommodating future revisions was developed to facilitate ability to compare practices and results, to promote efficient communication, and to improve quality of registry data.

Abstract 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 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 Background Management of patients with acute respiratory distress syndrome (ARDS) remains supportive with lung protective mechanical ventilation. In this article, we discuss the physiological concept of driving pressure, current data, ongoing trials, and future directions needed to clarify the role of driving pressure in patients with ARDS. Body Driving pressure is the plateau airway pressure minus PEEP. It can also be expressed as the ratio of tidal volume to respiratory system compliance, indicating the decreased functional size of the lung observed in patients with ARDS (i.e., baby lung). Driving pressure as a strong predictor of mortality in patients with ARDS is supported by a post hoc analysis of previous randomized controlled trials and a subsequent meta-analysis. Importantly, the meta-analysis suggested targeting driving pressure below 13–15 cmH2O. Ongoing clinical trials of driving pressure in patients with ARDS focus mainly on physiological rather than clinical outcome but will provide important insights for the design of future clinical trials. Conclusion Currently, no definite clinical recommendations on the routine use of driving pressure in patients with ARDS can be made, as the available data are hypothesis-generating. Randomized controlled trials are needed to evaluate the efficacy of a driving pressure-based ventilation strategy.

Abstract Background Despite a supportive evidence base and a push to implement, the uptake of early rehabilitation in critical care has been inconsistent. The objective of this study was to explore barriers and facilitators to early rehabilitation for critically ill patients receiving invasive mechanical ventilation. Methods Using the Theoretical Domains Framework (TDF) of behavior change, we conducted semi-structured interviews exploring barriers and facilitators to early rehabilitation among four purposively sampled ICU clinician groups (nurses, rehabilitation professionals, respiratory therapists, and physicians). The TDF is a comprehensive framework of 14 “construct domains,” synthesized from 33 theories of behavior that was developed to study determinants of behavior and to design interventions to improve evidence-based healthcare practice. A topic guide was developed and piloted based on the TDF and expert knowledge. Interviews were audio-recorded and transcribed verbatim. Transcripts were content analyzed by coding items into domains and then synthesized into more specific, over-arching themes or “beliefs.” An expert consensus group used structured decision rules to classify beliefs as high, moderate, or low in importance. Results We interviewed 40 stakeholders from the four clinician groups and identified 135 separate beliefs. Of these, 19 were classified as high, 40 as moderate, and 76 of low importance as barriers or facilitators. All beliefs classified as highly important fell within one of seven TDF domains: skills, social/professional role and identity, beliefs about capabilities, beliefs about consequences, environmental context/resources, social influences, and behavioral regulation. Beliefs of lower importance fell under the following seven domains: knowledge; optimism; reinforcement; intention; goals; memory, attention, and decision processes; and emotion. Quantitative differences in stated beliefs about early rehabilitation between professional groups were not common. Conclusions This study identified important barriers and facilitators to early rehabilitation in critical care patients. Domains identified as important should be considered when designing interventions to increase uptake of early rehabilitation.

Abstract Background Middle East respiratory syndrome (MERS) is caused by a coronavirus (MERS‐CoV) and is characterized by hypoxemic respiratory failure. The objective of this study is to compare the outcomes of MERS-CoV patients before and after the availability of extracorporeal membrane oxygenation (ECMO) as a rescue therapy in severely hypoxemic patients who failed conventional strategies. Methods We collected data retrospectively on MERS-CoV patients with refractory respiratory failure from April 2014 to December 2015 in 5 intensive care units (ICUs) in Saudi Arabia. Patients were classified into two groups: ECMO versus conventional therapy. Our primary outcome was in-hospital mortality; secondary outcomes included ICU and hospital length of stay. Results Thirty-five patients were included; 17 received ECMO and 18 received conventional therapy. Both groups had similar baseline characteristics. The ECMO group had lower in-hospital mortality (65 vs. 100%, P = 0.02), longer ICU stay (median 25 vs. 8 days, respectively, P

Abstract Background Patients meeting the Berlin definition for the acute respiratory distress syndrome (ARDS) might lack exposure to one or more “common” risk factors and exhibit different clinical phenotype and outcomes. We aimed to compare the clinical presentation and outcome of ARDS patients with or without risk factors, the impact on hospital mortality, and to assess the diagnostic work-up performed. The current study is an ancillary analysis of an international, multicenter, prospective cohort study (the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure, LUNG SAFE). Patients meeting ARDS criteria within 2 days of acute hypoxemic respiratory failure onset were included in the study and categorized as having risk factors or not. Outcomes were compared using propensity score matching. Results Among 2813 patients, 234 (8.3% [7.3–9.3]) had no ARDS risk factor identified. These were older, had more frequent chronic diseases and presented with less severe SOFA and non-pulmonary SOFA scores (p 0.99). Among ARDS with no risk factor, 45 patients (19.2%) had a specific diagnosis made. As compared to others, patients having ARDS with no risk factor had a lower ICU but not hospital mortality (34.6 vs 40.0%; p = 0.12). A matched cohort analysis confirmed the lack of significant difference in mortality. Conclusion Eight percent of ARDS patients have no identified risk factor, 80% of whom have no etiological diagnosis made. The outcome of ARDS with no risk factor was comparable to other ARDS but few had a comprehensive diagnostic work-up, potentially leading to missed curable diseases. Trial registration clinicaltrials.gov Identifier: NCT02010073

