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Prognostic factors in lung transplantation are those variables that are associated with transplant outcomes. Knowledge of donor and recipient prognostic variables can aid in the optimal allocation of donor lungs to transplant recipients and can also inform post-operative discussions with patients about prognosis. Current research findings related to prognostic factors in lung transplantation are inconsistent and the relative importance of various factors is unclear. This review aims to provide the best possible estimates of the association between putative prognostic variables and 1-year all-cause mortality in adult lung transplant recipients.We searched 5 bibliographic databases for studies assessing the associations between putative predictors (related to lung donors, recipients, or the transplant procedure) and 1-year recipient mortality. We pooled data across studies when justified and utilized GRADE methodology to assess the certainty in the evidence.From 72 eligible studies (2002-2020), there were 34 recipient variables, 4 donor variables, 10 procedural variables, and 7 post-transplant complication variables that were amenable to a meta-analysis. With a high degree of certainty in the evidence only post-transplant need for extra-corporeal membrane oxygenation (ECMO) (HR 1.91, 95% CI 1.79-2.04) predicted 1-year mortality. No donor variables appeared to predict transplant outcome with high or even moderate certainty.Across the range of contemporary donors and recipients that clinicians accept for lung transplantation, this review, with high certainty, found 1 prognostic factor that predicted 1-year mortality, and 37 additional factors with a moderate degree of certainty. The lack of prognostic significance for some widely accepted factors (e.g., donor smoking, age) likely relates to existing limits in the range of these variables at the time of donor and recipient selection.

International audience; BACKGROUND Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).

Introduction: Death investigators (DIs) such as coroners, medical examiners, and forensic pathologists play important and evolving roles in deceased organ donation. DIs communicate with organ donation organizations (ODOs) to gather case-specific information and release or restrict organs depending on the medicolegal requirements. This scoping review aims to identify the breadth of roles and decision-making processes that may facilitate or hinder deceased donation in DI cases. Methods: This study was conducted using a scoping literature review and subsequent thematic analysis. Results: Thirty-one eligible papers described 8 common themes with region-specific nuances. These include: 1) shared (ODO and DI) protocols for early communication around each case; 2) shared standards and education for death investigation practices related to organ donation; 3) DI support staff or teams to facilitate organ donation; 4) DI authority to order additional testing and imaging before organ recovery; 5) donation-specific legislation to enhance DI and/or ODO operations; 6) legally trained DI authority to veto medical decisions to proceed with organ donation; 7) DI attendance at organ recovery; and 8) surgeons recording specific DI evidence during organ recovery. Conclusion: These findings have cultural and resource-allocation implications and expose gaps in the international literature describing practices at the intersection of deceased organ donation and death investigation. A better understanding of the rationale and execution of various systems for DI and ODO cooperation may serve to advance both organ donation and death investigation.

We evaluated characteristics associated with neuromuscular blockade (NMB) use, center-level variation, and whether NMB mediated excess mortality among patients assigned to high-frequency oscillatory ventilation (HFOV) in the OSCILLATE trial.NMB exposure was defined as receipt after randomization; the primary outcome was hospital mortality. Descriptive analyses compared NMB-exposed vs unexposed patients. Multivariable analyses included patients not on baseline NMB. Cox regression evaluated associations of patient- and center-level variables with NMB use. A log-normal frailty model evaluated center effects. Mediation analysis examined the effect of NMB in HFOV-assigned patients.376/548 patients (39 centers) received post-randomization NMB, of whom 165 received baseline NMB. Patients receiving post-randomization NMB (vs. not) had worse lung mechanics and gas exchange, received more sedation and vasopressors (p 0.05), and had higher hospital mortality (44% vs. 34%, p = 0.03). Mean airway pressure ≥ 24 cmHIn OSCILLATE, receipt of post-randomization NMB was associated with worse outcomes, but NMB use did not mediate HFOV-associated higher mortality.

Purpose We sought to examine changes in acute respiratory distress syndrome (ARDS) management over a 12-year period of two successive randomized trials. Methods Analyses included baseline data, from eligible patients, prior to influence of trial protocols, and daily study data, from randomized patients, of variables not determined by trial protocols. Mixed linear regressions examined changes in practice year-on-year. Results A total of 2376 patients met the inclusion criteria. Over the 12-year period, baseline tidal volume index decreased (9.0 to 7.0 ml/kg, p < 0.001), plateau pressures decreased (30.8 to 29.0 cmH2O, p < 0.05), and baseline positive end-expiratory pressures increased (10.8 to 13.2 cmH2O, p < 0.001). Volume-controlled ventilation declined from 29.4 to 14.0% (p < 0.01). Use of corticosteroids increased (baseline: 7.7 to 30.3%; on study: 32.6 to 61.2%; both p < 0.001), as did neuromuscular blockade (baseline: 12.3 to 24.5%; on study: 55.5 to 70.0%; both p < 0.01). Inhaled nitric oxide use increased (24.9 to 65.8%, p < 0.05). We observed no significant change in prone positioning (16.2 to 18.9%, p = 0.70). Conclusions Clear trends were apparent in tidal volume, airway pressures, ventilator modes, adjuncts and rescue therapies. With the exception of prone positioning, and outside the context of rescue therapy, these trends appear consistent with the evolving literature on ARDS management.

Rationale: Choosing the best ventilation strategy for acute respiratory distress syndrome (ARDS) is complex, yet it is highly relevant to clinicians during a respiratory pandemic. Objectives: To co...

