Evidence
Alert

People with anaemia may not benefit from iron therapy ahead of major abdominal surgery, research finds

People with anaemia who were due to have major abdominal surgery did not see the expected benefits from receiving iron infusions in advance. A new study found that iron infusions did not reduce blood transfusions or deaths compared to a dummy treatment with salt water (placebo). There was no reduction in complications while people were in hospital and no reduction in the length of hospital stay.

Current guidelines recommend that patients with anaemia – whose red blood cell count (haemoglobin level) is lower than normal – have iron infusions ahead of surgery. But the PREVENTT trial – the first major study to assess the value of iron therapy in this setting – found no benefits for patients around the time of surgery.

The results strongly suggest that iron infusion ahead of major abdominal surgery is unnecessary for all patients with anaemia. They do not need to make this extra hospital visit.

However, PREVENTT found that people who received iron were less likely to have to go back to hospital with complications later. This implies that iron therapy could help in the recovery process. The researchers suggest that iron infusions could be given after surgery, before the patient is discharged.

What’s the issue?

Many patients (30% to 60%) due to have major planned surgery, have anaemia. This can mean they are tired, less fit, and not physically well-prepared for the stresses of a big operation.

It has been thought that this could result in a longer hospital stay, complications, poor recovery and an increased chance of needing a blood transfusion compared to people who do not have anaemia.

Current guidance exists from NICE and the NHS England Commissioning for Quality and Innovation Scheme for 2020-21. It recommends that patients about to have major surgery, in which they would be expected to lose 500 millilitres or more of blood, should be screened for anaemia in advance.

Iron infusion is recommended for people with anaemia. The iron is given by intravenous drip, directly into the bloodstream. This is usually done during an outpatient visit to hospital a couple of weeks before surgery.

However, this practice is based on limited evidence and has not been comprehensively tested in a clinical trial. A major review of the research in this field by experts (Cochrane review) in December 2019 found that iron infusions given to people with anaemia do not reduce their need for blood transfusions around the time of major surgery. But it called for more and better research.

The PREVENTT study informs the debate. It tested whether intravenous iron given to patients before major abdominal surgery would reduce deaths and the need for blood transfusion.

What’s new?

The study provides the highest quality evidence to date. It included 487 adult patients with anaemia who were due to have surgery at 46 different hospitals in the UK. Half were given the iron infusion 10-42 days prior to surgery. The other half received placebo (salt water).

All underwent abdominal surgery lasting three to four hours between 2014 and 2018. The researchers compared outcomes among those who received iron with those in the placebo group.

The key findings were that:

  • rates of death were similar in each group (4-5%)
  • numbers of blood transfusions due to blood loss were also similar (28-29%).

The study found that iron infusions corrected anaemia in only a minority of patients. They did not reduce the length of hospital stay or the chance of complications in patients while in hospital for surgery. There were no benefits to quality of life either before surgery or in the six months afterwards.

However:

  • giving iron ahead of surgery did increase haemoglobin levels
  • fewer patients who received iron had complications after leaving hospital, and they were less likely to be readmitted (13% compared with 22% in the placebo group)
  • people who received iron had a higher haemoglobin levels six months later.

Why is this important?

People with anaemia come into hospital to receive the iron infusion ahead of surgery. Oral iron tablets work too slowly to make a difference before surgery. The treatment requires an extra hospital visit, taking up nursing staff time and patients’ time.

The most common cause of anaemia is iron deficiency. It can be caused by inadequate iron intake in the diet or excess loss through bleeding. In addition, chronic illness that causes inflammation can disrupt the body’s ability to use its stores of iron. But PREVENTT found that, regardless of the cause of anaemia, iron infusions did not reduce the need for blood transfusion during surgery.

The lack of clear benefit to preoperative iron infusions led researchers to say that giving it routinely before surgery to people with anaemia is of no benefit. The results are reassuring during the coronavirus pandemic, during which people with underlying health conditions face a greater threat from COVID-19. There is no need for the extra hospital visit.

