Effect of Fibrinogen Concentrate on Intraoperative Blood Loss Among Patients With Intraoperative Bleeding During High-Risk Cardiac Surgery

Abstract

IMPORTANCE Fibrinogen concentrate might partly restore coagulation defects and reduce intraoperative bleeding.OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTSA 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.INTERVENTIONS 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.MAIN OUTCOMES AND MEASURES 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. RESULTS 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).CONCLUSIONS AND RELEVANCE 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.

The prophylactic use of fibrinogen concentrate in high‐risk cardiac surgery

“…Measured fibrinogen plasma levels were comparable to other previously published studies . Prophylactic and single‐dose administration of fibrinogen concentrate prevented fibrinogen plasma levels below 2g/L in the treatment group.…”

“…Our original study design had to be modified because of a very slow recruitment rate due to screening failures. Despite having a simpler bleeding assessment compared with other fibrinogen studies, we encountered no diffuse bleeding after 44 patients . In addition, we changed the inclusion criteria to only patients with lower pre‐operative fibrinogen levels.…”

“…Several studies have provided evidence supporting its superiority to conventional treatment using FFP and a recently published trial (FIBRES) demonstrated non‐inferiority of fibrinogen concentrate compared with Cryo usage in severe bleeding . Other studies have shown conflicting results . Results from single‐center studies with different designs (prophylactic approach or bleeding assessment) could not be confirmed by an international multicenter trial (REPLACE) .…”

Thrombocytopenia as a Preoperative Risk Assessment Tool in Patients With Rheumatic Heart Disease Undergoing Valve Replacement Surgery

“…In addition, a higher proportion of blood transfusions in the hospital were found in the thrombocytopenic group. Operative patients with high blood loss experienced adverse outcomes 31. Second, the large epidemiological data revealed that thrombocytopenia itself may also directly affect prognosis 32.…”

The Global Developments in Transfusion Replacements and Patient Blood Management

“…Use of fibrinogen concentrate is indicated for treatment of inherited fibrinogen (factor I) deficiency in the U.S. and Europe, but results supporting for its use in response to trauma-related coagulopathy has not been demonstrated yet [33,34].…”