Echocardiographic findings in critically Ill patients with COVID-19 treated with and without extracorporeal membrane oxygenation

Objectives: There is a paucity of data on echocardiographic findings in patients with COVID-19 supported with Venovenous Extracorporeal Membrane Oxygenation (VV ECMO). This study aimed to compare baseline echocardiographic characteristics of mechanically ventilated patients for acute respiratory distress syndrome (ARDS) due to COVID-19 infection with and without VV ECMO support and to describe the incidence of new echocardiographic abnormalities in these patients. Method(s): Single-center, retrospective cohort study of patients admitted from March 2020 to June 2021 with COVID-19 infection, that required mechanical ventilation, and had an available echocardiogram within 72 hours of admission. Follow-up echocardiograms during ICU stay were reviewed. Result(s): A total of 242 patients were included in the study. One-hundred and forty-five (60%) patients were supported with VV ECMO. Median (IQR) PaO2/ FiO2 was 76 (65-95) and 98 (85-140) in the VV ECMO and non-ECMO patients, respectively (P = < 0.001). On the admission echocardiograms, the prevalence of left ventricular (LV) systolic dysfunction (10% vs 15%, P= 0.31) and right ventricular (RV) systolic dysfunction (38% vs. 27%, P = 0.27) was not significantly different in the ECMO and non-ECMO groups. However, there was a higher proportion of acute cor pulmonale (41% vs. 26 %, P = 0.02) in the ECMO group. During their ICU stay, echocardiographic RV systolic function worsened in 44 (36%) patients in the ECMO group compared with six (10%) patients in the non-ECMO group (P< 0.001). The overall odds ratio for death for patients with worsening RV systolic function was 1.8 (95% confidence interval 0.95-3.37). Conclusion(s): Echocardiographic findings suggested that the presence of RV systolic dysfunction in COVIDECMO patients was comparable to the non-ECMO group on admission. However, a higher percentage of patients on ECMO developed worsening RV systolic function during follow-up.

Awake Prone Positioning in Acute Hypoxemic Respiratory Failure from COVID-19: A Randomized Clinical Trial

Background: The efficacy and safety of awake prone positioning (APP) in hypoxemic patients with coronavirus disease 2019 (COVID-19) is unclear. Aim(s): To evaluate the efficacy and safety of APP in non-intubated adults with COVID-19. Method(s): We performed a pragmatic, international, randomized trial at 21 centers in Canada, Saudi Arabia, Kuwait, and the United States between May 19, 2020, and May 18, 2021. Eligible patients were hospitalized adults with COVID-19 requiring >40% oxygen. Patients were randomized to APP (n=205) or usual care (n=195). The primary outcome was intubation by day 30. Secondary outcomes included mortality at 60 days, ventilation-free days at 30 days, intensive care unit (ICU) and hospital-free days at 60 days, adverse events, and serious adverse events. Result(s): Patients in the APP group proned for a median of 4.8 hours per day (IQR 1.8 to 8.0) in the first 4 days. By day 30, 70/205 patients (34.1%) in the APP group and 79/195 (40.5%) in the control group were intubated (hazard ratio [HR] 0.81;95% confidence interval [CI] 0.59 to 1.12). APP did not reduce mortality at 60 days (HR 0.93;95% CI 0.62 to 1.40) and had no effect on days alive invasively or noninvasively ventilated at 30 days, or days out of ICU or hospital at 60 days. There were no serious adverse events in either group. A prespecified subgroup analysis suggested that APP reduced intubation among patients with SpO2:FiO2 >150 (HR of 0.44, 95% CI 0.23 to 0.87) but not among patients with SpO2:FiO2 <150 (HR 1.02;95% CI 0.70 to 1.48;P-interaction= 0.03). Conclusion(s): APP did not significantly reduce intubation at 30 days or mortality at 60 days overall, but may be effective in patients with SpO2:FiO2 >150.

