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Intravenous albumin for the prevention of hemodynamic instability during sustained low-efficiency dialysis: a randomized controlled feasibility trial (The SAFER-SLED Study)
Clark EG, McIntyre L, Watpool I, Kong JWY, Ramsay T, Sabri E, Canney M, Hundemer GL, Brown PA, Sood MM, et al
Annals of intensive care. 2021;11(1):174
Abstract
BACKGROUND Hemodynamic instability is a frequent complication of sustained low-efficiency dialysis (SLED) treatments in the ICU. Intravenous hyperoncotic albumin may prevent hypotension and facilitate ultrafiltration. In this feasibility trial, we sought to determine if a future trial, powered to evaluate clinically relevant outcomes, is feasible. METHODS This single-center, blinded, placebo-controlled, randomized feasibility trial included patients with acute kidney injury who started SLED in the ICU. Patients were randomized to receive 25% albumin versus 0.9% saline (control) as 100 mL boluses at the start and midway through SLED, for up to 10 sessions. The recruitment rate and other feasibility outcomes were determined. Secondary exploratory outcomes included ultrafiltration volumes and metrics of hemodynamic instability. RESULTS Sixty patients (271 SLED sessions) were recruited over 10 months. Age and severity of illness were similar between study groups. Most had septic shock and required vasopressor support at baseline. Protocol adherence occurred for 244 sessions (90%); no patients were lost to follow-up; no study-related adverse events were observed; open label albumin use was 9% and 15% in the albumin and saline arms, respectively. Ultrafiltration volumes were not significantly different. Compared to the saline group, the albumin group experienced less hemodynamic instability across all definitions assessed including a smaller absolute decrease in systolic blood pressure (mean difference 10.0 mmHg, 95% confidence interval 5.2-14.8); however, there were significant baseline differences in the groups with respect to vasopressor use prior to SLED sessions (80% vs 61% for albumin and saline groups, respectively). CONCLUSIONS The efficacy of using hyperoncotic albumin to prevent hemodynamic instability in critically ill patients receiving SLED remains unclear. A larger trial to evaluate its impact in this setting, including evaluating clinically relevant outcomes, is feasible. Trial registration ClinicalTrials.gov (NCT03665311); First Posted: Sept 11th, 2018. https://clinicaltrials.gov/ct2/show/NCT03665311?term=NCT03665311&draw=2&rank=1.
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2.
Audit and feedback to improve laboratory test and transfusion ordering in critical care: a systematic review
Foster M, Presseau J, McCleary N, Carroll K, McIntyre L, Hutton B, Brehaut J
Implement Sci. 2020;15(1):46
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Editor's Choice
Abstract
BACKGROUND Laboratory tests and transfusions are sometimes ordered inappropriately, particularly in the critical care setting, which sees frequent use of both. Audit and Feedback (A&F) is a potentially useful intervention for modifying healthcare provider behaviors, but its application to the complex, team-based environment of critical care is not well understood. We conducted a systematic review of the literature on A&F interventions for improving test or transfusion ordering in the critical care setting. METHODS Five databases, two registries, and the bibliographies of relevant articles were searched. We included critical care studies that assessed the use of A&F targeting healthcare provider behaviors, alone or in combination with other interventions to improve test and transfusion ordering, as compared to historical practice, no intervention, or another healthcare behaviour change intervention. Studies were included only if they reported laboratory test or transfusion orders, or the appropriateness of orders, as outcomes. There were no restrictions based on study design, date of publication, or follow-up time. Intervention characteristics and absolute differences in outcomes were summarized. The quality of individual studies was assessed using a modified version of the Effective Practice and Organisation of Care Cochrane Review Group's criteria. RESULTS We identified 16 studies, including 13 uncontrolled before-after studies, one randomized controlled trial, one controlled before-after study, and one controlled clinical trial (quasi-experimental). These studies described 17 interventions, mostly (88%) multifaceted interventions with an A&F component. Feedback was most often provided in a written format only (41%), more than once (53%), and most often only provided data aggregated to the group-level (41%). Most studies saw a change in the hypothesized direction, but not all studies provided statistical analyses to formally test improvement. Overall study quality was low, with studies often lacking a concurrent control group. CONCLUSIONS Our review summarizes characteristics of A&F interventions implemented in the critical care context, points to some mechanisms by which A&F might be made more effective in this setting, and provides an overview of how the appropriateness of orders was reported. Our findings suggest that A&F can be effective in the context of critical care; however, further research is required to characterize approaches that optimize the effectiveness in this setting alongside more rigorous evaluation methods. TRIAL REGISTRATION PROSPERO CRD42016051941.
