Bram Rochwerg

OBJECTIVES:To perform a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with sepsis.DATA SOURCES:We searched PubMed, Embase, and the Cochrane Library, up to January 10, 2023.STUDY SELECTION:We included randomized controlled trials (RCTs) comparing corticosteroids with placebo or standard care with sepsis.DATA EXTRACTION:The critical outcomes of interest included mortality, shock reversal, length of stay in the ICU, and adverse events.DATA ANALYSIS:We performed both a pairwise and dose-response meta-analysis to evaluate the effect of different corticosteroid doses on outcomes. We used Grading of Recommendations Assessment, Development and Evaluation to assess certainty in pooled estimates.DATA SYNTHESIS:We included 45 RCTs involving 9563 patients. Corticosteroids probably reduce short-term mortality (risk ratio [RR], 0 …

OBJECTIVES:To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients.

BackgroundAlbumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis.MethodsCochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations …

OBJECTIVES:We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). By pooling data across all trials that have examined corticosteroids in these three acute conditions, we aim to examine the side effects of corticosteroid use in critical illness.DATA SOURCES:We performed a comprehensive search of MEDLINE, Embase, Centers for Disease Control and Prevention library of COVID research, CINAHL, and Cochrane center for trials.STUDY SELECTION:We included randomized controlled trials (RCTs) that compared corticosteroids to no corticosteroids or placebo in patients with sepsis, ARDS, and CAP.DATA EXTRACTION:We summarized data addressing the most described side effects of corticosteroid use in critical care: gastrointestinal bleeding, hyperglycemia, hypernatremia …

OBJECTIVES:To perform a systematic review and meta-analysis to evaluate the association of various measures of glycemic variability, including time-domain and complexity-domain, with short-term mortality in patients with critical illness.DATA SOURCES:We searched Embase Classic+, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to November 3, 2023.STUDY SELECTION:We included English language studies that assessed metrics of glycemic variation or complexity and short-term mortality in patients admitted to the ICU.DATA EXTRACTION:Two authors performed independent data abstraction and risk-of-bias assessments. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios and mean difference. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations …

Guidelines on Use of Corticosteroids in Critically Ill Patients With Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia Focused Update 2024: Critical Care Medicine

OBJECTIVES:Given the uncertainty regarding the optimal approach for airway management for adult patients with out-of-hospital cardiac arrest (OHCA), we conducted a systematic review and meta-analysis to compare the use of supraglottic airways (SGAs) with tracheal intubation for initial airway management in OHCA.DATA SOURCES:We searched MEDLINE, PubMed, Embase, Cochrane Library, as well as unpublished sources, from inception to February 7, 2023.STUDY SELECTION:We included randomized controlled trials (RCTs) of adult OHCA patients randomized to SGA compared with tracheal intubation for initial prehospital airway management.DATA EXTRACTION:Reviewers screened abstracts, full texts, and extracted data independently and in duplicate. We pooled data using a random-effects model. We used the modified Cochrane risk of bias 2 tool and assessed certainty of evidence using the …

BackgroundExtracorporeal cardiopulmonary resuscitation (ECPR) may reduce mortality and improve neurological outcomes in patients with cardiac arrest. We updated our existing meta-analysis and trial sequential analysis to further evaluate ECPR compared to conventional CPR (CCPR).MethodsWe searched three international databases from 1 January 2000 through 1 November 2023, for randomised controlled trials or propensity score matched studies (PSMs) comparing ECPR to CCPR in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). We conducted an updated random-effects meta-analysis, with the primary outcome being in-hospital mortality. Secondary outcomes included short- and long-term favourable neurological outcome and survival (30 days–1 year). We also conducted a trial sequential analysis to evaluate the required information size in the meta-analysis to detect …

Objectives:COVID-19 pandemic surges strained hospitals globally. We performed a systematic review to examine measures of pandemic caseload surge and its impact on mortality of hospitalized patients.Data Sources:PubMed, Embase, and Web of Science.Study Selection:English-language studies published between December 1, 2019, and November 22, 2023, which reported the association between pandemic “surge”-related measures and mortality in hospitalized patients.Data Extraction:Three authors independently screened studies, extracted data, and assessed individual study risk of bias. We assessed measures of surge qualitatively across included studies. Given multidomain heterogeneity, we semiquantitatively aggregated surge–mortality associations.Data Synthesis:Of 17,831 citations, we included 39 studies, 17 of which specifically described surge effects in ICU settings. The majority of studies were …

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four “PICO questions” (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional …

Background The optimal dose of dexamethasone for severe/critical COVID‐19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID‐19 and hypoxia. Methods We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID‐19 and hypoxia. The primary outcome was mortality at 1 month. Secondary outcomes were mortality closest to 90 days; days alive without life support; and the occurrence of serious adverse events/reactions (SAEs/SARs) closest to 1 month. We assessed the risk of bias using the Cochrane RoB2 tool, risk of random errors using trial sequential analysis, and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results We included eight trials (2478 participants), of …

Background & ObjectivesBlunt cerebrovascular injury (BCVI) includes carotid and/or vertebral artery injury following trauma, and conveys an increased stroke risk. We conducted a systematic review and meta-analysis to provide a comprehensive summary of prognostic factors associated with risk of stroke following BCVI.MethodsWe searched the EMBASE and MEDLINE databases from January 1946 to June 2023. We identified studies reporting associations between patient or injury factors and risk of stroke following BCVI. We performed meta-analyses of odds ratios (ORs) using the random effects method and assessed individual study risk of bias using the QUIPS tool. We separately pooled adjusted and unadjusted analyses, highlighting the estimate with the higher certainty.ResultsWe included 26 cohort studies, involving 20,458 patients with blunt trauma. The overall incidence of stroke following BCVI was 7.7 …

BackgroundThe Canadian Critical Care Society (CCCS) recognizes a shared history and a shared present between First Nations, Métis, and Inuit/Inuk Peoples and non-Indigenous Peoples of Canada. Indigenous populations experience inequities in health care access and outcomes as a direct result of colonialism and Canadian governmental actions such as residential schools and the Sixties Scoop. Harms perpetrated by the health system against Indigenous Peoples in Canada have included, but are not limited to, nutritional experimentation, forced sterilization procedures, and inferior treatment in the Indian hospital system. Today, Indigenous Peoples have reduced lifespans compared with the general Canadian population (ten fewer years of life on average), 1 suffer increased prevalence of chronic and infectious diseases (including tuberculosis, acquired immunodeficiency syndrome, diabetes mellitus …

PurposeThe ordering of routine blood test panels in advance is common in intensive care units (ICUs), with limited consideration of the pretest probability of finding abnormalities. This practice contributes to anemia, false positive results, and health care costs. We sought to understand practices and attitudes of Canadian adult intensivists regarding ordering of blood tests in critically ill patients.MethodsWe conducted a nationwide Canadian cross-sectional survey consisting of 15 questions assessing three domains (global perceptions, test ordering, daily practice), plus 11 demographic questions. The target sample was one intensivist per adult ICU in Canada. We summarized responses using descriptive statistics and present data as mean with standard deviation (SD) or count with percentage as appropriate.ResultsOver seven months, 80/131 (61%) physicians responded from 77 ICUs, 50% of which were from …

