Weight-adjusted dosing of fibrinogen concentrate and cryoprecipitate in the treatment of hypofibrinogenaemic bleeding adult cardiac surgical patients: a post hoc analysis of the Fibrinogen Replenishment in cardiac surgery randomised controlled trial

Cian Devine; Justyna Bartoszko; Jeannie Callum; Keyvan Karkouti; FIBRES Study Investigators

doi:10.1016/j.bjao.2022.100016

Weight-adjusted dosing of fibrinogen concentrate and cryoprecipitate in the treatment of hypofibrinogenaemic bleeding adult cardiac surgical patients: a post hoc analysis of the Fibrinogen Replenishment in cardiac surgery randomised controlled trial

BJA Open. 2022 Jun 9:2:100016. doi: 10.1016/j.bjao.2022.100016. eCollection 2022 Jun.

Authors

Cian Devine¹, Justyna Bartoszko^{2

3

4}, Jeannie Callum^{5

6}, Keyvan Karkouti^{2

3

4}; FIBRES Study Investigators

Affiliations

¹ Department of Anesthesiology and Pain Medicine, University of Ottawa, Ottawa, Canada.
² Department of Anesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
³ Peter Munk Cardiac Centre and Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
⁴ Department of Anesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁵ Department of Pathology and Molecular Medicine, School of Medicine, Queen's University, Kingston, Ontario, Canada.
⁶ Department of Pathology and Molecular Medicine, Kingston Health Sciences Centre, Kingston, Ontario, Canada.

Abstract

Background: Hypofibrinogenaemia is associated with excessive bleeding after cardiac surgery. Our aim was to compare the efficacy and safety of weight-adjusted vs empiric dosing of fibrinogen replacement in cardiac surgery.

Methods: In the Fibrinogen Replenishment in Cardiac Surgery (FIBRES) RCT, patients (n=735) received fibrinogen concentrate (4 g) or cryoprecipitate (10 units). In this post-hoc analysis, patients were grouped into quartiles based on increasing weight-adjusted dosing. Generalised estimating equations were used to account for hospital site, age, sex, surgical complexity, urgency, and critical preoperative status. The primary outcome was the number of units of red blood cells transfused within 24 h of cardiopulmonary bypass. Secondary outcomes included allogeneic blood components within 24 h, tamponade or major bleeding, and thromboembolic complications, ischaemic complications, or both within 28 days of cardiopulmonary bypass.

Results: The median weight-adjusted doses were 52 mg kg^-1 of fibrinogen concentrate (inter-quartile range [IQR], 45-61; n=372) and 1.30 units per 10 kg of cryoprecipitate (IQR, 1.11-1.54; n=363). When patients were divided into quartiles of lowest to highest weight-adjusted dosing, no differences were seen in the primary outcome of red blood cell units transfused within 24 h of cardiopulmonary bypass between the lowest and highest quartiles in either the fibrinogen group (adjusted relative risk [RR]=0.90; 95% confidence interval [CI], 0.71-1.13; P=0.36) or the cryoprecipitate group (adjusted RR=1.04; 95% CI, 0.76-1.43; P=0.80). Results were similar for all secondary outcomes.

Conclusion: Outcomes for the lowest and highest weight-adjusted doses of fibrinogen replacement were comparable. Weight-adjusted dosing does not appear to offer advantages over empiric dosing in this context.

Clinical trial registration: NCT03037424.

Keywords: cardiac surgery; coagulopathy; fibrinogen; haemostasis; transfusion.

Associated data

ClinicalTrials.gov/NCT03037424