PICO Summary
Population
Healthcare professionals ordering laboratory tests or blood transfusion components for patients in an intensive care unit (16 studies).
Intervention
17 different Audit and Feedback (A&F) interventions to improve laboratory test and transfusion ordering.
Comparison
Usual care (no intervention; historical or concurrent), or any other single or multifaceted behavioral intervention that did not involve A&F (e.g., education, incentives, reminders, or systems-based changes).
Outcome
The included studies described 17 interventions, mostly (88%) multifaceted interventions with an A&F component. Feedback was most often provided in a written format only (41%), more than once (53%), and most often only provided data aggregated to the group-level (41%). Most studies saw a change in the hypothesized direction, but not all studies provided statistical analyses to formally test improvement. Overall study quality was low, with studies often lacking a concurrent control group.
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3.
The impact of perioperative red blood cell transfusions in patients undergoing liver resection: a systematic review
Bennett S, Baker LK, Martel G, Shorr R, Pawlik TM, Tinmouth A, McIsaac DI, Hebert PC, Karanicolas PJ, McIntyre L, et al
Hpb : the Official Journal of the International Hepato Pancreato Biliary Association. 2017;19((4):):321-330
Abstract
BACKGROUND Liver resection is associated with a high proportion of red blood cell transfusions. There is a proposed association between perioperative transfusions and increased risk of complications and tumor recurrence. This study reviews the evidence of this association in the literature. METHODS The Medline, EMBASE, and Cochrane databases were searched for clinical trials or observational studies of patients undergoing liver resection that compared patients who did and did not receive a perioperative red blood cell transfusion. Outcomes were mortality, complications, and cancer survival. RESULTS Twenty-two studies involving 6832 patients were included. All studies were retrospective, with no clinical trials. No studies were scored as low risk of bias. The overall proportion of patients transfused was 38.3%. After multivariate analysis, 1 of 5 studies demonstrated an association between transfusion and increased mortality; 5 of 6 demonstrated an association between transfusion and increased complications; and 10 of 18 demonstrated an association between transfusion and decreased cancer survival. CONCLUSION This review supports the evidence linking perioperative blood transfusions to negative outcomes. The most convincing association was with post-operative complications, some association with long-term cancer outcomes, and no convincing association with mortality. These findings support the initiation, and further study, of restrictive transfusion protocols.
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Effect of blood donor characteristics on transfusion outcomes: a systematic review and meta-analysis
Chasse M, McIntyre L, English SW, Tinmouth A, Knoll G, Wolfe D, Wilson K, Shehata N, Forster A, van Walraven C, et al
Transfusion Medicine Reviews. 2016;30((2):):69-80
Abstract
Optimal selection of blood donors is critical for ensuring the safety of blood products. The current selection process is concerned principally with the safety of the blood donor at the time of donation and of the recipient at the time of transfusion. Recent evidence suggests that the characteristics of the donor may affect short- and long-term transfusion outcomes for the transfused recipient. We conducted a systematic review with the primary objective of assessing the association between blood donor characteristics and red blood cell (RBC) transfusion outcomes. We searched MEDLINE, EMBASE, and Cochrane Central databases and performed manual searches of top transfusion journals for all available prospective and retrospective studies. We described study characteristics, methodological quality, and risk of bias and provided study-level effect estimates and, when appropriate, pooled estimates with 95% confidence intervals using the Mantel-Haenszel or inverse variance approach. The overall quality of the evidence was graded using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. From 6121 citations identified by our literature search, 59 studies met our eligibility criteria (50 observational, 9 interventional). We identified the evaluation of association of 17 donor characteristics on RBC transfusion outcome. The risk of bias and confounding of the included studies was high. The quality of evidence was graded as very low to low for all 17 donor characteristics. Potential associations were observed for donor sex with reduced survival at 90 days and 6 months in male recipients that receive donated blood from females (hazard ratio 2.60 [1.09, 6.20] and hazard ratio 2.40 [1.10, 5.24], respectively; n = 1), Human Leukocyte Antigen - antigen D Related (HLA-DR) selected transfusions (odds ratio [OR] 0.39 [0.15, 0.99] for the risk of transplant alloimmunization, n = 9), presence of antileukocyte antibodies (OR 5.84 [1.66, 20.59] for risk of transfusion-related acute lung injury, n = 4), and donor RBC antigens selection (OR 0.20 [0.08, 0.52] for risk of alloimmunization, n = 4). Based on poor quality evidence, positive antileukocyte antibodies, female donor to male recipients, HLA-DR selected RBC transfusion, or donor RBC antigen selection may affect RBC transfusion outcome. Our findings that donor characteristics may be associated with transfusion outcomes warrant establishing vein-to-vein data infrastructure to allow for large robust evaluations. PROSPERO registration number: CRD42013006726.