COVID-19 pandemic: the impact on Canada's intensive care units

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. © 2022 Gibney et al.

Distribution of the Intensity of Spontaneous Breathing Effort During Mechanical Ventilation

Rationale:Both insufficient and excessive respiratory effort during mechanical ventilation are associated with lung and diaphragm injury, and poor outcome. The characteristics of respiratory effort under MV has not been systematically described. The expiratory occlusion pressure (Pocc) is a non-invasive technique to estimate effort and lung-distending pressure from spontaneous breathing during MV. We set out to describe the frequency and magnitude of effort and lung-distending pressure in patients receiving MV. Methods:In a retrospective cohort study, we collected data from charts of patients receiving invasive MV at Toronto General Hospital from July 2019 to June 2021. Pocc is routinely measured once daily in every patient on MV. Data on patient demographic characteristics and ventilator settings was collected in a registry of ventilated patients in Toronto. For each day, we calculated the proportion of patients in whom effort was absent (Pocc = 0), low (Pocc -1 to -5 cm H2O), moderate (-5 to -15 cm H2O), high (-16 to -30 cm H2O), and very high (< -30 cm H2O). Excessive dynamic transpulmonary driving pressure was defined as estimated ΔPL,dyn was >20 cm H2O. Results:We included 854 patients who received invasive MV for at least 1 day. Of 577 patients in whom Pocc was measured on day 1 (within 24 hours of initiation of MV), effort was absent in 434 (75%) patients, moderate in 70 (12%), and high or very high 43 (7%). Of 328 patients in whom Pocc was measured on day 5, effort was absent in 127 (39%) patients, moderate in 80 (24%) patients and high or very high in 91 (28%). Among spontaneously breathing patients (Pocc <0 cm H2O), estimated dynamic transpulmonary driving pressure exceeded 20 cm H2O in 49/116 (42%) on day 1 and 77/150 (51%) on day 5. On patient-days on which estimated dynamic transpulmonary driving pressure exceeded 20 cm H2O, on average the ventilator contributed 62% (SD 24%) of total lung-distending pressure and the patient contributed 38% (SD 24%) of total lung-distending pressure. Over days 1 through 10, respiratory efforts were more vigorous in patients with COVID-19 pneumonia compared to those without (mean Pocc -12 cm H2O vs -7 cm H2O, p= <0.01). Conclusions:Respiratory effort is frequently absent or excessive during MV. Patients frequently exhibited excessive lung-distending pressures during spontaneous breathing. COVID-19 pneumonia was associated with higher respiratory effort. (Figure Presented).

Nationwide strategies employed to provide and integrate palliative care to patients with covid-19

Background: Little is known on what palliative care (PC) has been provided to patients with COVID-19. Aims: To understand what PC was provided nationwide to patients with COVID-19 and strategies implemented to overcome barriers during the pandemic. Methods: Semi-structured interviews were conducted with physicians across Canada about their experiences providing PC to patients with COVID-19. Thematic analysis was used to describe and interpret overarching themes. Results: Twelve specialized PC (SPC) and 11 primary PC (PPC) were interviewed. Interim analysis of 16 coded interviews demonstrated SPC and PPC physicians used traditional strategies (such as opioids, oxygen and serious illness conversations) to manage symptoms, support end of life, and engage patients and families in goals of care conversations (GOC). Neither SPC nor PPC indicated strong adoption of GOC and symptom management tools circulated early in the pandemic. Both SPC and PPC indicated a shift to virtual communication due to restrictive visitor policies, highlighting the need for distanced support and planned communication. Care coordination for PC patients was challenged by a lack of community resources, family infected with COVID-19, prolonged hospital stays, and increased number of PC patients discharged to rehabilitation services. New PC structures included;GOC teams that functioned in the emergency department and medicine floors, integrated clinical rounding by non-PC clinicians with PC teams, and hospital-based PC outreach to long term care. Strategies to improve PC implementation included: virtual technologies, team collaboration, patient and family engagement tools, and symptom management and GOC conversations tools. Conclusions: While PC management approaches to support patients with COVID-19 were mostly unchanged, new structures and strategies were developed to ensure patients and their families were provided with support.

