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      What is the effect of perioperative intravenous iron therapy in patients undergoing non-elective surgery? A systematic review with meta-analysis and trial sequential analysis

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          Abstract

          Background

          Guidelines to treat anaemia with intravenous (IV) iron have focused on elective surgical patients with little attention paid to those undergoing non-elective/emergency surgery. Whilst these patients may experience poor outcomes because of their presenting illness, observational data suggests that untreated anaemia may also be a contributing factor to poor outcomes. We conducted a systematic review to investigate the safety and efficacy of IV iron in patients undergoing non-elective surgery.

          Methods

          We followed a pre-defined review protocol and included randomised controlled trials (RCTs) in patients undergoing non-elective surgery who received IV iron. Primary outcomes were all-cause infection and mean difference in haemoglobin (Hb) at follow-up. Secondary outcomes included transfusion requirements, hospital length of stay (LOS), health-related quality of life (HRQoL), mortality and adverse events.

          Results

          Three RCTs (605 participants) were included in this systematic review of which two, in both hip fracture (HF) patients, provided data for meta-analysis. Both of these RCTs were at low risk of bias. We found no evidence of a difference in the risk of infection (RR 0.99, 95% CI 0.55 to 1.80, I 2 = 9%) or in the Hb concentration at ‘short-term’ (≤ 7 days) follow-up (mean difference − 0.32 g/L, 95% CI − 3.28 to 2.64, I 2 = 37%). IV iron did not reduce the risk of requiring a blood transfusion (RR 0.90, 95% CI 0.73 to 1.11, p = 0.46, I 2 = 0%), and we observed no difference in mortality, LOS or adverse events. One RCT reported on HRQoL and found no difference between treatment arms.

          Conclusion

          We found no conclusive evidence of an effect of IV iron on clinically important outcomes in patients undergoing non-elective surgery. Further adequately powered trials to evaluate its benefit in emergency surgical specialties with a high burden of anaemia are warranted.

          Trial registration

          This systematic review was registered on PROSPERO ( CRD42018096288)

          Electronic supplementary material

          The online version of this article (10.1186/s13741-018-0109-4) contains supplementary material, which is available to authorized users.

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          Most cited references18

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          International consensus statement on the peri-operative management of anaemia and iron deficiency.

          M Muñoz, A Acheson, M Auerbach … (2017)
          Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources.
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            Hepcidin in the diagnosis of iron disorders.

            Domenico Girelli, Elizabeta Nemeth, Dorine W. Swinkels (2016)
            The discovery of the iron-regulatory hormone hepcidin in 2001 has revolutionized our understanding of iron disorders, and its measurement should advance diagnosis/treatment of these conditions. Although several assays have been developed, a gold standard is still lacking, and efforts toward harmonization are ongoing. Nevertheless, promising applications can already be glimpsed, ranging from the use of hepcidin levels for diagnosing iron-refractory iron deficiency anemia to global health applications such as guiding safe iron supplementation in developing countries with high infection burden.
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              Anaemia impedes functional mobility after hip fracture surgery.

              N. Foss, Morten Tange Kristensen, Henrik Kehlet (2008)
              the impact of anaemia on the outcome after a hip fracture surgery is controversial, but anaemia can potentially decrease the physical performance and thereby impede post-operative rehabilitation. We therefore conducted a prospective study to establish whether anaemia affected functional mobility in the early post-operative phase after a hip fracture surgery. four hundred and eighty seven consecutive hip fracture patients, treated according to a well-defined multimodal rehabilitation programme with a uniform, liberal transfusion threshold, were studied. Hb was measured on each of the first three post-operative days, and anaemia defined as Hb <100 g/l. Functional mobility was measured with the Cumulated Ambulation Score (CAS). the results were obtained from 170, 132 and 116 patients who were found anaemic on the first, second and third post-operative day, respectively. A significant association between anaemia and the ability to walk independently before the correction of anaemia was present on each of the 3 days separately (P<0.05). A significant correlation was also found on each day between the functional score and the Hb level. A multivariate analysis integrating the type of surgery, medical complications and prefracture function showed that anaemia at the time of the physiotherapy session was an independent risk factor for not being able to walk on the third post-operative day [OR 0.41 (0.14-0.73) P = 0.002]. anaemia impedes functional mobility in the early post-operative phase after a hip fracture surgery and is an independent risk factor for patients not being able to walk post-operatively. The potential for a liberal transfusion policy to improve the rehabilitation potential in hip fracture patients with anaemia should be investigated.
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                Author and article information

                Contributors
                Akshay Shah:
                ORCID: http://orcid.org/0000-0002-1869-2231
                +441865387906 , Akshay.shah@ndcls.ox.ac.uk
                Journal
                Journal ID (nlm-ta): Perioper Med (Lond)
                Journal ID (iso-abbrev): Perioper Med (Lond)
                Title: Perioperative Medicine
                Publisher: BioMed Central (London )
                ISSN (Electronic): 2047-0525
                Publication date (Electronic): 12 December 2018
                Publication date PMC-release: 12 December 2018
                Publication date Collection: 2018
                Volume: 7
                Electronic Location Identifier: 30
                Affiliations
                [1 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Radcliffe Department of Medicine, John Radcliffe Hospital, , University of Oxford, ; Level 4 Academic Block, Oxford, OX3 9DU UK
                [2 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, , University of Oxford, ; Oxford, UK
                [3 ]ISNI 0000 0004 0581 2008, GRID grid.451052.7, Frimley Health NHS Foundation Trust, ; Camberley, Surrey GU16 7UJ UK
                [4 ]ISNI 0000 0000 8685 6563, GRID grid.436365.1, Systematic Review Initiative, NHS Blood & Transplant, ; Oxford, UK
                [5 ]GRID grid.410725.5, Brighton and Sussex University Hospitals NHS Trust, ; Brighton, UK
                Author information
                http://orcid.org/0000-0002-1869-2231
                Article
                Publisher ID: 109
                DOI: 10.1186/s13741-018-0109-4
                PMC ID: 6290500
                PubMed ID: 30559962
                SO-VID: ef318381-ab64-4105-80c2-4838f7765e64
                Copyright © © The Author(s). 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 14 September 2018
                Date accepted : 13 November 2018
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                Keywords: anaemia,iron,surgery
                Data availability:
                Keywords: anaemia, iron, surgery

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