Elsevier

The Lancet Haematology

Volume 4, Issue 10, October 2017, Pages e465-e474
The Lancet Haematology

Articles
Outcomes of restrictive versus liberal transfusion strategies in older adults from nine randomised controlled trials: a systematic review and meta-analysis

https://doi.org/10.1016/S2352-3026(17)30141-2Get rights and content

Summary

Background

Guidelines for patient blood management recommend restrictive transfusion practice for most adult patients. These guidelines are supported by evidence from randomised controlled trials (RCTs); however, one of the patient groups not explicitly examined in these studies is the geriatric population. We examined RCTs relevant to transfusion outcomes in older patients. Our aim was to determine whether special guidelines are warranted for geriatric patients, recognising the different pathophysiological characteristics of this group.

Methods

For this systematic review and meta-analysis, we searched PubMed, Scopus, and the Cochrane Library databases from their inception to May 5, 2017, for evidence relating to transfusion outcomes in adults aged 65 years and older. This criterion was widened to include RCTs where a substantial proportion of the study population was older than 65 years. We also included study populations of all clinical settings, and did not limit the search by date, language, or study type. For articles not in English, only available translations of the abstracts were reviewed. Studies were excluded if they did not specify age. Observational studies and duplicate patient and outcome data from studies that generated multiple publications were also excluded. We screened bibliographies of retrieved articles for additional publications. We analysed data extracted from published RCTs comparing restrictive and liberal transfusion strategies in older adults. We generated fixed effects risk ratios (RR) for pooled study data using the Mantel-Haenszel method. Primary outcomes were 30-day and 90-day mortality events for patients enrolled in restrictive and liberal transfusion study groups. We included intention-to-treat outcome data in the meta-analysis when available, otherwise we used per-protocol outcome data.

Findings

686 articles were identified by the search, and a further 37 by the snowball approach. Of these articles, 13 eligible papers described findings from nine RCTs (five trials investigating orthopaedic surgery, three cardiac surgery, and one oncology surgery; including 5780 patients). The risk of 30-day mortality was higher in older patients who followed a restrictive transfusion strategy than in those who followed a liberal transfusion strategy (risk ratio [RR] 1·36, 95% CI 1·05–1·74; p=0·017). The risk of 90-day mortality was also higher in those who followed a restrictive transfusion strategy than in those who followed a liberal transfusion strategy (RR 1·45, 95% CI 1·05–1·98; p=0·022).

Interpretation

Liberal transfusion strategies might produce better outcomes in geriatric patients than restrictive transfusion strategies. This outcome contradicts current restrictive transfusion approaches. Population ageing will challenge resources globally, and this finding has implications for blood supply and demand, and optimal care of older adults. Further research is needed to formulate evidence-based transfusion practice across clinical specialties specific to the geriatric population, and to examine resource effects.

Funding

Australia's National Blood Authority.

Introduction

Currently, a range of blood transfusion guidelines developed by diverse organisations in different countries exists. Guidelines are supported by studies that have reported that restrictive transfusion strategies do not produce worse outcomes than liberal strategies, with restrictive transfusion conserving resources and minimising patient exposure to allogenic blood.1, 2, 3, 4, 5 An accumulating body of evidence is based on randomised controlled trials (RCTs).1 One of the patient groups not explicitly examined in most studies of transfusion strategies is the geriatric population.6, 7, 8

Consideration of general guidelines and individual patient condition is important in making transfusion decisions.9 For geriatric patients, underlying comorbidities might alter their physiological reserve and their ability to respond to a range of stressors. Among the 15 diseases with the highest burden for the older adult population, those with implications for transfusion decision making include ischaemic heart disease, stroke, and chronic obstructive pulmonary disease.10 It is unclear whether increasing age per se creates circumstances of increased risk associated with anaemia and transfusion.11 The perceived frailty of a geriatric individual might be of greater importance than their chronological age when determining appropriate courses of treatment.12

Evidence regarding links between morbidity, mortality, and blood transfusion is conflicted. Some observational studies have reported worse outcomes associated with transfusion, such as increased mortality, cardiac complications, infection incidence, and length of hospital stay.13, 14 Several studies report no effect of transfusion on those outcomes, whereas some studies indicate reduced or increased numbers of complications and mortality associated with transfusion.13, 14

Research in context

Evidence before this study

Much effort has been directed towards development of patient blood management strategies and guidelines. There is now increased focus on assessment of individual risk and benefit during transfusion decision making. Paediatric guidelines have been published, recognising the special physiological needs of young patients. However, we did not identify any specific patient blood management guidelines for older patients.