Barriers and facilitators to specialized palliative care integration for patients with COVID-19

Background: Specialized palliative care (SPC) teams are well placed to support patients with advanced COVID-19 in Canada, but evidence indicates integration so far has been variable. Aim: To understand barriers and facilitators of SPC integration in the management of patients with COVID-19. Methods: Semi-structured interviews were conducted with physicians across Canada about their experiences providing care to patients with COVID-19. Thematic analysis was used to describe and interpret overarching themes. Results: Twenty-three physicians (12 SPC, 5 intensivists, 6 general internists) were interviewed. Interim analysis of 16 coded interviews demonstrated that facilitators/barriers to providing COVID-19 care fell into 5 main categories: patient-related, provider-related, Disease-specific, SPC service, and leadership factors. Patient-related items included age, comorbidities, goals, speed of decline and clustering of patients. Non- SPC provider-related factors included experience providing palliative care and working with the SPC team, time, and motivation. Uncertainty around COVID-19 progression, management and infection control practices were identified disease-specific barriers. SPC service factors included stigma related to palliative care, the accessibility, availability, and readiness of SPC services to meet the perceived needs of patients with COVID-19. Leadership facilitators included institutional mandated or supported integration, and SPC? presence at COVID-19 planning tables. Ways to improve integration included educational initiatives, relationship building, formal integrated structures and presence at institutional COVID-19 planning tables. Conclusion: Preliminary analysis highlights the need for high-level support for formal SPC integrated structures, a SPC role in pandemic planning, and the need for ongoing educational and relationship building initiatives to overcome barriers of SPC integration in COVID-19 care.

Identifying the consequences of restrictive visitor policies on palliative care providers, their patients and caregivers

Background: Restrictive institution visitor policies were implemented to minimize infection risks during the COVID-19 pandemic. Little data exists on the relationship between these policies and the provision of palliative care(PC). Aim: To describe the experiences and reflections of PC physicians on the effects of restrictive visitor policies. Methods: Semi-structured interviews were conducted with physicians about their experience providing PC in institutions with restrictive visitor policies. Thematic analysis was used to describe and interpret overarching themes. Results: Twelve specialized PC and 11 primary PC were interviewed. Interim analysis of 16 coded interviews demonstrates 4 main thematic categories including patient, caregiver, provider, and system effects. Patient-related items included isolation, dying alone, lack of caregiver advocacy and forced care decisions to allow for visitor presence. Caregiver factors included the inability to support or provide care to patients, poor communication with care teams, poor illness understanding, the need to make distanced care decisions, and challenges in identifying visitors. Provider factors included increased time and effort on communication, lack of caregiver input on patient status, increased complaints, the need to be a caregiver surrogate, visitor advocate or gatekeeper. System effects included the increased interest to be provided care in the community and the lack of interest in palliative care units. These factors were often exacerbated by several issues including the lack of clear evidence on their validity, and inconsistent enforcement or interpretation of policies at the unit, which led to patient and caregiver anger and distrust, and provider frustration. Conclusion: Preliminary analysis highlights substantial negative consequences of restrictive visitor policies at the patient, caregiver, provider and system levels which were exacerbated by their lack of evidence and inconsistent enforcement.

