In findings that challenge current guidance, a randomised controlled trial has found no evidence of clinical benefit in giving intravenous iron preoperatively to patients undergoing major abdominal surgery.
The UK study, published in The Lancet, is at odds with advice that patients with an expected blood loss of 500 mL or more should be screened for anaemia before surgery and treated with iron therapy if necessary.
In the multicentre study, 487 adult patients were screened for anaemia (less than 130 g/L for men and 120 g/L for women ) at preoperative hospital visits before elective major open abdominal surgery. Patients were then randomly assigned to receive intravenous iron (a single 1000 mg dose of ferric carboxymaltose in 100 mL normal saline) or placebo 10–42 days before surgery.
The overall findings were that intravenous iron increased haemoglobin concentrations before surgery, but did not reduce the frequency of blood transfusion or complications in the perioperative period relative to placebo.
At baseline, haemoglobin concentrations were similar between the placebo and intravenous iron groups (mean 111·0 and 111·2 g/L). Haemoglobin levels increased significantly in the intravenous iron group by the time of surgery (mean difference 4·7 g/L).
However, anaemia was corrected in only a minority of patients (21%) in the intravenous iron group compared with 10% of 243 patients in the placebo group (risk ratio 2·06).
The treatment effect on mean haemoglobin values was greater after surgery, when the mean difference in levels was 10·7 g/L, at eight weeks and 7.3 g/L at 6 months following intervention.
There were no differences in the other main outcome of blood transfusion or death, which occurred in 67 (28%) of the 237 patients in the placebo group and 69 (29%) of the 237 patients in the intravenous iron group (risk ratio 1·03).
Similarly there was no reduction in the risk of postoperative in-hospital complications or length of hospital stay, and no benefits to quality of life. However, there was a reduced risk of readmission to hospital for complications in those patients who received intravenous iron (13% vs 22% for placebo, rate ratio 0.61).
There were no significant differences between the two groups for any of the safety endpoints.
The study authors said their findings from a RCT in a large group of patients should overcome the uncertainty created by inconsistent findings from previous studies. They noted that a smaller trial of 72 patients in Australia found that intravenous iron for patients with iron deficiency anaemia (ferritin <300 μg/L, transferrin saturation <25%) did reduce perioperative blood transfusion (12% vs 31%).
They said the lack of benefit from intravenous iron might be due to the difficulty of correcting anaemia in a brief period (as little as 10 days) prior to surgery, and that treatment with concurrent erythropoietin might be required.
They said their findings were in agreement with a recently updated Cochrane review that found the use of iron therapy for preoperative anaemia did not show a clinically significant reduction in blood transfusion.
“The evidence base now suggests that current guidance on preoperative iron therapy by, for example, NHS England and NICE, should be revised and now state that preoperative iron therapy is not recommended in major elective surgery patients with anaemia,” they concluded.
Study lead author Professor Toby Richards, who is now at the University of WA, said it may well be that giving iron after an operation, rather than prior, can improve patients’ recovery.
“ The outcomes of this trial merit national bodies to rewrite guidelines,” he said.
“The reassuring aspect is that in this new era of COVID this trial supports one less visit to hospital and that patients are safe to proceed to operation, despite anaemia.”
In Australia, the most recent Patient Blood Management (PBM) guidelines from 2012 recommend that : “surgical patients with suboptimal iron stores (as defined by a ferritin level <100 μg/L) in whom substantial blood loss (blood loss of a volume great enough to induce anaemia that would require therapy) is anticipated, should be treated with preoperative iron therapy.
The Australia and NZ Society for Blood Transfusion also notes that a recent report found that currently about half (56%) of health services surveyed had formalised processes for preoperative anaemia assessment and management in elective surgical procedures.