We did a literature review and examined evidence from randomised controlled trials (RCTs) regarding transfusion outcomes for older patients. We searched PubMed, Scopus, and the Cochrane Library databases from their inception to May 5, 2017. The search was not limited by clinical setting, date, language, or study type. Articles not in English were excluded if translations of the abstracts were not available, and if studies did not specify age. Observational studies and duplicate patient and outcome data from studies that generated multiple publications were also excluded. Medical Subject Headings and free-text terms relating to the concepts of geriatric and transfusion were used. 13 papers relating to nine recent RCTs with a geriatric focus were identified. The studies examined orthopaedic, cardiac, and oncology surgery settings. Outcome data for 5780 patients from these RCTs were included in our meta-analysis and assessment of bias, following Cochrane and PRISMA methods.

Added value of this study

To our knowledge, this study is the first published meta-analysis of RCTs focused on geriatric-specific transfusion outcomes. Pooled RCT outcome data analysed in our study identify that liberal transfusion strategies had better geriatric patient outcomes with respect to 30-day and 90-day mortality and cardiovascular complications than restrictive transfusion strategies. Risk of myocardial infarction showed no difference; and risks of infections and length of hospital stay were equivalent between the transfusion groups. These findings bring into question the appropriateness of restrictive transfusion strategies for older patients. It highlights the need for geriatric-specific consideration in the development and revision of patient blood management guidelines, to bookend the paediatric guidelines that have been developed.

Implications of all the available evidence

There is a growing body of evidence from RCTs to address several conflicts in transfusion medicine. RCT evidence was identified that is specific to transfusion in older adults. Meta-analysis of these RCTs indicates that liberal transfusion strategies might provide better outcomes for the geriatric patient groups included in the studies than restrictive transfusion strategies. Further geriatric-specific studies are needed to guide the development and revision of patient blood management and transfusion guidelines for older adults.

Specific patient blood management guidelines have been developed to recognise the special needs of the paediatric population.15, 16 Patients aged 65 years and older (from now on referred to as older adults) use the greatest proportion of the blood supply.17, 18, 19 Recognising the accumulation of comorbidities and changes in physiological function and capacity with age, we postulate that specific patient blood management guidance is warranted for this older population.

In this paper, we critically assessed the findings from several RCTs that had examined restrictive versus liberal transfusion strategies in older adults, as distinct from the patient population of younger adults. We present a meta-analysis of outcome data related to mortality, cardiac complications, myocardial infarction, infection incidence, and length of hospital stay.

Section snippets

Search strategy and selection criteria

We did a systematic review following the PRISMA20 guideline to assess the quality and quantity of peer-reviewed, geriatric-transfusion-specific evidence. Subsequently, we did a meta-analysis with the RCTs yielded from the search.

The research team developed and agreed on the search and screening protocols (appendix p 1) before the database searches were done. The initial inclusion criteria of the search strategy were study findings specific to patients aged 65 years or older, and study

Results

Of 686 articles screened, 98 were reviewed in full (figure 1). 625 articles were excluded because the study population was not specific to geriatrics and transfusion. 13 papers described findings from nine RCTs, because two studies were represented by more than one paper each. The findings of the RCTs were published between 2009 and 2016, with eight (62%) of 13 papers published in 2015–16.

Nine geriatric-transfusion-related RCTs,6, 21, 22, 23, 24, 25, 32, 33, 34, 35, 36, 37, 38 representing 5780

Discussion

The meta-analysis of nine RCTs that focused on transfusion outcomes in older patients identified that a liberal rather than a restrictive transfusion strategy provided improved outcomes with respect to 30-day mortality, 90-day mortality, and composite cardiac complications. In these studies, transfusion strategy did not affect the infection incidence or influence length of hospital stay. The risk of myocardial infarction was lower in the liberal strategy cohort, but analysis did not reach

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