Systematic reviews and meta-analyses comparing mortality in restrictive and liberal haemoglobin thresholds for red cell transfusion: an overview of systematic reviews.
ABSTRACT: BACKGROUND:There are no overviews of systematic reviews investigating haemoglobin thresholds for transfusion. This is important as the literature on transfusion thresholds has grown considerably in recent years. Our aim was to synthesise evidence from systematic reviews and meta-analyses of the effects of restrictive and liberal transfusion strategies on mortality. METHODS:This was a systematic review of systematic reviews (overview). We searched MEDLINE, Embase, Web of Science Core Collection, PubMed, Google Scholar, and the Joanna Briggs Institute EBP Database, from 2008 to 2018. We included systematic reviews and meta-analyses of randomised controlled trials comparing mortality in patients assigned to red cell transfusion strategies based on haemoglobin thresholds. Two independent reviewers extracted data and assessed methodological quality. We assessed the methodological quality of included reviews using AMSTAR 2 and the quality of evidence pooled using an algorithm to assign GRADE levels. RESULTS:We included 19 systematic reviews reporting 33 meta-analyses of mortality outcomes from 53 unique randomised controlled trials. Of the 33 meta-analyses, one was graded as high quality, 15 were moderate, and 17 were low. Of the meta-analyses presenting high- to moderate-quality evidence, 12 (75.0%) reported no statistically significant difference in mortality between restrictive and liberal transfusion groups and four (25.0%) reported significantly lower mortality for patients assigned to a restrictive transfusion strategy. We found few systematic reviews addressed clinical differences between included studies: variation was observed in haemoglobin threshold concentrations, the absolute between group difference in haemoglobin threshold concentration, time to randomisation (resulting in transfusions administered prior to randomisation), and transfusion dosing regimens. CONCLUSIONS:Meta-analyses graded as high to moderate quality indicate that in most patient populations no difference in mortality exists between patients assigned to a restrictive or liberal transfusion strategy. TRIAL REGISTRATION:PROSPERO CRD42019120503.
Project description:This study sought to evaluate whether restrictive blood transfusion strategies are associated with a risk of infection in orthopedic patients by conducting a meta-analysis of randomized controlled trials (RCTs). RCTs with restrictive versus liberal red blood cell (RBC) transfusion strategies were identified by searching Medline, Embase, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from their inception to December 2014. Eight RCTs with infections as outcomes were included in the final analysis. According to the Jadad scale, all studies were considered to be of high quality. The pooled risk ratio [RR] for the association between transfusion strategy and infection was 0.65 (95% CI, 0.47-0.91; p = 0.012), and the number of patients needed to treat to avoid an infection using a restrictive transfusion strategy was 62. No heterogeneity was observed. The sensitivity analysis indicated unstable results, and no significant publication bias was observed. This meta-analysis of RCTs demonstrates that restrictive transfusion strategies in orthopedic patients result in a significant reduction in infections compared with more liberal strategies.
Project description:<h4>Objective</h4>To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions.<h4>Design</h4>Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.<h4>Data sources</h4>Cochrane central register of controlled trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials.<h4>Trial selection</h4>Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size.<h4>Data extraction</h4>Two authors independently screened titles and abstracts of trials identified, and relevant trials were evaluated in full text for eligibility. Two reviewers then independently extracted data on methods, interventions, outcomes, and risk of bias from included trials. random effects models were used to estimate risk ratios and mean differences with 95% confidence intervals.<h4>Results</h4>31 trials totalling 9813 randomised patients were included. The proportion of patients receiving red blood cells (relative risk 0.54, 95% confidence interval 0.47 to 0.63, 8923 patients, 24 trials) and the number of red blood cell units transfused (mean difference -1.43, 95% confidence interval -2.01 to -0.86) were lower with the restrictive compared with liberal transfusion strategies. Restrictive compared with liberal transfusion strategies were not associated with risk of death (0.86, 0.74 to 1.01, 5707 patients, nine lower risk of bias trials), overall morbidity (0.98, 0.85 to 1.12, 4517 patients, six lower risk of bias trials), or fatal or non-fatal myocardial infarction (1.28, 0.66 to 2.49, 4730 patients, seven lower risk of bias trials). Results were not affected by the inclusion of trials with unclear or high risk of bias. Using trial sequential analyses on mortality and myocardial infarction, the required information size was not reached, but a 15% relative risk reduction or increase in overall morbidity with restrictive transfusion strategies could be excluded.<h4>Conclusions</h4>Compared with liberal strategies, restrictive transfusion strategies were associated with a reduction in the number of red blood cell units transfused and number of patients being transfused, but mortality, overall morbidity, and myocardial infarction seemed to be unaltered. Restrictive transfusion strategies are safe in most clinical settings. Liberal transfusion strategies have not been shown to convey any benefit to patients.<h4>Trial registration</h4>PROSPERO CRD42013004272.