IMPORTANCE: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19. OBJECTIVE: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021. INTERVENTION: Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195). MAIN OUTCOMES AND MEASURES: The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events. RESULTS: Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, −6.37% [95% CI, −15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, −1.15% [95% CI, −9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group. CONCLUSIONS AND RELEVANCE: In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04350723

The objectives of this study were to systematically identify and describe guidelines for the care of neurologically deceased donors and to evaluate their methodological quality, with the aim of informing and supporting the new Canadian guidelines for the management of organ donors.Following a systematic search, we included any document endorsed by an organ donation organization, a professional society, or a government, that aims to direct the medical management of adult, neurologically deceased, multi-organ donors. We extracted recommendations pertaining to six domains: the autonomic storm, hemodynamic instability, hormone supplementation, ventilation, blood product transfusions, and general intensive care unit (ICU) care. Methodological quality of the guidelines was assessed by the validated AGREE-II tool.This review includes 27 clinical practice guidelines representing 26 countries published between 1993 and 2019. Using the AGREE-II validated tool for the evaluation of guidelines' quality, documents generally scored well on their scope and clarity of presentation. Nevertheless, quality was limited in terms of the scientific rigor of guideline development. Recommendations varied substantially across the domains of managing the autonomic storm, subsequent management of hemodynamic instability, hormone therapy, mechanical ventilation, blood product transfusion, and general ICU care. We found consistent recommendations for low tidal volume ventilation subsequent to the publication of a landmark clinical trial.Highly inconsistent recommendations for deceased donor care summarized in this review likely reflect the relatively slow emergence of high-quality clinical research in this field, as well as a late uptake of recent validated guideline methodology. Even in this context of few randomized-controlled trials, our group supported the need for new Canadian guidelines for the management of organ donors that follow rigorous recognized methodology and grading of the evidence.PROSPERO (CRD42018084012); registered 25 February 2016.RéSUMé: OBJECTIF: Les objectifs de cette étude étaient d’identifier et de décrire de façon systématique les lignes directrices concernant les soins à prodiguer aux donneurs suivant un décès neurologique et d’évaluer leur qualité méthodologique, avec pour but d’informer et d’appuyer les nouvelles lignes directrices canadiennes de prise en charge des donneurs d’organes. MéTHODOLOGIE: À la suite d’une recherche systématique, nous avons inclus tout document endossé par un organisme de dons d’organes, une société professionnelle ou un gouvernement et ayant pour but d’orienter la prise en charge médicale des donneurs adultes d’organes multiples à la suite d’un décès neurologique. Nous avons extrait les recommandations touchant six domaines : la tempête catécholaminergique, l’instabilité hémodynamique, la supplémentation hormonale, la ventilation, les transfusions de produits sanguins et les soins généraux à l’unité de soins intensifs (USI). La qualité méthodologique des lignes directrices a été évaluée avec l’outil validé AGREE-II. CONSTATIONS PRINCIPALES: Cette revue porte sur 27 guides d’exercice cliniques représentant 26 pays et publiés entre 1993 et 2019. En se fondant sur l’outil validé AGREE-II pour l’évaluation de la qualité des lignes directrices, les documents ont en règle générale obtenu un bon score en ce qui touchait à leurs objectifs et à la clarté de leur présentation. Toutefois, la qualité était limitée en matière de rigueur scientifique employée pour la mise au point des lignes directrices. Les recommandations variaient considérablement concernant les questions pertinentes à la prise en charge de la tempête catécholaminergique, à la prise en charge subséquente de l’instabilité hémodynamique, à l’hormonothérapie, à la ventilation mécanique, à la transfusion de produits sanguins, et aux soins généraux à l’USI. À la suite de la publication d’une étude clinique importante, les recommandations concernant la ventilation à volume courant bas étaient constantes. CONCLUSION: Le manque de cohérence des lignes directrices touchant les soins aux donneurs décédés résumées dans cette revue est probablement le reflet de l’émergence relativement lente de recherches cliniques de qualité élevée dans ce domaine, ainsi que de l’adoption tardive des méthodologies récentes et validées pour l’élaboration de lignes directrices. Même dans le contexte actuel de rareté d’études randomisées contrôlées, notre groupe appuie la nécessité de nouvelles lignes directrices canadiennes concernant la prise en charge des donneurs d’organes qui respectent une méthodologie reconnue et rigoureuse ainsi qu’une classification des données probantes. ENREGISTREMENT DE L’éTUDE: PROSPERO (CRD42018084012); enregistrée le 25 février 2016.

End-of-life (EOL) care is a key aspect of critical care medicine (CCM) training. The goal of this study was to survey CCM residents and program directors (PDs) across Canada to describe current EOL care education. Using a literature review, we created a self-administered survey encompassing 10 CCM national objectives of training to address: (1) curricular content and evaluation methods, (2) residents’ preparedness to meet these objectives, and (3) opportunities for educational improvement. We performed pilot testing and clinical sensibility testing, then distributed it to all residents and PDs across the 13 Canadian CCM programs. Our response rate was 84.3% overall (77 [81.1%] for residents and 13 [100%] for PDs). Residents rated direct observation, informal advice, and self-reflection as both the top 3 most utilized and perceived most effective teaching modalities. Residents most commonly reported comfort with skills related to pain and symptom management (n = 67, 94.3%; score > 3 on 5-point Likert scale), and least commonly reported comfort with donation after cardiac death skills (n = 26-38; 44.8%-65.5%). Base specialty and time in CCM training were independently associated with comfort ratings for some, but not all, EOL skills. With respect to family meetings, residents infrequently received feedback; however, most PDs believed feedback on 6 to 10 meetings is required for competence. When PD perceptions of teaching effectiveness were compared with resident comfort ratings, differences were most apparent for skills related to pain and symptom management, cultural awareness, and ethical principles. By the end of their first subspecialty training year, PDs expect residents to be competent at most, but not all, EOL skills. In summary, trainees and programs rely on clinical activities to develop competency in EOL care, resulting in some educational gaps. Transitioning to competency-based medical education presents an opportunity to address some of these gaps, while other gaps will require more specific curricular intervention.

Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices. This prospective observational cohort study enrolled consecutive, newly consented organ donors from August 1 2015 to July 31 2018 at 27 academic and five community adult intensive care units in British Columbia, Alberta, Ontario, and Quebec. Research staff prospectively recorded donor management data. Provincial organ donation organizations verified the organs donated. We formally compared practices across provinces. Over a median collection period of eight months, 622 potential donors were classified at baseline as having neurologic determination of death (NDD donors; n = 403) or circulatory death (DCD donors; n = 219). Among NDD donors, 85.6% underwent apnea testing (rarely with carbon dioxide insufflation), 33.2% underwent ancillary testing, and subsequent therapeutic hypothermia (34–35°C) was rare. Neurologic determination of death donors were more hemodynamically unstable with most having received vasopressin and norepinephrine infusions, with a large majority having received high-dose corticosteroids and intravenous thyroxine. Among DCD donors, 61.6% received corticosteroids, and 8.9% received thyroxine. Most donors did not receive lung-protective ventilation strategies. Invasive procedures after donation consent included bronchoscopy (71.7%), cardiac catheterization (NDD donors only; 21.3%), and blood transfusions (19.3%). Physicians ordered intravenous antemortem heparin for 94.8% of DCD donors. The cohort donated 1,629 organs resulting in 1,532 transplants. Case selection, death determinations, and hormone, nutrition and heparin practices all varied across provinces. These study findings highlight areas for knowledge translation and further clinical research. Interprovincial discrepancies will likely pose unique challenges to national randomized trials. Trial registration: www.clinicaltrials.gov (NCT03114436); registered 10 April, 2017.