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Age of transfused blood in critically ill adults
Lacroix J, Hebert PC, Fergusson DA, Tinmouth A, Cook DJ, Marshall JC, Clayton L, McIntyre L, Callum J, Turgeon AF, et al
New England Journal of Medicine. 2015;372((15):):1410-8.
Abstract
BACKGROUND Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage. METHODS In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality. RESULTS Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (+/-SD) of 6.1+/-4.9 days in the fresh-blood group as compared with 22.0+/-8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (35.3%) in the standard-blood group had died (absolute risk difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In the survival analysis, the hazard ratio for death in the fresh-blood group, as compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38). There were no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory, hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions) or in the subgroup analyses. CONCLUSIONS Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.).
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Red blood cell transfusion and mortality effect in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis protocol
English SW, Chasse M, Turgeon AF, Tinmouth A, Boutin A, Pagliarello G, Fergusson D, McIntyre L
Systems Review. 2015;4((1)):41.
Abstract
BACKGROUND Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease that leads to important morbidity and mortality in a young patient population. Anemia following aSAH is common and may be exacerbated by the treatments instituted by clinicians as part of standard care. The role and optimal thresholds for red blood cell (RBC) transfusion in this patient population remains unknown. METHODS/DESIGN We will conduct a systematic review of the literature using MEDLINE, EMBASE, and EBM Reviews (including Cochrane Central databases) using a comprehensive search strategy for observational and interventional studies of RBC transfusion in aSAH. Our primary objective is to evaluate the association of RBC transfusion with mortality in aSAH patients. Secondary objectives include a) determining associations between RBC transfusion and poor neurologic outcome, b) defining an optimal RBC transfusion threshold in aSAH patients, and c) describing complications associated with RBC transfusion in aSAH patients. We plan a descriptive reporting of all included citations including study characteristics, methodological quality, and reported outcomes. Clinical and statistical heterogeneity observed between studies will be described. If appropriate, meta-analyses of suitable studies and interpretation of their results will be performed. Effect measures will be converted to obtain relative risks and odds ratios (RR and ORs) with 95% confidence intervals and pooled according to study design (randomized trials and observational studies respectively) using a random effects model. DISCUSSION This review will summarize the existing observational and trial evidence regarding RBC transfusion in aSAH patients. The analytical plan has made considerations for different study designs, both observational and interventional in nature, and will summarize the best available evidence to inform the end user and policy and guideline producers and to highlight areas in need of further study. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42014014806.
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Effect of blood donor characteristics on transfusion outcomes: a protocol for systematic review and meta-analysis
Chasse M, English SW, McIntyre L, Knoll G, Shehata N, Forster A, Wilson K, van Walraven C, Tinmouth A, Fergusson DA
Systems Review. 2014;3((1):):28.