What’s next?

There is a growing body of research and opinion on the use of iron infusions ahead of surgery. Many groups have been using and promoting its use. PREVENTT provides the first large well-conducted trial to address the question, and the emerging results do not concur with current NHS England and NICE guidelines on preoperative iron therapy. The researchers say that the PREVENTT results make a strong case for the guidelines to be reviewed.

Further investigation is warranted on the link between iron infusion and the correction of anaemia after surgery, the potential benefits in recovery and in reducing hospital readmissions. The researchers suggest that iron infusions could be given easily and efficiently after surgery, while patients are still in hospital. Future research is needed to confirm this.

You may be interested to read

The full paper: Richards T, and others. Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT): a randomised, double-blind, controlled trial. Lancet. 2020;396:1353–1361

Study on iron therapy in people with anaemia having surgery for colorectal cancer: Keeler BD, and others. Randomized clinical trial of preoperative oral versus intravenous iron in anaemic patients with colorectal cancer. Br J Surg. 2017;104:214-221

Further research on use of iron before abdominal surgery: Froessler B, and others. The Important Role for Intravenous Iron in Perioperative Patient Blood Management in Major Abdominal Surgery: A Randomized Controlled Trial. Ann Surg. 2016;264:41-46

Study examining anaemia in heart patients: Spahn DR, and others. Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial. Lancet. 2019;393:2201-2212

NICE guidance: Blood transfusion [NG24] (2015)

The Cochrane Library review: Ng O, and others. Iron therapy for preoperative anaemia. Cochrane Library. 2019. doi: 10.1002/14651858.CD011588.pub3

Funding

This study was funded by the NIHR Health Technology Assessment Programme.

Commentaries

Study author

These findings are clear and mean that patients with anaemia do not need to have the additional treatment of intravenous iron therapy before surgery. We were really surprised at the trial findings, as this seemed a sensible and plausible solution for patients with anaemia. But it really does highlight the fact that an idea, no matter how apparent, should always be tested properly in the setting of a clinical trial. This trial shows that the guidelines should change; that intravenous iron should not be a standard of care for treatment of anaemia; and that intravenous iron is not a one-size-fits-all treatment. However, the results are timely and offer reassurance that patients are not being disadvantaged because of COVID-19.

An interesting secondary finding in PREVENTT was that after the operation, those people who had placebo often remained anaemic up to six months later whereas those who received intravenous iron therapy to correct their haemoglobin had fewer complications requiring readmission to hospital.

Toby Richards, Professor of Surgery at the University of Western Australia and also University of London

Lived experience

The findings contradict current guidelines on iron treatment before surgery and make the case for a change to practice. There are, and are going to be more, financial constraints on the NHS during and post-COVID. So while there was no indication of how much this pre-op iron treatment costs, if it is ineffective, then there is a cost saving to be made.

As a previous surgery patient, I know how stressful the pre-op period is. To be called in for treatments that don’t have an effect seems unnecessarily harsh. Although it was a relatively small sample size, the findings were clear and seemed to echo previous findings. Also, covering 46 sites means that different social, ethnic and cultural backgrounds will have been taken into account.

Mel Guthrie, Public Contributor, West Midlands

Surgeon

This paper builds on recent randomized evidence that routinely using iron transfusions before major abdominal surgery for people with anaemia of all causes – not just those with iron deficiency – does improve haemoglobin levels, but not outcomes (including blood transfusions, major complications, death and length of stay). The finding is somewhat unexpected and will have an impact in centres where iron transfusions are routinely given.

Further research is needed to explore the lack of benefit from iron transfusions in people with anaemia due to iron deficiency.

John Findlay, Consultant Upper GI and Abdominal Wall Surgeon, North Devon Comprehensive Hernia Centre, North Devon District Hospital

Conflicts of Interest

Several authors have received fees and funding from pharmaceutical companies.