Research to inform the care of neurologically deceased organ donors is complicated by a lack of standards for research consent. In this systematic review, we aim to describe current practices of soliciting consent for participation in prospective studies of neurologically deceased donors, including the frequency and justification for these various models of consent. Among the 74 studies included, 14 did not report on any regulatory review, and 13 did not report on the study consent procedures. Of the remaining 47 studies, 24 utilized a waiver of research consent. The most common justification for a waiver of research consent related to the fact that neurologically deceased donors are not considered human subjects. In conclusion, among studies of neurologically deceased donors, research consent models vary and are inconsistently reported. Consensus and standardization in the application of research consent models will help to advance this emerging field of research.

Purpose: The 3 Wishes Project (3WP) promotes holistic end-of-life care in the intensive care unit (ICU) to honor dying patients, support families, and encourage clinician compassion. Organ donation is a wish that is sometimes made by, or on behalf of, critically ill patients. Our objective was to describe the interface between the 3WP and organ donation as experienced by families, clinicians, and organ donation coordinators. Methods: In a multicenter evaluation of the 3WP in 4 Canadian ICUs, we conducted a thematic analysis of transcripts from interviews and focus groups with clinicians, organ donation coordinators, and families of dying or died patients for whom donation was considered. Results: We analyzed transcripts from 26 interviews and 2 focus groups with 18 family members, 17 clinicians, and 6 organ donation coordinators. The central theme describes the mutual goals of the 3WP and organ donation—emphasizing personhood and agency across the temporal continuum of care. During family decision-making, conversations encouraged by the 3WP can facilitate preliminary discussions about donation. During preparation for donation, memory-making activities supported by the 3WP redirect focus toward personhood. During postmortem family care, the 3WP supports families, including when donation is unsuccessful, and highlights aspirational pursuits of donation while encouraging reflections on other fulfilled wishes. Conclusions: Organ donation and the 3WP provide complementary opportunities to engage in value-based conversations during the dying process. The shared values of these programs may help to incorporate organ donation and death into a person’s life narrative and incorporate new life into a person’s death narrative.

Purpose Right ventricular RV dysfunction among transplant recipients correlates with transplant outcome, but its frequency in donors is unknown. The purpose of this study was to describe the epidemiology of RV dysfunction in potential heart donors.” Methods In a seven-year retrospective study of potential heart donors, we explored the incidence of RV dysfunction as observed on echocardiography and explored the association of four distinct factors with RV dysfunction: brain injury diagnosis, thoracic trauma, vasopressin infusion and left ventricular (LV) dysfunction. Results All 123 potential heart donors underwent echocardiography: 55 had RV dysfunction (44.7%). Fourty-one (33.3%) had LV dysfunction. Isolated RV dysfunction was present in 27 subjects (22%). LV dysfunction was the only factor significantly associated with RV dysfunction (OR = 4.6 (95% CI 1.9–11.4)). We observed no difference in heart acceptance between subjects with or without RV dysfunction. Conclusion We observed a high frequency of RV dysfunction in a sample of potential heart donors. However, the temporal evolution of RV dysfunction, the hemodynamic predictors of RV dysfunction, as well the link between donor RV dysfunction and recipient outcomes need to be assessed with further prospective studies.

Key Points Question Do clinical practice guidelines (CPGs) that report on pharmacologic treatments of hospitalized patients with COVID-19 meet the National Academy of Medicine standards for trustworthiness? Findings In this systematic review of 32 CPGs of predominantly low quality, few reported funding sources or conflicts of interest, included a methodologist, described a search strategy or study selection process, or synthesized evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, they infrequently rated the confidence in the quality of the evidence (6 [18.8%]), described potential benefits and harms (6 [18.8%]), or graded the strength of recommendations (5 [15.6%]). Meaning The findings of this study suggest that few COVID-19 CPGs meet National Academy of Medicine standards for trustworthy guidelines., This systematic review evaluates the quality and trustworthiness of clinical practice guidelines for pharmacologic treatment of hospitalized patients with COVID-19 using the National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards instrument., Importance The COVID-19 pandemic created the need for rapid and urgent guidance for clinicians to manage COVID-19 among patients and prevent transmission. Objective To appraise the quality of clinical practice guidelines (CPGs) using the National Academy of Medicine (NAM) criteria. Evidence Review A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to December 14, 2020, and a search of related articles to February 28, 2021, that included CPGs developed by societies or by government or nongovernment organizations that reported pharmacologic treatments of hospitalized patients with COVID-19. Teams of 2 reviewers independently abstracted data and assessed CPG quality using the 15-item National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards (NEATS) instrument. Findings Thirty-two CPGs were included in the review. Of these, 25 (78.1%) were developed by professional societies and emanated from a single World Health Organization (WHO) region. Overall, the CPGs were of low quality. Only 7 CPGs (21.9%) reported funding sources, and 12 (37.5%) reported conflicts of interest. Only 5 CPGs (15.6%) included a methodologist, described a search strategy or study selection process, or synthesized the evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, they infrequently rated confidence in the quality of the evidence (6 of 32 [18.8%]), described potential benefits and harms (6 of 32 [18.8%]), or graded the strength of the recommendations (5 of 32 [15.6%]). External review, patient or public perspectives, or a process for updating were rare. High-quality CPGs included a methodologist and multidisciplinary collaborations involving investigators from 2 or more WHO regions. Conclusions and Relevance In this review, few COVID-19 CPGs met NAM standards for trustworthy guidelines. Approaches that prioritize engagement of a methodologist and multidisciplinary collaborators from at least 2 WHO regions may lead to the production of fewer, high-quality CPGs that are poised for updates as new evidence emerges. Trial Registration PROSPERO Identifier: CRD42021245239

