Donat R Spahn1, Felix Schoenrath2, Gabriela H Spahn3, Burkhardt Seifert4, Philipp Stein3, Oliver M Theusinger5, Alexander Kaserer3, Inga Hegemann6, Axel Hofmann7, Francesco Maisano8, Volkmar Falk9. 1. Institute of Anaesthesiology, University of Zurich and University Hospital Zurich, Zurich, Switzerland. Electronic address: donat.spahn@usz.ch. 2. Department of Cardiothoracic and Vascular Surgery, German Heart Centre Berlin, Berlin, Germany; German Centre for Cardiovascular Research, partner site Berlin, Germany. 3. Institute of Anaesthesiology, University of Zurich and University Hospital Zurich, Zurich, Switzerland. 4. Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Switzerland. 5. Department of Anaesthesiology, University of Zurich and University Hospital Balgrist, Zurich, Switzerland. 6. Division of Haematology, University of Zurich and Zurich University Hospital, Zurich, Switzerland. 7. Institute of Anaesthesiology, University of Zurich and University Hospital Zurich, Zurich, Switzerland; School of Surgery, University of Western Australia and School of Public Health Research, Curtin University, Perth, Western Australia, Australia. 8. Department of Cardiovascular Surgery, University of Zurich and University Hospital Zurich, Zurich, Switzerland. 9. Department of Cardiothoracic and Vascular Surgery, German Heart Centre Berlin, Berlin, Germany; German Centre for Cardiovascular Research, Berlin, Germany; Department of Cardiothoracic Surgery, Charité - Universitätsmedizin Berlin Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Abstract
BACKGROUND:Anaemia and iron deficiency are frequent in patients scheduled for cardiac surgery. This study assessed whether immediate preoperative treatment could result in reduced perioperative red blood cell (RBC) transfusions and improved outcome. METHODS: In this single-centre, randomised, double-blind, parallel-group controlled study, patients undergoing elective cardiac surgery with anaemia (n=253; haemoglobin concentration (Hb) <120 g/L in women and Hb <130 g/L in men) or isolated iron deficiency (n=252; ferritin <100 mcg/L, no anaemia) were enrolled. Participants were randomly assigned (1:1) with the use of a computer-generated range minimisation (allocation probability 0·8) to receive either placebo or combination treatment consisting of a slow infusion of 20 mg/kg ferric carboxymaltose, 40 000 U subcutaneous erythropoietin alpha, 1 mg subcutaneous vitamin B12, and 5 mg oral folic acid or placebo on the day before surgery. Primary outcome was the number of RBC transfusions during the first 7 days. This trial is registered with ClinicalTrials.gov, number NCT02031289. FINDINGS:Between Jan 9, 2014, and July 19, 2017, 1006 patients were enrolled; 505 with anaemia or isolated iron deficiency and 501 in the registry. The combination treatment significantly reduced RBC transfusions from a median of one unit in the placebo group (IQR 0-3) to zero units in the treatment group (0-2, during the first 7 days (odds ratio 0·70 [95% CI 0·50-0·98] for each threshold of number of RBC transfusions, p=0·036) and until postoperative day 90 (p=0·018). Despite fewer RBC units transfused, patients in the treatment group had a higher haemoglobin concentration, higher reticulocyte count, and a higher reticulocyte haemoglobin content during the first 7 days (p≤0·001). Combined allogeneic transfusions were less in the treatment group (0 [IQR 0-2]) versus the placebo group (1 [0-3]) during the first 7 days (p=0·038) and until postoperative day 90 (p=0·019). 73 (30%) serious adverse events were reported in the treatment group group versus 79 (33%) in the placebo group. INTERPRETATION: An ultra-short-term combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12, and oral folic acid reduced RBC and total allogeneic blood product transfusions in patients with preoperative anaemia or isolated iron deficiency undergoing elective cardiac surgery. FUNDING: Vifor Pharma and Swiss Foundation for Anaesthesia Research.
RCT Entities:
BACKGROUND:Anaemia and iron deficiency are frequent in patients scheduled for cardiac surgery. This study assessed whether immediate preoperative treatment could result in reduced perioperative red blood cell (RBC) transfusions and improved outcome. METHODS: In this single-centre, randomised, double-blind, parallel-group controlled study, patients undergoing elective cardiac surgery with anaemia (n=253; haemoglobin concentration (Hb) <120 g/L in women and Hb <130 g/L in men) or isolated iron deficiency (n=252; ferritin <100 mcg/L, no anaemia) were enrolled. Participants were randomly assigned (1:1) with the use of a computer-generated range minimisation (allocation probability 0·8) to receive either placebo or combination treatment consisting of a slow infusion of 20 mg/kg ferric carboxymaltose, 40 000 U subcutaneous erythropoietin alpha, 1 mg subcutaneous vitamin B12, and 5 mg oral folic acid or placebo on the day before surgery. Primary outcome was the number of RBC transfusions during the first 7 days. This trial is registered with ClinicalTrials.gov, number NCT02031289. FINDINGS: Between Jan 9, 2014, and July 19, 2017, 1006 patients were enrolled; 505 with anaemia or isolated iron deficiency and 501 in the registry. The combination treatment significantly reduced RBC transfusions from a median of one unit in the placebo group (IQR 0-3) to zero units in the treatment group (0-2, during the first 7 days (odds ratio 0·70 [95% CI 0·50-0·98] for each threshold of number of RBC transfusions, p=0·036) and until postoperative day 90 (p=0·018). Despite fewer RBC units transfused, patients in the treatment group had a higher haemoglobin concentration, higher reticulocyte count, and a higher reticulocyte haemoglobin content during the first 7 days (p≤0·001). Combined allogeneic transfusions were less in the treatment group (0 [IQR 0-2]) versus the placebo group (1 [0-3]) during the first 7 days (p=0·038) and until postoperative day 90 (p=0·019). 73 (30%) serious adverse events were reported in the treatment group group versus 79 (33%) in the placebo group. INTERPRETATION: An ultra-short-term combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12, and oral folic acid reduced RBC and total allogeneic blood product transfusions in patients with preoperative anaemia or isolated iron deficiency undergoing elective cardiac surgery. FUNDING: Vifor Pharma and Swiss Foundation for Anaesthesia Research.
Authors: Serdar Günaydın; Donat R Spahn; Kanat Özışık; Aslı Demir; Göktan Aşkın; Doğan Emre Sert; Hale Bozkurt; Ali Şampiyon; Dilek Kazancı; Arnel Boke Kılıçlı; Şeref Alp Küçüker; Ümit Kervan; Mehmet Ali Özatik Journal: Turk Gogus Kalp Damar Cerrahisi Derg Date: 2020-07-28 Impact factor: 0.332
Authors: Toby Richards; Ravishankar Rao Baikady; Ben Clevenger; Anna Butcher; Sandy Abeysiri; Marisa Chau; Rebecca Swinson; Tim Collier; Matthew Dodd; Laura Van Dyck; Iain Macdougall; Gavin Murphy; John Browne; Andrew Bradbury; Andrew Klein Journal: Health Technol Assess Date: 2021-02 Impact factor: 4.014