Health care providers' experiences with establishing goals of care for patients with covid-19

Background: Exploring patients' goals of care (GOC) is integral to palliative care practice. COVID-19 may present new challenges to establishing GOC. Aim: To describe the experiences and reflections of physicians regarding exploring GOC for patients with COVID-19. Methods: Semi-structured interviews were conducted with physicians about their experience assessing GOC for patients with COVID-19. Thematic analysis was used to describe and interpret over-arching themes. Results: Twenty-three physicians (12 Palliative Care, 5 Internal Medicine, and 6 Critical Care) were interviewed. Interim analysis of 16 coded interviews revealed 4 thematic categories of factors influencing establishment of GOC: resource availability, COVID-19 factors, patients' baseline health, and unusual communication challenges between health care providers and substitute decision makers (SDMs) or patients. Resourcerelated factors included impact of ICU/ventilator availability and personal protective equipment (PPE) shortages on GOC discussions. COVID-19 factors affecting GOC conversations included physician uncertainty of the course of illness;lack of definitive, evidence-based treatment;patient and family preconceived ideas about COVID-19;and risk of rapid decline. Factors associated with patients' baseline health included comorbid disease and ability to treat comorbid disease in parallel with COVID-19. Unusual communication challenges impacting GOC discussions included a high level of SDM involvement for GOC conversations, visitor policies potentially limiting SDMs' illness understanding, and virtual discussions or discussions taking place under layers of PPE creating barriers to effective communication between physicians, patients, and SDMs. Conclusion: Preliminary analysis highlights the unique challenges faced by both health care providers and patients/SDMs to facilitate and participate in GOC conversations in the context of the COVID-19 pandemic.

Reflections and experiences of physicians working during the COVID-19 pandemic: A qualitative study

Background: The need to recognize and attend to physician health and wellness has recently been emphasized, due to high levels of documented distress and burnout. The global pandemic has imposed even greater stressors and novel work demands on clinicians. Aim: To understand the experiences of physicians providing care during a global pandemic. Methods: Semi-structured interviews were conducted with physicians across Canada about their experiences providing care to patients during the COVID-19 pandemic. Thematic analysis methodology was used to describe overarching themes. Results: Twenty-three physicians (12 specialized palliative care, 5 intensivists, 6 general internists) were interviewed. Interim analysis of 16 coded interviews revealed 8 main categories: confusion and uncertainty;exhaustion and burnout;trauma;ethical considerations;isolation;professional re-evaluation;altruism;and cohesion. Confusion and uncertainty related mainly to the novel virus, leadership, and institutional preparedness. Exhaustion and burnout encompassed workload, personal protective equipment, family life, and complexity. The trauma theme included visitor policies, family surrogates, and patient management. Ethical considerations included job demands vs personal and family safety. Isolation was largely related to infection control measures. Professional re-evaluation items included job satisfaction due to changed patient encounters or novel structuring. Altruism items included unique personal contribution to pandemic response and societal needs. Cohesion items included supporting each other and team building. Conclusion: Preliminary analysis revealed trauma and distress, but also altruism and cohesion. These findings may inform interventions for physician health and wellness, as well as indicating ways to integrate meaning and purpose into negative experiences to promote resilience.

An appraisal of respiratory system compliance in mechanically ventilated COVID-19 patients

Rationale Heterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous smallcase series or studies conducted at a national level.Methods We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe the impact of CRS on the ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide.Results We enrolled 318 COVID-19 patients enrolled into the study from January 14th through September 31th, 2020 in 19 countries and stratified into two CRS groups. CRS was calculated as: tidal volume/[airway plateau pressure-positive endexpiratory pressure (PEEP)] and available within 48h from commencement of MV in 318 patients. Patients were mean±SD of 58.0±12.2, predominantly from Europe (54%) and males (68%). Median CRS (IQR) was 34.1 mL/cmH2O (26.5-45.5) and PaO2/FiO2 was 119 mmHg (87.1-164) and was not correlated with CRS. Female sex presented lower CRS than in males (95% CI:-13.8 to-8.5 P<0.001) and higher body mass index (34.7±10.9 vs 29.1±6.0, p<0.001). Median (IQR) PEEP was 12 cmH2O (10-15), throughout the range of CRS, while median (IQR) driving pressure was 12.3 (10-15) cmH2O and significantly decreased as CRS improved (p<0.001). No differences were found in comorbidities and clinical management between CRS strata. In addition, 28-day ICU mortality and hospital mortality did not differ between CRSgroups.Conclusions This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV-predominantly males or overweight females, in their late 50s-admitted to ICU during the first international outbreaks. Phenotypes associated with different CRS upon commencement of MV could not be identified.