IntroductionThe objective of this study was to create a definition of patient-important upper gastrointestinal bleeding during critical illness as an outcome for a randomized trial.DesignThis was a sequential mixed-methods qualitative-dominant multi-center study with an instrument-building aim. In semi-structured individual interviews or focus groups we elicited views from survivors of critical illness and family members of patients in the intensive care unit (ICU) regarding which features indicate important gastrointestinal bleeding. Quantitative demographic characteristics were collected. We analyzed qualitative data using inductive content analysis to develop a definition for patient-important upper gastrointestinal bleeding.SettingCanada and the United States.Participants51 ICU survivors and family members of ICU patients.ResultsParticipants considered gastrointestinal bleeding to be important if it resulted in death …

PurposeWe sought to understand the beliefs and practices of Canadian intensivists regarding their use of ketamine as a sedative in critically ill patients and to gauge their interest in a randomized controlled trial (RCT) examining its use in the intensive care unit (ICU).MethodsWe designed and validated an electronic self-administered survey examining the use of ketamine as a sedative infusion for ICU patients. We surveyed 400 physician members of the Canadian Critical Care Society (CCCS) via email between February and April 2022 and sent three reminders at two-week intervals. The survey was redistributed in January 2023 to improve the response rate.ResultsWe received 87/400 (22%) completed questionnaires. Most respondents reported they rarely use ketamine as a continuous infusion for sedation or analgesia in the ICU (52/87, 58%). Physicians reported the following conditions would make them more …

Background Systemic treatments for atopic dermatitis (AD) are evaluated primarily in placebo-controlled trials with binary efficacy outcomes. In a living systematic review and network meta-analysis (NMA), we previously analysed continuous efficacy measures. Objectives To compare binary efficacy outcomes of systemic treatments for AD. Methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American and Caribbean Health Science Information (LILACS) database, Global Resource for Eczema Trials (GREAT) database and trial registries up to 1 March 2023. We included randomized trials examining ≥ 8 weeks of treatment with systemic immunomodulatory medications for moderate-to-severe AD. We screened titles, abstracts and full texts and abstracted data independently, in duplicate. Outcomes …

Cardiogenic shock (CS) is a syndrome of progressive depression of myocardial function with systemic hypoperfusion. It occurs due to various aetiologies such as acute myocardial infarction, myocarditis, acute decompensated heart failure and postcardiotomy. Cardiogenic shock carries poor prognosis, and medical therapy alone is not effective. Mechanical circulatory support is required to unload the ventricles, decrease the myocardial demand, prevent further injury, improve the coronary perfusion, stabilise the haemodynamics and maintain the end-organ perfusion before definitive interventions such as coronary reperfusion can take place. Currently, there are several methods of mechanical circulatory support. These include extracorporeal life support, paracorporeal or extracorporeal ventricular-assist devices, percutaneous ventricular assist devices, intra-aortic balloon counterpulsation and total artificial heart. In …

For critically ill patients who are recovering from critical illness requiring invasive ventilation, liberation from mechanical ventilation refers to the processes of weaning and a Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada; b Department of Medicine and Division of Critical Care, Unity Health Toronto, St. Michaels Hospital, Toronto, Ontario, Canada; c Li Ka Shing Knowledge Institute, Unity Health Toronto, St. Michael’s Hospital, Toronto, Ontario, Canada; d Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; e Department of Medicine, Hamilton Health Sciences, Juravinski Hospital, Hamilton, Ontario, Canada; f Department of Critical Care, Hamilton Health Sciences, Juravinski Hospital, Hamilton, Ontario, Canada; g Department of Critical Care, Ottawa Hospital, Ottawa, Ontario, Canada; h Division of …

PurposePatients with hematologic malignancy (HM) commonly develop critical illness. Their long-term survival and functional outcomes have not been well described.MethodsWe conducted a prospective, observational study of HM patients admitted to seven Canadian intensive care units (ICUs) (2018–2020). We followed survivors at 7 days, 6 months and 12 months following ICU discharge. The primary outcome was 12-month survival. We evaluated functional outcomes at 6 and 12 months using the functional independent measure (FIM) and short form (SF)-36 as well as variables associated with 12-month survival.ResultsWe enrolled 414 patients including 35% women. The median age was 61 (interquartile range, IQR: 52–69), median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR: 6–12), and 22% had moderate–severe frailty (clinical frailty scale [CFS] ≥ 6). 51% had acute leukemia, 38 …

Intensive care unit (ICU) demographics are shifting. Recent data from the United States has demonstrated that patients aged 85 and older account for 20% of all ICU admissions, 1 and Canada has seen a similar aging of its ICU population compared to 15 years ago. 2 These trends coincide with medical advances that have allowed for a higher quality of life into older age and reduced mortality from critical illness. With the emergence of novel critical care therapeutics, the question arises whether older adults respond similarly to such treatments given differences in homeostasis and underlying pathophysiology. However, it is not clear whether patients with increased age, frailty, or multimorbidity respond differently to ICU interventions, as very few trials have specifically examined these populations.

Glucocorticoids (GCs) are agonist compounds that bind to the GC receptor (GRα), producing a rapid pharmacological response. Clinical efficacy depends on the magnitude and duration of exposure to GRα; the effect is systemic, including lung tissue and circulating cells. The extraordinary research advancements of the last decade have radically reshaped our understanding of the GRα's multifaceted actions, the effector of GC actions.In this chapter, we first examine the pathogenetic rationale for GC treatment by (i) placing ARDS in the context of the general adaptation to critical illness and (ii) as an acute multifactorial interstitial lung disease (not a syndrome). We examine the progression of each integrated stratum of this disease—pathogenesis—morphology—physiology—in patients with adaptive versus maladaptive responses. During the three phases of disease progression, the GC-GRα operates as the central …

BackgroundWe aimed to evaluate the comparative effectiveness and safety of various i.v. pharmacologic agents used for procedural sedation and analgesia (PSA) in the emergency department (ED) and ICU. We performed a systematic review and network meta-analysis to enable direct and indirect comparisons between available medications.MethodsWe searched Medline, EMBASE, Cochrane, and PubMed from inception to 2 March 2023 for RCTs comparing two or more procedural sedation and analgesia medications in all patients (adults and children >30 days of age) requiring emergent procedures in the ED or ICU. We focused on the outcomes of sedation recovery time, patient satisfaction, and adverse events (AEs). We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate …

This is a protocol for a scoping review. The aim of this scoping review is to understand the use, parameters, safety and outcomes of physical rehabilitation for individuals with sepsis. The incidence of sepsis is growing; approximately 75,000 individuals are diagnosed with sepsis each year in Canada (1). Sepsis is a life-threatening illness caused by the body’s overreaction to infection (2, 3). While short-term mortality related to this condition is improving (4-6), survivors of sepsis suffer from a number of health consequences which may last for years post hospital discharge and impact health and quality of life (4, 7). Poor functional status is associated with an increased risk of recurrent critical illness (4). Rehabilitation includes interventions designed to optimize functioning and reduce disability in individuals with health conditions in interaction with their environment (8). Rehabilitation improves a variety of outcomes for those living with a broad range of health conditions (9-16). There is little research available describing the use and benefit of rehabilitation for individuals with sepsis. A systematic review and meta-analysis published in 2018 examining rehabilitation for patients with sepsis included just two studies (17). While this review did suggest improvements in quality of life with rehabilitation compared to usual care, the certainty of this evidence was deemed ‘very low’(17). Further, this study did not provide details describing the type or parameters of the interventions provided, the safety or feasibility of rehabilitation for individuals with sepsis, or provide stakeholder perspectives on the use of rehabilitation in this population. Research Objective …

Society of Critical Care Medicine Guidelines on Recognizing and Responding to Clinical Deterioration Outside the ICU: Critical Care Medicine

We read with great interest the article by Parhar et al. describing triage protocols in Alberta for extracorporeal life support (ECLS) resources, but are concerned that it raises questions by not explicitly mentioning which pre-existing medical conditions would justify exclusion from resources (1).While we acknowledge that it is reasonable in a pandemic situation to limit access to some intensive resources like ECLS for patients with conditions that limit their chance of survival, these decisions need to be based on predicted patient outcome as judged by the best available evidence, using the most objective criteria possible. They must also be blind to societal factors such as race, religion, or ability to pay. However, in the Canadian context, there is little reason to suspect that those societal factors would be considered by clinicians or systems.

