Iron treatment for low red blood cell count prior to surgery

Review question: we reviewed the evidence for giving iron treatment to people with a low red blood cell count (anaemia) before they had major surgery, to see if it reduced their need for blood transfusions around the time of surgery. We found six studies that looked at this question.

Background: anaemia is a common problem for people about to have surgery. Anaemia can cause dizziness, shortness of breath and lack of energy, as well as increase the risks of surgery and of blood transfusion. Anaemia is commonly due to lack of iron, and iron treatment - with tablets or injections - has been shown to be effective in other situations for treating anaemia. Limited research has looked at whether iron treatment works before surgery.

Search date: on 30 July 2018 we conducted a wide ranging search of the medical literature to identify relevant medical studies.

Study characteristics: 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.

Key results: 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.

Quality of evidence: 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.

Authors' conclusions: 

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.

Read the full abstract...
Background: 

Preoperative anaemia is common and occurs in 5% to 76% of patients preoperatively. It is associated with an increased risk of perioperative allogeneic blood transfusion, longer hospital stay, and increased morbidity and mortality. Iron deficiency is one of the most common causes of anaemia. Oral and intravenous iron therapy can be used to treat anaemia. Parenteral iron preparations have been shown to be more effective in conditions such as inflammatory bowel disease, chronic heart failure and postpartum haemorrhage due to rapid correction of iron stores. A limited number of studies has investigated iron therapy for the treatment of preoperative anaemia. The aim of this Cochrane Review is to summarise the evidence for iron supplementation, both enteral and parenteral, for the management of preoperative anaemia.

Objectives: 

To evaluate the effects of preoperative iron therapy (enteral or parenteral) in reducing the need for allogeneic blood transfusions in anaemic patients undergoing surgery.

Search strategy: 

We ran the search on 30 July 2018. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic and Embase (Ovid), CINAHL Plus (EBSCO), PubMed, and clinical trials registries, and we screened reference lists. We ran a top-up search on 28 November 2019; one study is now awaiting classification.

Selection criteria: 

We included all randomised controlled trials (RCTs) that compared preoperative iron monotherapy to placebo, no treatment, standard care or another form of iron therapy for anaemic adults undergoing surgery. We defined anaemia as haemoglobin values less than 13 g/dL for males and 12 g/dL for non-pregnant females.

Data collection and analysis: 

Two review authors collected data and a third review author checked all collected data. Data were collected on the proportion of patients who receive a blood transfusion, the amount of blood transfused per patient (units), quality of life, ferritin levels and haemoglobin levels, measured as continuous variables at the following predetermined time points: pretreatment (baseline), preoperatively but postintervention, and postoperatively. We performed statistical analysis using the Cochrane software, Review Manager 5. We summarised outcome data in tables and forest plots. We used the GRADE approach to describe the quality of the body of evidence.

Main results: 

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.

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