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1.
Efficacy and Safety of Tranexamic Acid in Major Non-Cardiac Surgeries at High Risk for Transfusion: A Systematic Review and Meta-Analysis
Houston BL, Uminski K, Mutter T, Rimmer E, Houston DS, Menard CE, Garland A, Ariano R, Tinmouth A, Abou-Setta AM, et al
Transfusion medicine reviews. 2019
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Editor's Choice
Abstract
Tranexamic acid (TXA) reduces transfusion requirements in cardiac surgery and total hip and knee arthroplasty, where it has become standard of care. Our objective is to determine the efficacy and safety of TXA in other surgeries associated with a high risk for red blood cell (RBC) transfusion. We identified randomized controlled trials in Medline, Embase, CENTRAL, and CAB abstracts from inception to June 2019. We included trials evaluating intraoperative IV TXA in adult patients undergoing a non-cardiac and non-hip and knee arthroplasty surgeries at high-risk for RBC transfusion, defined as a baseline transfusion rate ≥5% in comparator arm. We assessed risk of bias using the Cochrane Risk of Bias tool. We used GRADE methodology to assess certainty of evidence. From 8565 citations identified, we included 69 unique trials, enrolling 6157 patients. TXA reduces both the proportion of patients transfused RBCs (relative risk (RR) 0.59; 95% confidence interval (CI) 0.48 to 0.72; low certainty evidence) and the volume of RBC transfused (MD -0.51 RBC units; 95%CI -0.13 to -0.9 units; low certainty evidence) when compared to placebo or usual care. TXA was not associated with differences in deep vein thrombosis, pulmonary embolism, all-cause mortality, hospital length of stay, need for re-operation due to hemorrhage, myocardial infarction, stroke or seizure. In patients undergoing a broad range of non-cardiac and non-hip and knee arthroplasty surgeries at high risk for RBC transfusion, perioperative TXA reduced exposure to RBC transfusion. No differences in thrombotic outcomes were identified; however, summary effect estimates were limited by lack of systemic screening and short duration of follow-up.
PICO Summary
Population
Adult patients undergoing a non-cardiac and non-hip and knee arthroplasty surgeries at high-risk for RBC transfusion, (69 studies, n=6157).
Intervention
Intraoperative IV tranexamic acid (TXA).
Comparison
Placebo, usual care and active comparators.
Outcome
TXA reduces both the proportion of patients transfused RBCs (relative risk (RR) 0.59 and the volume of RBC transfused (MD -0.51 RBC units) when compared to placebo or usual care. TXA was not associated with differences in deep vein thrombosis, pulmonary embolism, all-cause mortality, hospital length of stay, need for re-operation due to hemorrhage, myocardial infarction, stroke or seizure. In patients undergoing a broad range of non-cardiac and non-hip and knee arthroplasty surgeries at high risk for RBC transfusion, perioperative TXA reduced exposure to RBC transfusion. No differences in thrombotic outcomes were identified; however, summary effect estimates were limited by lack of systemic screening and short duration of follow-up.
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2.
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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3.
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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4.
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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5.
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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The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis
Rimmer, Houston BL, Kumar A, Abou-Setta AM, Friesen C, Marshall JC, Rock G, Turgeon AF, Cook DJ, Houston DS, et al
Critical Care (London, England). 2014;18((6):):699.