Background: Home non-invasive positive pressure ventilation (NPPV) may improve chronic hypercarbia in COPD and patient important outcomes. The efficacy of home high flow nasal cannula (HFNC) as an alternative is unclear.Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL, SCOPUS, and Clinicaltrials.gov for randomized trials of patients from inception to March 31st and updated the search on July 14, 2023. We performed a frequentist network meta-analysis and assessed the certainty of the evidence using the GRADE approach. We analyzed randomized trials (RCTs) comparing NPPV, HFNC, or standard care in adult COPD patients with chronic hypercapnic respiratory failure. Outcomes included mortality, COPD exacerbations, hospitalizations, and quality of life (SGRQ).Results: We analyzed twenty-four RCTs (1850 patients). We found that NPPV may reduce death risk compared to standard …

Objectives:To develop evidence-based recommendations for use of corticosteroids in hospitalized adults and children with sepsis, ARDS, and CAP.

IntroductionIn-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults.Methods and analysisWe report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion …

IntroductionVenous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. Venous congestion can be measured by Doppler ultrasound at the bedside through interrogation of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV) and intrarenal veins (IRV). The objective of this study is to quantify the association between Doppler identified venous congestion and the need for renal replacement therapy (RRT) or death for patients with septic shock.Methods and analysisThis study is a prespecified substudy of the ANDROMEDA-SHOCK 2 (AS-2) randomised control trial (RCT) assessing haemodynamic resuscitation in septic shock and will enrol at least 350 patients across multiple sites. We will include adult patients within 4 hours of …

Methods:The electronic databases (PubMed, Cochrane Library, Google Scholar and Web of Sciences) were searched for published randomised controlled trials (RCTs) till 5 April 2023 comparing PENG block vs. FICB following hip arthroplasty. The primary outcome was pain scores [numerical rating scale (NRS) or visual analogue scale (VAS)] between 0 and 10 at rest and during movement at 24 h. Secondary outcomes included pain scores at rest and during movement within 30 min, at 6 h and 12 h, time to first rescue analgesia and cumulative postoperative opioid use in 24 h. We assessed the risk of bias using the Cochrane Collaboration Risk-of-Bias 2 tool. Using Grading of Recommendations Assessment, Development, and Evaluation (GRADE), the certainty of the evidence was assessed. Subgroup analysis was performed to explore the source of heterogeneity.Results:We included 12 RCTs examining 644 …

We aimed to assess the impact of allocation concealment and blinding on the results of coronavirus disease 2019 (COVID-19) trials, using the World Health Organization COVID-19 database (to February 2022). We identified 488 randomized trials comparing drug therapeutics with placebo or standard care in patients with COVID-19. We performed random-effects meta-regressions comparing the results of trials with and without allocation concealment and blinding of health-care providers and patients. We found that, compared with trials with allocation concealment, trials without allocation concealment may estimate treatments to be more beneficial for mortality, mechanical ventilation, hospital admission, duration of hospitalization, and duration of mechanical ventilation, but results were imprecise. We did not find compelling evidence that, compared with trials with blinding, trials without blinding produce …

IntroductionInternational guidelines provide heterogenous guidance on use of corticosteroids for community-acquired pneumonia (CAP).MethodsWe performed a systematic review of randomized controlled trials examining corticosteroids in hospitalized adult patients with suspected or probable CAP. We performed a pairwise and dose-response meta-analysis using the restricted maximum likelihood (REML) heterogeneity estimator. We assessed the certainty of the evidence using GRADE methodology and the credibility of subgroups using the ICEMAN tool.ResultsWe identified 18 eligible studies that included 4661 patients. Corticosteroids probably reduce mortality in more severe CAP (RR 0.62 [95% CI 0.45 to 0.85]; moderate certainty) with possibly no effect in less severe CAP (RR 1.08 [95% CI 0.83 to 1.42]; low certainty). We found a non-linear dose-response relationship between corticosteroids and mortality …

Introduction Clinically important upper gastrointestinal bleeding is conventionally defined as bleeding accompanied by haemodynamic changes, requiring red blood cell transfusions or other invasive interventions. However, it is unclear if this clinical definition reflects patient values and preferences. This protocol describes a study to elicit views from patients and families regarding features, tests, and treatments for upper gastrointestinal bleeding that are important to them. Methods and analysis This is a sequential mixedmethods qualitative-dominant multi-centre study with an instrument-building aim. We developed orientation tools and educational materials in partnership with patients and family members, including a slide deck and executive summary. We will invite intensive care unit (ICU) survivors and family members of former ICU patients to participate. Following a virtual interactive presentation, participants will …

PurposeWhile opioids are part of usual care for analgesia in the intensive care unit (ICU), there are concerns regarding excess use. This is a systematic review of non-steroidal anti-inflammatories (NSAIDs) use in critically ill adult patients.MethodsWe conducted a systematic search of MEDLINE, EMBASE, CINAHL, and Cochrane Library. We included randomized control trials (RCTs) comparing NSAIDs alone or as an adjunct to opioids for analgesia. The primary outcome was opioid utilization. We reported mean difference for continuous outcomes and relative risk for dichotomous outcomes with 95% confidence intervals (CIs). We evaluated study risk of bias using the Cochrane risk of bias tool and evidence certainty using GRADE.ResultsWe included 15 RCTs (n=1621 patients). Adjunctive NSAID therapy to opioids reduced 24-hour oral morphine equivalent consumption by 21.4mg (95% CI: 11.8-31.0mg reduction, high certainty) and probably reduced pain scores (measured by visual analogue scale) by -6.1mm (95% CI: -12.2 to +0.1, moderate certainty). Adjunctive NSAIDs probably had no impact on duration of mechanical ventilation (-1.6 hours, 95% CI: -0.4 to -2.7 hours, moderate certainty) and may have no impact on ICU length of stay (-2.1 hours, 95% CI: -6.1 to +2.0 hours, low certainty). Variability in reporting of adverse outcomes (e.g. gastrointestinal bleeding, acute kidney injury) precluded their meta-analysis.ConclusionIn critically ill adult patients, NSAIDs reduced opioid use, probably reduced pain scores, but were uncertain for duration of mechanical ventilation or ICU length of stay. Further research is required to characterize the …