IMPORTANCE: Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported. OBJECTIVE: To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). DESIGN, SETTING, AND PARTICIPANTS: Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). INTERVENTIONS: Enteral L rhamnosus GG (1 × 10(10) colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. MAIN OUTCOMES AND MEASURES: The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. RESULTS: Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, –2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P

Rationale: Mortality in acute respiratory distress syndrome (ARDS) has decreased after the adoption of lung-protective strategies. Lower VT, lower driving pressure (DP), lower respiratory rates (RR), and higher end-expiratory pressure have all been suggested as key components of lung protection strategies. A unifying theoretical explanation has been proposed that attributes lung injury to the energy transfer rate (mechanical power) from the ventilator to the patient, calculated froma combination of several ventilator variables. Objectives: To assess the impact of mechanical power on mortality in patients with ARDS as compared with that of primary ventilator variables such as the DP, VT, and RR. Methods: We obtained data on ventilatory variables and mechanical power from a pooled database of patients with ARDS who had participated in six randomized clinical trials of protective mechanical ventilation and one large observational cohort of patients with ARDS. The primary outcome was mortality at 28 days or 60 days. Measurements and Main Results: We included 4,549 patients (38% women; mean age, 55623 yr). The average mechanical power was 0.3260.14 J _ min21 _ kg21 of predicted body weight, the DP was 15.065.8 cm H2O, and the RR was 25.767.4 breaths/ min. The driving pressure, RR, and mechanical power were significant predictors of mortality in adjusted analyses. The impact of the DP on mortality was four times as large as that of the RR. Conclusions: Mechanical power was associated with mortality during controlled mechanical ventilation in ARDS, but a simpler model using only the DP and RR was equivalent.

Background and objectives With expansion of the pool of kidney grafts, through the use of higher-risk donors, and increased attention to donor management strategies, the 1-year graft survival rate is subject to change. It is, therefore, useful to elucidate 1-year graft survival rates by dissecting the characteristics of the low-risk and high-risk kidney transplant cases. The objective of our study was to evaluate factors purported to influence the risk of 1-year graft loss in kidney transplant recipients. Design, setting, participants, & measurements We searched bibliographic databases from 2000 to 2017 and included observational studies that measured the association between donor, recipient, the transplant operation, or early postoperative complications, and 1-year death-censored graft loss. Results We identified 35 eligible primary studies, with 20 risk factors amenable to meta-analysis. Six factors were associated with graft loss, with moderate to high degree of certainty: donor age (hazard ratio [HR], 1.11 per 10-year increase; 95% confidence interval [95% CI], 1.04 to 1.18), extended criteria donors (HR, 1.35; 95% CI, 1.28 to 1.42), deceased donors (HR, 1.54; 95% CI, 1.32 to 1.82), number of HLA mismatches (HR, 1.08 per one mismatch increase; 95% CI, 1.07 to 1.09), recipient age (HR, 1.17 per 10-year increase; 95% CI, 1.09 to 1.25), and delayed graft function (HR, 1.89; 95% CI, 1.46 to 2.47) as risk factors for 1-year graft loss. Pooled analyses also excluded, with a high degree of certainty, any associations of cold ischemia time, recipient race, pretransplant body mass index, diabetes, and hypertension with 1-year graft loss. Conclusions Recipient age, donor age, standard versus extended criteria donor, living versus deceased donor, HLA mismatch, and delayed graft function all predicted 1-year graft survival. The effect of each risk factor is small.

We sought to characterize Canadian physicians’ perspectives and stated practices regarding their hemodynamic care of deceased organ donors. We designed a 24-item electronic survey that was independently pretested for relevance, clarity, and intra-rater reliability by ten critical care clinicians. With the help of provincial organ donation organizations (ODO), we identified intensive care units (ICUs) with a high volume of adult deceased donors (defined by the management of five or more donors per year for two consecutive years). Medical directors of these high-volume ICUs helped identify ICU physicians to whom our survey was emailed. Of the 448 ICU physicians from 37 centres in nine provinces that were emailed, 184/448 (41.1%) responded to one or more survey questions. Respondents identified specialist nurses from ODOs as their primary source of guidance in donor care (107/165; 60%). They typically diagnosed an autonomic storm according to a rise in blood pressure (159/165; 96.4%) and/or heart rate (135/165; 81.8%); nevertheless, their stated management varied substantially. After termination of the autonomic storm, preferred first-line vasopressors were norepinephrine (93/164; 56.7%) and vasopressin (68/164; 41.5%). Twenty-one respondents (21/162; 13.0%) reported that they never administer inotropes to donors. Corticosteroid and thyroid hormone prescriptions for all donors was reported by 62/161 (37.6%) and 50/161 (31.1%) respondents, respectively. Respondents perceived an influence from ODO nurses or transplant physicians when prescribing corticosteroids (77/161; 47.8%) and/or thyroid hormones (33/161; 20.5%) We observed important variability in self-perceived practices of ICU physicians in the hemodynamic management of deceased donors, particularly in the treatment of the autonomic storm, in the prescription of hormone therapy, and in the administration of inotropes.

Background Upon surviving the first year post-lung transplantation, recipients can expect a median survival of 8 years. Within the first year, graft failure and multi-organ failure (possibly secondary to graft failure) are common causes of mortality. To better understand the prognosis within the first year, we plan on conducting a systematic review and meta-analysis of observational studies addressing the association between the patient, donor, and transplant operative factors and graft loss 1-year post-lung transplant. Methods We searched MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register, and PubMed supplemental for non-MEDLINE records for observational studies identifying independent risk factors for early mortality (1 year) in adult lung transplant recipients. We plan on including cohort studies and secondary analyses of randomized controlled trials studying adult lung transplant recipients undergoing their first lung transplant, without any simultaneous organ transplant. We will conduct a random-effects meta-analysis that pools the effect estimates from all eligible studies to obtain a summary estimate and confidence interval for all independent non-therapeutic factors identified in the primary studies. Discussion The results from this study may inform future guidelines on the selection of candidates and donors for transplantation and predictive model development and inform the decision-making process that the physician and patient undertake together. Furthermore, through the conduction of this review, we can identify the limitations with the current best evidence, which will encourage the need for studies with a better methodology to reassess the predictors of mortality. Electronic supplementary material The online version of this article (10.1186/s13643-019-1049-x) contains supplementary material, which is available to authorized users.

