All eligible subjects undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) at New York Presbyterian Hospital-Weill Cornell Medical College will be invited to participate. Consenting subjects will be enrolled and treated according to the protocol. Study investigators anticipate that by consenting all eligible cardiovascular surgical subjects, investigators will not omit the results of subjects who may present with microvascular bleeding after CPB. It is well known that microvascular bleeding occurs more often in reoperations or complex, open cardiac procedures, such as coronary revascularization and valve repair/replacement, or aortic replacements under deep hypothermic circulatory arrest.
Enrolled subjects will receive intraoperative anesthetic, anticoagulation, laboratory testing, and hemodynamic management according to WCMC standards of practice. The need for blood products, including fibrinogen supplementation (CRYO/FIB), will be assessed using a point-of-care (ROTEM) based transfusion algorithm (Appendix A) to ensure consistency and accuracy of treatment. The cardiac anesthesiologists and surgeons are currently using the ROTEM algorithm for the treatment of bleeding during cardiovascular surgery with CPB as part of routine clinical practice at WCMC. The algorithm will have been in place for greater than 9 months prior to study initiation. Randomization will occur in the blood bank when study product (CRYO/FIB) is requested to treat intraoperative acquired hypofibrinogenemia (based on ROTEM tracings). Transfusion of the randomized study product (CRYO/FIB), however, will only occur when the surgeon declares the presence of microvascular bleeding. Surgeons will be blinded to the subject's ROTEM results and randomized study arm. Intraoperative anesthesiologists will not be blinded as the two products require different preparation and administration techniques and cannot be blinded easily.
Once the subject is randomized to their study intervention they will receive that product at all subsequent points during the procedure when fibrinogen replacement is required. If microvascular bleeding occurs and there is no indication by the ROTEM algorithm to administer CRYO/FIB, the subject will revert to standard of care treatment guided by ROTEM or traditional laboratory testing. The subject will not be randomized in the study. In the case of abnormal ROTEM parameters but no clinical evidence of microvascular bleeding as evaluated by the cardiac surgeon, the subject will continue to be monitored carefully for bleeding for the remainder of the procedure. If non-surgical bleeding is subsequently observed prior to chest closure and the consensus is that fibrinogen is needed based on ROTEM results (FIBTEM A10 less than or equal to 10 mm), the subject will be treated with their randomized study product according to the algorithm. Following completion of the procedure, postoperative coagulation management will be according to standard practice and guided by standard laboratory testing, when possible. Unless persistent bleeding is noted, all subjects will receive aspirin (300 mg per rectum) 6 hours postoperatively. Subjects with mechanical or mitral tissue valves will be anticoagulated with warfarin (no heparin bridge) starting on postoperative day two (POD#2). Any subjects experiencing significant arrhythmias (e.g. atrial fibrillation in the perioperative setting) will also be anticoagulated with warfarin. Pharmacologic deep vein thrombosis (DVT) prophylaxis will follow the usual standard of care. Subjects enrolled, randomized, and transfused study product will be observed until hospital discharge (total observation time). Research staff from the Department of Anesthesiology will collect outcomes data, including transfused blood products, laboratory results, evidence of perioperative thrombosis or infection, returns to the OR, length of stay, and mortality using case report forms reports and enter all collected data into a secure REDCap database.