Project description:<h4>Objective</h4>To compare patient outcomes of restrictive versus liberal blood transfusion strategies in patients with cardiovascular disease not undergoing cardiac surgery.<h4>Design</h4>Systematic review and meta-analysis.<h4>Data sources</h4>Randomised controlled trials involving a threshold for red blood cell transfusion in hospital. We searched (to 2 November 2015) CENTRAL, Medline, Embase, CINAHL, PubMed, LILACS, NHSBT Transfusion Evidence Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ISRCTN Register, and EU Clinical Trials Register. Authors were contacted for data whenever possible.<h4>Trial selection</h4>Published and unpublished randomised controlled trials comparing a restrictive with liberal transfusion threshold and that included patients with cardiovascular disease.<h4>Data extraction and synthesis</h4>Data extraction was completed in duplicate. Risk of bias was assessed using Cochrane methods. Relative risk ratios with 95% confidence intervals were presented in all meta-analyses. Mantel-Haenszel random effects models were used to pool risk ratios.<h4>Main outcome measures</h4>30 day mortality, and cardiovascular events.<h4>Results</h4>41 trials were identified; of these, seven included data on patients with cardiovascular disease. Data from a further four trials enrolling patients with cardiovascular disease were obtained from the authors. In total, 11 trials enrolling patients with cardiovascular disease (n=3033) were included for meta-analysis (restrictive transfusion, n=1514 patients; liberal transfusion, n=1519). The pooled risk ratio for the association between transfusion thresholds and 30 day mortality was 1.15 (95% confidence interval 0.88 to 1.50, P=0.50), with little heterogeneity (I(2)=14%). The risk of acute coronary syndrome in patients managed with restrictive compared with liberal transfusion was increased (nine trials; risk ratio 1.78, 95% confidence interval 1.18 to 2.70, P=0.01, I(2)=0%).<h4>Conclusions</h4>The results show that it may not be safe to use a restrictive transfusion threshold of less than 80 g/L in patients with ongoing acute coronary syndrome or chronic cardiovascular disease. Effects on mortality and other outcomes are uncertain. These data support the use of a more liberal transfusion threshold (>80 g/L) for patients with both acute and chronic cardiovascular disease until adequately powered high quality randomised trials have been undertaken in patients with cardiovascular disease.<h4>Registration</h4>PROSPERO CRD42014014251.
