title: Effect of Fibrinogen Concentrate on Intraoperative Blood Loss Among Patients With Intraoperative Bleeding During High-Risk Cardiac Surgery: A Randomized Clinical Trial.
abstract: Fibrinogen concentrate might partly restore coagulation defects and reduce intraoperative bleeding.
  
  
  
  To determine whether fibrinogen concentrate infusion dosed to achieve a plasma fibrinogen level of 2.5 g/L in high-risk cardiac surgery patients with intraoperative bleeding reduces intraoperative blood loss.
  
  
  
  A randomized, placebo-controlled, double-blind clinical trial conducted in Isala Zwolle, the Netherlands (February 2011-January 2015), involving patients undergoing elective, high-risk cardiac surgery (ie, combined coronary artery bypass graft [CABG] surgery and valve repair or replacement surgery, the replacement of multiple valves, aortic root reconstruction, or reconstruction of the ascending aorta or aortic arch) with intraoperative bleeding (blood volume between 60 and 250 mL suctioned from the thoracic cavity in a period of 5 minutes) were randomized to receive either fibrinogen concentrate or placebo.
  
  
  
  Intravenous, single-dose administration of fibrinogen concentrate (n = 60) or placebo (n = 60), targeted to achieve a postinfusion plasma fibrinogen level of 2.5 g/L.
  
  
  
  The primary outcome was blood loss in milliliters between intervention (ie, after removal of cardiopulmonary bypass) and closure of chest. Safety variables (within 30 days) included: in-hospital mortality, myocardial infarction, cerebrovascular accident or transient ischemic attack, renal insufficiency or failure, venous thromboembolism, pulmonary embolism, and operative complications.
  
  
  
  Among 120 patients (mean age; 71 [SD, 10] years, 37 women [31%]) included in the study, combined CABG and valve repair or replacement surgery comprised 72% of procedures and had a mean (SD) cardiopulmonary bypass time of 200 minutes (83) minutes. For the primary outcome, median blood loss in the fibrinogen group was 50 mL (interquartile range [IQR], 29-100 mL) compared with 70 mL (IQR, 33-145 mL) in the control group (P = .19), the absolute difference 20 mL (95% CI, -13 to 35 mL). There were 6 cases of stroke or transient ischemic attack (4 in the fibrinogen group); 4 myocardial infarctions (3 in the fibrinogen group); 2 deaths (both in the fibrinogen group); 5 cases with renal insufficiency or failure (3 in the fibrinogen group); and 9 cases with reoperative thoracotomy (4 in the fibrinogen group).
  
  
  
  Among patients with intraoperative bleeding during high-risk cardiac surgery, administration of fibrinogen concentrate, compared with placebo, resulted in no significant difference in the amount of intraoperative blood loss.
  
  
  
  clinicaltrials.gov Identifier: NCT01124981 and EudraCT No: 2009-018086-12.
authors.affiliation: Division of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center Utrecht, Utrecht, the Netherlands2Department of Cardiothoracic Anesthesia and Intensive Care, Isala Zwolle, the Netherlands.
authors.forename: Süleyman
authors.initials: S
authors.lastname: Bilecen
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Joris A H
authors.initials: JA
authors.lastname: de Groot
authors.affiliation: Division of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Cor J
authors.initials: CJ
authors.lastname: Kalkman
authors.affiliation: Department of Cardiothoracic Anesthesia and Intensive Care, Isala Zwolle, the Netherlands.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Spanjersberg
authors.affiliation: Department of Cardiothoracic Surgery, Isala Zwolle, the Netherlands.
authors.forename: George J
authors.initials: GJ
authors.lastname: Brandon Bravo Bruinsma
authors.affiliation: Division of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center Utrecht, Utrecht, the Netherlands3Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Karel G M
authors.initials: KG
authors.lastname: Moons
authors.affiliation: Department of Cardiothoracic Anesthesia and Intensive Care, Isala Zwolle, the Netherlands.
authors.forename: Arno P
authors.initials: AP
authors.lastname: Nierich
mesh_terms: D000368:Aged; D001011:Aorta / Q000601:surgery; D016063:Blood Loss, Surgical / Q000517:prevention & control* / Q000706:statistics & numerical data; D006348:Cardiac Surgical Procedures / Q000009:adverse effects* / Q000379:methods; D002315:Cardiopulmonary Bypass; D003029:Coagulants / Q000008:administration & dosage*; D004311:Double-Blind Method; D017558:Elective Surgical Procedures / Q000009:adverse effects / Q000379:methods; D005260:Female; D005340:Fibrinogen / Q000008:administration & dosage* / Q000032:analysis; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects; D006801:Humans; D007431:Intraoperative Complications / Q000097:blood / Q000453:epidemiology; D002546:Ischemic Attack, Transient / Q000453:epidemiology; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology; D009426:Netherlands; D061646:Operative Time; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000453:epidemiology; D012306:Risk; D018401:Sample Size; D020521:Stroke / Q000453:epidemiology
chemical_list: D003029:Coagulants; D005340:Fibrinogen