Factors associated with mortality in patients with COVID-19 requiring mechanical ventilation: An international cohort study from 139 intensive care unit across 6 continents

Rationale: Patients with COVID-19 commonly develop severe hypoxemic respiratory failure and require invasive mechanical ventilation (MV). The disease burden and predictors of mortality in this population remain uncertain. Methods: Prospective observational cohort study from 139 intensive care units of the international COVID-19 Critical Care Consortium. Patients enrolled from January 14th through November 31st 2020 were included in the analysis. Patient's characteristics and clinical data were assessed. Multivariable Cox proportional hazards analysis was conducted to identify indipendent predictors of mortality within 28 days from commencement of MV. Results: 1578 patients on MV were included into the analysis. Mean±SD age was 59 years±13 and patients were predominantly males (66%). 542 Patients (34.4%) died within 28 days from commencement of MV. Nonsurvivors were slightly older (mean age±SD 62±13 vs. 59±13) and presented more frequently hypertension, chronic cardiac disease and diabetes. Median (IQR) PaO2/FiO2 upon commencement of MV was 96 (68-135) and 111 (81-173) in patients who did not survive vs. survivors, respectively (p=0.04). ECMO (13% vs 25%, p<0.01), inhaled nitric oxide (11% vs 15%, p=0.02) and recruitment manoeauvres (26% vs 31%, p<0.01) were used less frequently in patients who did not survive. Independent risk factors associated with 28-day mortality included age older than 70 years (hazard ratio [HR], 2.83;95% CI, 1.32-6.07), higher creatinine levels upon ICU admission (HR, 1.20;95% CI, 1.03-1.40), and lower pH within 24h from commencement of MV (HR, 0.12;95% CI, 0.02-0.62), while a shorter period (day) from early symptoms to hospitalisation reduced mortality risks (HR, 0.96;95% CI, 0.93-0.99). Conclusions: Our findings from a large international cohort of critically-ill COVID-19 patients on mechanical ventilation emphasises that elderly patients, not promptly admitted to the hospital, and who present higher creatinine levels and acidosis are at higher risk of mortality.

Transesophageal echocardiography guidance for bedside extracorporeal membrane oxygenation cannulation in COVID-19 patients

Objective: To describe the use and safety of transesophageal echocardiography guidance for bedside ECMO cannulation in a large academic center. Methods: In this retrospective cohort study, we studied all patients who underwent bedside (in the intensive care unit) venovenous ECMO (VV-ECMO) cannulation under TEE guidance between May 4 to November 4, 2020, in a tertiary care center. Patient characteristics, physiological, and ventilatory parameters, as well as echocardiographic findings, were recorded and analyzed. Results: During the study period, 35 patients were placed on VV-ECMO. Nineteen patients (54%) were cannulated under TEE guidance of which sixteen (84%) had a confirmed COVID SARS-COV-2 pneumonia;two patients (11%) had mild to moderate right ventricular systolic dysfunction, and one (5%) had biventricular dysfunction. Cannula position was adequate in 18 cases (95%). No significant complications, such as post-cannulation complications, nosocomial COVID transmission or TEE related complications, were reported during this study. Conclusions: We report the safe utilization of bedside TEE-guidance for VV-ECMO cannulation in patients with severe respiratory failure, including in COVID patients. No TEE related complications, nor nosocomial transmission occurred in our cohort. Besides one superficial vascular injury, we did not encounter significant ECMO related complications.

Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial.

Importance: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies. Objective: To assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy. Design, Setting, and Participants: This double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study. Interventions: Patients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed. Main Outcomes and Measures: The primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16. Results: Among 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P = .004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P = .08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis. Conclusions and Relevance: A dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03733301.