When should blood transfusions be given after cardiac surgery?
Press release issued: 12 March 2015
New research led by the University of Bristol has shown that patients having heart surgery do not benefit if doctors wait until a patient has become substantially anaemic before giving a blood transfusion.
In the UK, about half of all patients having cardiac surgery are given a red blood cell transfusion after the operation, using up to ten per cent of the nation’s blood supply. The proportion of patients having a transfusion is high because blood loss and severe anaemia are common after cardiac surgery and transfusion is the preferred treatment. Blood loss causes anaemia which doctors detect by measuring the red cell count or haemoglobin level – a low level triggers transfusion.
The trial, led by academics at Bristol, and published in the New England Journal of Medicine, was carried out to resolve uncertainty about when to give blood transfusions after heart surgery. The trial, funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme, compared two groups of patients, one which had transfusions at a low haemoglobin level and the other which had transfusions at a higher haemoglobin level.
Cardiac surgery patients who receive blood transfusions are believed to have more complications such as infections, heart attacks and strokes, and this has led to speculation that avoidance of transfusion will improve clinical outcomes.
Unnecessary blood transfusions may also increase healthcare costs both directly, because blood is an increasingly scarce and expensive resource, and indirectly due to the complications associated with transfusion. However, the association between transfusions and complications does not necessarily mean that transfusions are bad for patients because sicker patients are more likely to have a transfusion. Better evidence is needed to guide transfusion decisions.
To resolve this issue doctors and researchers from the universities of Bristol and Oxford conducted a randomised controlled trial to compare policies of transfusing cardiac surgery patients at a ‘low’ or ‘high’ haemoglobin level. The aim of the study was to determine whether transfusing at a low level was safer, or more cost-effective, as has been shown in other patient groups.
Patients over 16 years of age undergoing non-emergency cardiac surgery were recruited to the clinical trial at 17 UK hospitals. Participants with a haemoglobin (Hb) level of less than 9 g/dL after their operations were randomised to have a transfusion either when they became substantially anaemic (transfuse when Hb is ‘low,’ i.e. less than 7.5 g/dL) or straightaway, when they were mildly anaemic (transfuse when Hb is ‘high,’ i.e. less than 9 g/dL).
To compare the two transfusion strategies the research team counted the number of patients who had a serious infection, stroke, heart attack, dead gut or kidney failure during the first three months after the operation. The trial analysed information for 2,003 participants, about four times more than the next largest similar trial of low and high thresholds for transfusion in patients having heart surgery.
The researchers found almost all the patients in the ‘high’ group had a blood transfusion (92 per cent), whereas just over half of the patients in the ‘low’ group had a blood transfusion (53 per cent).
Slightly more patients had one or more of the serious complications listed above in the ‘low’ group (35 per cent) than the ‘high’ group (33 per cent). Moreover, more patients died in the ‘low’ group (4.2 per cent) than the ‘high’ group (2.6 per cent). This latter finding is clearly very important but it is difficult to interpret because the trial was not primarily designed to compare the difference in the number of deaths.
There were no substantial differences between the ‘high’ and ‘low’ groups with respect to other information measured to assess recovery but some of the other findings in the trial showed a trend in the same direction. Health care costs up to three months after surgery were similar in the ‘high’ and ‘low’ groups. Based on the overall pattern of findings, the researchers propose a new theory that a ‘high’ or liberal threshold is better after cardiac surgery. This challenges most prevailing guidelines and current health policy.
Barnaby Reeves, Professorial Research Fellow in Health Services Research in the School of Clinical Sciences at the University of Bristol and corresponding author on the paper, said: “Although only a hypothesis, the suggestion that it might be better rather than worse to transfuse patients who are only mildly anaemic goes against the evidence about when to transfuse in non-cardiac surgery settings.
“Transfusing more rather than fewer patients would create a challenge for hospitals. With an ageing population and possibly an increase in heart disease, obesity and diabetes, it can only become more difficult in the future to maintain the national blood supply in the UK and in other developed countries around the world. Our findings emphasise the importance of interventions to reduce blood loss in the first place.”
