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1.
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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2.
Quality of evidence-based guidelines for transfusion of red blood cells and plasma: a systematic review
Pavenski K, Stanworth S, Fung M, Wood E M, Pink J, Murphy M F, Hume H, Nahirniak S, Webert K E, Tanael S, et al
Transfusion Medicine Reviews. 2018
Abstract
Many transfusion guidelines are available, but little appraisal of their quality has been undertaken. The quality of guidelines may potentially influence adoption. Our aim was to determine the quality of evidence-based transfusion guidelines (EBG) for red cells and plasma, using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, and assess duplication and consistency of recommendations. MEDLINE and EMBASE were systematically searched for EBG from 2005 to June 3, 2016. Citations were reviewed for inclusion in duplicate. A guideline was included if it had a specified clinical question, described a systematic search strategy, included critical appraisal of the literature and a description of how recommendations were developed. Four to six physicians used AGREE II to appraise each guideline. Median and scaled scores were calculated, with each item scored on a scale of one to seven, seven representing the highest score. Of 6174 citations, 30 guidelines met inclusion criteria. Twenty six guidelines had recommendations for red cells and 18 included recommendations for plasma use. The median score, the scaled score and the interquartile range of the scaled score were: scope and purpose: median score 5, scaled score 60%, IQR (49-74%); stakeholder involvement 4, 43%, (33-49%); rigor of development 4, 41%, (19-59%); clarity of presentation 5, 69%, (52-81%); applicability 1, 16%, (9-23%); editorial independence 3, 43%, (20-58%). Sixteen guidelines were evaluated to have a scaled domain score of 50% or less. Variations in recommendations were found for the use of hemoglobin triggers for red cell transfusion in patients with acute coronary syndromes and for plasma use for patients with bleeding. Our findings document, limited rigor in guideline development and duplication and inconsistencies in recommendations for the same topic. The process of developing guidelines for red cells and plasma transfusion can be enhanced to improve implementation.
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3.
The Age of BLood Evaluation (ABLE) randomised controlled trial: description of the UK-funded arm of the international trial, the UK cost-utility analysis and secondary analyses exploring factors associated with health-related quality of life and health-care costs during the 12-month follow-up
Walsh TS, Stanworth S, Boyd J, Hope D, Hemmatapour S, Burrows H, Campbell H, Pizzo E, Swart N, Morris S
Health Technology Assessment (Winchester, England). 2017;21((62)):1-118.
Abstract
BACKGROUND At present, red blood cells (RBCs) are stored for up to 42 days prior to transfusion. The relative effectiveness and safety of different RBC storage times prior to transfusion is uncertain. OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of transfusing fresher RBCs (stored for ≤ 7 days) compared with current standard-aged RBCs in critically ill patients requiring blood transfusions. DESIGN The international Age of BLood Evaluation (ABLE) trial was a multicentre, randomised, blinded trial undertaken in Canada, the UK, the Netherlands and France. The UK trial was funded to contribute patients to the international trial and undertake a UK-specific health economic evaluation. SETTING Twenty intensive care units (ICUs) in the UK, as part of 64 international centres. PARTICIPANTS Critically ill patients aged ≥ 18 years (≥ 16 years in Scotland) expected to require mechanical ventilation for ≥ 48 hours and requiring a first RBC transfusion during the first 7 days in the ICU. INTERVENTIONS All decisions to transfuse RBCs were made by clinicians. One patient group received exclusively fresh RBCs stored for ≤ 7 days whenever transfusion was required from randomisation until hospital discharge. The other group received standard-issue RBCs throughout their hospital stay. MAIN OUTCOME MEASURES The primary outcome was 90-day mortality. Secondary outcomes included development of organ dysfunction, new thrombosis, infections and transfusion reactions. The primary economic evaluation was a cost-utility analysis. RESULTS The international trial took place between March 2009 and October 2014 (UK recruitment took place between January 2012 and October 2014). In total, 1211 patients were assigned to receive fresh blood and 1219 patients to receive standard-aged blood. RBCs were stored for a mean of 6.1 days [standard deviation (SD) +/- 4.9 days] in the group allocated to receive fresh blood and 22.0 days (SD +/- 8.4 days) in the group allocated to receive standard-aged blood. Patients received a mean of 4.3 RBC units (SD +/- 5.2 RBC units) and 4.3 RBC units (SD +/- 5.5 RBC units) in the groups receiving fresh blood and standard-aged blood, respectively. At 90 days, 37.0% of patients in the group allocated to receive fresh blood and 35.3% of patients in the group allocated to receive standard-aged blood had died {absolute risk difference 1.7% [95% confidence interval (CI) -2.1% to 5.5%]}. There were no between-group differences in any secondary outcomes. The UK cohort comprised 359 patients randomised and followed up for 12 months for the cost-utility analysis. UK patients had similar characteristics and outcomes to the international cohort. Mean total costs per patient were pound32,346 (95% CI pound29,306 to pound35,385) in the group allocated to receive fresh blood and pound33,353 (95% CI pound29,729 to pound36,978) in the group allocated to receive standard-aged blood. Approximately 85% of the total costs were incurred during the index hospital admission. There were no significant cost differences between the two groups [mean incremental costs for those receiving fresh vs. standard-aged blood: - pound231 (95% CI - pound4876 to pound4415)], nor were there significant differences in outcomes (mean difference in quality-adjusted life-years -0.010, 95% CI -0.078 to 0.057). LIMITATIONS Adverse effects from the exclusive use of older RBCs compared with standard or fresh RBCs cannot be excluded. CONCLUSIONS The use of RBCs aged ≤ 7 days confers no clinical or economic benefit in critically ill patients compared with standard-aged RBCs. FUTURE WORK Future studies should address the safety of RBCs near the end of the current permitted storage age. TRIAL REGISTRATION Current Controlled Trials ISRCTN44878718. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 62. See the NIHR Journals Library website for further project information. The
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4.
