Prone positioning of patients with moderate hypoxaemia due to covid-19: multicentre pragmatic randomised trial (COVID-PRONE).

OBJECTIVES: To assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19. DESIGN: Multicentre pragmatic randomised clinical trial. SETTING: 15 hospitals in Canada and the United States from May 2020 until May 2021. PARTICIPANTS: Eligible patients had a laboratory confirmed or a clinically highly suspected diagnosis of covid-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients who were assessed for eligibility, 257 were randomised and 248 were included in the analysis. INTERVENTION: Patients were randomised 1:1 to prone positioning (that is, instructing a patient to lie on their stomach while they are in bed) or standard of care (that is, no instruction to adopt prone position). MAIN OUTCOME MEASURES: The primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as needing at least 60% fraction of inspired oxygen for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to fraction of inspired oxygen. RESULTS: The trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomisation was 1 day, the median age of patients was 56 (interquartile range 45-65) years, 89 (36%) patients were female, and 222 (90%) were receiving oxygen via nasal prongs at the time of randomisation. The median time spent prone in the first 72 hours was 6 (1.5-12.8) hours in total for the prone arm compared with 0 (0-2) hours in the control arm. The risk of the primary outcome was similar between the prone group (18 (14%) events) and the standard care group (17 (14%) events) (odds ratio 0.92, 95% confidence interval 0.44 to 1.92). The change in the ratio of oxygen saturation to fraction of inspired oxygen after 72 hours was similar for patients randomised to prone positioning and standard of care. CONCLUSION: Among non-critically ill patients with hypoxaemia who were admitted to hospital with covid-19, a multifaceted intervention to increase prone positioning did not improve outcomes. However, wide confidence intervals preclude definitively ruling out benefit or harm. Adherence to prone positioning was poor, despite multiple efforts to increase it. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning. STUDY REGISTRATION: ClinicalTrials.gov NCT04383613.

Non-invasive ventilation in children and adults in low- and low-middle income countries: A systematic review and meta-analysis.

PURPOSE: We systematically reviewed the effects of NIV for acute respiratory failure (ARF) in low- and low-middle income countries. MATERIALS AND METHODS: We searched MEDLINE, CENTRAL, and EMBASE (to January 2016) for observational studies and trials of NIV for ARF or in the peri-extubation period in adults and post-neonatal children. We abstracted outcomes data and assessed quality. Meta-analyses used random-effect models. RESULTS: Fifty-four studies (ten pediatric/n=1099; 44 adult/n=2904), mostly South Asian, were included. Common diagnoses were pneumonia and chronic obstructive pulmonary disease (COPD). Considering observational studies and the NIV arm of trials, NIV was associated with moderate risks of mortality (pooled risk 9.5%, 95% confidence interval (CI) 4.6-14.5% in children; 16.2% [11.2-21.2%] in adults); NIV failure (10.5% [4.6-16.5%] in children; 28.5% [22.4-34.6%] in adults); and intubation (5.3% [0.8-9.7%] in children; 28.8% [21.9-35.8%] in adults). The risk of mortality was greater (p=0.035) in adults with hypoxemic (25.7% [15.2-36.1%]) vs. hypercapneic (12.8% [7.0-18.6%]) ARF. NIV reduced mortality in COPD (relative risk [RR] 0.47 [0.27-0.79]) and in patients weaning from ventilation (RR 0.48 [0.28-0.80]). The pooled pneumothorax risk was 2.4% (0.8-3.9%) in children and 5.2% (1.0-9.4%) in adults. Meta-analyses had high heterogeneity. CONCLUSIONS: NIV for ARF in these settings appears to be effective.

Non-pulmonary infections but not specific pathogens are associated with increased risk of AKI in septic shock.

