Evidence from randomized controlled trials (RCTs) is required to guide treatment of critically ill children, but the number of RCTs available is limited and the publications are often difficult to ...find. The objectives of this review were to systematically identify RCTs in pediatric critical care and describe their methods and reporting.
We searched MEDLINE, EMBASE, LILACS and CENTRAL (from inception to April 16, 2013) and reference lists of included RCTs and relevant systematic reviews. We included published RCTs administering any intervention to children in a pediatric ICU. We excluded trials conducted in neonatal ICUs, those enrolling exclusively preterm infants, and individual patient crossover trials. Pairs of reviewers independently screened studies for eligibility, assessed risk of bias, and abstracted data. Discrepancies were resolved by consensus.
We included 248 RCTs: 45 (18%) were multicentered and 14 (6%) were multinational. Trials most frequently enrolled both medical and surgical patients (43%) but postoperative cardiac surgery was the single largest population studied (19%). The most frequently evaluated types of intervention were medications (63%), devices (11%) and nutrition (8%). Laboratory or physiological measurements were the most frequent type of primary outcomes (18%). Half of these trials (50%) reported blinding. Of the 107 (43%) trials that reported an a priori sample size, 34 (32%) were stopped early. The median number of children randomized per trial was 49 and ranged from 6 to 4,947. The frequency of RCT publications increased at a mean rate of 0.7 RCTs per year (P<0.001) from 1 to 20 trials per year.
This scoping review identified the available RCTs in pediatric critical care and made them accessible to clinicians and researchers (http://epicc.mcmaster.ca). Most focused on medications and intermediate or surrogate outcomes, were single-centered and were conducted in North America and Western Europe. The results of this review underscore the need for trials with rigorous methodology, appropriate outcome measures, and improved quality of reporting to ensure that high quality evidence exists to support clinical decision-making in this vulnerable population.
To describe pre-ICU frailty in critically ill patients using the Clinical Frailty Scale (CFS).
We included patients ≥18years admitted to 2 ICUs in Hamilton, Canada. The ICU Research Coordinator (RC) ...generated 3 CFS scores using: 1) chart review, 2) family interview, 3) patient interview. Subsequently, an overall impression was captured in a final score. Mean differences were calculated to assess the RC intra-rater reliability and inter-rater reliability of chart reviews by the RC, Occupational Therapist (OT), and Geriatrics Resident (GR). Scores were also compared between younger and older patients. We also analyzed the relationship between CFS scores and mortality.
We prospectively enrolled 150 patients (mean age 63.8 SD 15.3 years, APACHE II score 21 SD 7.3). CFS were similar between RC, OT, and GR chart reviews (p>0.05 for all comparisons). There was no difference between RC chart review and RC final score, or between RC patient interview and RC final score. Scores following the RC family interview and the RC final score were significantly different (−0.24, 95% CI −0.38, −0.09, p<0.01). Each 1-point increase in the final CFS scored by the RC was weakly associated with ICU mortality (odds ratio 1.18, 95% CI 0.84–1.66, p=0.33), and hospital mortality (OR 1.19, 95% CI 0.89, −1.59, p=0.24).
CFS scores can be generated using medical chart review and can be reliably completed by ICU clinicians and research staff.
•Using the Clinical Frailty Scale is feasible in the ICU.•Frailty scores are similar across ages despite higher illness severity in older patients.•Chart review and interviews yield similar frailty scores.
Constipation is common among critically ill patients and has been associated with adverse patient outcomes. Many ICUs have developed bowel protocols to treat constipation; however, their effect on ...clinical outcomes remains uncertain. We conducted a systematic review to determine the impact of bowel protocols in critically ill adults.
We searched MEDLINE, Embase, CINAHL, CENTRAL, ISRCTN, ClinicalTrials.gov, and conference abstracts until January 2016.
Two authors independently screened titles and abstracts for randomized controlled trials comparing bowel protocols to control (placebo, no protocol, or usual care) in critically ill adults.
Two authors independently, and in duplicate, extracted study characteristics, outcomes, assessed risk of bias, and appraised the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.
We retrieved 4,520 individual articles, and excluded 4,332 articles during title and abstract screening and 181 articles during full-text screening. Four trials, including 534 patients, were eligible for analysis. The use of a bowel protocol was associated with a trend toward a reduction in constipation (risk ratio, 0.50 95% CI, 0.25-1.01; p = 0.05; low-quality evidence); no reduction in tolerance of enteral feeds (risk ratio, 0.94 95% CI, 0.62-1.42; p = 0.77; low-quality evidence), and no change in the duration of mechanical ventilation (mean difference, 0.01 d 95% CI, -2.67 to 2.69 d; low-quality evidence).
Large, rigorous, randomized control trials are needed to determine whether bowel protocols impact patient-important outcomes in critically ill adults.