Objectives:. To identify actionable processes of care, quality indicators, or performance measures and their evidence base relevant to patients with persistent or chronic critical illness and their family members including themes relating to patient/family experience. Data Sources:. Two authors independently searched electronic, systemic review, and trial registration databases (inception to November 2016). Study Selection:. We included studies with an ICU length of stay of greater than or equal to 7 days as an inclusion criterion and reported actionable processes of care; quality improvement indicators, measures, or tools; or patient/family experience. We excluded case series/reports of less than 10 patients. Data Extraction:. Paired authors independently extracted data and performed risk of bias assessment. Data Synthesis:. We screened 13,130 references identifying 114 primary studies and 102 relevant reviews. Primary studies reported data on 24,252 participants; median (interquartile range) sample size of 70 (32–182). We identified 42 distinct actionable processes of care, the most commonly investigated related to categories of 1) weaning methods (21 studies; 27 reviews); 2) rehabilitation, mobilization, and physiotherapy (20 studies; 40 reviews); and 3) provision of information, prognosis, and family communication (14 studies; 11 reviews). Processes with limited evidence were generally more patient-centered categories such as communication, promotion of sleep, symptom management, or family support. Of the 21 randomized controlled trials, only two were considered at low risk of bias across all six domains, whereas just two cohort studies and one qualitative study were considered of high quality. Conclusions:. We identified 42 distinct actionable processes of care relevant to patients with persistent or chronic critical illness and their families, with most frequently studied processes relating to weaning, rehabilitation/mobilization, and family communication. Qualitative studies highlighted the need to address psychologic needs and distressing symptoms as well as enabling patient communication. Our findings are informative for clinicians and decision-makers when planning high-quality patient and family-focused care.

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.

BACKGROUND: West Nile virus (WNV) is a rapidly spreading infectious disease in North America. Critical care issues related to WNV are not well described.

Rationale: Response to positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome depends on recruitability. We propose a bedside approach to estimate recruitability accounting for the presence of complete airway closure.Objectives: To validate a single-breath method for measuring recruited volume and test whether it differentiates patients with different responses to PEEP.Methods: Patients with acute respiratory distress syndrome were ventilated at 15 and 5 cm H2O of PEEP. Multiple pressure-volume curves were compared with a single-breath technique. Abruptly releasing PEEP (from 15 to 5 cm H2O) increases expired volume: the difference between this volume and the volume predicted by compliance at low PEEP (or above airway opening pressure) estimated the recruited volume by PEEP. This recruited volume divided by the effective pressure change gave the compliance of the recruited lung; the ratio of this compliance to the compliance at low PEEP gave the recruitment-to-inflation ratio. Response to PEEP was compared between high and low recruiters based on this ratio.Measurements and Main Results: Forty-five patients were enrolled. Four patients had airway closure higher than high PEEP, and thus recruitment could not be assessed. In others, recruited volume measured by the experimental and the reference methods were strongly correlated (R2 = 0.798; P < 0.0001) with small bias (-21 ml). The recruitment-to-inflation ratio (median, 0.5; range, 0-2.0) correlated with both oxygenation at low PEEP and the oxygenation response; at PEEP 15, high recruiters had better oxygenation (P = 0.004), whereas low recruiters experienced lower systolic arterial pressure (P = 0.008).Conclusions: A single-breath method quantifies recruited volume. The recruitment-to-inflation ratio might help to characterize lung recruitability at the bedside.Clinical trial registered with www.clinicaltrials.gov (NCT02457741). [ABSTRACT FROM AUTHOR]