Abstract
BACKGROUND Optimal selection of blood donors is of paramount importance in ensuring the safety of blood products. The current selection process is concerned principally with the safety of the blood donor and the safety of the patient that receives the blood. Recent evidence suggests that the characteristics of the donor may affect transfusion outcomes for the recipient. METHODS We will conduct a systematic review of the association between major blood donor characteristics and red blood cell (RBC) transfusion outcomes. The primary objective is to assess the association of blood donor characteristics and the risk of adverse short-term and long-term clinical outcomes after RBC transfusion. We will search MEDLINE, EMBASE, Cochrane Central databases, as well as perform manual searches of top transfusion medical journals for prospective and retrospective studies. Study characteristics will be reported and the methodological quality of studies will be assessed. When appropriate, we will provide pooled odds ratio with 95% confidence intervals of the effect estimates, study clinical heterogeneity using pre-defined sensitivity and subgroup analyses, and study statistical heterogeneity using the I2 test. DISCUSSION The results of this systematic review will provide an evidence base regarding the potential clinical effects of donor characteristics on transfusion recipients to better guide policy and clinical practice. The evidence gathered from this review will also identify strengths and weaknesses of published studies regarding donor characteristics and transfusion outcomes and will identify knowledge gaps to inform future research in this field of transfusion medicine. TRIAL REGISTRATION PROSPERO Registration Number: CRD42013006726.
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The Age of Blood Evaluation (ABLE) randomized controlled trial: study design
Lacroix J, Hebert P, Fergusson D, Tinmouth A, Blajchman MA, Callum J, Cook D, Marshall JC, McIntyre L, Turgeon AF
Transfusion Medicine Reviews. 2011;25((3):):197-205.
Abstract
Red blood cells (RBCs) are transfused to treat anemia and to maintain oxygen delivery to vital organs during critical illness. Laboratory and observational studies have raised the possibility that prolonged RBC storage may adversely affect clinical outcomes. Compared with RBCs stored less than 1 week, there are no clinical data demonstrating that RBCs stored longer remain as effective at carrying or releasing oxygen, and observational studies have risen to possibility that prolonged RBC storage might result in harm to vulnerable patients requiring blood transfusions. The Age of Blood Evaluation(ABLE) study (ISRCTN44878718) is a double-blind, multicenter, parallel randomized controlled clinical trial. It will test the hypothesis that the transfusion of prestorage leukoreduced RBCs stored for 7 days or less (fresh arm) as compared with standard-issue RBCs stored, on average, 15 to 20 days (control arm) will lead to lower 90-day all-cause mortality and reduced morbidity in critically ill adults. We include adults in intensive care units (ICUs) who (1) have had a request for a first RBC unit transfusion during the first 7 days of ICU admission and (2) have an anticipated requirement for ongoing invasive and noninvasive mechanical ventilation exceeding 48 hours. Enrolled patients are randomized at the time of transfusion to receive either standard-issue RBC units or RBCs stored 7 days or less issued by the local hospital transfusion service. The primary outcome is 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, organ failure, and serious nosocomial infections. With 2510 patients, we will be able to detect a 5% absolute risk reduction (from 25% to 20%). The ABLE study is currently enrolling patients in 23 university-affiliated and community-hospital ICUs across Canada; sites in France and United Kingdom are expected to start recruitment in 2011. Regardless of the results, ABLE study will have significant implications on the duration of RBC storage. A negative trial will reassure clinicians and blood bankers regarding the effectiveness and safety of standard-issue RBCs. A positive trial will have significant implications with respect to inventory management of RBCs given to critically ill adults with a high risk of mortality and will also prompt research to better understand the RBC storage lesion in the hopes of minimizing its clinical consequences through the development of better storage methods.
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9.
Meta-analysis: intravenous immunoglobulin in critically ill adult patients with sepsis
Turgeon AF, Hutton B, Fergusson DA, McIntyre L, Tinmouth AA, Cameron DW, Hebert PC
Annals of Internal Medicine. 2007;146((3):):193-203.