OBJECTIVES:In children with diabetic ketoacidosis (DKA), insulin infusions are the mainstay of treatment; however, optimal dosing remains unclear. Our objective was to compare the efficacy and safety of different insulin infusion doses for the treatment of pediatric DKA.DATA SOURCES:We searched MEDLINE, EMBASE, PubMed, and Cochrane from inception to April 1, 2022.STUDY SELECTION:We included randomized controlled trials (RCTs) of children with DKA comparing intravenous insulin infusion administered at 0.05 units/kg/hr (low dose) versus 0.1 units/kg/hr (standard dose).DATA EXTRACTION:We extracted data independently and in duplicate and pooled using a random effects model. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach.DATA SYNTHESIS:We included four RCTs (n= 190 …

Rationale: Corticosteroids are standard of care for patients with severe coronavirus disease (COVID-19). However, the optimal dose is uncertain. Objectives: To compare higher doses of corticosteroids with lower doses in patients with COVID-19. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, MedRxiv, and Web of Science from inception to August 1, 2022, for trials that randomized patients with severe-to-critical COVID-19 to corticosteroids, standard care, or placebo. Reviewers, working in duplicate, screened references, extracted data, and assessed risk of bias using a modified version of the Cochrane risk of bias 2.0 tool. We performed a dose–response meta-analysis and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess the certainty of evidence. We present our results both in relative risk and absolute risk …

IMPORTANCEOveractivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.ObjectiveTo determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.DESIGN, SETTING, AND PARTICIPANTSIn an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).INTERVENTIONSPatients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.MAIN …

AimsThe identification of venous thromboembolism (VTE) using administrative databases is frequently required for reporting and research. The accuracy of International Classification of Diseases 10th revision (ICD-10) codes for VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), remains unclear. We examined the accuracy of ICD-10 codes for identifying VTE in adult and pediatric inpatients and outpatients.MethodsFor this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Web of Science, CENTRAL, Epistemonikos and McMaster Superfilters from inception to July 25, 2023 for studies evaluating the sensitivity, specificity, positive predictive value (PPV), and/or negative predictive value (NPV) of ICD-10 codes for VTE in any anatomical location. We assessed risk of bias using QUADAS and certainty of evidence using GRADE. We calculated pooled sensitivity and …

IntroductionClinically important upper gastrointestinal bleeding is conventionally defined as bleeding accompanied by haemodynamic changes, requiring red blood cell transfusions or other invasive interventions. However, it is unclear if this clinical definition reflects patient values and preferences. This protocol describes a study to elicit views from patients and families regarding features, tests, and treatments for upper gastrointestinal bleeding that are important to them.Methods and analysisThis is a sequential mixed-methods qualitative-dominant multi-centre study with an instrument-building aim. We developed orientation tools and educational materials in partnership with patients and family members, including a slide deck and executive summary. We will invite intensive care unit (ICU) survivors and family members of former ICU patients to participate. Following a virtual interactive presentation, participants will …

PurposeThe under-representation of Black people within critical care research limits the generalizability of randomized controlled trials (RCTs). This meta-epidemiologic study investigated the proportionate representation of Black people enrolled at USA and Canadian study sites from high impact critical care RCTs.SourceWe searched for critical care RCTs published in general medicine and intensive care unit (ICU) journals between 1 January 2016 and 31 December 2020. We included RCTs that enrolled critically ill adults at USA or Canadian sites and provided race-based demographic data by study site. We compared study-based racial demographics with site-level city-based demographics and pooled representation of Black people across studies, cities, and centres using a random effects model. We used meta-regression to explore the impact of the following variables on Black representation in critical care …

Post–intensive care syndrome (PICS) encompasses new or worsening cognitive or physical impairments following admission to an ICU that persist beyond hospitalization for acute care. 1 Anticipated increases in PICS prevalence owing to the aging population in Canada have important implications for ICU patients, their families, and the Canadian health care system. Greater prevalence of PICS also has implications for family physicians, as they manage most posthospital care for individuals who survive stays in ICUs. This paper summarizes key points from an article published in the Canadian Geriatrics Society Journal of CME. 2

BackgroundExtracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established.MethodsWe conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach.Findings: We …

BackgroundEpinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed.Research QuestionWhat are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA?Study Design and MethodsIn this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95% CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation …

Background.Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia–reperfusion injury to improve transplant outcomes.Methods.We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively.Results.Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses …

Hemorrhagic shock remains the most common cause of preventable mortality in trauma1. In order to guide clinical practice, RCTs provide high-quality evidence to inform clinical decision making2. The clinical relevance and inferences made by RCTs are dependent on assumptions made during sample size calculation3. Many sample size calculations are poorly conducted and reported or based on unrealistic assumptions regarding baseline risk and anticipated risk reduction3. Prognostic enrichment strategies can inform more precise estimates and decrease heterogeneity of baseline risk4. Using the minimally important difference (MID) ensures RCTs are targeting a treatment effect that is both plausible but also one that would be important to patients, rather than using an arbitrary effect estimate based on assumptions5.

Crystalloids are commonly used intraoperative fluids due to their low cost, ease of use, and effectiveness in fluid resuscitation. Balanced crystalloids, such as Ringer’s lactate or plasmalyte, are crystalloids which have an electrolyte composition that closely resembles blood plasma. Whereas 0.9% saline (saline), an unbalanced crystalloid, contains only sodium and chloride. The evidence regarding optimal crystalloid use in the intraoperative period remains unclear. 1

Multiple myeloma (MM) is an incurable blood cancer that primarily affects older adults. Several frailty tools have been developed to address the heterogeneity of aging in this population. Uptake of these measures has been variable, leading to a gap in knowledge regarding the proportion of enrolled trial participants considered frail and uncertainty in the treatment-related effects and outcomes among this high-risk population. We performed a systematic review of therapeutic interventional MM clinical trials reporting on frailty. We included 43 clinical trials (24 randomized controlled trials and 19 non-randomized trials) which met eligibility criteria. Frailty was increasingly incorporated in studies in more recent years with 41.9% of included studies being reported in the last two years. Commonly used frailty tools included the International Myeloma Working Group (IMWG) frailty index (41.8%), and the simplified frailty score …

OBJECTIVES:The optimal timing of coronary angiography remains unclear following out-of-hospital cardiac arrest (OHCA) without ST elevation on electrocardiogram. The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of early angiography versus delayed angiography following OHCA without ST elevation.DATA SOURCES:The databases MEDLINE, PubMed EMBASE, and CINHAL, as well as unpublished sources from inception to March 9, 2022.STUDY SELECTION:A systematic search was performed for randomized controlled trials of adult patients after OHCA without ST elevation who were randomized to early as compared to delayed angiography.DATA EXTRACTION:Reviewers screened and abstracted data independently and in duplicate. The certainty of evidence was assessed for each outcome using the Grading Recommendations Assessment, Development …

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists’ Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.

