Randomized, Double‐Blinded, Placebo‐Controlled Trial of Fibrinogen Concentrate Supplementation After Complex Cardiac Surgery

Abstract

BackgroundPostoperative bleeding after heart operations is still a common finding, leading to allogeneic blood products transfusion. Fibrinogen and coagulation factors deficiency are possible determinants of bleeding. The experimental hypothesis of this study is that a first-line fibrinogen supplementation avoids the need for fresh frozen plasma (FFP) and reduces the need for any kind of transfusions.Methods and ResultsThis was a single-center, prospective, randomized, placebo-controlled, double-blinded study. One-hundred sixteen patients undergoing heart surgery with an expected cardiopulmonary bypass duration >90 minutes were admitted to the study. Patients in the treatment arm received fibrinogen concentrate after protamine administration; patients in the control arm received saline solution. In case of ongoing bleeding, patients in the treatment arm could receive prothrombin complex concentrates (PCCs) and those in the control arm saline solution. The primary endpoint was avoidance of any allogeneic blood product. Patients in the treatment arm had a significantly lower rate of any allogeneic blood products transfusion (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.84, P=0.015). The total amount of packed red cells and FFP units transfused was significantly lower in the treatment arm. Postoperative bleeding was significantly (P=0.042) less in the treatment arm (median, 300 mL; interquartile range, 200 to 400 mL) than in the control arm (median, 355 mL; interquartile range, 250 to 600 mL).ConclusionsFibrinogen concentrate limits postoperative bleeding after complex heart surgery, leading to a significant reduction in allogeneic blood products transfusions. No safety issues were raised.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01471730.

Fibrinogen in traumatic haemorrhage: A narrative review

“…shown that a fixed dose of 6g FC reduced post-operative bleeding and blood product transfusion (159). However, subsequent data analysis revealed that a reduced dose of FC would have likely yielded the same results (160).…”

Diagnostic and therapeutic medical devices for safer blood management in cardiac surgery: systematic reviews, observational studies and randomised controlled trials

“…In a study in 4202 cardiac surgery patients, Karkouti et al 163 observed a fibrinogen threshold of 2 g/dl below which blood loss increased. Several small RCTs have also shown that fibrinogen administration reduces bleeding in cardiac surgery 164,165 and a Cochrane review of cardiac and non-cardiac surgery trials reported a similar finding. 87 No previous study has evaluated the predictive accuracy of low fibrinogen levels.…”

Outcome measures and quality markers for perioperative blood loss and transfusion in cardiac surgery

“…The amount of perioperative bleeding was defined in a heterogeneous way, either as a primary or (more frequently) secondary endpoint of the study. The following treatments have recently been evaluated for efficacy in reducing perioperative bleeding: use of transfusion algorithms based on point of care, 15 fibrinogen concentrate, 9,10,16,17 tranexamic acid/epsilonaminocaproic acid, [18][19][20] antithrombin-III, 21 heparin monitoring systems, 22 and shed blood processing. 23,24 Notably, the objective for all these treatments was a direct reduction in postoperative bleeding; however, in the majority of the cases, the primary endpoint was avoidance of transfusion.…”

“…Some might consider transfusion as a surrogate for perioperative bleeding, e.g., in studies exploring the effects of hemostatic drugs or techniques. 18,30 Nevertheless, even in this setting, some important methodological points must be considered. The most important consideration is that transfusions in cardiac surgery patients may be triggered by factors other than directly from bleeding-e.g., preoperative anemia and intraoperative hemodilution.…”

“…To limit the effects of these confounders, some RCTs have successfully introduced strict exclusion criteria based on preoperative anemia and/or very low body surface area as well as withdrawal criteria in case of excessive hemodilution during CPB. 18,30 In addition, whenever transfusions are the primary endpoint in an RCT, a well-defined transfusion protocol needs to be strictly followed with few protocol deviations.…”