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The effect of restrictive versus liberal transfusion strategies on longer-term outcomes after cardiac surgery: a systematic review and meta-analysis with trial sequential analysis
Kashani HH, Lodewyks C, Kavosh MS, Jeyaraman MM, Neilson C, Okoli G, Rabbani R, Abou-Setta AM, Zarychanski R, Grocott HP
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2020
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Editor's Choice
Abstract
PURPOSE Blood transfusions are frequently administered in cardiac surgery. Despite a large number of published studies comparing a "restrictive" strategy with a "liberal" strategy, no clear consensus has emerged to guide blood transfusion practice in cardiac surgery patients. The purpose of this study was to identify, critically appraise, and summarize the evidence on the overall effect of restrictive transfusion strategies compared with liberal transfusion strategies on mortality, other clinical outcomes, and transfusion-related outcomes in adult patients undergoing cardiac surgery. SOURCE We searched MEDLINE (OvidSP), EMBASE (OvidSP) and Cochrane CENTRAL (Wiley) from inception to 1 December 2017 and queried clinical trial registries and conference proceedings for randomized-controlled trials of liberal vs restrictive transfusion strategies in cardiac surgery. PRINCIPAL FINDINGS From 7,908 citations, we included ten trials (9,101 patients) and eight companion publications. Overall, we found no significant difference in mortality between restrictive and liberal transfusion strategies (risk ratio [RR], 1.08; 95% confidence interval [CI], 0.76 to 1.54; I(2) = 33%; seven trials; 8,661 patients). The use of a restrictive transfusion strategy did not appear to adversely impact any of the secondary clinical outcomes. As expected, the proportion of patients who received red blood cells (RBCs) in the restrictive group was significantly lower than in the liberal group (RR, 0.68; 95% CI, 0.64 to 0.73; I(2) = 56%; 5 trials; 8,534 patients). Among transfused patients, a restrictive transfusion strategy was associated with fewer transfused RBC units per patient than a liberal transfusion strategy. CONCLUSIONS In adult patients undergoing cardiac surgery, a restrictive transfusion strategy reduces RBC transfusion without impacting mortality rate or the incidence of other perioperative complications. Nevertheless, further large trials in subgroups of patients, potentially of differing age, are needed to establish firm evidence to guide transfusion in cardiac surgery. TRIAL REGISTRATION PROSPERO (CRD42017071440); registered 20 April, 2018.
PICO Summary
Population
Adult patients undergoing cardiac surgery (10 studies, n= 9101).
Intervention
Restrictive transfusion strategies.
Comparison
Liberal transfusion strategies.
Outcome
No significant difference was found in mortality between restrictive and liberal transfusion strategies (risk ratio [RR], 1.08; I2 (2) = 33%. The proportion of patients who received red blood cells (RBCs) in the restrictive group was significantly lower than in the liberal group (RR, 0.68; I2 (2) = 56%. Among transfused patients, a restrictive transfusion strategy was associated with fewer transfused RBC units per patient than a liberal transfusion strategy.
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Effect of age of transfused red blood cells on neurologic outcome following traumatic brain injury (ABLE-tbi Study): a nested study of the Age of Blood Evaluation (ABLE) trial
Ruel-Laliberte J, Lessard Bonaventure P, Fergusson D, Lacroix J, Zarychanski R, Lauzier F, Tinmouth A, Hebert PC, Green R, Griesdale D, et al
Canadian Journal of Anaesthesia. 2019;66(6):696-705
Abstract
BACKGROUND Anemia is common in critically ill patients with traumatic brain injury, and often requires red blood cell transfusion. Studies suggest that prolonged storage causes lesions of the red blood cells, including a decreased ability to carry oxygen. Considering the susceptibility of the brain to hypoxemia, victims of traumatic brain injury may thus be more vulnerable to exposure to older red blood cells. METHODS Our study aimed to ascertain whether the administration of fresh red blood cells (seven days or less) results in a better neurologic outcome compared with standard red blood cells in critically ill patients with traumatic brain injury requiring transfusion. The Age of Blood Evaluation in traumatic brain injury (ABLE-tbi) study was a nested study within the ABLE study (ISRCTN44878718). Our primary outcome was the extended Glasgow Outcome Scale (GOSe) at six months. RESULTS In the ABLE study, 217 subjects suffered a traumatic brain injury: 110 in the fresh group, and 107 in the standard group. In the fresh group, 68 (73.1%) of the patients had an unfavourable neurologic outcome (GOSe <= 4) compared with 60 (64.5%) in the standard group (P = 0.21). Using a sliding dichotomy approach, we observed no overall effect of fresh red blood cells on neurologic outcome (odds ratio [OR], 1.34; 95% confidence interval [CI], 0.72 to 2.50; P = 0.35) but observed differences across prognostic bands with a decreased odds of unfavourable outcome in patients with the best prognosis at baseline (OR, 0.33; 95% CI, 0.11 to 0.96; P = 0.04) but an increased odds in those with intermediate and worst baseline prognosis (OR, 5.88; 95% CI,1.66 to 20.81; P = 0.006; and OR, 1.67; 95% CI, 0.53 to 5.30; P = 0.38, respectively). CONCLUSION Overall, transfusion of fresh red blood cells was not associated with a better neurologic outcome at six months in critically ill patients with traumatic brain injury. Nevertheless, we cannot exclude a differential effect according to the patient baseline prognosis. TRIAL REGISTRATION ABLE study (ISRCTN44878718); registered 22 August, 2008.