A systematic review and meta-analysis of risks of red cell transfusion for neonatal morbidities or mortality
Keir AK, Pal S, Trivella M, Lieberman L, Callum J, Shehata N, Stanworth S
Vox Sanguinis. 2015;109((Suppl. 1)):31-32.. Abstract No. 3D-S12-02.
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5.
Adverse effects of RBC transfusions in neonates: a systematic review and meta-analysis
Keir A, Pal S, Trivella M, Lieberman L, Callum J, Sheheta N, Stanworth S
Abstracts of the HAA 2015 Annual Scientific Meeting. 2015;:196-7.. Abstract No. 151.
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6.
Red blood cell transfusion for people undergoing hip fracture surgery
Brunskill SJ, Millette SL, Shokoohi A, Pulford EC, Doree C, Murphy MF, Stanworth S
Cochrane Database of Systematic Reviews. 2015;((4))
Abstract
BACKGROUND The incidence of hip fracture is increasing and it is more common with increasing age. Surgery is used for almost all hip fractures. Blood loss occurs as a consequence of both the fracture and the surgery and thus red blood cell transfusion is frequently used. However, red blood cell transfusion is not without risks. Therefore, it is important to identify the evidence for the effective and safe use of red blood cell transfusion in people with hip fracture. OBJECTIVES To assess the effects (benefits and harms) of red blood cell transfusion in people undergoing surgery for hip fracture. SEARCH METHODS We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (31 October 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 10), MEDLINE (January 1946 to 20 November 2014), EMBASE (January 1974 to 20 November 2014), CINAHL (January 1982 to 20 November 2014), British Nursing Index Database (January 1992 to 20 November 2014), the Systematic Review Initiative's Transfusion Evidence Library, PubMed for e-publications, various other databases and ongoing trial registers. SELECTION CRITERIA Randomised controlled trials comparing red blood cell transfusion versus no transfusion or an alternative to transfusion, different transfusion protocols or different transfusion thresholds in people undergoing surgery for hip fracture. DATA COLLECTION AND ANALYSIS Three review authors independently assessed each study's risk of bias and extracted data using a study-specific form. We pooled data where there was homogeneity in the trial comparisons and the timing of outcome measurement. We used GRADE criteria to assess the quality (low, moderate or high) of the evidence for each outcome. MAIN RESULTS We included six trials (2722 participants): all compared two thresholds for red blood cell transfusion: a 'liberal' strategy to maintain a haemoglobin concentration of usually 10 g/dL versus a more 'restrictive' strategy based on symptoms of anaemia or a lower haemoglobin concentration, usually 8 g/dL. The exact nature of the transfusion interventions, types of surgery and participants varied between trials. The mean age of participants ranged from 81 to 87 years and approximately 24% of participants were men. The largest trial enrolled 2016 participants, over 60% of whom had a history of cardiovascular disease. The percentage of participants receiving a red blood cell transfusion ranged from 74% to 100% in the liberal transfusion threshold group and from 11% to 45% in the restrictive transfusion threshold group. There were no results available for the smallest trial (18 participants). All studies were at some risk of bias, in particular performance bias relating to the absence of blinding of personnel. We judged the evidence for all outcomes, except myocardial infarction, was low quality reflecting risk of bias primarily from imbalances in protocol violations in the largest trial and imprecision, often because of insufficient events. Thus, further research is likely to have an important impact on these results.There was no evidence of a difference between a liberal versus restricted threshold transfusion in mortality, at 30 days post hip fracture surgery (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.67 to 1.26; five trials; 2683 participants; low quality evidence) or at 60 days post surgery (RR 1.08, 95% CI 0.80 to 1.44; three trials; 2283 participants; low quality evidence). Assuming an illustrative baseline risk of 50 deaths per 1000 participants in the restricted threshold group at 30 days, these data equate to four fewer (95% CI 17 fewer to 14 more) deaths per 1000 in the liberal threshold group at 30 days.There was no evidence of a difference between a liberal versus restricted threshold transfusion in functional recovery at 60 days, assessed in terms of the inability to walk 10 feet (3 m) without human assistance (RR 1.00, 95% CI 0.87 to 1.15; two trials; 2083 participants; low quality evidence).There was low quality evidence of no difference betwe
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7.
