Abstract: Six RCTs, with a total of 372 participants, evaluated preoperative iron therapy to correct anaemia before planned surgery. Four studies compared iron therapy (either oral (one study) or intravenous (three studies)) with no treatment, placebo or usual care, and two studies compared intravenous iron therapy with oral iron therapy. Iron therapy was delivered over a range of periods that varied from 48 hours to three weeks prior to surgery. The 372 participants in our analysis fall far short of the 819 required - as calculated by our information size calculation - to detect a 30% reduction in blood transfusions. Five trials, involving 310 people, reported the proportion of participants who received allogeneic blood transfusions. Meta-analysis of iron therapy versus placebo or standard care showed no difference in the proportion of participants who received a blood transfusion (risk ratio (RR) 1.21, 95% confidence interval (CI) 0.87 to 1.70; 4 studies, 200 participants; moderate-quality evidence). Only one study that compared oral versus intravenous iron therapy measured this outcome, and reported no difference in risk of transfusion between groups. There was no difference between the iron therapy and placebo/standard care groups for haemoglobin level preoperatively at the end of the intervention (mean difference (MD) 0.63 g/dL, 95% CI -0.07 to 1.34; 2 studies, 83 participants; low-quality evidence). However, intravenous iron therapy produced an increase in preoperative postintervention haemoglobin levels compared with oral iron (MD 1.23 g/dL, 95% CI 0.80 to 1.65; 2 studies, 172 participants; low-quality evidence). Ferritin levels were increased by intravenous iron, both when compared to standard care ((MD 149.00, 95% CI 25.84 to 272.16; 1 study, 63 participants; low-quality evidence) or to oral iron (MD 395.03 ng/mL, 95% CI 227.72 to 562.35; 2 studies, 151 participants; low-quality evidence). Not all studies measured quality of life, short-term mortality or postoperative morbidity. Some measured the outcomes, but did not report the data, and the studies which did report the data were underpowered. Therefore, uncertainty remains regarding these outcomes. The inclusion of new research in the future is very likely to change these results. The use of iron therapy for preoperative anaemia does not show a clinically significant reduction in the proportion of trial participants who received an allogeneic blood transfusion compared to no iron therapy. Results for intravenous iron are consistent with a greater increase in haemoglobin and ferritin when compared to oral iron, but do not provide reliable evidence. These conclusions are drawn from six studies, three of which included very small numbers of participants. Further, well-designed, adequately powered, RCTs are required to determine the true effectiveness of iron therapy for preoperative anaemia. Two studies are currently in progress, and will include 1500 randomised participants.

Plain-language summary: we looked at adults with anaemia who were due to have an operation, who received iron treatment or usual care, or a 'pretend' iron treatment (placebo) prior to their surgery. We also compared different forms of iron therapy with each other. We included six studies and a total of 372 participants. iron treatment did not reduce the risk of blood transfusion. There is currently insufficient evidence to say whether iron therapy given before surgery prevents transfusions. To date, too few studies involving too small a number of people have been undertaken, and it is not yet possible to obtain a reliable result for the effects of this treatment. the major limitation in study design for all trials was the small size of the sample groups. More research in larger, well-designed trials is needed before a definitive answer can be given about whether iron therapy before surgery is helpful. The Cochrane Review authors judged that five of the six studies included in this review were at a low risk of bias (and so their results are likely to be reliable). This was despite a lack of blinding of participants in five of the trials (which would usually decrease the reliability of the evidence), as the measurement used to assess how well the therapy had worked (blood haemoglobin level) was unlikely to be influenced by the participant or investigator knowing which treatment had been received. The results of one study are at a high risk of bias because participants who did not take 80% of their assigned treatment were not included in the analysis. Overall the quality of evidence is low (according to the GRADE criteria). When additional research becomes available in the future, it is likely to change the results obtained in this review.