Objectives It is unknown whether more frequent screening of invasively ventilated patients, identifies patients earlier for a spontaneous breathing trial, and shortens the duration of ventilation. We assessed the feasibility of conducting a large trial to evaluate screening frequency in critically ill adults in the North American context. Design We conducted two contemporaneous, multicenter, pilot, randomized controlled trials (the LibeRation from MEchanicaL VEntilAtion and ScrEening Frequency [RELEASE] and Screening Elderly PatieNts For InclusiOn in a Weaning [SENIOR] trials) to address concerns regarding the potential for higher enrollment, fewer adverse events, and better outcomes in younger patients. Setting Ten and 11 ICUs in Canada, respectively. Patients Parallel trials of younger (RELEASE Interventions Each trial compared once daily screening to "at least twice daily" screening led by respiratory therapists. Measurements and main results In both trials, we evaluated recruitment (aim: 1-2 patients/month/ICU) and consent rates, reasons for trial exclusion, protocol adherence (target: ≥ 80%), crossovers (aim: ≤ 10%), and the effect of the alternative screening frequencies on adverse events and clinical outcomes. We included 155 patients (53 patients [23 once daily, 30 at least twice daily] in RELEASE and 102 patients [54 once daily, 48 at least twice daily] in SENIOR). Between trials, we found similar recruitment rates (1.32 and 1.26 patients/month/ICU) and reasons for trial exclusion, high consent and protocol adherence rates (> 92%), infrequent crossovers, and few adverse events. Although underpowered, at least twice daily screening was associated with a nonsignificantly faster time to successful extubation and more successful extubations but significantly increased use of noninvasive ventilation in both trials combined. Conclusions Similar recruitment and consent rates, few adverse events, and comparable outcomes in younger and older patients support conduct of a single large trial in North American ICUs assessing the net clinical benefits associated with more frequent screening.

BACKGROUND: Studies on the association of obesity with mortality in subjects with ARDS have yielded inconsistent results. METHODS: In a sub-analysis of the Oscillation for ARDS Treated Early (OSCILLATE) randomized controlled trial, 451 subjects were divided into 5 strata based on their body mass index (BMI) using the World Health Organization definitions: underweight 40 kg/m2. The primary outcome was all-cause hospital mortality across BMI strata for all subjects and for the 2 study arms (high-frequency oscillatory ventilation [HFOV] vs conventional ventilation) separately using multivariable logistic regression adjusting for potential confounding variables. RESULTS: Hospital mortality was not different across the BMI strata for all subjects (P = .86), for the HFOV arm (P = .94) or for the conventional ventilation arm (P = .59). After risk adjustment, BMI was not associated with increased risk for hospital mortality (odds ratio 1.01, 95% CI 0.97–1.04, P = .67), whereas HFOV was independently associated with increased mortality (odds ratio 1.74, 95% CI 1.11–2.72, P = .02) with no effect modification by BMI strata (for this interaction, P = .56). Although there was no difference in the use of rescue therapies or in the number of days on sedation or analgesia, higher daily doses of fentanyl and midazolam were administered as BMI increased. CONCLUSION: There was no difference in adjusted hospital mortality across BMI strata in subjects with moderate to severe ARDS. Processes of care were not different across BMI strata except for higher daily doses of fentanyl as BMI increased. (ClinicalTrials.gov registration NCT0150640)

Introduction: Rates of successful organ donation vary between otherwise comparable intensive care units (ICUs). The ICU staff have a unique perspective into the facilitators and barriers underlying this variation in successful deceased organ donation. Research Question: What do ICU staff perceive to be the most meaningful facilitators and barriers to deceased organ donation? Design: We designed and conducted a survey of all disciplines working in the ICU to ascertain the perceived facilitators and barriers to donation in an academic tertiary care hospital. Survey reliability was assessed using Cronbach α. Factor analysis was used to assess construct validity and identify potentially redundant survey items. Results: We had responses from 108 ICU staff, including nurses (n = 75), respiratory therapists (n = 14), physicians (n = 12), chaplains (n = 2), as well as social work, pharmacy, physiotherapy, and occupational therapy (n = 1 each). Perceived facilitators included availability of organ donation organization coordinators, explicit institutional support for donation, ICU staff culture toward donation, standardized order sets for donation, presence of ICU staff with donation experience, and bedside nurse presence at discussions about donation. Perceived barriers included ICU staff ruling out potentially suitable donors before consulting a donor coordinator, physician communication skills, low priority for organ donation among operating room staff, limited family understanding of patient prognosis and organ donation, and limited emotional readiness of families to discuss donation. Discussion: Several staff-perceived facilitators and barriers to deceased organ donation were identified in the ICU. Future research could identify strategies to promote these facilitators and overcome barriers.

Background Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality. Methods We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing. Results We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3 days (lower respiratory tract and gastric aspirates; interquartile range [IQR] 2–4) and 6 days (stool; IQR 4.25–6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r = − 0.46, p = 0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p = 0.045). Conclusions The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients. Trial registration ClinicalTrials.gov ID NCT01782755. Registered February 4 2013. Electronic supplementary material The online version of this article (10.1186/s12931-018-0950-5) contains supplementary material, which is available to authorized users.

Purpose To assess the feasibility of a trial evaluating whether hyperoncotic albumin, in addition to diuretics, improves diuresis and facilitates liberation from mechanical ventilation in critically ill adults. Materials and methods We randomized 46 hemodynamically stable patients with hypoalbuminemia, prescribed diuretics by treating clinicians, to receive 100 mL of 25% albumin or 0.9% saline placebo BID, for three days, in blinded fashion. We chose five feasibility measurements: enrolment of 50% of eligible patients, at least one patient/week; administration of study treatment within 2 h of diuretics in 85% of patients; completion of study regimen in 80% of patients; and avoidance of open label albumin in 85% of patients. Clinical outcomes included fluid balance, ventilator-free days, and mortality. Results We randomized 85% of eligible patients. Eighty-four percent received study treatment within 2 h of diuretics, 69% received all doses of study treatment. Study treatment was held in the albumin and placebo groups because of no further need for diuresis (4 vs. 1), hypotension (2 v. 4), and albumin > 35 (1 v. 0). Twenty percent of patients received open-label albumin. Clinical outcomes were similar between groups. Conclusions The current study design did not demonstrate feasibility, but can inform the design of a definitive trial.

