Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion - PubMed (original) (raw)

Review

Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion

Jeffrey L Carson et al. Cochrane Database Syst Rev. 2016.

Update in

Abstract

Background: There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce resource, and in some countries, transfusions are less safe than others because of a lack of testing for viral pathogens. Therefore, reducing the number and volume of transfusions would benefit patients.

Objectives: The aim of this review was to compare 30-day mortality and other clinical outcomes in participants randomized to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all conditions. The restrictive transfusion threshold uses a lower haemoglobin level to trigger transfusion (most commonly 7 g/dL or 8 g/dL), and the liberal transfusion threshold uses a higher haemoglobin level to trigger transfusion (most commonly 9 g/dL to 10 g/dL).

Search methods: We identified trials by searching CENTRAL (2016, Issue 4), MEDLINE (1946 to May 2016), Embase (1974 to May 2016), the Transfusion Evidence Library (1950 to May 2016), the Web of Science Conference Proceedings Citation Index (1990 to May 2016), and ongoing trial registries (27 May 2016). We also checked reference lists of other published reviews and relevant papers to identify any additional trials.

Selection criteria: We included randomized trials where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered.

Data collection and analysis: We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two people extracted the data and assessed the risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as 'restrictive transfusion' and to the higher transfusion threshold as 'liberal transfusion'.

Main results: A total of 31 trials, involving 12,587 participants, across a range of clinical specialities (e.g. surgery, critical care) met the eligibility criteria. The trial interventions were split fairly equally with regard to the haemoglobin concentration used to define the restrictive transfusion group. About half of them used a 7 g/dL threshold, and the other half used a restrictive transfusion threshold of 8 g/dL to 9 g/dL. The trials were generally at low risk of bias .Some items of methodological quality were unclear, including definitions and blinding for secondary outcomes.Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 43% across a broad range of clinical specialties (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.49 to 0.65; 12,587 participants, 31 trials; high-quality evidence), with a large amount of heterogeneity between trials (I² = 97%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.97, 95% CI 0.81 to 1.16, I² = 37%; N = 10,537; 23 trials; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (high-quality evidence)). Liberal transfusion did not affect the risk of infection (pneumonia, wound, or bacteraemia).

Authors' conclusions: Transfusing at a restrictive haemoglobin concentration of between 7 g/dL to 8 g/dL decreased the proportion of participants exposed to RBC transfusion by 43% across a broad range of clinical specialities. There was no evidence that a restrictive transfusion strategy impacts 30-day mortality or morbidity (i.e. mortality at other points, cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. There were insufficient data to inform the safety of transfusion policies in certain clinical subgroups, including acute coronary syndrome, myocardial infarction, neurological injury/traumatic brain injury, acute neurological disorders, stroke, thrombocytopenia, cancer, haematological malignancies, and bone marrow failure. The findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds above 7 g/dL to 8 g/dL.

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Conflict of interest statement

Jeffrey Carson reports receiving grant support to his institution from the US National Institutes of Health. He is involved with guideline development and has received a grant from the US National Institutes of Health to evaluate transfusion thresholds in patients with acute myocardial infarction.

Carolyn Doree: nothing to declare.

Dean Ferugussion is a Co‐Prinical Investigator on the TRICSIII trial, and a member of the Steering Committee for the MINT trial.

Paul Hebert and Jeffrey Carson have received a grant from the Canadian Institutes of Health Research for a pilot trial of transfusion in patients with acute myocardial infarction.

Nareg Roubinian: nothing to declare.

Simon Stanworth has received funding for two RBC transfusion trials in patients with haematological malignancies.

Darryl Triluizi is a member of the Steering Committee for the MINT trial and a member of the scientific advisory board for Fresenius‐Kabi.

Figures

1

1

PRISMA Flow Diagram

2

2

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies. Thirty studies are included in this review.

3

3

'Risk of bias' summary: review authors' judgements about each methodological quality item for each included study.

4

4

Funnel plot of comparison: 1 Mortality, outcome: 1.1 30‐day mortality.