OBJECTIVES:Children with chronic critical illness (CCI) are hypothesized to be a high-risk patient population with persistent multiple organ dysfunction and functional morbidities resulting in recurrent or prolonged critical care; however, it is unclear how CCI should be defined. The aim of this scoping review was to evaluate the existing literature for case definitions of pediatric CCI and case definitions of prolonged PICU admission and to explore the methodologies used to derive these definitions.DATA SOURCES:Four electronic databases (Ovid Medline, Embase, CINAHL, and Web of Science) from inception to March 3, 2021.STUDY SELECTION:We included studies that provided a specific case definition for CCI or prolonged PICU admission. Crowdsourcing was used to screen citations independently and in duplicate. A machine-learning algorithm was developed and validated using 6,284 citations assessed in …

INTRODUCTION Little is known regarding the impact of varying blood flow rates and drainage cannula size on the outcome of patients with ARDS receiving ECMO. Higher blood flow rates and larger cannula size have potential physiological benefits (better oxygenation and lung rest), but may be associated with increased risks (bleeding, thrombosis, and positive fluid balance). Using data from the ELSO registry we explored the hypothesis that optimal ratio between blood flow rate and drainage cannula size impacts clinical outcomes. METHODS We enrolled all adult patients with ARDS receiving veno-venous ECMO entered in the ELSO registry between 2012 and 2021 (single-site cannulation and patients with COVID-19 were excluded). We analyzed data from the first ECMO run and collected information on ECMO set-up, demographics, clinical and physiological data, complications and in-hospital outcomes. We …

ImportanceBlood collection for laboratory testing in intensive care unit (ICU) patients is a modifiable contributor to anemia and red blood cell (RBC) transfusion. Most blood withdrawn is not required for analysis and is discarded.ObjectiveTo determine whether transitioning from standard-volume to small-volume vacuum tubes for blood collection in ICUs reduces RBC transfusion without compromising laboratory testing procedures.Design, Setting, and ParticipantsStepped-wedge cluster randomized trial in 25 adult medical-surgical ICUs in Canada (February 5, 2019 to January 21, 2021).InterventionsICUs were randomized to transition from standard-volume (n = 10 940) to small-volume tubes (n = 10 261) for laboratory testing.Main Outcomes and MeasuresThe primary outcome was RBC transfusion (units per patient per ICU stay). Secondary outcomes were patients receiving at least 1 RBC transfusion …

PurposeSociodemographic risks contributing to health inequities are often inadequately captured and reported in critical care studies. To address the lack of standardized terms and definitions, we sought to develop a practical and convenient resource of questions and response options for collecting sociodemographic variables for critical care research.SourceTo identify domains and variables that impact health equity, we searched: 1) PubMed for critical care randomized trials (2010 to 2021); 2) high-impact critical care and general medicine journals for special issues relating to equity; and 3) governmental and nongovernmental resources.Principal findingsWe identified 23 domains associated with health equity, including pronouns, age, sex, gender identity, sexual orientation, race and ethnicity, visible minorities, language, household income, marital/relationship status, education, disabilities, immigrant and …

Le syndrome post-soins intensifs (SPSI) comprend une déficience cognitive ou physique, nouvelle ou aggravée, à la suite d’une admission à l’USI, qui persiste au-delà de l’hospitalisation pour soins aigus1. La hausse anticipée de la prévalence du SPSI en raison du vieillissement de la population au Canada a des répercussions importantes sur les patients à l’USI, leur famille et le système de santé canadien. La prévalence plus élevée du SPSI a aussi des conséquences pour les médecins de famille, car ils prennent en charge la majorité des soins post-hospitalisation des personnes qui survivent à leur séjour à l’USI. Cet article résume les faits saillants de travaux publiés dans le Canadian Geriatrics

BackgroundThis update summarizes key changes made to the protocol for the Frequency of Screening and Spontaneous Breathing Trial (SBT) Technique Trial—North American Weaning Collaborative (FAST-NAWC) trial since the publication of the original protocol. This multicenter, factorial design randomized controlled trial with concealed allocation, will compare the effect of both screening frequency (once vs. at least twice daily) to identify candidates to undergo a SBT and SBT technique [pressure support + positive end-expiratory pressure vs. T-piece] on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American intensive care units.Methods/designProtocols for the pilot, factorial design trial and the full trial were previously published in J Clin Trials (https://doi.org/10.4172/2167-0870.1000284) and Trials (https://doi: 10.1186 …

BackgroundThe evidence regarding optimal crystalloid use in the perioperative period remains unclear. As the primary aim of this study, we sought to summarise the data from RCTs examining whether use of balanced crystalloids compared with 0.9% saline (saline) leads to differences in patient-important outcomes.MethodsWe searched Ovid MEDLINE, Embase, the Cochrane library, and Clinicaltrials.gov, from inception until December 15, 2022, and included RCTs that intraoperatively randomised adult participants to receive either balanced fluids or saline. We pooled data using a random-effects model and present risk ratios (RRs) or mean differences (MDs), along with 95% confidence intervals (CIs). We assessed individual study risk of bias using the modified Cochrane tool, and certainty of evidence using GRADE.ResultsOf 5959 citations, we included 38 RCTs (n=3776 patients). Pooled analysis showed that …

Conducting clinical research during a 2-year critical care fellowship is a challenging endeavor. Fellows are often met with multiple barriers when considering clinical research projects during fellowship, including time, mentorship, resources, and clinical support. This paper presents the perspective and experiences of a group of critical care fellows who conducted the DRIVE-SAFE (Driving Pressure in Assisted Ventilation as a Predictor for Successful Liberation from Invasive Mechanical Ventilation) feasibility study, which aimed to determine measurable physiological variables that could be associated with lung injury and affect duration of mechanical ventilation. This paper provides a guide for trainees on how to conduct prospective clinical research at the bedside. We describe three key steps, including formulating a research question, developing appropriate methodology, and establishing outcomes. We also …

• There is lack of consensus about the optimal definition of pneumonia acquired in the intensive care unit (ICU)[1].

ImportanceThe longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.ObjectiveTo determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.Design, Setting, and ParticipantsPrespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.InterventionsPatients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).Main Outcomes …

BackgroundStandard dose (≤ 1 g) tranexamic acid (TXA) has established mortality benefit in trauma patients. The role of high dose IV TXA (≥2 g or ≥30 mg/kg as a single bolus) has been evaluated in the surgical setting, however, it has not been studied in trauma. We reviewed the available evidence of high dose IV TXA in any setting with the goal of informing its use in the adult trauma population.MethodsWe searched MEDLINE, EMBASE and unpublished sources from inception until July 27, 2022 for studies that compared standard dose with high dose IV TXA in adults (≥ 16 years of age) with hemorrhage. Screening and data abstraction was done independently and in duplicate. We pooled trial data using a random effects model and considered randomized controlled trials (RCTs) and observational cohort studies separately. We assessed the individual study risk of bias using the Cochrane Risk of Bias for …

OBJECTIVES:Balancing the risks of hypotension and vasopressor-associated adverse effects is a daily challenge in ICUs. We conducted a systematic review with meta-analysis to examine the effect of lower versus higher exposure to vasopressor therapy on mortality among adult ICU patients with vasodilatory hypotension.DATA SOURCES:We searched Ovid Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies published from inception to October 15, 2021.STUDY SELECTION:We included randomized controlled trials of lower versus higher exposure to vasopressor therapy in adult ICU patients with vasodilatory hypotension without language or publication status limits.DATA EXTRACTION:The primary outcome was 90-day all-cause mortality, with seven prespecified subgroups. Secondary outcomes included shorter-and longer-term mortality, use of life-sustaining therapies …

ObjectivesAdaptive platforms allow for the evaluation of multiple interventions at a lower cost and have been growing in popularity, especially during the COVID-19 pandemic. The objective of this review is to summarize published platform trials, examine specific methodological design features among these studies, and hopefully aid readers in the evaluation and interpretation of platform trial results.MethodsWe performed a systematic review of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov from January 2015 to January 2022 for protocols or results of platform trials. Pairs of reviewers, working independently and in duplicate, collected data on trial characteristics of trial registrations, protocols, and publications of platform trials. We reported our results using total numbers and percentages, as well as medians with interquartile range (IQR) when appropriate …