Abstract
INTRODUCTION Sepsis and septic shock are leading causes of intensive care unit (ICU) mortality. They are characterized by excessive inflammation, upregulation of procoagulant proteins and depletion of natural anticoagulants. Plasma exchange has the potential to improve survival in sepsis by removing inflammatory cytokines and restoring deficient plasma proteins. The objective of this study is to evaluate the efficacy and safety of plasma exchange in patients with sepsis. METHODS We searched MEDLINE, EMBASE, CENTRAL, Scopus, reference lists of relevant articles, and grey literature for relevant citations. We included randomized controlled trials comparing plasma exchange or plasma filtration with usual care in critically ill patients with sepsis or septic shock. Two reviewers independently identified trials, extracted trial-level data and performed risk of bias assessments using the Cochrane Risk of Bias tool. The primary outcome was all-cause mortality reported at longest follow-up. Meta-analysis was performed using a random-effects model. RESULTS Of 1,957 records identified, we included four unique trials enrolling a total of 194 patients (one enrolling adults only, two enrolling children only, one enrolling adults and children). The mean age of adult patients ranged from 38 to 53 years (n=128) and the mean age of children ranged from 0.9 to 18 years (n=66). All trials were at unclear to high risk of bias. The use of plasma exchange was not associated with a significant reduction in all-cause mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.45 to 1.52, I(2) 60%). In adults, plasma exchange was associated with reduced mortality (RR 0.63, 95% CI 0.42 to 0.96; I(2) 0%), but was not in children (RR 0.96, 95% CI 0.28 to 3.38; I(2) 60%). None of the trials reported ICU or hospital lengths of stay. Only one trial reported adverse events associated with plasma exchange including six episodes of hypotension and one allergic reaction to fresh frozen plasma. CONCLUSIONS Insufficient evidence exists to recommend plasma exchange as an adjunctive therapy for patients with sepsis or septic shock. Rigorous randomized controlled trials evaluating clinically relevant patient-centered outcomes are required to evaluate the impact of plasma exchange in this condition.
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The use of higher platelet: RBC transfusion ratio in the acute phase of trauma resuscitation: a systematic review
Hallet J, Lauzier F, Mailloux O, Trottier V, Archambault P, Zarychanski R, Turgeon AF
Critical Care Medicine. 2013;41((12):):2800-11.
Abstract
OBJECTIVE With the recognition of early coagulopathy, trauma resuscitation has shifted toward liberal platelet transfusions. The overall benefit of this strategy remains controversial. Our objective was to compare the effects of a liberal use of platelet (higher platelet:RBC ratios) with a conservative approach (lower ratios) in trauma resuscitation. DATA SOURCES We systematically searched Medline, Embase, Web of Science, Biosis, Cochrane Central, and Scopus. STUDY SELECTION Two independent reviewers selected randomized controlled trials and observational studies comparing two or more platelet:RBC ratios in trauma resuscitation. We excluded studies investigating the use of whole blood or hemostatic products. DATA EXTRACTION Two independent reviewers extracted data and assessed the risk of bias. Primary outcomes were early (in ICU or within 30 d) and late (in hospital or after 30 d) mortality. Secondary outcomes were multiple organ failure, lung injury, and sepsis. DATA SYNTHESIS From 6,123 citations, no randomized controlled trials were identified. We included seven observational studies (4,230 patients) addressing confounders through multivariable regression or propensity scores. Heterogeneity of studies precluded meta-analysis. Among the five studies including exclusively patients requiring massive transfusions, four observed a lower mortality with higher ratios. Two studies considering nonmassively bleeding patients observed no benefit of using higher ratios. Two studies evaluated the implementation of a massive transfusion protocol; only one study observed a decrease in mortality with higher ratios. Of the two studies at low risk of survival bias, one study observed a survival benefit. Three studies assessed secondary outcomes. One study observed an increase in multiple organ failure with higher ratios, whereas no study demonstrated an increased risk in lung injury or sepsis. CONCLUSIONS There is insufficient evidence to strongly support the use of a precise platelet:RBC ratio for trauma resuscitation, especially in nonmassively bleeding patients. Randomized controlled trials evaluating both the safety and efficacy of liberal platelet transfusions are warranted.
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The efficacy and safety of therapeutic apheresis in sepsis and septic shock: a systematic review and meta-analysis
Rimmer EK, Houston BL, Kumar A, Abou-Setta A, Friesen C, Turgeon AF, Cook DJ, Houston DS, Zarychanski R
Blood. 2013;122((21):):1119.
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9.
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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10.
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.