Transfusion of fresher versus older red blood cells for all conditions
Brunskill SJ, Wilkinson KL, Doree C, Trivella M, Stanworth S
Cochrane Database of Systematic Reviews.. 2015;((5)):CD010801.
Abstract
BACKGROUND Red blood cell transfusion is a common treatment for anaemia in many clinical conditions. One current concern is uncertainty as to the clinical consequences (notably efficacy and safety) of transfusing red blood cell units that have been stored for different durations of time before a transfusion. If evidence from randomised controlled trials were to indicate that clinical outcomes are affected by storage age, the implications for inventory management and clinical practice would be significant. OBJECTIVES To assess the effects of using fresher versus older red blood cells in people requiring a red blood cell transfusion. SEARCH METHODS We ran the search on 29th September 2014. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), Embase (OvidSP), CINAHL (EBSCO), PubMed (for e-publications), three other databases and trial registers. SELECTION CRITERIA We included randomised controlled trials comparing fresher red blood cell transfusion versus active transfusion of older red blood cells, and comparing fresher red blood cell transfusion versus current standard practice. All definitions of 'fresher' and 'older'/'standard practice' red blood cells were included. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted from the trial report data on adverse red blood cell transfusion reactions, when reported. MAIN RESULTS We included 16 trials (1864 participants) in the review. Eight trials (279 participants) compared transfusion of fresher red blood cells versus transfusion of older stored red blood cells ('fresher' vs 'older'). Eight trials (1585 participants) compared the transfusion of fresher red blood cells versus current standard practice ('fresher' vs 'standard practice'). Five trials enrolled neonates, one trial enrolled children and 12 trials enrolled adults. Overall sample sizes were small: only two trials randomly assigned more than 100 participants.We performed no meta-analyses for a variety of reasons: no uniform definition of 'fresher' or 'older' red blood cell storage; overlap in the distribution of the age of red blood cells; and heterogeneity in measurements and reporting of outcomes of interest to this review. We tabulated and reported results by individual trial. Overall risk of bias was low or unclear, with four incidences of high risk of bias: in allocation concealment (three trials) and in incomplete outcome data (one trial).No trial measured all of the outcomes of interest in this review. Four trials comparing 'fresher' with 'older' red blood cells reported the primary outcome: mortality within seven days (one study; 74 participants) and at 30 days (three trials; 62 participants). Six trials comparing 'fresher' with 'standard practice' red blood cells reported the primary outcome: mortality within seven days (three studies; 159 participants) and at 30 days (three trials; 1018 participants). All 10 trials reported no clear differences in mortality at either time point between intervention arms.Three trials comparing 'fresher' with 'standard practice' red blood cells reported red blood cell transfusion-associated adverse events. No adverse reactions were reported in two trials, and one incidence of cytomegalovirus (CMV) infection was described in the 'standard practice' arm in one trial.Overall the trials reported no clear difference between either of the intervention comparisons in long-term mortality (three trials; 478 participants); clinically accepted measures of multiple organ dysfunction (two trials: 399 participants); incidence of in-hospital infection (two trials; 429 participants); duration of mechanical ventilation (three trials: 95 participants); and number of participants requiring respiratory organ support (five trials; 528 participants) or renal support (one trial; 57 participants). The outcome 'physiological markers of oxygen consumption or alterations in microcirculation' was reported by 11 studies, but the measures used were highly varied, and no formal statistical analysis was undert
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8.
Adverse effects of small-volume red blood cell transfusions in the neonatal population
Keir A, Pal S, Trivella M, Lieberman L, Callum J, Shehata N, Stanworth S
Systems Review. 2014;3((1):):92.