5

5

Funnel plot of comparison: 2 Blood transfusions, outcome: 2.1 Participants exposed to blood transfusion (all studies).

1.1

1.1. Analysis

Comparison 1 Mortality at 30 days, Outcome 1 30‐day mortality.

1.2

1.2. Analysis

Comparison 1 Mortality at 30 days, Outcome 2 30‐day mortality subgroup by restrictive haemoglobin level.

1.3

1.3. Analysis

Comparison 1 Mortality at 30 days, Outcome 3 30‐day mortality subgroup analysis by clinical specialities.

1.4

1.4. Analysis

Comparison 1 Mortality at 30 days, Outcome 4 30‐day mortality by clinical specialities: myocardial infarction versus all others.

1.5

1.5. Analysis

Comparison 1 Mortality at 30 days, Outcome 5 30‐day mortality in participants with cardiac surgery and myocardial infarction.

2.1

2.1. Analysis

Comparison 2 Subgroup analysis by registered trials, Outcome 1 30‐day mortality.

3.1

3.1. Analysis

Comparison 3 Sensitivity analysis by allocation concealment, Outcome 1 30‐day mortality.

4.1

4.1. Analysis

Comparison 4 Sensitivity analysis by blinding of outcome assessment, Outcome 1 30‐day mortality.

5.1

5.1. Analysis

Comparison 5 Mortality: other time intervals, Outcome 1 Hospital mortality.

5.2

5.2. Analysis

Comparison 5 Mortality: other time intervals, Outcome 2 90‐day mortality.

6.1

6.1. Analysis

Comparison 6 Blood transfusions, Outcome 1 Participants exposed to blood transfusion (all studies).

6.2

6.2. Analysis

Comparison 6 Blood transfusions, Outcome 2 Participants exposed to blood transfusion by clinical specialties.

6.3

6.3. Analysis

Comparison 6 Blood transfusions, Outcome 3 Participants exposed to blood transfusion (by transfusion threshold).

6.4

6.4. Analysis

Comparison 6 Blood transfusions, Outcome 4 Participants exposed to blood transfusion by transfusion threshold.

6.5

6.5. Analysis

Comparison 6 Blood transfusions, Outcome 5 Units of blood transfused.

7.1

7.1. Analysis

Comparison 7 Haemoglobin concentration, Outcome 1 Haemoglobin concentration.

8.1

8.1. Analysis

Comparison 8 Morbidity: clinical outcomes, Outcome 1 Cardiac events.

8.2

8.2. Analysis

Comparison 8 Morbidity: clinical outcomes, Outcome 2 Myocardial infarction.

8.3

8.3. Analysis

Comparison 8 Morbidity: clinical outcomes, Outcome 3 Congestive heart failure.

8.4

8.4. Analysis

Comparison 8 Morbidity: clinical outcomes, Outcome 4 Cerebrovascular accident (CVA) ‐ stroke.

8.5

8.5. Analysis

Comparison 8 Morbidity: clinical outcomes, Outcome 5 Rebleeding.

8.6

8.6. Analysis

Comparison 8 Morbidity: clinical outcomes, Outcome 6 Sepsis/bacteraemia.

8.7

8.7. Analysis

Comparison 8 Morbidity: clinical outcomes, Outcome 7 Pneumonia.

8.8

8.8. Analysis

Comparison 8 Morbidity: clinical outcomes, Outcome 8 Pneumonia or wound infection.

8.9

8.9. Analysis

Comparison 8 Morbidity: clinical outcomes, Outcome 9 Thromboembolism.

8.10

8.10. Analysis

Comparison 8 Morbidity: clinical outcomes, Outcome 10 Renal failure.

8.11

8.11. Analysis

Comparison 8 Morbidity: clinical outcomes, Outcome 11 Mental confusion.

9.1

9.1. Analysis

Comparison 9 Function and fatigue, Outcome 1 Function.

9.2

9.2. Analysis

Comparison 9 Function and fatigue, Outcome 2 Function and fatigue.

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