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists’ Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation …

BACKGROUNDTrauma hemorrhage remains the most common cause of preventable mortality in trauma. To guide clinical practice, RCTs provide high-quality evidence to inform clinical decision making. The clinical relevance and inferences made by RCTs are dependent on assumptions made during sample size calculation.METHODSTo describe the quality of methodology for sample size determination, we conducted a systemic review RCTs evaluating interventions that aim to improve survival in adults with trauma-related hemorrhage. Estimated and actual outcome data are compared, including components of sample size determination.RESULTSA total of 13 RCTs were included. We noted a high rate of negative trial results (11 of 13 studies). Most studies were multi-center and conducted in North America, evaluating patients with blunt and penetrating injuries. The criteria for hemorrhagic shock varied across …

OBJECTIVES:While opioids are part of usual care for analgesia in the ICU, there are concerns regarding excess use. This is a systematic review of nonsteroidal anti-inflammatory drugs (NSAIDs) use in postoperative critical care adult patients.DATA SOURCES:We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, trial registries, Google Scholar, and relevant systematic reviews through March 2023.STUDY SELECTION:Titles, abstracts, and full texts were reviewed independently and induplicate by two investigators to identify eligible studies. We included randomized control trials (RCTs) that compared NSAIDs alone or as an adjunct to opioids for systemic analgesia. The primary outcome was opioid utilization.DATA EXTRACTION:In duplicate, investigators independently extracted study …

ImportanceThe efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain.ObjectiveTo determine whether vitamin C improves outcomes for patients with COVID-19.Design, Setting, and ParticipantsTwo prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents.InterventionsPatients were randomized to receive vitamin C administered intravenously or control (placebo or no vitamin C) every 6 hours for 96 hours (maximum of 16 doses).Main Outcomes and MeasuresThe primary outcome was a composite of organ support–free days defined as days alive and free of respiratory and cardiovascular organ support in the intensive care unit up to day 21 and survival to hospital discharge. Values ranged from –1 organ support …

Although IV fluid resuscitation is a fundamental element of sepsis management, debate regarding the ideal volume, type, timing, and physiologic targets is ongoing. A number of large randomized trials have been published addressing this important topic, and in this issue of CHEST, Sivapalan et al 1 have updated a previous systematic review and metaanalysis comparing lower with higher volumes of IV fluid for adult patients with sepsis.IV fluid resuscitation aims to increase venous return and cardiac output, thereby restoring blood flow to underperfused organs. Since the 2010s, a multitude of observational studies have described a consistent association between administration of greater volumes of IV fluid, leading to positive fluid balance, and adverse patient outcomes in sepsis and other critical illness. This has stimulated an interest in alternative, more conservative, fluid strategies. 2 The landmark Fluid …

BackgroundAbnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and iron deficiency anemia (IDA). Depletion of iron stores has negative implications on physical, social, and emotional health, as well as quality of life. Iron supplements are safe, effective, and readily available, while red blood cell (RBC) transfusions have inherent risks including infectious and immune reactions. Despite high prevalence of IDA among women with AUB, there are limited studies on the impact of iron therapies on patient outcomes. This systematic review and meta-analysis will evaluate the impact of iron supplementation on patient outcomes for women with AUB, when compared to combination therapy, no intervention, placebo, or standard of care.MethodsWe will conduct a systematic review and meta-analysis of …

Peer review in the reporting of science is intended to identify potential errors in experimental concept, design, and conduct—shortcomings that can often be addressed through new experiments and analysis. The path to confirmation and publication is arduous but necessary to maintain scientific integrity. Most investigators, authors, reviewers, and editors have found it necessary to explore and explain why two groups performing similar experiments generate discrepant results. These anomalies can usually be attributed to differences in the design, methods, and/or interpretation of data. Sometimes a procedural or interpretive flaw is uncovered that may invalidate findings and conclusions. This is one reason why science is built on testable theories and models—to promote ongoing validation of theory so that such errors made, whether consciously or not, are exposed and corrected. Errors must not be perpetuated in …

Objective:To evaluate the impact of direct discharge home (DDH) from ICUs compared with ward transfer on safety outcomes of readmissions, emergency department (ED) visits, and mortality.Data Sources:We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature from inception until March 28, 2022.Study Selection:Randomized and nonrandomized studies of DDH patients compared with ward transfer were eligible.Data Extraction:We screened and extracted studies independently and in duplicate. We assessed risk of bias using the Newcastle-Ottawa Scale for observational studies. A random-effects meta-analysis model and heterogeneity assessment was performed using pooled data (inverse variance) for propensity-matched and unadjusted cohorts. We assessed the overall certainty of evidence for each outcome using the …

To the Editor: In CHEST, Saleem et al 1 present a systematic review and meta-analysis that evaluate the effectiveness of corticosteroids for pneumonia. This is a comprehensive review that includes very recently published data, such as the Extended Steroid in Use in Community Acquired Pneumonia (ESCAPe) study. 2 Although we applaud the investigators’ efforts, there are several important considerations when considering methodology.As compared with previously published reviews that have evaluated this topic, these investigators did not perform subgroup analysis to assess for effect modification based on severity. 3 Another departure from previous reviews is the grading of recommendations assessment, development, and evaluation (GRADE) certainty assessments, which are very low across all outcomes. Specifically, the authors rate down two levels for risk of bias and one level for publication bias for all …

Introduction Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. Venous congestion can be measured by Doppler ultrasound at the bedside through interrogation of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV) and intrarenal veins (IRV). The objective of this study is to quantify the association between Doppler identified venous congestion and the need for renal replacement therapy (RRT) or death for patients with septic shock.Methods and analysis This study is a prespecified substudy of the ANDROMEDA-SHOCK 2 (AS-2) randomised control trial (RCT) assessing haemodynamic resuscitation in septic shock and will enrol at least 350 patients across multiple sites. We will include adult patients within 4 hours of …

BackgroundVenovenous extracorporeal membrane oxygenation (ECMO) can be considered for patients with COVID-19-associated acute respiratory distress syndrome (ARDS) who continue to deteriorate despite evidence-based therapies and lung-protective ventilation. The Extracorporeal Life Support Organization has emphasised the importance of patient selection; however, to better inform these decisions, a comprehensive and evidence-based understanding of the risk factors associated with poor outcomes is necessary. We aimed to summarise the association between pre-cannulation prognostic factors and risk of mortality in adult patients requiring venovenous ECMO for the treatment of COVID-19.MethodsIn this systematic review and meta-analysis, we searched MEDLINE and Embase from Dec 1, 2019, to April 14, 2022, for randomised controlled trials and observational studies involving adult patients who …

OBJECTIVES:To evaluate the efficacy and cost-effectiveness of high-flow nasal cannula (HFNC) when compared with noninvasive positive pressure ventilation (NIPPV) in patients with acute hypoxic respiratory failure (AHRF).DATA SOURCES:We performed a comprehensive search of MEDLINE, Embase, CINAHL, the Cochrane library, and the international Health Technology Assessment database from inception to September 14, 2022.STUDY SELECTION:We included randomized control studies that compared HFNC to NIPPV in adult patients with AHRF. For clinical outcomes, we included only parallel group and crossover randomized control trials (RCTs). For economic outcomes, we included any study design that evaluated cost-effectiveness, cost-utility, or cost benefit analyses.DATA EXTRACTION:Clinical outcomes of interest included intubation, mortality, ICU and hospital length of stay (LOS), and patient …