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Red blood cell transfusion in patients with traumatic brain injury: a systematic review and meta-analysis
Boutin A, Chasse M, Shemilt M, Lauzier F, Moore L, Zarychanski R, Griesdale D, Desjardins P, Lacroix J, Fergusson D, et al
Transfusion Medicine Reviews. 2016;30((1)):15-24.
Abstract
Our objectives were to evaluate the frequency of red blood cell (RBC) transfusion in patients with traumatic brain injury (TBI) as well as potential determinants and outcomes associated with RBC transfusion in this population. We conducted a systematic review of cohort studies and randomized trials of patients with TBI. We searched Medline, Embase, the Cochrane Library, and BIOSIS databases from their inception up to April 2015. We selected studies of adult patients with acute TBI reporting data on RBC transfusions. Cumulative incidences of transfusion were pooled using random-effect models with a DerSimonian approach. To evaluate the association between RBC transfusion and potential determinants or clinical outcomes, we pooled risk ratios or mean differences with random-effect models and the Mantel-Haenszel method. We identified 24 eligible studies (17414 patients). After pooling data from 23 studies (7524 patients), approximately 36% (95% confidence interval [CI], 28-44; I(2) = 98%) of patients received RBC transfusion at some point during their hospital stay. Hemoglobin thresholds for transfusion were rarely available (reported in 9 studies) and varied from 6 to 10 g/dL. Glasgow Coma Scale scores at admission were lower in patients who were transfused than those who were not (3 cohort studies; 1371 patients; mean difference of 1.38 points [95% CI, 0.86-1.89]; I(2) = 12%). Mortality was not significantly different among transfused and nontransfused patients in univariate and multivariate meta-analyses. Hospital length of stay was longer among patients receiving RBC transfusion compared to those who did not (3 studies; n = 455; mean difference, 9.58 days [95% CI, 3.94-15.22]; I(2) = 74%). Results should be considered cautiously due to the high heterogeneity and high risk of confounding from the observational nature of included studies. Red blood cell transfusion is frequent in patients with TBI, and transfusion practices varied widely between studies. Current published data highlight the lack of clinical evidence guiding transfusion strategies in TBI. Copyright © 2015 Elsevier Inc. All rights reserved.
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Red blood cell transfusion in patients with traumatic brain injury: a systematic review protocol
Boutin A, Chasse M, Shemilt M, Lauzier F, Moore L, Zarychanski R, Lacroix J, Fergusson DA, Desjardins P, Turgeon AF
Systems Review. 2014;3((1):):66.
Abstract
BACKGROUND Anemia is a prevalent condition in critically ill patients and red blood cell transfusions are frequent. Although transfusions at low hemoglobin levels have been shown to be associated with equivalent or better outcomes than higher hemoglobin thresholds, clinical equipoise persists in patients with traumatic brain injury considering their susceptibility to secondary cerebral insults such as those from hypoxemia. METHODS Our objectives are to estimate the frequency of red blood cell transfusion in patients with traumatic brain injury and to evaluate transfusion thresholds, determinants and outcomes associated with transfusion strategies.We will conduct a systematic review of cohort studies and randomized controlled trials of patients with traumatic brain injury. We will search MEDLINE, Embase, BIOSIS and the Cochrane Library for eligible studies. Two independent reviewers will screen all identified references. Studies including adult patients with traumatic brain injury reporting data on red blood cell transfusions will be eligible. We will collect data on baseline demographics, trauma characteristics, hemoglobin thresholds, blood transfusions and clinical outcomes (mortality, length of stay, complications, and so on). Two independent reviewers will extract data using a standardized form. We will pool cumulative incidences using DerSimonian and Lair random-effect models after a Freeman-Tukey transformation to stabilize variances. We will pool risk ratios or mean differences with random-effect models and Mantel-Haenszel or inverse variance methods in order to evaluate the association between red blood cell transfusion and potential determinants or outcomes. Sensitivity and subgroup analysis according to timing of red blood cell transfusion, traumatic brain injury severity, year of conduction of the study, risk of bias, notably, are planned. DISCUSSION We expect to observe high heterogeneity in the proportion of transfused patients across studies and that the global proportion will be similar to the frequency observed in the general medical critically ill population. Our systematic review will allow us to better describe and understand current transfusion practices in patients with traumatic brain injury, a clinical population in which liberal transfusions are still advocated in the absence of evidence-based data. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42014007402.