Venous thromboembolism prevention during critical illness is a widely used quality metric. The objective of this systematic review was to systematically review the efficacy and safety of heparin ...thromboprophylaxis in medical-surgical patients in the ICU.
We searched EMBASE, MEDLINE, the Cochrane Controlled Trials Register, Clinicaltrials.gov, and personal files through May 2012.
Randomized trials in adult medical-surgical ICU patients comparing any heparin (unfractionated heparin or low-molecular-weight heparin) with each other or no anticoagulant prophylaxis, evaluating deep vein thrombosis, pulmonary embolism, major bleeding, or mortality.
Independently, in duplicate, we abstracted trial characteristics, outcomes, and risk of bias.
Seven trials involved 7,226 patients. Any heparin thromboprophylaxis compared with placebo reduced rates of deep vein thrombosis (pooled risk ratio, 0.51 95% CI, 0.41, 0.63; p<0.0001; I=77%) and pulmonary embolism (risk ratio, 0.52 95% CI, 0.28, 0.97; p=0.04; I=0%) but not symptomatic deep vein thrombosis (risk ratio, 0.86 95% CI, 0.59, 1.25; p=0.43). Major bleeding (risk ratio, 0.82 95% CI, 0.56, 1.21; p=0.32; I=50%) and mortality (risk ratio, 0.89 95% CI, 0.78, 1.02; p=0.09; I=0%) rates were similar. Compared with unfractionated heparin, low-molecular-weight heparin reduced rates of pulmonary embolism (risk ratio, 0.62 95% CI, 0.39, 1.00; p=0.05; I=53%) and symptomatic pulmonary embolism (risk ratio, 0.58 95% CI, 0.34, 0.97; p=0.04) but not deep vein thrombosis (risk ratio, 0.90 95% CI, 0.74, 1.08; p=0.26; I=0%), symptomatic deep vein thrombosis (risk ratio, 0.87 95% CI, 0.60, 1.25; p=0.44; I=0%), major bleeding (risk ratio, 0.97 95% CI, 0.75, 1.26; p=0.83; I=0%), or mortality (risk ratio, 0.93 95% CI, 0.82, 1.04; p=0.20; I=31%).
Trial evidence to date suggests that any type of heparin thromboprophylaxis decreases deep vein thrombosis and pulmonary embolism in medical-surgical critically ill patients, and low-molecular-weight heparin compared with bid unfractionated heparin decreases pulmonary embolism and symptomatic pulmonary embolism. Major bleeding and mortality rates do not appear to be significantly influenced by heparin thromboprophylaxis in the ICU setting. Trial methodology, indirectness, and the heterogeneity and imprecision of some results temper inferences from this literature.
The epidemiology of thrombocytopenia in critically ill patients has not been well characterized. The objective of this study was to systematically review the prevalence, incidence, and consequences ...of, and risk factors for, thrombocytopenia among critically ill patients.
We searched MEDLINE, EMBASE, the Cochrane Registry for controlled trials (until May 2010), and the Online Computer Library, as well as bibliographies of relevant studies, to identify investigations designed to examine the frequency, risk factors, and/or outcomes associated with thrombocytopenia among patients admitted to the ICU. We independently selected studies, abstracted data, and assessed methodologic quality in duplicate. Heterogeneity of design and analysis precluded statistical pooling of results.
We identified 24 studies (12 prospective) enrolling 6,894 patients from medical, surgical, mixed, or trauma ICUs. Prevalent thrombocytopenia (on ICU admission) occurred in 8.3% to 67.6% of patients; incident thrombocytopenia (developing during the course of the ICU stay) occurred in 13.0% to 44.1% of patients. High illness severity, sepsis, and organ dysfunction often correlated with thrombocytopenia. Only one study using multivariate analysis examined whether thrombocytopenia was associated with major bleeding, but it found no association. Six out of eight studies using multivariate analysis found that thrombocytopenia increased the risk of death.
The frequency of thrombocytopenia during critical illness varies widely, based on case mix and definition. After confounding factors are adjusted for, thrombocytopenia appears to increase the risk of death.
This is the first of 2 articles evaluating cardiac events in patients undergoing noncardiac surgery. In this article, we review the magnitude of the problem, the pathophysiology of these events, ...approaches to risk assessment and communication of risk. The number of patients undergoing noncardiac surgery worldwide is growing, and annually 500,000 to 900,000 of these patients experience perioperative cardiac death, nonfatal myocardial infarction (MI) or nonfatal cardiac arrest. Although the evidence is limited, a substantial proportion of fatal perioperative MIs may not share the same pathophysiology as nonoperative MIs. A clearer understanding of the pathophysiology is needed to direct future research evaluating prophylactic, acute and long-term interventions. Researchers have developed tools to facilitate the estimation of perioperative cardiac risk. Studies suggest that the Lee index is the most accurate generic perioperative cardiac risk index. The limitations of the studies evaluating the ability of noninvasive cardiac tests to predict perioperative cardiac risk reveals considerable uncertainty as to the role of these popular tests. Similarly, there is uncertainty as to the predictive accuracy of the American College of Cardiology/American Heart Association algorithm for cardiac risk assessment. Patients are likely to benefit from improved estimation and communication of cardiac risk because the majority of noncardiac surgeries are elective and accurate risk estimation is important to allow informed patient and physician decision-making.