MethodsWe searched the EMBASE and MEDLINE databases from inception to August 2023. We identified studies reporting confounding adjusted associations between patient, injury or post-injury care factors and risk of VTE. We performed meta-analyses of odds ratios (ORs) using the random effects method and assessed individual study risk of bias using the QUIPS toolResultsWe included 31 studies involving 1,981,946 patients. Studies were predominantly observational cohorts from North America. Factors with moderate or higher certainty of association with increased risk of VTE include older age, obesity, male sex, higher injury severity score, pelvic injury, lower extremity injury, spinal injury, delayed VTE prophylaxis, need for surgery and tranexamic acid use. After accounting for other important contributing prognostic variables, a delay in the delivery of appropriate pharmacologic prophylaxis for as little as 24 …

Purpose:Trauma patients are at high risk of venous thromboembolism (VTE). We summarize the comparative efficacy and safety of anti-Xa-guided versus fixed dosing for low molecular weight heparin (LMWH) for the prevention of VTE in adult trauma patients.Methods:We searched Medline and Embase from inception through June 1, 2022. We included randomized controlled trials or observational studies comparing anti-Xa-guided versus fixed dosing of LMWH for thromboprophylaxis in adult trauma patients. We incorporated primary data from 2 large observational cohorts. We pooled effect estimates using a random-effects model. We assessed risk of bias using the ROBINS-I tool for observational studies and assessed certainty of findings using GRADE methodology.Results:We included 15 observational studies involving 10,348 patients. No randomized controlled trials were identified. determined that, compared …

IntroductionWe aimed to analyze intensive care unit (ICU)-acquired pneumonia according to 7 definitions, estimating associated hospital mortality.MethodsThis cohort study was nested within an international randomized trial, evaluating the effect of probiotics on ICU-acquired pneumonia in 2650 mechanically ventilated adults. Each clinically suspected pneumonia was adjudicated by two physicians blinded to allocation and center. The primary outcome was ventilator-associated pneumonia (VAP) informed by ventilation for ≥2 days, new, progressive or persistent infiltrate plus 2 of: temperature > 38 °C or < 36 °C; leukopenia (<3 × 10(Fernando et al., 20206)/L) or leukocytosis (>10 × 10(Fernando et al., 20206)/L); and purulent sputum. We also used 6 other definitions estimating the risk of hospital mortality.ResultsThe frequency of ICU-acquired pneumonia varied by definition: the trial primary outcome VAP (21.6 …

ObjectivesTo describe how systematic reviews with network meta-analyses (NMAs) that used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) NMA approach addressed intransitivity when assessing certainty of evidence.DesignSystematic survey.Data sourcesMedline, Embase and Cochrane Database of Systematic Reviews from September 2014 to October 2022.Eligibility criteriaSystematic reviews of randomised controlled trials with aggregate data NMAs that used the GRADE NMA approach for assessing certainty of evidence.Data extraction and synthesisWe documented how reviewers described methods for addressing intransitivity when assessing certainty of evidence, how often they rated down for intransitivity and their explanations for rating down.ResultsOf the 268 eligible systematic reviews, 44.8% (120/268) mentioned intransitivity when describing methods for …

Objectives:To identify factors associated with failure of noninvasive ventilation (NIV) in the post-extubation period.Data Sources:We searched Embase Classic+, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to February 28, 2022.Study Selection:We included English language studies that provided predictors of post-extubation NIV failure necessitating reintubation.Data Extraction:Two authors conducted data abstraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios (ORs) mean difference (MD), respectively. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty.Data Synthesis:We included 25 studies (n= 2,327). Illness-related factors associated with …

MethodsIn the present study, data from the ELSO (Extracorporeal Life Support Organization) Registry (1, 8) were analyzed; consent for use of the data followed local regulations. The aim was to assess the impact of the ratio of blood flow to the square of the cannula size (BF/C 2; a close estimate of the velocity of blood flow inside the cannula) at 24 hours of ECMO on clinical outcomes and complications. BF/C 2 ratio was used rather than blood flow rate itself because obtaining the same flow rate with different-sized cannulae could lead to discrepant physiological consequences (eg, more negative drainage pressure with smaller cannulae).

ObjectivesThe pharmacological options used for procedural sedation and analgesia (PSA) are diverse; understanding which agents offer preferred safety and efficacy profiles is essential. We performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) comparing the efficacy and safety of various intravenous PSA medications for emergent procedures in the emergency department (ED) and Intensive Care Unit (ICU).MethodsWe searched Medline, EMBASE, Cochrane, and PubMed from inception to March 2023 for RCTs comparing two or more PSA medications in patients (adults and children> 30 days of age) requiring emergent procedures in the ED or ICU. We examined the effect on recovery time, patient satisfaction, and adverse events (AEs). We performed frequentist random-effects network meta-analysis for all outcomes and used the Grading of Recommendations …

There is a high prevalence of mental illness in nursing home residents compared to older adults living in the community. This was highlighted in the most recent comprehensive systematic review on the topic, published in 2010. In the context of a rapidly aging population and increased numbers of older adults requiring residential care, this study aims to provide a contemporary account of the prevalence of mental illness among nursing home residents. This protocol was prepared in line with the PRISMA-P 2015 Statement. Systematic searches will be undertaken across six electronic databases: PubMed, Embase, Web of Science, PsycNET, CINAHL, and Abstracts in Social Gerontology. Peer-reviewed studies published from 2009 onwards which report the prevalence of mental illness within nursing home populations will be included. Database searches will be supplemented by forward and backward citation searching. Titles and abstracts of records will be screened using a semi-automated process. The full text of selected records will be assessed to confirm inclusion criteria are met. Study selection will be recorded in a PRISMA flowchart. A pilot-tested form will be used to extract data from included studies, alongside the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data. A study characteristics and results table will be prepared to present key details from each included study, supported by a narrative synthesis. Random-effects restricted maximum likelihood meta-analyses will be performed to compute pooled prevalence estimates for mental illnesses represented in the identified studies. Heterogeneity will be assessed using …

Introduction In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early inbed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults. Methods and analysis We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥ 18 years old), who could ambulate independently before their critical illness (with or without a gait aid),≤ 4 days of invasive mechanical ventilation and≤ 7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion …

Methods: We included randomized controlled trials (RCTs) published in English or French comparing CEN to IEN in critically ill patients with no date restrictions. We searched Medline, Embase, The Cochrane Library, and the WHO ICTRP Search Portal. Independently and in duplicate, we screened, extracted data, and performed a risk of bias assessment using the Cochrane Collaboration’s RoB 2 tool. We collected data on GI outcomes (diarrhea, constipation, abdominal pain, nausea, and vomiting) and mortality. We pooled data using a random effects model and presented it as risk ratios with 95% confidence intervals. We assessed certainty of evidence using GRADE methodology.Results: Of 388 citations, we included a total of 9 RCTs (640 patients). The overall risk of bias was high. In those receiving IEN compared to CEN, there was an uncertain effect in diarrhea (RR 1.22, 95% CI 0.84 to 1.79, very low certainty …

