Iron supplementation to treat anaemia in adult critical care patients: a systematic review and meta-analysis.
BACKGROUND
Anaemia affects 60-80 % of patients admitted to intensive care units (ICUs). Allogeneic red blood cell (RBC) transfusions remain the mainstay of treatment for anaemia but are associated with risks and are costly. Our objective was to assess the efficacy and safety of iron supplementation by any route, in anaemic patients in adult ICUs.


METHODS
Electronic databases (CENTRAL, MEDLINE, EMBASE) were searched through March 2016 for randomized controlled trials (RCT)s comparing iron by any route with placebo/no iron. Primary outcomes were red blood cell transfusions and mean haemoglobin concentration. Secondary outcomes included mortality, infection, ICU and hospital length of stay, mean difference (MD) in iron biomarkers, health-related quality of life and adverse events.


RESULTS
Five RCTs recruiting 665 patients met the inclusion criteria; intravenous iron was tested in four of the RCTs. There was no difference in allogeneic RBC transfusion requirements (relative risk 0.87, 95 % confidence interval (CI) 0.70 to 1.07, p = 0.18, five trials) or mean number of RBC units transfused (MD -0.45, 95 % CI -1.34 to 0.43, p = 0.32, two trials) in patients receiving or not receiving iron. Similarly, there was no difference between groups in haemoglobin at short-term (up to 10 days) (MD -0.25, 95 % CI -0.79 to 0.28, p = 0.35, three trials) or mid-term follow up (last measured time point in hospital or end of trial) (MD 0.21, 95 % CI -0.13 to 0.55, p = 0.23, three trials). There was no difference in secondary outcomes of mortality, in-hospital infection, or length of stay. Risk of bias was generally low although three trials had high risk of attrition bias; only one trial had low risk of bias across all domains.


CONCLUSIONS
Iron supplementation does not reduce RBC transfusion requirements in critically ill adults, but there is considerable heterogeneity between trials in study design, nature of interventions, and outcomes. Well-designed trials are needed to investigate the optimal iron dosing regimens and strategies to identify which patients are most likely to benefit from iron, together with patient-focused outcomes.


BACKGROUND
PROSPERO International prospective register of systematic reviews CRD42015016627 . Registered 2 March 2015.
Nuffield Department of Anaesthetics, Level 2 John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. akshayshah@doctors.org.uk.
Akshay
http://orcid.org/0000-0002-1869-2231
A
Shah
Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Noémi B
NB
Roy
Nuffield Department of Anaesthetics, Level 2 John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Stuart
S
McKechnie
Systematic Review Initiative, NHS Blood & Transplant, Oxford, UK.
Carolyn
C
Doree
Systematic Review Initiative, NHS Blood & Transplant, Oxford, UK.
Sheila A
SA
Fisher
NHS Blood and Transplant, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK.|Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Simon J
SJ
Stanworth
Anaemia; Haemoglobin; Iron; Meta-analysis; Red blood cell; Transfusion
Cochrane Database Syst Rev. 2011 Oct 05;(10):CD003094
21975735
Crit Care Med. 2008 Sep;36(9):2667-74
18679112
Crit Care Med. 2000 Aug;28(8):2773-8
10966249
Crit Care. 2016 Sep 29;20(1):306
27681259
Intensive Care Med. 2006 Jan;32(1):100-9
16328221
Sci Transl Med. 2014 May 7;6(235):235re3
24807559
Interact Cardiovasc Thorac Surg. 2012 Dec;15(6):1013-8
22940889
Transfusion. 2004 Oct;44(10):1405-11
15383011
Transfusion. 2012 Jul;52(7):1584-92
22211566
Intensive Care Med. 2010 Jul;36(7):1138-46
20440603
Am J Kidney Dis. 1999 Oct;34(4 Suppl 2):S47-52
10516376
JAMA. 2002 Sep 25;288(12):1499-507
12243637
J Cardiothorac Vasc Anesth. 2004 Feb;18(1):59-63
14973801
Circulation. 2007 Nov 27;116(22):2544-52
17998460
Transfus Med Rev. 2011 Apr;25(2):89-101
21345639
Surg Infect (Larchmt). 2009 Feb;10(1):9-19
19245362
Cochrane Database Syst Rev. 2012 Jan 18;1:CD007857
22258974
BMJ. 2013 Aug 15;347:f4822
23950195
Crit Care Med. 2014 Sep;42(9):2048-57
24797376
Transfusion. 2011 May;51(5):943-8
21077908
Crit Care Resusc. 2014 Dec;16(4):285-90
25437223
Am J Respir Crit Care Med. 2012 May 15;185(10):1049-57
22281832
Eur J Heart Fail. 2016 Jul;18(7):774-85
27121474
Am J Hematol. 2013 Feb;88(2):97-101
23335357
BMJ. 2010 Sep 03;341:c4408
20817679
Stat Med. 2008 Dec 20;27(29):6072-92
18800342
BMJ. 2003 Sep 6;327(7414):557-60
12958120