BACKGROUND: Stress index provides a noninvasive approach to detect injurious ventilation patterns and to personalize ventilator settings. Obtaining the stress index (SI), however, requires quantitatively analyzing the shape of pressure-time curve with dedicated instruments or a specific ventilator, which may encumber its clinical implementation. We hypothesized that the SI could be qualitatively determined through a visual inspection of ventilator waveforms. METHODS: Thirtysix adult subjects undergoing volume controlled ventilation without spontaneous breathing were enrolled. For each subject, 2 trained clinicians visually inspected the pressure-time curve directly from the ventilator screen. They then qualitatively categorized the shape of pressure-time curve as linear, a downward concavity, or an upward concavity at the bedside. We simultaneously recorded airway pressure and flow signals using a dedicated instrument. A quantitative off-line analysis was performed to calculate the SI using specific research software. This quantitative analysis of the SI served as the reference method for classifying the shape of the pressure-time curve (ie, linear, a downward concavity, or an upward concavity). We compared the SI categorized by visual inspection with that by the reference. RESULTS: We obtained 200 SI assessments of pressure-time curves, among which 125 (63%) were linear, 55 (27%) were a downward concavity, and 20 (10%) were an upward concavity as determined by the reference method. The overall accuracy of visual inspection and weighted kappa statistic (95% CI) was 93% (88-96%) and 0.88 (0.82-0.94), respectively. The sensitivity and specificity to distinguish a downward concavity from a linear shape were 91% and 98%, respectively. The respective sensitivity and specificity to distinguish an upward concavity from a linear shape were 95% and 95%. CONCLUSIONS: Visual inspection of the pressure-time curve on the ventilator screen is a simple and reliable approach to assess SI at the bedside. This simplification may facilitate the implementation of SI in clinical practice to personalize mechanical ventilation. [ABSTRACT FROM AUTHOR]

Groundbreaking research into the pathophysiology of the adult acute respiratory distress syndrome (ARDS) and the prevention of ventilator-induced lung injury has led to dramatic improvements in survival. Investigations over the last two decades have revolved around the development of rescue therapies that can be used for patients with severe ARDS and refractory hypoxemia. To date, the techniques of using high levels of positive end-expiratory pressure (PEEP), prompt institution of neuromuscular blockade, and early prolonged prone positioning have been shown to reduce mortality in patients with severe ARDS. PEEP titration using transpulmonary pressure estimations assisted by esophageal manometry has been shown to result in a substantial improvement in oxygenation. Extracorporeal membrane oxygenation (ECMO) has been used increasingly since the mid-2000s in part due to the H1N1 epidemic. A major randomized controlled trial conducted during this period showed a significant mortality benefit for patients with severe ARDS who were referred to a center with ECMO capabilities. The routine use of inhaled nitric oxide for patients with severe ARDS has not been shown to lead to more than a transient and limited improvement in oxygenation, which may hinder its use as a sole rescue therapy. Finally, recent studies have found that the routine use of high-frequency oscillatory ventilation in severe ARDS does not result in decreased mortality, although the technique has not been specifically investigated as rescue therapy for severe refractory hypoxemia. [ABSTRACT FROM AUTHOR]

Biocides, in the form of sanitisers and disinfectants, are used extensively to reduce the risk of microbial contamination to beverage products and to ensure the safety of potable water used in processing. To better understand consumers’ perceptions of biocide use and to explore messaging strategies regarding their importance to ensure product safety, eight focus groups were conducted in New Zealand (n = 4) and China (n = 4). Consumers generally did not understand why or how biocides were used. In both countries, their most trustworthy source of information on biocide use was government sources. New Zealand and Chinese participants did not like the word “biocide” mentioned on labels due to its perceived negative connotations. Interestingly, acceptance for the word was higher if the phrase “environmentally friendly” was simultaneously communicated. The findings from this study have provided the beverage industry with guidance on how best to initiate conversations with consumers on the use of biocides.

OBJECTIVE:: To review the use of high-frequency oscillatory ventilation (HFOV) with adjunctive therapies (inhaled nitric oxide [iNO] and prone positioning [PP]) in adult patients with acute respiratory distress syndrome (ARDS). DATA SOURCES:: Published studies evaluating the use of iNO, PP, and HFOV in adult patients with ARDS. DATA SUMMARY:: Despite ongoing preclinical and clinical research, the therapeutic armamentarium for ARDS remains limited. Although a pressure- and volume-limited strategy aimed at mitigating ventilator-associated lung injury has demonstrated mortality benefit, patients with severe ARDS may still develop life-threatening hypoxemia. As a result, various salvage therapies aimed at improving oxygenation, including HFOV, iNO, and PP alone or in combination, have been evaluated in patients with refractory ARDS. Although the few preclinical and clinical trials of combination therapy to date have shown promising improvements in oxygenation and other physiological variables, with few adverse clinical events, the impact on survival awaits the performance of large randomized trials. CONCLUSIONS:: There is limited clinical data to recommend the widespread use of combination therapy in patients with ARDS. In the subset of patients with life-threatening hypoxemia from refractory ARDS, combination therapy is safe and may be considered for salvage therapy. More rigorous randomized, controlled trials are needed to help delineate the therapeutic role of combination therapy in adults with ARDS. [ABSTRACT FROM AUTHOR]