Gavin Murphy, British Heart Foundation (BHF) Professor of Cardiac Surgery, formerly of Bristol’s School of Clinical Sciences and now at the University of Leicester, who led the trial, added: “Existing national and international transfusion guidelines recommend that blood transfusions only be given to patients who develop very low haemoglobin concentrations. We have shown that this strategy may increase the number of deaths in cardiac surgery.
“This was the largest randomised trial ever conducted in the UK in a surgical or cardiac surgery population. It was the largest trial ever conducted that has considered indications for transfusion in cardiac surgery, and recruited over twice the number of patients recruited in all the previous trials put together. It was a pragmatic effectiveness trial that recruited patients from the majority of NHS cardiac surgery centres in the UK and therefore reflects current UK practice and is relevant to UK patients.”
Sarah Wordsworth, Associate Professor of Health Economics in the Nuffield Department of Population Health at the University of Oxford, said “Even though the ‘high’ group were given more blood, it was interesting that this did not lead to them costing more once the costs of treating complications were added to the analysis.”
Professor Peter Weissberg, Medical Director at the British Heart Foundation (BHF), commented: “Donated blood is a precious commodity and needs to be used safely and effectively. While emergency blood transfusions are life-saving in patients who are bleeding heavily, it is unclear whether ‘topping up’ blood levels in patients with reduced blood counts after major surgery is beneficial. Indeed, some previous studies have suggested it may be harmful.
“This research did not show that topping up patients with modestly low blood counts was harmful. The results showed that it may actually reduce deaths in the weeks following surgery, although more research is needed to determine if this was a direct consequence of their transfusion or something else. Patients undergoing heart surgery in the UK can be reassured that they have a very good outcome regardless of the transfusion policy of their surgical unit.”
‘Liberal or restrictive transfusion after cardiac surgery’ by Gavin Murphy, Katie Pike, Chris Rogers, Sarah Wordsworth, Elizabeth Stokes, Gianni Angelini and Barnaby Reeves in the New England Journal of Medicine.
The trial was funded by a grant awarded to the University of Bristol by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme (ref: 06/402/94).
This article presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
The economic evaluation for the trial was carried out by Dr Sarah Wordsworth and Elizabeth Stokes from the University of Oxford’s Health Economics Research Centre (HERC) in the Nuffield Department of Population Health.
Barnaby Reeves, Professorial Research Fellow in Health Services Research in the School of Clinical Sciences, is part-funded by the NIHR Bristol Biomedical Research Unit in Cardiovascular Disease and this award also supported the research nurse team in Bristol.
Background information about transfusion
The benefits of red cell blood transfusions for managing life-threatening bleeding are clear but this situation only applies to a minority of patients undergoing surgery. In fact, the severity of anaemia (low red cell count or haemoglobin concentration) is usually (for about 80 per cent of patients) the information that guides doctors to transfuse a patient or not.
One strategy to reduce transfusion is only to transfuse patients who develop very severe anaemia (haemoglobin concentrations of 7.5 g/dL relative to normal concentrations in adults of greater than 12 g/dL for women and greater than 13 g/dL for men).
Randomised trials to measure the effects of ‘restrictive’ transfusion strategy, compared to transfusing when anaemia is less severe (a ‘liberal’ strategy) in non-cardiac surgery patients, indicate that restrictive practice in all probability reduces death rates. Restrictive practice is now recommended in most transfusion guidelines and more recently in NHS England’s Patient Blood Management Strategy.
However, severe anaemia represents a specific risk to patients with heart disease and there is uncertainty as to whether the findings of this previous research should apply to cardiac surgery patients. This uncertainty is reflected by wide variations in clinical practice, with transfusion rates varying from 25 per cent to 75 per cent of patients between centres in the UK.
About the NIHR HTA
The National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme funds research about the effectiveness, costs, and broader impact of health technologies for those who use, manage and provide care in the NHS. It is the largest NIHR programme and publishes the results of its research in the Health Technology Assessment journal, with over 700 issues published to date. The journal’s 2013 Impact Factor (5.116) ranked it two out of 85 publications in the Health Care Sciences and Services category. All issues are available for download, free of charge, from the website. The HTA Programme is funded by the NIHR, with contributions from the CSO in Scotland, NISCHR in Wales, and the HSC R&D Division, Public Health Agency in Northern Ireland.
About the NIHR
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