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Meta-Analysis
. 2019 Dec 7;12(12):CD011588.
doi: 10.1002/14651858.CD011588.pub3.

Iron therapy for preoperative anaemia

Oliver Ng  1 , Barrie D Keeler  1 , Amitabh Mishra  1 , J A Simpson  1 , Keith Neal  2 , Hafid Omar Al-Hassi  3 , Matthew J Brookes  4 , Austin G Acheson  1
Affiliations
Meta-Analysis

Iron therapy for preoperative anaemia

Oliver Ng et al. Cochrane Database Syst Rev. .

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 methods: 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.

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.

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Conflict of interest statement

The lead author, ON, is in breach of Cochrane Commercial policy due to having received honoraria and travel support from Pharmacosmos (Denmark) and Vifor Pharma (Switzerland) within the last three years. The Cochrane Funding Arbiter's panel recommended that:

  1. a new, unconflicted author should check the data extraction and risk of bias tables;

  2. a member of the editorial group should check that this has been done;

  3. the final published version of the review should include a clear statement that the lead author is in breach of Cochrane Commercial policy together with a description of the Funding Arbiter Panel’s recommendation and the actions taken.

A new unconflicted author, HA, has independently checked all data extraction, 'Risk of bias' tables and conclusions, including Keeler 2017, to ensure there was no bias in the review findings, and has agreed that the reporting of the review was valid. Elizabeth Royle (Editor/Managing Editor for the Cochrane Injuries Group) also checked the data. The clear statement relating to the Funding Arbiter Panel's recommendation is quoted above.

MB's research department has received grant support from Syner‐Med (UK) and Vifor Pharma (Switzerland). MB has received honoraria and travel support for consulting or lecturing from Vifor Pharma and Merck Sharp and Dohme Limited (UK).

AA's research department has received grant support from Syner‐Med (UK), Vifor Pharma (Switzerland) and Pharmacosmos (Denmark). AA has received honoraria and travel support for consulting or lecturing from Ethicon (UK), Johnson & Johnson (UK), Olympus (UK) and Vifor Pharma (Switzerland).

BK, ON, JS, MB and AA are authors of one of the included trials, Keeler 2017, but AM independently extracted data from Keeler 2017 to avoid bias.

HA, KN, AS and AM have no interests to declare.

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. Six studies are included in this review.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Study flow diagram for combined searches to 30 July 2018 (fully incorporated into review)
4
4
Study flow diagram for 28 November 2019 top‐up searches (not completely incorporated into review)
1.1
1.1. Analysis
Comparison 1 Iron therapy versus placebo, no treatment or standard care, Outcome 1 Proportion of participants who received a blood transfusion.
1.2
1.2. Analysis
Comparison 1 Iron therapy versus placebo, no treatment or standard care, Outcome 2 Quality of life (SF‐36) 4 weeks postoperatively.
1.3
1.3. Analysis
Comparison 1 Iron therapy versus placebo, no treatment or standard care, Outcome 3 Haemoglobin levels preoperatively postintervention (g/dL).
1.4
1.4. Analysis
Comparison 1 Iron therapy versus placebo, no treatment or standard care, Outcome 4 Haemoglobin levels postintervention postoperatively (g/dL).
1.5
1.5. Analysis
Comparison 1 Iron therapy versus placebo, no treatment or standard care, Outcome 5 Ferritin level post‐treatment (ng/mL).
2.1
2.1. Analysis
Comparison 2 Intravenous versus oral iron therapy, Outcome 1 Number of participants who received a blood transfusion.
2.2
2.2. Analysis
Comparison 2 Intravenous versus oral iron therapy, Outcome 2 Number of units of red blood cells received.
2.3
2.3. Analysis
Comparison 2 Intravenous versus oral iron therapy, Outcome 3 Haemoglobin level preoperatively postintervention (g/dL).
2.4
2.4. Analysis
Comparison 2 Intravenous versus oral iron therapy, Outcome 4 Ferritin level pretreatment (ng/mL).
2.5
2.5. Analysis
Comparison 2 Intravenous versus oral iron therapy, Outcome 5 Ferritin level preoperatively postintervention (ng/mL).
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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References to other published versions of this review

Ng 2015a
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