title: The effect of intravenous iron on postoperative transfusion requirements in hip fracture patients: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Anaemia following hip fracture is common. Approximately 30 to 45% of patients have haemoglobin concentrations below population norms on admission, and around 10% are severely anaemic. Anaemia on admission, and in the postoperative period, is associated with poor outcomes with regard to mobility, postoperative mortality and readmission. There is currently no clear consensus on the optimal method of managing perioperative anaemia in this group of frail patients with frequent comorbidity. Liberal red cell transfusion in the postoperative period does not appear to improve outcome, whereas tranexamic acid appears to reduce transfusion rate at the expense of increased cardiovascular morbidity. There are encouraging results from one centre with the use of agents to stimulate red cell production, including intravenous iron and erythropoietin. UK practice differs significantly from these patients and these studies, and it is not clear whether these promising results will translate to the UK population.
  
  
  METHODS
  This is a single-centre randomized controlled parallel group trial, in a British university hospital.Randomization is achieved using a website and computer-generated concealed tables. Participants are 80 patients 70 years or over with acute hip fracture undergoing operative repair. The intervention group receive three daily infusions of 200 mg iron sucrose, starting within 24 hours of admission. The control group receive standard hospital care at the discretion of the clinical team. Red cell transfusions for each group are given in accordance with standard clinical triggers. The primary outcome is an increase in mean reticulocyte count in the intervention group at day 7. Secondary outcome measures include haemoglobin concentrations, early and late transfusion rates, infectious and cardiovascular complications, mobility and 30-day mortality.
  
  
  CONCLUSIONS
  This is a pilot study to demonstrate haematopoietic efficacy of intravenous iron in this setting. Hence, we have chosen to measure change in reticulocyte count rather than the more clinically relevant differences in haemoglobin concentration or transfusion rate. If our results are positive, the study will provide the necessary information for development of a full-scale trial of intravenous iron.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN76424792; UK Medicines and Healthcare products Regulatory Authority (EuDRACT: 2011-003233-34).
authors.affiliation: Division of Anaesthesia and Intensive Care, University of Nottingham, Nottingham, UK. iain.moppett@nottingham.ac.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Rowlands
authors.forename: Daren P
authors.initials: DP
authors.lastname: Forward
authors.forename: Opinder
authors.initials: O
authors.lastname: Sahota
authors.forename: Iain K
authors.initials: IK
authors.lastname: Moppett
mesh_terms: D000368:Aged; D000740:Anemia / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D004739:England; D017707:Erythrocyte Transfusion; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077605:Ferric Oxide, Saccharated; D005592:Fracture Fixation / Q000009:adverse effects* / Q000401:mortality; D005937:Glucaric Acid / Q000008:administration & dosage* / Q000009:adverse effects; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects; D006454:Hemoglobins / Q000378:metabolism; D006620:Hip Fractures / Q000401:mortality / Q000601:surgery*; D006785:Hospitals, University; D006801:Humans; D007262:Infusions, Intravenous; D010865:Pilot Projects; D019106:Postoperative Hemorrhage / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D012107:Research Design; D017701:Reticulocyte Count; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005290:Ferric Compounds; D006397:Hematinics; D006454:Hemoglobins; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid
references.citation: JAMA. 1987 Apr 24;257(16):2181-4
references.pmid: 3560399
references.citation: Transfusion. 2003 Oct;43(10):1358-65
references.pmid: 14507265
references.citation: Injury. 2020 Jul;51(7):1419-1421
references.pmid: 32553413
references.citation: Crit Care Clin. 2010 Jul;26(3):527-47, x
references.pmid: 20643305
references.citation: Trials. 2011 Sep 28;12:213
references.pmid: 21955538
references.citation: Transfusion. 2003 Dec;43(12):1717-22
references.pmid: 14641869
references.citation: J Bone Joint Surg Am. 2010 Feb;92(2):265-9
references.pmid: 20124051
references.citation: Br J Anaesth. 2011 Apr;106(4):501-4
references.pmid: 21278153
references.citation: Transfusion. 1998 Jun;38(6):522-9
references.pmid: 9661685
references.citation: Vox Sang. 2005 May;88(4):235-43
references.pmid: 15877644
references.citation: Anaesthesia. 2010 Mar;65(3):243-8
references.pmid: 20039864
references.citation: Br J Anaesth. 2012 Oct;109(4):546-50
references.pmid: 22728204
references.citation: J Indian Med Assoc. 2009 Jun;107(6):403-5
references.pmid: 19886379
references.citation: Injury. 2011 Nov;42(11):1230-3
references.pmid: 21183180
references.citation: Transfusion. 2006 Dec;46(12):2192-206
references.pmid: 17176334
references.citation: Br J Anaesth. 2008 May;100(5):599-604
references.pmid: 18372258
references.citation: Lancet. 2010 Jul 3;376(9734):23-32
references.pmid: 20554319
references.citation: Age Ageing. 2012 May;41(3):322-6
references.pmid: 22083839
references.citation: Transfusion. 2004 Oct;44(10):1447-52
references.pmid: 15383017
references.citation: J Orthop Trauma. 2004 Jul;18(6):369-74
references.pmid: 15213502
references.citation: J Trauma. 2003 May;54(5):908-14
references.pmid: 12777903
references.citation: Arch Orthop Trauma Surg. 2005 Jun;125(5):342-7
references.pmid: 15789233
references.citation: JAMA. 2007 Jun 13;297(22):2481-8
references.pmid: 17565082
references.citation: N Engl J Med. 2011 Dec 29;365(26):2453-62
references.pmid: 22168590
references.citation: Age Ageing. 2008 Mar;37(2):173-8
references.pmid: 18349013
references.citation: Transfusion. 2011 Jan;51(1):97-104
references.pmid: 20630042
references.citation: BJOG. 2006 Nov;113(11):1248-52
references.pmid: 17004982
references.citation: Br J Anaesth. 2008 Oct;101(4):511-7
references.pmid: 18723517
references.citation: Eur J Clin Invest. 1995 Jun;25(6):383-9
references.pmid: 7656915
references.citation: Br J Anaesth. 2010 Jan;104(1):23-30
references.pmid: 19926634
references.citation: J Am Geriatr Soc. 2002 Jul;50(7):1257-64
references.pmid: 12133021
references.citation: Curr Opin Hematol. 2001 May;8(3):170-87
references.pmid: 11303151
references.citation: J Orthop Trauma. 2002 Jan;16(1):39-44
references.pmid: 11782632