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Hemoglobin levels and transfusions in neurocritically ill patients: a systematic review of comparative studies
Desjardins P, Turgeon AF, Tremblay M-H, Lauzier F, Zarychanski R, Boutin A, Moore L, McIntyre LA, English SW, Rigamonti A, et al
Critical Care. 2012;16((2):):R54.
Abstract
INTRODUCTION Accumulating evidence suggests that, in critically ill patients, a lower hemoglobin transfusion threshold is safe. However, the optimal hemoglobin level and associated transfusion threshold remain unknown in neurocritically ill patients. METHODS We conducted a systematic review of comparative studies (randomized and nonrandomized) to evaluate the effect of hemoglobin levels on mortality, neurologic function, intensive care unit (ICU) and hospital length of stay, duration of mechanical ventilation, and multiple organ failure in adult and pediatric neurocritically ill patients. We searched MEDLINE, The Cochrane Central Register of Controlled Trials, Embase, Web of Knowledge, and Google Scholar. Studies focusing on any neurocritical care conditions were included. Data are presented by using odds ratios for dichotomous outcomes and mean differences for continuous outcomes. RESULTS Among 4,310 retrieved records, six studies met inclusion criteria (n = 537). Four studies were conducted in traumatic brain injury (TBI), one in subarachnoid hemorrhage (SAH), and one in a mixed population of neurocritically ill patients. The minimal hemoglobin levels or transfusion thresholds ranged from 7 to 10 g/dl in the lower-Hb groups and from 9.3 to 11.5 g/dl in the higher-Hb groups. Three studies had a low risk of bias, and three had a high risk of bias. No effect was observed on mortality, duration of mechanical ventilation, or multiple organ failure. In studies reporting on length of stay (n = 4), one reported a significant shorter ICU stay (mean, -11.4 days (95% confidence interval, -16.1 to -6.7)), and one, a shorter hospital stay (mean, -5.7 days (-10.3 to -1.1)) in the lower-Hb groups, whereas the other two found no significant association. CONCLUSIONS We found insufficient evidence to confirm or refute a difference in effect between lower- and higher-Hb groups in neurocritically ill patients. Considering the lack of evidence regarding long-term neurologic functional outcomes and the high risk of bias of half the studies, no recommendation can be made regarding which hemoglobin level to target and which associated transfusion strategy (restrictive or liberal) to favor in neurocritically ill patients.
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Survival of trauma patients after massive red blood cell transfusion using a high or low red blood cell to plasma transfusion ratio
Rajasekhar A, Gowing R, Zarychanski R, Arnold DM, Lim W, Crowther MA, Lottenberg R
Critical Care Medicine. 2011;39((6):):1507-13.
Abstract
OBJECTIVE Early and aggressive treatment of trauma-associated coagulopathy through transfusion of high plasma to packed red blood cell ratios is gaining favor. Whether this strategy is associated with improved survival is unclear. We performed a systematic review to determine whether higher plasma to packed red blood cell ratios compared with lower plasma to packed red blood cell ratios were associated with a survival advantage. DATA SOURCES We searched electronic databases MEDLINE, Embase, and Web of Science from 1950 to February 2010 for studies comparing mortality in massively transfused trauma cohorts receiving different plasma to packed red blood cell ratios. STUDY SELECTION Two reviewers independently performed study selection. Discrepancies in study selection were resolved by discussion and consensus. DATA EXTRACTION Two reviewers independently extracted data from each study using a standardized form. Two authors independently assessed study quality using the Newcastle-Ottawa Scale. DATA SYNTHESIS Eleven observational studies and no randomized controlled trials were identified. Three studies found a survival benefit with a 1:1 plasma to packed red blood cell transfusion ratio compared with either higher or lower ratios. Six studies did not examine a 1:1 ratio but concluded that higher plasma to packed red blood cell ratios improved survival. Secondary outcomes, including multiorgan system failure, packed red blood cell transfusion, respiratory outcomes, and coagulation variables, did not uniformly fav or 1:1 or higher plasma to packed red blood cell ratios. CONCLUSIONS Methodological flaws, including survival bias, and heterogeneity between studies preclude statistical comparisons concerning the effects of a 1:1 plasma to packed red blood cell transfusion ratio. There is insufficient evidence to support a survival advantage with a 1:1 plasma to packed red blood cell transfusion strategy. Randomized controlled trials evaluating safety and efficacy are warranted before a high plasma to packed red blood cell transfusion ratio can be recommended.