BackgroundPost-cardiac arrest, outcomes for most patients are poor, regardless of setting. Many patients who do achieve spontaneous return of circulation require vasopressor therapy to maintain organ perfusion. There is some evidence to support the use of corticosteroids in cardiac arrest.Research questionAssess the efficacy and safety of corticosteroids in patients following in- and out-of-hospital cardiac arrest.Study design and methodsWe searched databases CINAHL, EMBASE, LILACS, MEDLINE, Web of Science, CENTRAL, ClinicalTrails.gov, and ICTRP. We included randomized controlled trials (RCTs) that examined the efficacy and safety of corticosteroids, as compared to placebo or usual care in patients post-cardiac arrest. We pooled estimates of effect size using random effects meta-analysis and report relative risk (RR) with 95% confidence intervals (CIs). We assessed risk of bias (ROB) for the …

Purpose The helmet is a novel interface for delivering non-invasive ventilation (NIV). We conducted a case series to characterize introduction of the helmet interface in both COVID and non-COVID patients at two-centres. Methods We enrolled all patients with respiratory failure admitted to the Juravinski Hospital (Hamilton, Canada) and St. Joseph’s Health Center (Syracuse, New York) between November 1, 2020 and June 30, 2021 who used the helmet interface (Intersurgical StarMed) as part of this introduction into clinical practice. We collected patient demographics, reason for respiratory failure, NIV settings, device-related complications and outcomes. We report respiratory therapist’s initial experiences with the helmet using descriptive results. Results We included 16 patients with a mean age of 64.3 ± 10.9 years. The most common etiology for respiratory failure was pneumonia (81.3%). The median duration of NIV during the ICU admission was 67.5 (15.3, 80.8) hours, with a mean maximum PS of 13.9 ± 6.6 cm H2O and a mean maximum PEEP of 10.4 ± 5.1 cm H20. Three patients (18.7%) did not tolerate the helmet. Ten (62.5%) patients ultimately required intubation, and 7 (43.4%) patients died while in the ICU. The most common reason for intubation was worsening hypoxia (70%). No adverse events related to the helmet were recorded. Conclusion Over the 8-month period of this study, we found that the helmet was well tolerated in over 80% of patients, although, more than half ultimately required intubation. Randomized controlled trials with this device are required to fully assess the efficacy of this interface.

BackgroundPatients surviving an ICU admission for deliberate self-harm are at high risk of recurrent self-harm or suicide after discharge. It is unknown whether mental health follow-up after discharge (with either a family physician or psychiatrist) reduces this risk.Research QuestionWhat is the association between mental health follow-up after discharge and recurrent self-harm among patients admitted to the ICU for intentional self-harm?Study Design and MethodsPopulation-based cohort study of consecutive adults (≥ 18 years of age) from Ontario, Canada, who were admitted to ICU because of intentional self-harm between 2009 and 2017. We categorized patients according to follow-up, with ‘early follow-up’ indicating 1 to 21 days after discharge, ‘late follow-up’ indicating 22 to 60 days after discharge, and ‘no follow-up’ indicating no follow-up within 60 days of discharge. We conducted analyses using a cause …

Background Acute hypoxemic respiratory failure is one of the leading causes of intensive care unit admission and is associated with high mortality. Noninvasive oxygenation strategies such as high-flow nasal cannula, standard oxygen therapy, and noninvasive ventilation (delivered by either face mask or helmet interface) are widely available interventions applied in these patients. It remains unclear which of these interventions are more effective in decreasing rates of invasive mechanical ventilation and mortality. The primary objective of this network meta-analysis is to summarize the evidence and compare the effect of noninvasive oxygenation strategies on mortality and need for invasive mechanical ventilation in patients with acute hypoxemic respiratory failure. Methods We will search key databases for randomized controlled trials assessing the effect of noninvasive oxygenation strategies in adult patients with …

BackgroundAcute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) increases mortality risk, but which factors increase mortality is unknown. We aimed to perform a prognostic review of factors associated with mortality in patients with IPF.Study designand methods: We searched MEDLINE, EMBASE, and CINAHL for studies that reported on the association between any prognostic factor and AE-IPF. We assessed risk of bias using the QUIPS tool. We conduced pairwise meta-analyses using REML heterogeneity estimator, and GRADE approach to assess the certainty of the evidence.ResultsWe included 35 studies in our analysis. We found that long-term supplemental oxygen at baseline (aHR 2.52 [95 % CI 1.68 to 3.80]; moderate certainty) and a diagnosis of IPF compared to non-IPF ILD (aHR 2.19 [95 % CI 1.22 to 3.92]; moderate certainty) is associated with a higher risk of death in patients with AE-IPF. A …

IntroductionClostridioides difficile infection (CDI) is a serious complication of critical illness. The objective of the study was to determine its incidence, prevalence, timing, severity, predictors, and outcomes.MethodsWe performed a prospective nested cohort study of CDI within a randomized trial comparing Lactobacillus rhamnosus GG to placebo. We adjudicated cases of CDI using standardized definitions, assessed timing (pre-ICU, in ICU, post-ICU) and severity. We analyzed risk factors and outcomes.ResultsOf 2650 patients, 86 were diagnosed with CDI during 90,833 hospital-days (0.95/1000 hospital-days); CDI prevalence was 3.2%. CDI incidence varied in timing; 0.3% patients had CDI pre-ICU, 2.2% in the ICU; an 0.8% developed CDI post-ICU. Relapse or recurrence of CDI was documented in 9.3% patients. Infections were mild/moderate in severity. Complications included septic shock (26.7%), organ failure …

Purpose To compare the relative efficacy of supportive therapies (inotropes, vasopressors, and mechanical circulatory support [MCS]) for adult patients with cardiogenic shock complicating acute myocardial infarction. Source We conducted a systematic review and network meta-analysis and searched six databases from inception to December 2021 for randomized clinical trials (RCTs). We evaluated inotropes, vasopressors, and MCS in separate networks. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to rate the certainty in findings. The critical outcome of interest was 30-day all-cause mortality. Principal findings We included 17 RCTs. Among inotropes (seven RCTs, 1,145 patients), levosimendan probably reduces mortality compared with placebo (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.87; moderate certainty), but primarily in lower severity shock. Milrinone (OR, 0.52; 95% CI, 0.19 to 1.39; low certainty) and dobutamine (OR, 0.67, 95% CI, 0.30 to 1.49; low certainty) may have no effect on mortality compared with placebo. With regard to MCS (eight RCTs, 856 patients), there may be no effect on mortality with an intra-aortic balloon pump (IABP)(OR, 0.94; 95% CI, 0.69 to 1.28; low certainty) or percutaneous MCS (pMCS)(OR, 0.96; 95% CI, 0.47 to 1.98; low certainty), compared with a strategy involving no MCS. Intra-aortic balloon pump use was associated with less major bleeding compared with pMCS. We found only two RCTs evaluating vasopressors, yielding insufficient data for meta-analysis …

PurposeWe sought to compare the cost-effectiveness of probiotics and usual care with usual care without probiotics in mechanically ventilated, intensive care unit patients alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT).MethodsWe conducted a health economic evaluation alongside the PROSPECT randomized control trial (October 2013–March 2019). We adopted a public healthcare payer’s perspective. Forty-four intensive care units in three countries (Canada/USA/Saudi Arabia) with adult critically ill, mechanically ventilated patients (N = 2,650) were included. Interventions were probiotics (Lactobacillus rhamnosus GG) vs placebo administered enterally twice daily. We collected healthcare resource use and estimated unit costs in 2019 United States dollars (USD) over a time horizon from randomization to hospital discharge/death. We calculated …