Abstract
BACKGROUND Adverse transfusion reactions in the neonatal population are poorly understood and defined. The incidence and pattern of adverse effects due to red blood cell (RBC) transfusion are not well known, and there has been no systematic review of published adverse events. RBC transfusions continue to be linked to the development of morbidities unique to neonates, including chronic lung disease, retinopathy of prematurity, intraventricular haemorrhage and necrotising enterocolitis. Uncertainties about the exact nature of risks alongside benefits of RBC transfusion may contribute to evidence of widespread variation in neonatal RBC transfusion practice.Our review aims to describe clinical adverse effects attributed to small-volume (10-20 mL/kg) RBC transfusions and, where possible, their incidence rates in the neonatal population through the systematic identification of all relevant studies. METHODS A comprehensive search of the following bibliographic databases will be performed: MEDLINE (PubMed/OVID which includes the Cochrane Library) and EMBASE (OVID). The intervention of interest is small-volume (10-20 mL/kg) RBC transfusions in the neonatal population.We will undertake a narrative synthesis of the evidence. If clinical similarity and data quantity and quality permit, we will also carry out meta-analyses on the listed outcomes. DISCUSSION This systematic review will identify and synthesise the reported adverse effects and associations of RBC transfusions in the neonatal population. We believe that this systematic review is timely and will make a valuable contribution to highlight an existing research gap. TRIAL REGISTRATION PROSPERO, CRD42013005107http://www.crd.york.ac.uk/PROSPERO/display_record.asp? ID=CRD42013005107.
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9.
The safety and efficacy of red cell transfusions in neonates: a systematic review of randomized controlled trials
Venkatesh V, Khan R, Curley A, Hopewell S, Doree C, Stanworth S
British Journal of Haematology. 2012;158((3):):370-85.
Abstract
Premature neonates commonly receive red blood cell (RBC) transfusions. This study systematically identified and appraised randomized controlled trials (RCTs) where the intervention was 'transfusion of red blood cells' from searches of multiple databases. Primary review outcomes were mortality, neurodevelopmental and respiratory endpoints. Two reviewers extracted data and assigned overall quality. Twenty-seven RCTs were identified and grouped into four predefined categories: trials comparing RBC transfusion versus no transfusion/placebo (n=3); different thresholds for transfusion (n=6); differing doses or administration schedule (n=4), or different types or products of RBC (n=14). In the threshold group of trials, enrolling 679 neonates, no significant differences in mortality (relative risk 1.22, 95% confidence interval 0.84-1.75) or chronic lung disease were found. Only two trials assessed neurodevelopment outcomes, both within the threshold group, but with differing results. The largest subgroup of RCTs by number evaluated different media for storage of red cells (n=7), enrolling 221 neonates. The methodological quality of many RCTs was poor. The design of future RCTs can be informed by the lessons from this review. Many trials failed to report on outcomes that would be considered of primary importance to clinicians. Consistent reporting of adverse events is required, and endpoints need to include neurodevelopmental outcomes. Copyright 2012 Blackwell Publishing Ltd.
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10.
The clinical effects of red blood cell transfusions: an overview of the randomized controlled trials evidence base
Wilkinson KL, Brunskill SJ, Doree C, Hopewell S, Stanworth S, Murphy MF, Hyde C
Transfusion Medicine Reviews. 2011;25((2):):145-155.e2.
Abstract
No up-to-date overview of randomized controlled trials (RCTs) in red blood cell (RBC) transfusion exists. This systematic review examines the quantity and quality of the evidence for the clinical effects of RBC transfusion. One hundred forty-two eligible RCTs were identified through searches of The Cochrane Library (issue 4, 2009), MEDLINE (1950 to November 2009), EMBASE (1974 to November 2009), and other relevant sources. After data extraction and methodological quality assessment, trials were grouped by clinical specialty and type of RBC transfusion. Data analysis was predominantly descriptive. The 142 RCTs covered 11 specialties and 10 types of RBC transfusion. The number of included patients varied widely across the RCTs (median, 57; IQ range, 27-167). Most trials were single center comparing 2 parallel study arms. Overall, the reporting of methodological assessment was poor, although it improved markedly from 2001. Clinical areas with few trials are highlighted. Comparison with a study of RBC use in clinical practice highlighted a lack of correlation between the size of the evidence base for a given clinical specialty and the proportion of total RBC use by that clinical specialty. The gaps in the evidence base and the poor methodology of trials particularly in the past do not provide a strong evidence base for the use of RBC transfusions, but they indicate important targets for future research. Crown Copyright Copyright 2011. Published by Elsevier Inc. All rights reserved.