INTRODUCTION: Little is known regarding the relationship between the anatomic infection site and etiologic pathogen with the occurrence of acute kidney injury (AKI) in severe infections. We set out to determine the association between the site of infection, type of pathogen in septic shock and occurrence of AKI. METHODS: Using a large, international multicenter database that included data from 28 academic and community hospitals, we retrospectively analyzed adult (age >18 years) cases of septic shock occurring between January 1996 and December 2008. Early acute kidney injury (AKI) was classified by the RIFLE criteria at or within 24 h of shock diagnosis. Multivariate logistic regression was used to determine the association between the infection site/microbial pathogen and occurrence of AKI. Analyses were adjusted for demographics, illness severity, comorbidities and intensive care unit interventions (partial adjustment) ± site of infection and microbial pathogen (full adjustment). RESULTS: After exclusions, 4,493 cases from potentially eligible patients in the database were included in the analytic cohort of whom 3,298 (73.4 %) experienced AKI. Patients with AKI were older (p < 0.0001), had a higher mean Acute Physiology and Chronic Health Evaluation score (p < 0.0001), and had greater laboratory and hemodynamic abnormalities. The most common site of infection among septic shock patients with AKI was the lung (34.5 %), followed by gastrointestinal (GI) (26.2 %) and urinary (15.3 %) sources. Likewise, the most common infecting organism among septic shock patients with AKI was E. coli (23.9 %) followed by S. aureus (GI) (16.1 %) and other enterobacteriaceae (15.7 %). There was a large degree of variability in the occurrence of AKI based on the site of infection and the pathogen in unadjusted analysis (p < 0.0001), which persisted with partial (excluding infection site and microbial pathogen grouping) adjustment (p < 0.0001). Fully adjusted multivariate analysis showed significant variations in AKI only in relation to the anatomic source of infection, with non-pulmonary infections having higher risk than pulmonary infections. The pathogen group/pathogen had no significant independent impact on AKI. CONCLUSION: This study demonstrates that the presence of septic AKI varies significantly based on the site of infection but not the type of causative organism.

Effect of time on dialysis and renal transplantation on endothelial function: a longitudinal analysis.

BACKGROUND: Soluble vascular cell adhesion molecule-1 (sVCAM-1) is a marker of endothelial injury and a potent predictor of cardiovascular mortality in patients with kidney failure on dialysis. The longitudinal effects of dialysis on endothelial dysfunction and in particular the effects of renal transplantation on markers of endothelial function including sVCAM-1 have not been well characterized. METHODS: We used the Transplant Manitoba registry and biobank to assemble a retrospective cohort of all patients receiving a first kidney transplant between January 1, 2000, and December 31, 2005 (n=186). One hundred seventy-four patients had at least two serum samples pretransplant and at least two samples posttransplant. In total, 1,004 serial samples (median 5/patient) were analyzed. Factors associated with sVCAM-1 were examined using mixed linear models. RESULTS: The sVCAM-1 levels increased progressively on dialysis (0.15 [0.10 to 0.20] ng/mL/day; P<0.0001), fell significantly within 1 month after transplantation (-625 ng/mL/day; P<0.0001) and continued to fall thereafter (-0.23 [-0.34 to -0.12] ng/mL/day). Smoking and heart failure were associated with higher sVCAM-1 levels, whereas transplantation was associated with lower sVCAM-1 levels. The relationship between sVCAM-1 and transplantation was not changed by multivariate adjustment. CONCLUSION: Endothelial injury worsens over time on dialysis but improves significantly after renal transplantation.

Critical care trainees' career goals and needs: A Canadian survey.

BACKGROUND: For training programs to meet the needs of trainees, an understanding of their career goals and expectations is required. OBJECTIVES: Canadian critical care medicine (CCM) trainees were surveyed to understand their career goals in terms of clinical work, research, teaching, administration and management; and to identify their perceptions regarding the support they need to achieve their goals. METHODS: The online survey was sent to all trainees registered in a Canadian adult or pediatric CCM program. It documented the participants' demographics; their career expectations; the perceived barriers and enablers to achieve their career goals; and their perceptions relating to their chances of developing a career in different areas. RESULTS: A response rate of 85% (66 of 78) was obtained. The majority expected to work in an academic centre. Only approximately one-third (31%) estimated their chances of obtaining a position in CCM as >75%. The majority planned to devote 25% to 75% of their time performing clinical work and <25% in education, research or administration. The trainees perceived that there were limited employment opportunities. Networking and having specialized expertise were mentioned as being facilitators for obtaining employment. They expressed a need for more protected time, resources and mentorship for nonclinical tasks during training. CONCLUSION: CCM trainees perceived having only limited support to help them to achieve their career goals and anticipate difficulties in obtaining successful employment. They identified several gaps that could be addressed by training programs, including more mentoring in the areas of research, education and administration.