Project description:Blood transfusion might affect long-term mortality by changing immune function and thus potentially increasing the risk of subsequent infections and cancer recurrence. Compared with a restrictive transfusion strategy, a more liberal strategy could reduce cardiac complications by lowering myocardial damage, thereby reducing future deaths from cardiovascular disease. We aimed to establish the effect of a liberal transfusion strategy on long-term survival compared with a restrictive transfusion strategy.In the randomised controlled FOCUS trial, adult patients aged 50 years and older, with a history of or risk factors for cardiovascular disease, and with postoperative haemoglobin concentrations lower than 100 g/L within 3 days of surgery to repair a hip fracture, were eligible for enrolment. Patients were recruited from 47 participating hospitals in the USA and Canada, and eligible participants were randomly allocated in a 1:1 ratio by a central telephone system to either liberal transfusion in which they received blood transfusion to maintain haemoglobin level at 100 g/L or higher, or restrictive transfusion in which they received blood transfusion when haemoglobin level was lower than 80 g/L or if they had symptoms of anaemia. In this study, we analysed the long-term mortality of patients assigned to the two transfusion strategies, which was a secondary outcome of the FOCUS trial. Long-term mortality was established by linking the study participants to national death registries in the USA and Canada. Treatment assignment was not masked, but investigators who ascertained mortality and cause of death were masked to group assignment. Analyses were by intention to treat. The FOCUS trial is registered with ClinicalTrials.gov, number NCT00071032.Between July 19, 2004, and Feb 28, 2009, 2016 patients were enrolled and randomly assigned to the two treatment groups: 1007 to the liberal transfusion strategy and 1009 to the restrictive transfusion strategy. The median duration of follow-up was 3·1 years (IQR 2·4-4·1 years), during which 841 (42%) patients died. Long-term mortality did not differ significantly between the liberal transfusion strategy (432 deaths) and the restrictive transfusion strategy (409 deaths) (hazard ratio 1·09 [95% CI 0·95-1·25]; p=0·21).Liberal blood transfusion did not affect mortality compared with a restrictive transfusion strategy in a high-risk group of elderly patients with underlying cardiovascular disease or risk factors. The underlying causes of death did not differ between the trial groups. These findings do not support hypotheses that blood transfusion leads to long-term immunosuppression that is severe enough to affect long-term mortality rate by more than 20-25% or cause of death.National Heart, Lung, and Blood Institute.
Project description:OBJECTIVES:We employed a comprehensive systematic review and meta-analysis to assess benefits and risks of a threshold of haemoglobin level below 7?g/dL versus liberal transfusion strategy among critically ill patients, and even patients with septic shock. DESIGN:Systematic review and meta-analysis. DATA SOURCES:We performed systematical searches for relevant randomised controlled trials (RCTs) in the Cochrane Library, EMBASE and PubMed databases up to 1 September 2019. ELIGIBILITY CRITERIA:RCTs among adult intensive care unit (ICU) patients comparing 7?g/dL as restrictive strategy with liberal transfusion were incorporated. DATA EXTRACTION AND SYNTHESIS:The clinical outcomes, including short-term mortality, length of hospital stay, length of ICU stay, myocardial infarction (MI) and ischaemic events, were screened and analysed after data collection. We applied odds ratios (ORs) to analyse dichotomous outcomes and standardised mean differences (SMDs) to analyse continuous outcomes with fixed or random effects models based on heterogeneity evaluation for each outcome. RESULTS:Eight RCTs with 3415 patients were included. Compared with a more liberal threshold, a red blood cell (RBC) transfusion threshold <7?g/dL haemoglobin showed no significant difference in short-term mortality (OR: 0.90, 95%?CI: 0.67 to 1.21, p=0.48, I2=53%), length of hospital stay (SMD: -0.11, 95%?CI: -0.30 to 0.07, p=0.24, I2=71%), length of ICU stay (SMD: -0.03, 95%?CI: -0.14 to 0.08, p=0.54, I2=0%) or ischaemic events (OR: 0.80, 95%?CI: 0.43 to 1.48, p=0.48, I2=51%). However, we found that the incidence of MI (OR: 0.54, 95%?CI: 0.30 to 0.98, p=0.04, I2=0%) was lower in the group with the threshold <7?g/dL than that with the more liberal threshold. CONCLUSIONS:An RBC transfusion threshold <7?g/dL haemoglobin is incapable of decreasing short-term mortality in ICU patients according to currently published evidences, while it might have potential role in reducing MI incidence.
