title: Iron therapy for pre-operative anaemia.
abstract: BACKGROUND
  Pre-operative anaemia is common and occurs in up to 76% of patients. It is associated with increased peri-operative allogeneic blood transfusions, longer hospital lengths of stay and increased morbidity and mortality. Iron deficiency is one of the most common causes of this anaemia. Oral iron therapy has traditionally been used to treat anaemia but newer, safer parenteral iron preparations have been shown to be more effective in other conditions such as inflammatory bowel disease, chronic heart failure and post-partum haemorrhage. A limited number of studies look at iron therapy for the treatment of pre-operative anaemia. The aim of this Cochrane review is to summarise the evidence for use of iron supplementation, both enteral and parenteral, for the management of pre-operative anaemia.
  
  
  OBJECTIVE
  The objective of this review is to evaluate the effects of pre-operative iron therapy (enteral or parenteral) in reducing the need for allogeneic blood transfusions in anaemic patients undergoing surgery.
  
  
  METHODS
  We ran the search on 25 March 2015. 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, clinical trials registries, conference abstracts, and we screened reference lists.
  
  
  METHODS
  We included all randomised controlled trials (RCTs) which compared pre-operative iron monotherapy to placebo, no treatment, standard of care or another form of iron therapy for anaemic adults undergoing surgery. Anaemia was defined by haemoglobin values less than 13 g/dL for males and 12 g/dL for non-pregnant females.
  
  
  METHODS
  Data were collected by two authors on the proportion of patients who receive a blood transfusion, amount of blood transfused per patient (units) and haemoglobin measured as continuous variables at pre-determined time-points: pre-treatment, pre-operatively but post-treatment, and post-operatively. Statistical analysis was performed using the Cochrane statistical software, Review Manager 2014. Outcome data were summarised in tables and a forest plot.
  
  
  RESULTS
  Three prospective randomised controlled studies evaluated pre-operative iron therapy to correct anaemia (two in colorectal and one in gynaecological surgery) and included 114 patients in total. One compared oral iron versus standard care (Lidder 2007); one intravenous iron versus control (Edwards 2009); and one study compared oral versus intravenous iron (Kim 2009). Both colorectal trials reported the primary outcome (proportion of patients who received allogeneic blood transfusions) and meta-analysis showed a reduction in blood transfusions with the administration of iron therapy, but the reduction was not statistically significant (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.27 to 1.18). All studies reported haemoglobin change but data for the anaemic patients were only available for two studies (Edwards 2009 and Kim 2009). Edwards 2009 showed no difference in haemoglobin at the end of treatment pre-operatively. The intravenous versus oral iron study showed an increase in haemoglobin with intravenous iron at the end of treatment pre-operatively (MD 1.90 g/dL, 95% CI 1.16 to 2.64; participants = 56), but the results are at high risk of bias because participants with less than 80% compliance with therapy were excluded from the analysis and compliance was lower in the oral iron group due to the side-effects of treatment (Kim 2009).None of the studies reported quality of life, short- or long-term mortality or post-operative morbidity.
  
  
  CONCLUSIONS
  The use of iron therapy for pre-operative anaemia does not show a statistically significant reduction in the proportion of patients who received an allogeneic blood transfusion compared to no iron therapy. However, the 38 patients in our analysis falls far short of the 819 patients our information size calculation recommended to detect a 30% reduction in blood transfusions. Intravenous iron may be more effective than oral iron at increasing haemoglobin. However, all these conclusions are drawn from only three small randomised controlled studies. Further well designed, adequately powered randomised controlled studies are required to determine the true effectiveness of iron therapy for pre-operative anaemia.
authors.affiliation: Nottingham Digestive Disease Centre, E Floor West Block, Derby Rd, Nottingham, UK, NG7 2UH.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ng
authors.forename: Barrie D
authors.initials: BD
authors.lastname: Keeler
authors.forename: Amitabh
authors.initials: A
authors.lastname: Mishra
authors.forename: Alastair
authors.initials: A
authors.lastname: Simpson
authors.forename: Keith
authors.initials: K
authors.lastname: Neal
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Brookes
authors.forename: Austin G
authors.initials: AG
authors.lastname: Acheson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000740:Anemia / Q000097:blood / Q000628:therapy*; D001803:Blood Transfusion / Q000706:statistics & numerical data*; D005293:Ferritins / Q000097:blood; D006400:Hematocrit; D006441:Hemoglobin A / Q000032:analysis; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage*; D011300:Preoperative Care; D016032:Randomized Controlled Trials as Topic; D017701:Reticulocyte Count; D013514:Surgical Procedures, Operative
chemical_list: D005293:Ferritins; D006441:Hemoglobin A; D007501:Iron