Donation after circulatory death determination frequently involves antemortem heparin administration to mitigate peri-arrest microvascular thrombosis. We systematically reviewed the literature to: (1) describe heparin administration practices and (2) explore the effects on transplant outcomes. We searched MEDLINE and EMBASE for studies reporting donation after circulatory death determination heparin practices including use, dosage, and timing (objective 1). To explore associations between antemortem heparin and transplant outcomes (objective 2), we (1) summarized within-study comparisons and (2) used meta-regression analyses to examine associations between proportions of donors that received heparin and transplant outcomes. We assessed risk of bias using the Newcastle Ottawa Scale and applied the GRADE methodology to determine certainty in the evidence. For objective 1, among 55 eligible studies, 48 reported heparin administration to at least some donors (range: 15.8%-100%) at variable doses (up to 1000 units/kg) and times relative to withdrawal of life-sustaining therapy. For objective 2, 7 studies that directly compared liver transplants with and without antemortem heparin reported lower rates of primary nonfunction, hepatic artery thrombosis, graft failure at 5 y, or recipient mortality (low certainty of evidence). In contrast, meta-regression analysis of 32 liver transplant studies detected no associations between the proportion of donors that received heparin and rates of early allograft dysfunction, primary nonfunction, hepatic artery thrombosis, biliary ischemia, graft failure, retransplantation, or patient survival (very low certainty of evidence). In conclusion, antemortem heparin practices vary substantially with an uncertain effect on transplant outcomes. Given the controversies surrounding antemortem heparin, clinical trials may be warranted.

Importance Although most critically ill patients receive invasive mechanical ventilation (IMV), few studies have characterized how IMV is discontinued in practice. Objective To describe practice variation in IMV discontinuation internationally, associations between initial discontinuation events and outcomes, and factors associated with the use of select discontinuation strategies and failed initial spontaneous breathing trials (SBTs). Design, Setting, and Participants Prospective, multinational, observational study of critically ill adults who received IMV for at least 24 hours from 142 intensive care units (ICUs) in 19 countries within 6 regions (27 in Canada, 23 in India, 22 in the UK, 26 in Europe, 21 in Australia/New Zealand, and 23 in the US). Exposures Receiving IMV. Main Outcomes and Measures Primary analyses characterized types of initial IMV discontinuation events (extubation, SBT, or tracheostomy) and associations with clinical outcomes (including duration of ventilation, ICU and hospital mortality, and ICU and hospital length of stay). Secondary analyses examined the associations between SBT outcome and SBT timing and clinical outcomes. Results Among 1868 patients (median [interquartile range] age, 61.8 [48.9-73.1] years; 1173 [62.8%] men) 424 (22.7%) underwent direct extubation, 930 (49.8%) had an initial SBT (761 [81.8%] successful), 150 (8.0%) underwent direct tracheostomy, and 364 (19.5%) died before a weaning attempt. Across regions, there was variation in the use of written directives to guide care, daily screening, SBT techniques, ventilator modes, and the roles played by clinicians involved in weaning. Compared with initial direct extubation, patients who had an initial SBT had higher ICU mortality (20 [4.7%] vs 96 [10.3%]; absolute difference, 5.6% [95% CI, 2.6%-8.6%]), longer duration of ventilation (median of 2.9 vs 4.1 days; absolute difference, 1.2 days [95% CI, 0.7-1.6]), and longer ICU stay (median of 6.7 vs 8.1 days; absolute difference, 1.4 days [95% CI, 0.8-2.4]). Patients whose initial SBT failed (vs passed) had higher ICU mortality (29 [17.2%] vs 67 [8.8%]; absolute difference, 8.4% [95% CI, 2.0%-14.7%]), longer duration of ventilation (median of 6.1 vs 3.5 days; absolute difference, 2.6 days [95% CI, 1.6-3.6]), and longer ICU stay (median of 10.6 vs 7.7 days; absolute difference, 2.8 days [95% CI, 1.1-5.2]). Compared with patients who underwent early initial SBTs, patients who underwent late initial SBTs (>2.3 days after intubation) had longer duration of ventilation (median of 2.1 vs 6.1 days; absolute difference, 4.0 days [95% CI, 3.7-4.5]), longer ICU stay (median of 5.9 vs 10.8 days; absolute difference, 4.9 days [95% CI, 4.0-6.3]), and longer hospital stay (median of 14.3 vs 22.8 days; absolute difference, 8.5 days [95% CI, 6.0-11.0]). Conclusions and Relevance In this observational study of invasive mechanical ventilation discontinuation in 142 ICUs in Canada, India, the UK, Europe, Australia/New Zealand, and the US from 2013 to 2016, weaning practices varied internationally. Trial Registration ClinicalTrials.gov Identifier:NCT03955874

Background: The effectiveness of evidence-based, goal-directed care to reduce losses of brain-dead potential organ donors through cardiac arrest is unclear. DONORS aimed to determine whether guiding clinical management with an evidence-based goal-directed checklist can reduce losses of potential organ donors to cardiac arrest. Methods: This open cluster randomized trial assigned adult intensive care units from hospitals across Brazil with 10 or more annual brain death reports to guide the management of potential donors with the checklist (intervention group) or to maintain usual care without the checklist (control group). Intervention group was instructed to apply a checklist with 13 clinical goals and 14 corresponding actions, every six hours, from study enrollment to organ retrieval. Consecutive potential donors between 14 and 90 years of age were included. Primary outcome was incidence of loss of brain-dead potential organ donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed checklist adherence as an effect modifier. Findings: Among 1771 potential donors screened, 1535 were included from 63 hospitals: 31 assigned to checklist guidance (743 potential donors) and 32 to usual care (792 potential donors). Seventy (9.4%) potential donors at intervention hospitals and 117 (14.8%) at control met the primary outcome (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.53 to 1.05; P=0.09). Median checklist adherence was 79% (interquartile range, 64% to 90%). Among those with adherence greater than 79%, primary outcome rate was lower than control group (5.3% vs. 14.8%; HR, 0.45; 9% CI, 0.26 to 0.75). Among those with low adherence, primary outcome rate was comparable to the control group. Interpretation: Overall use of the checklist in preventing donor loss due to cardiac arrest was inconclusive. However, predefined subgroup analysis suggests that high adherence to the checklist may reduce donor losses to cardiac arrest. Funding: Brazilian Ministry of Health through PROADI-SUS. Declaration of Interests: The authors have no conflicts of interest to disclose. Ethics Approval Statement: In accordance with ethical principles stated in the Resolution No. 466/2012 of the Brazilian National Health Council/Ministry of Health, the Research Ethics Committee of each participating hospital approved the conduct of this study with a waiver of consent for eligible potential donors. Trial Registration: ClinicalTrials.gov number, NCT03179020 (https://clinicaltrials.gov/ct2/show/NCT03179020)