Project description:Restrictive red blood cell transfusion strategies remain controversial in patients undergoing cardiac surgery. We performed a meta-analysis to assess the prognostic benefits of restrictive red blood cell transfusion strategies in patients undergoing cardiac surgery.We identified randomized clinical trials through the 9th of December 2017 that investigated a restrictive red blood cell transfusion strategy versus a liberal transfusion strategy in patients undergoing cardiac surgery. Individual patient data from each study were collected. Meta-analyses were performed for the primary and secondary outcomes. The risk of bias was assessed using the Cochrane Risk of Bias Tool. A trial sequential analysis (TSA)-adjusted random-effects model was used to pool the results from the included studies for the primary outcomes.Seven trials involving a total of 8886 patients were included. The TSA evaluations suggested that this meta-analysis could draw firm negative results, and the data were sufficient. There was no evidence that the risk of 30-day mortality differed between the patients assigned to a restrictive blood cell transfusion strategy and a liberal transfusion strategy (odds ratio (OR) 0.98; 95% confidence interval (CI) 0.77 to 1.24; p?=?0.87). Furthermore, the study suggested that the restrictive transfusion strategy was not associated with significant increases in pulmonary morbidity (OR 1.09; 95% CI 0.88 to 1.34; p?=?0.44), postoperative infection (OR 1.11; 95% CI 0.95 to 1.3; p?=?0.58), acute kidney injury (OR 1.03; 95% CI 0.92 to 1.14; p?=?0.71), acute myocardial infarction (OR 1.01; 95% CI 0.80 to 1.27; p?=?0.78), or cerebrovascular accidents (OR 0.97; 95% CI 0.72 to 1.30; p?=?0.66).Our meta-analysis demonstrates that the restrictive red blood cell transfusion strategy was not inferior to the liberal strategy with respect to 30-day mortality, pulmonary morbidity, postoperative infection, cerebrovascular accidents, acute kidney injury, or acute myocardial infarction, and fewer red blood cells were transfused.
Project description:Most non-oncologic clinical practice guidelines recommend restrictive allogeneic blood transfusion practices; however, there is a lack of consensus regarding the best transfusion practice in oncology. We conducted a systematic review of the literature to compare the efficacy and safety of restrictive versus liberal transfusion strategies in patients with cancer.A literature search using MEDLINE, PUBMED and EMBASE identified all controlled studies comparing the use of restrictive with liberal transfusion in adult oncology participants up to August 10, 2015. Two review authors independently assessed studies for inclusion, extracted data and appraised the quality of the included studies. The primary outcomes of interest were blood utilization and all-cause mortality.Out of 4241 citations, six studies (3 randomized and 3 non-randomized) involving a total of 983 patients were included in the final review. The clinical context of the studies varied with 3 chemotherapy and 3 surgical studies. The overall risk of bias in all studies was moderate to high. Restrictive transfusion strategies were associated with a 36% reduced risk of receiving a perioperative transfusion (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.49-0.83). There was no difference in mortality between the strategies (RR 1.00, 95% CI 0.32-3.18). There were no differences in adverse events reported between the restrictive and liberal transfusion strategies.Restrictive strategy appears to decrease blood utilization without increasing morbidity or mortality in oncology. This review is limited by a paucity of high quality studies on this topic. Better designed studies are warranted.
Project description:INTRODUCTION:There has been a significant increase in the number of systematic reviews and meta-analyses of randomised controlled trials investigating thresholds for red blood cell transfusion. To systematically collate, appraise and synthesise the results of these systematic reviews and meta-analyses, we will conduct an overview of systematic reviews. METHODS AND ANALYSIS:This is a protocol for an overview of systematic reviews. We will search five databases: MEDLINE, Embase, Web of Science Core Collection, PubMed (for prepublication, in process and non-Medline records) and Google Scholar. We will consider systematic reviews and meta-analyses of randomised controlled trials evaluating the effect of haemoglobin thresholds for red blood cell transfusion on mortality. Two authors will independently screen titles and abstracts retrieved in the literature search and select studies meeting the eligibility criteria for full-text review. We will extract data onto a predefined form designed to summarise the key characteristics of each review. We will assess the methodological quality of included reviews and the quality of evidence in included reviews. ETHICS AND DISSEMINATION:Formal ethics approval is not required for this overview as we will only analyse published literature. The findings of this study will be presented at relevant conferences and submitted for peer-review publication. The results are likely to be used by clinicians, policy makers and developers of clinical guidelines and will inform suggestions for future systematic reviews and randomised controlled trials. PROSPERO REGISTRATION NUMBER:CRD42019120503.