Abstract
BACKGROUND Intravenous immunoglobulin therapy has been proposed as an adjuvant treatment for sepsis. Yet, its benefit remains unclear, and its use is not currently recommended. PURPOSE To evaluate the effect of polyclonal intravenous immunoglobulin therapy on death in critically ill adult patients with sepsis. DATA SOURCES MEDLINE (1966 to May 2006) and the Cochrane Central Register of Controlled Trials (May 2006 edition). STUDY SELECTION All randomized, controlled trials of critically ill adult patients with sepsis, severe sepsis, or septic shock who received polyclonal intravenous immunoglobulin therapy or placebo or no intervention were selected. No restrictions were made for study language or type of publication. Data extraction: Data were independently extracted by 2 investigators using a standardized form. DATA SYNTHESIS The literature search identified 4096 articles, of which 33 were deemed to be potentially eligible. Twenty trials (n = 2621) met eligibility criteria and were included in the analysis. Polyclonal intravenous immunoglobulin therapy was associated with an overall survival benefit (risk ratio, 0.74 (95% CI, 0.62 to 0.89)) compared with placebo or no intervention. In sensitivity analyses, documented survival improved when the analysis was limited to published, peer-reviewed trials (risk ratio, 0.72 (CI, 0.58 to 0.89)) (17 trials (n = 1865)) and blinded trials (risk ratio, 0.61 (CI, 0.40 to 0.93) (7 trials (n = 896)). Severe sepsis or septic shock (risk ratio, 0.64 (CI, 0.52 to 0.79)) (11 trials (n = 689)), receiving a total dose regimen of 1 gram or more per kilogram of body weight (risk ratio, 0.61 (CI, 0.40 to 0.94)) (7 trials (n = 560)), and receiving therapy for longer than 2 days (risk ratio, 0.66 (CI, 0.53 to 0.82)) (17 trials (n = 1847)) were strongly associated with this survival benefit. LIMITATIONS Most trials were published before new developments modifying the care and outcome of critically ill patients with sepsis including early goal-directed therapy and activated protein C treatment, were introduced. CONCLUSIONS A survival benefit was observed for patients with sepsis who received polyclonal intravenous immunoglobulin therapy compared with those who received placebo or no intervention. A large, randomized, controlled trial of polyclonal intravenous immunoglobulin therapy should be performed on the basis of the methodological limitations of the current literature, the potential benefit from this therapy in more severely ill patients, and the potential effect of dosage and duration of this therapy.
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10.
Erythropoietin-receptor agonists in critically ill patients: a meta- analysis of randomized controlled trials
Zarychanski R, Turgeon AF, McIntyre L, Fergusson DA
CMAJ [Canadian Medical Association Journal]. 2007;177((7):):725-34.
Abstract
INTRODUCTION Anemia and the need for red blood cell transfusions are common among patients admitted to intensive care units. Erythropoietin has been used to decrease the need for transfusions; however, its ability to improve clinical outcomes is unknown. We evaluated the effect of erythropoietin-receptor agonists on clinically important outcomes, including mortality, length of stay in hospital or intensive care unit, ventilator use, transfusion requirements and major adverse events. METHODS To identify relevant studies, we searched electronic databases covering 1950 to 2007 (MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the Scopus database). We also searched conference proceedings and grey literature sources. We selected all randomized controlled trials involving critically ill patients that compared an erythropoietin-receptor agonist with a placebo or no intervention. No language restrictions were considered. Data were extracted using a standardized extraction template. We used a fixed effects model to calculate all summary measures of treatment effects. RESULTS Of 673 identified records, 9 studies that investigated erythropoietin alpha met the eligibility criteria and were included in our analysis. Erythropoietin, compared with placebo or no intervention, had no statistically significant effect on overall mortality (odds ratio (OR) 0.86, 95% confidence interval (CI) 0.71-1.05, I2 = 0%). The treatment and control groups did not differ in the length of stay in hospital or intensive care unit, or in the duration of mechanical ventilation, in the 3 studies that reported these outcomes. Erythropoietin, compared with placebo, significantly reduced the odds of a patient receiving at least 1 transfusion (OR 0.73, 95% CI 0.64-0.84, I2 = 54.7%). The mean number of units of blood transfused per patient was decreased by 0.41 units in the erythropoietin group (95% CI 0.10-0.74, I2 = 79.2%). Most of the included studies were performed before the widespread adoption of a restrictive transfusion strategy. Only 1 study provided detailed reports of adverse events, and none of the studies systematically evaluated all patients for venous thromboembolism. INTERPRETATION At this time, we do not recommend the routine use of erythropoietin- receptor agonists in critically ill patients. The reduction in red blood cell transfusions per patient was very small, and there is insufficient evidence to determine whether this intervention results in clinically important benefits with acceptable risks.