Internationally adopted variant interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) are generic and require disease-specific refinement. Here we developed ...CardioClassifier ( http://www.cardioclassifier.org ), a semiautomated decision-support tool for inherited cardiac conditions (ICCs).
CardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation. Combining disease- and gene-specific knowledge with variant observations in large cohorts of cases and controls, we refined 14 computational ACMG criteria and created three ICC-specific rules.
We benchmarked CardioClassifier on 57 expertly curated variants and show full retrieval of all computational data, concordantly activating 87.3% of rules. A generic annotation tool identified fewer than half as many clinically actionable variants (64/219 vs. 156/219, Fisher's P = 1.1 × 10
), with important false positives, illustrating the critical importance of disease and gene-specific annotations. CardioClassifier identified putatively disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with leading ICC laboratories. Through addition of manually curated data, variants found in over 40% of cardiomyopathy cases are fully annotated, without requiring additional user-input data.
CardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines.
To analyse the association between survival from critical illness and suicide or self-harm after hospital discharge.
Population based cohort study using linked and validated provincial databases.
...Ontario, Canada between January 2009 and December 2017 (inclusive).
Consecutive adult intensive care unit (ICU) survivors (≥18 years) were included. Linked administrative databases were used to compare ICU hospital survivors with hospital survivors who never required ICU admission (non-ICU hospital survivors). Patients were categorised based on their index hospital admission (ICU or non-ICU) during the study period.
The primary outcome was the composite of death by suicide (as noted in provincial death records) and deliberate self-harm events after discharge. Each outcome was also assessed independently. Incidence of suicide was evaluated while accounting for competing risk of death from other causes. Analyses were conducted by using overlap propensity score weighted, cause specific Cox proportional hazard models.
423 060 consecutive ICU survivors (mean age 61.7 years, 39% women) were identified. During the study period, the crude incidence (per 100 000 person years) of suicide, self-harm, and the composite of suicide or self-harm among ICU survivors was 41.4, 327.9, and 361.0, respectively, compared with 16.8, 177.3, and 191.6 in non-ICU hospital survivors. Analysis using weighted models showed that ICU survivors (
non-ICU hospital survivors) had a higher risk of suicide (adjusted hazards ratio 1.22, 95% confidence interval 1.11 to 1.33) and self-harm (1.15, 1.12 to 1.19). Among ICU survivors, several factors were associated with suicide or self-harm: previous depression or anxiety (5.69, 5.38 to 6.02), previous post-traumatic stress disorder (1.87, 1.64 to 2.13), invasive mechanical ventilation (1.45, 1.38 to 1.54), and renal replacement therapy (1.35, 1.17 to 1.56).
Survivors of critical illness have increased risk of suicide and self-harm, and these outcomes were associated with pre-existing psychiatric illness and receipt of invasive life support. Knowledge of these prognostic factors might allow for earlier intervention to potentially reduce this important public health problem.
Although most critically ill patients receive invasive mechanical ventilation (IMV), few studies have characterized how IMV is discontinued in practice.
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).
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).
Receiving IMV.
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.
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).
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.
ClinicalTrials.gov Identifier: NCT03955874.
Only a small proportion of COVID-19 patients in Canada have been recruited into clinical research studies. One reason is that few community intensive care units (ICUs) in Canada participate in ...research. The objective of this study was to examine the motivating factors, barriers and facilitators to research participation amongst Canadian community ICU stakeholders. A cross-sectional online survey was distributed between May and November 2020. The survey focused on 6 domains: participant demographics, ICU characteristics, ICU research infrastructure, motivating factors, perceived barriers, and perceived facilitators. Responses were received from 73 community ICU stakeholders, representing 18 ICUs. 7/18 ICUs had a clinical research program. Participants rated their interest in pandemic research at a mean of 5.2 (Standard Deviation SD = 1.9) on a 7-point Likert scale from 'not interested' to 'very interested'. The strongest motivating factor for research participation was the belief that research improves clinical care and outcomes. The most significant facilitators of research involvement were the availability of an experienced research coordinator and dedicated external funding to cover start-up costs, while the most significant barriers to research involvement were a lack of start-up funding for a research coordinator and a lack of ICU research experience. Canadian Community ICU stakeholders are interested in participating in pandemic research but lack basic infrastructure, research personnel, research experience and start-up funding. Evolution of a research support model at community hospitals, where most patients receive acute care, may increase research participation and improve the generalizability of funded research in Canada.
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