Project description:OBJECTIVE:To address the significant uncertainty as to whether transfusion thresholds for critical care versus surgical patients should differ. DESIGN:Meta-analysis of randomized controlled trials. SETTING:Medline, EMBASE, and Cochrane Library searches were performed up to 15 June 2016. PATIENTS:Trials had to enroll adult surgical or critically ill patients for inclusion. INTERVENTIONS:Studies had to compare a liberal versus restrictive threshold for the transfusion of allogeneic packed RBCs. MEASUREMENTS AND MAIN RESULTS:The primary outcome was 30-day all-cause mortality, sub-grouped by surgical and critical care patients. Secondary outcomes included myocardial infarction, stroke, renal failure, allogeneic blood exposure, and length of stay. Odds ratios and weighted mean differences were calculated using random effects meta-analysis. To assess whether subgroups were significantly different, tests for subgroup interaction were used. Subgroup analysis by trials enrolling critically ill versus surgical patients was performed. Twenty-seven randomized controlled trials (10,797 patients) were included. In critical care patients, restrictive transfusion resulted in significantly reduced 30-day mortality compared with liberal transfusion (odds ratio, 0.82; 95% CI, 0.70-0.97). In surgical patients, a restrictive transfusion strategy led to the opposite direction of effect for mortality (odds ratio, 1.31; 95% CI, 0.94-1.82). The subgroup interaction test was significant (p = 0.04), suggesting that the effect of restrictive transfusion on mortality is statistically different for critical care (decreased risk) versus surgical patients (potentially increased risk or no difference). Regarding secondary outcomes, for critically ill patients, a restrictive strategy resulted in reduced risk of stroke/transient ischemic attack, packed RBC exposure, transfusion reactions, and hospital length of stay. In surgical patients, restrictive transfusion resulted in reduced packed RBC exposure. CONCLUSIONS:The safety of restrictive transfusion strategies likely differs for critically ill patients versus perioperative patients. Further trials investigating transfusion strategies in the perioperative setting are necessary.
Project description:<h4>Background</h4>We assessed the effect of liberal versus restrictive red blood cell transfusion strategy on survival outcome in sepsis or septic shock by systematically reviewing the literature and synthesizing evidence from randomized controlled trials (RCTs).<h4>Methods</h4>We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases. We included RCTs that compared mortality between a liberal transfusion strategy with a hemoglobin threshold of 9 or 10?g/dL and a restrictive transfusion strategy with a hemoglobin threshold of 7?g/dL in adults with sepsis or septic shock. Two investigators independently screened citations and conducted data extraction. The primary outcome was 28- or 30-day mortality. Secondary outcomes were 60- and 90-day mortality, use of life support at 28?days of admission, and number of patients transfused during their intensive care unit stay. DerSimonian-Laird random-effects models were used to report pooled odds ratios (ORs).<h4>Results</h4>A total of 1516 patients from three RCTs were included; 749 were randomly assigned to the liberal transfusion group and 767 to the restrictive strategy group. Within 28-30?days, 273 patients (36.4%) died in the liberal transfusion group, while 278 (36.2%) died in the restrictive transfusion group (pooled OR, 0.99; 95% confidence interval [CI], 0.67-1.46). For the primary outcome, heterogeneity was observed among the studies (I<sup>2</sup>?=?61.0%, ?<sup>2</sup>?=?5.13, p?=?0.08). For secondary outcomes, only two RCTs were included. There were no significant differences in secondary outcomes between the two groups.<h4>Conclusions</h4>We could not show any difference in 28- or 30-day mortality between the liberal and restrictive transfusion strategies in sepsis or septic shock patients by meta-analysis of RCTs. Our results should be interpreted with caution due to the existence of heterogeneity. As sepsis complicates a potentially wide range of underlying diseases, further trials in carefully selected populations are anticipated.<h4>Trial registration</h4>This present study was registered in the PROSPERO database (CRD42018108578).