IntroductionCardiac transplantation remains the best treatment for patients with end-stage heart disease that is refractory to medical or device therapies, however, a major challenge for heart transplantation is the persistent discrepancy between the number of patients on waiting lists and the number of available hearts. While other countries (eg, UK, Australia and Belgium) have explored and implemented alternative models of transplantation, such as cardiac donation after circulatory determination of death (DCDD) to alleviate transplantation wait times, ethical concerns have hindered implementation in some countries. This study aims to explore the attitudes and opinions of healthcare providers and the public about cardiac DCDD in order to identify and describe opportunities and challenges in ensuring that proposed cardiac DCDD procedures in Canada are consistent with Canadian values and ethical norms.Methods and analysisThis study will include two parts that will be conducted concurrently. Part 1 is a qualitative study consisting of semi-structured interviews with Canadian healthcare providers who routinely care for organ donors and/or transplant recipients to describe their perceptions about cardiac DCDD. Part 2 is a convergent parallel mixed-methods design consisting of a series of focus groups and follow-up surveys with members of the Canadian general public to describe their perceptions about cardiac DCDD.Ethics and disseminationThis study has been approved by the Research Ethics Board at Western University. The findings will be presented at regional and national conferences and reported in peer-reviewed publications.

Background The quality of clinical care of brain-dead potential organ donors may help reduce donor losses caused by irreversible or unreversed cardiac arrest and increase the number of organs donated. We sought to determine whether an evidence-based, goal-directed checklist for donor management in intensive care units (ICUs) can reduce donor losses to cardiac arrest. Methods/design The DONORS study is a multicentre, cluster-randomised controlled trial with a 1:1 allocation ratio designed to compare an intervention group (goal-directed checklist for brain-dead potential organ donor management) with a control group (standard ICU care). The primary outcome is loss of potential donors due to cardiac arrest. Secondary outcomes are the number of actual organ donors and the number of solid organs recovered per actual donor. Exploratory outcomes include the achievement of relevant clinical goals during the management of brain-dead potential organ donors. The present statistical analysis plan (SAP) describes all primary statistical procedures that will be used to evaluate the results and perform exploratory and sensitivity analyses of the trial. Discussion The SAP of the DONORS study aims to describe its analytic procedures, enhancing the transparency of the study. At the moment of SAP subsmission, 63 institutions have been randomised and were enrolling study participants. Thus, the analyses reported herein have been defined before the end of the study recruitment and database locking. Trial registration ClinicalTrials.gov, NCT03179020. Registered on 7 June 2017.

KEY POINTS Demand for organs continues to exceed their availability, both in Canada and around the world.[1][1] Optimizing the medical management of potential organ donors is an important strategy for enhancing organ supply. The explicit goals for management of deceased organ donors in the intensive

Purpose Existing clinical practice guidelines support the use of neuromuscular blocking agents (NMBA) in acute respiratory distress syndrome (ARDS); however, a recent large randomized clinical trial (RCT) has questioned this practice. Therefore, we updated a previous systematic review to determine the efficacy and safety of NMBAs in ARDS. Methods We searched MEDLINE, EMBASE (October 2012 to July 2019), the Cochrane (Central) database, and clinical trial registries (ClinicalTrials.gov, ISRCTN Register, and WHO ICTRP) for RCTs comparing the effects of NMBA as a continuous infusion versus placebo or no NMBA infusion (but allowing intermittent NMBA boluses) on patient-important outcomes for adults with ARDS. Two independent reviewers assessed the methodologic quality of the primary studies and abstracted data. Results Seven RCTs, including four new RCTs, met eligibility criteria for this review. These trials enrolled 1598 patients with moderate to severe ARDS at centers in the USA, France, and China. All trials assessed short-term continuous infusions of cisatracurium or vecuronium. The pooled estimate for mortality outcomes showed significant statistical heterogeneity, which was only explained by a subgroup analysis by depth of sedation in the control arm. A continuous NMBA infusion did not improve mortality when compared to a light sedation strategy with no NMBA infusion (relative risk [RR] 0.99; 95% CI 0.86–1.15; moderate certainty; P = 0.93). On the other hand, continuous NMBA infusion reduced mortality when compared to deep sedation with as needed NMBA boluses (RR 0.71; 95% CI 0.57–0.89; low certainty; P = 0.003). Continuous NMBA infusion reduced the rate of barotrauma (RR 0.55; 95% CI 0.35–0.85, moderate certainty; P = 0.008) across eligible trials, but the effect on ventilator-free days, duration of mechanical ventilation, and ICU-acquired weakness was uncertain. Conclusions Inconsistency in study methods and findings precluded the pooling of all trials for mortality. In a pre-planned sensitivity analysis, the impact of NMBA infusion on mortality depends on the strategy used in the control arm, showing reduced mortality when compared to deep sedation, but no effect on mortality when compared to lighter sedation. In both situations, a continuous NMBA infusion may reduce the risk of barotrauma, but the effects on other patient-important outcomes remain unclear. Future research, including an individual patient data meta-analysis, could help clarify some of the observed findings in this updated systematic review.

Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices.This prospective observational cohort study enrolled consecutive, newly consented organ donors from August 1 2015 to July 31 2018 at 27 academic and five community adult intensive care units in British Columbia, Alberta, Ontario, and Quebec. Research staff prospectively recorded donor management data. Provincial organ donation organizations verified the organs donated. We formally compared practices across provinces.Over a median collection period of eight months, 622 potential donors were classified at baseline as having neurologic determination of death (NDD donors; n = 403) or circulatory death (DCD donors; n = 219). Among NDD donors, 85.6% underwent apnea testing (rarely with carbon dioxide insufflation), 33.2% underwent ancillary testing, and subsequent therapeutic hypothermia (34-35°C) was rare. Neurologic determination of death donors were more hemodynamically unstable with most having received vasopressin and norepinephrine infusions, with a large majority having received high-dose corticosteroids and intravenous thyroxine. Among DCD donors, 61.6% received corticosteroids, and 8.9% received thyroxine. Most donors did not receive lung-protective ventilation strategies. Invasive procedures after donation consent included bronchoscopy (71.7%), cardiac catheterization (NDD donors only; 21.3%), and blood transfusions (19.3%). Physicians ordered intravenous antemortem heparin for 94.8% of DCD donors. The cohort donated 1,629 organs resulting in 1,532 transplants. Case selection, death determinations, and hormone, nutrition and heparin practices all varied across provinces.These study findings highlight areas for knowledge translation and further clinical research. Interprovincial discrepancies will likely pose unique challenges to national randomized trials.www.clinicaltrials.gov (NCT03114436); registered 10 April, 2017.RéSUMé: OBJECTIF: Les pratiques canadiennes de prise en charge des donneurs n’ont pas été rapportées. Notre objectif était d’informer les cliniciens et autres parties intéressées quant à l’éventail des pratiques actuelles. MéTHODE: Cette étude de cohorte observationnelle et prospective a recruté des donneurs d’organes consécutifs ayant récemment consenti au don entre le 1

IntroductionIn Canada, deceased organ donation provides over 80% of transplanted organs. At the time of death, families, friends or others assume responsibility as substitute decision-makers (SDMs) to consent to organ donation. Despite their central role in this process, little is known about what barriers, enablers and beliefs influence decision-making among SDMs. This study aims to explore the experiences and perspectives of SDMs involved in making decisions around the withdrawal of life-sustaining therapies, end-of-life care and deceased organ donation.Methods and analysisSDMs of 60 patients admitted to intensive care units will be enrolled for this study. Ten hospitals across five provinces in Canada in a prospective multicentre qualitative cohort study. We will conduct semistructured telephone interviews in English or French with SDMs between 6 and 8 weeks after the patient’s death. Our sampling frame will stratify SDMs into three groups: SDMs who were not approached for organ donation; SDMs who were approached and consented to donate and SDMs who were approached but did not consent to donate. We will use two complementary theoretical frameworks—the Common-Sense Self-Regulation Model and the Theoretical Domains Framework— to inform our interview guide. Interview data will be analysed using deductive directed content analysis and inductive thematic analysis.Ethics and disseminationThis study has been approved by the Centre Hospitalier de l’Université de Montréal Research Ethics Board. The findings from this study will help identify key factors affecting substitute decision-making in deceased organ donation, reasons for non-consent and barriers to achieve congruency between SDM and patient wishes. Ultimately, these data will contribute to the development and evaluation of tools and training for healthcare providers to support SDMs in making decisions about organ donation.Trial registration numberNCT03850847.

Improving the medical care of deceased organ donors to increase transplant rates and improve allograft function requires an understanding of the current epidemiology and clinical practices of deceased donation within intensive care units (ICUs). Herein, we report the results of our investigation into the feasibility of a multicentre prospective cohort study addressing the afformentioned issues. We conducted a 12-month prospective observational cohort study in six ICUs and one coronary care unit in Hamilton, Canada. We included consecutive children and adults following consent for deceased organ donation (including neurologic determination of death [NDD] or donation after circulatory death [DCD]). Intensive care unit research staff recorded donor management data from hospital records, extending from one day prior to the consent for organ donation up to the time of organ retrieval. The provincial Organ Donation Organization (ODO) supplemented these data and, additionally, provided data on corresponding organ recipients. We identified, evaluated, and measured three potential obstacles to the feasibility of a national cohort study: obtaining authorization to implement the study with a waiver of research consent, accessibility of transplant recipient data, and the time required to complete very detailed case report forms (CRFs), with valuable lessons learned for implementation in future projects. The local Research Ethics Board and the ODO Privacy Office both authorized the recording of donor and recipient study data with a waiver of research consent. Sixty-seven consecutive consented donors were included (31 NDD and 36 DCD donors); 50 of them provided 144 organs for transplantation to 141 recipients. We identified the age and sex of the recipients as well as the location and date of transplant for all organ recipients in Ontario; however, we obtained no recipient data for six organs transported outside of Ontario. Intensive care unit research staff estimated that future CRF completion will require five to seven hours per patient. The Hamilton-DONATE pilot study supports the feasibility of a larger cohort study to describe the epidemiology and clinical practices related to deceased donor care in Canada. wwwclinicaltrials.gov (NCT02902783). Registered 16 September 2016.

Objective To better understand how local policies influence organ donation rates. Research methodology/design We conducted a document analysis of our ICU organ donation policies, protocols and order sets. We used a systematic search of our institution’s policy library to identify documents related to organ donation. We used Mindnode software to create a publication timeline, basic statistics to describe document characteristics, and qualitative content analysis to extract document themes. Setting Documents were retrieved from Hamilton Health Sciences, an academic hospital system with a high volume of organ donation, from database inception to October 2015. Findings We retrieved 12 active organ donation documents, including six protocols, two policies, two order sets, and two unclassified documents, a majority (75%) after the introduction of donation after circulatory death in 2006. Four major themes emerged: organ donation process, quality of care, patient and family-centred care, and the role of the institution. These themes indicate areas where documented institutional standards may be beneficial. Conclusion Further research is necessary to determine the relationship of local policies, protocols, and order sets to actual organ donation practices, and to identify barriers and facilitators to improving donation rates.

International audience; PURPOSE: Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets.METHODS: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration's instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality.RESULTS: Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87-1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p=0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors >6h before randomization (OR 3.00, 95% CI 1.33-6.74).CONCLUSIONS: Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.