The Combined Efficacy of Evicel and Tranexamic Acid on Total Knee Arthroplasty During the Early Perioperative Period

Introduction and Background: Total knee arthroplasty is characterized by a large amount of postoperative blood loss and frequent need for blood transfusions.1 Also of concern is the risk of hematomas which can potentially lead to infection or wound complications and delay the overall rehabilitation process.2 By reducing postoperative bleeding, the outcomes of total knee arthroplasty would be improved by better range of motion, less frequency of blood transfusion and decreased incidence of arthrofibrosis.3 Several studies have looked at different blood conservation strategies including reinfusion of drains, tourniquets, autologous blood transfusions, topical and intravenous antifibrinolytic alone, topical fibrin sealant alone, and monopolar and bipolar electrocautery. The combined use of a topical fibrin sealant (Evicel®) with an antifibrinolytic (Tranexamic acid) represents another approach to reducing blood loss in patients undergoing total knee arthroplasty. Evicel® is a fibrin sealant consisting of human-derived thrombin and fibrinogen that work in combination to form a stable blood clot at the bleeding site. Evicel® is regularly used in orthopaedic and other sub-specialty surgeries. One investigation has reported on the use of a topical hemostatic agent in total knee arthroplasty.4 It compared the use of a fibrin sealant for hemostasis with standard hemostasis protocols and found that the topical hemostatic agent decreased post operative blood loss, increased post operative hemoglobin levels, and resulted in a decrease in the need for post operative blood transfusion. Tranexamic Acid is given topically or intravenously to occlude the fibrin cleavage sites on plasminogen and inhibit the breakdown of fibrin clots. Tranexamic acid is also regularly used in orthopaedic and other sub-specialty surgeries. Studies have found that intravenous dosing of tranexamic acid prior to incision, and again after tourniquet release reduces the need for the blood transfusion versus standard hemostasis.5, 6

Research Questions/Objectives: Does the combination use of a fibrin sealant and an antifibrinolytic in our institutional total knee arthroplasty protocol decrease postoperative drain output/hematocrit drop/hemoglobin drop or the need for post operative blood transfusions compared to standard hemostasis technique? Secondary objectives will be measuring differences in postoperative pain, postoperative range of motion, and rates of postoperative complications including pulmonary embolism, deep vein thrombosis, and wound complications requiring a return to the operating room between treatment and control groups.

Study Design: The null hypothesis states that the combined use of a topical fibrin sealant and an antifibrinolytic in total knee arthroplasty will show no difference in the amount of postoperative blood loss compared to the standard means of hemostasis (tourniquet and electrocauterization). The study will be a prospective randomized trial with patients that are undergoing elective primary, unilateral, cemented total knee arthroplasty. Patients will be randomly divided into two groups. A control group, in which the standard means of hemostasis will be applied and a treatment group, in which the standard means of hemostasis will be applied with the additional use of Evicel® (a fibrin sealant) and Tranexamic acid (an antifibrinolytic). All operations will be standardized between four surgeons.

Subjects: The target population is patients seen in the outpatient office who are indicated for primary total knee arthroplasty. Patients will be asked if they would like to participate in the study; only patients capable of consenting to surgery will be enrolled. Patients undergoing total knee arthroplasty revisions and patients with blood disorders, on chronic anti-thrombotic medication such as Coumadin and any patients with a history of deep vein thrombosis and/or pulmonary embolism will be excluded. Despite that Evicel® contains human-derived blood products, Jehovah's Witnesses will not be excluded and these patients will be given an opportunity whether they would like to participate or not. As tranexamic acid is renally cleared, renally impaired individuals will be excluded.

Study Procedures: All participating surgeons will adhere to the same protocol. Upon enrolling in the study, patient demographics including age, gender, height, weight will be recorded and stored in an encrypted, protected database. Eligible / consenting patients will be randomized in a 1:1 ratio to receive either treatment or non-treatment. The randomization will be stratified by surgeon to ensure balanced assignment of treatment / non-treatment in each of participating surgeons. Randomization schemes will be generated and maintained by Dr. David Leibelt, the study statistician. Dr. Leibelt will provide Mr. Bharat Tiwari with a set of randomization envelopes to be stored and used in the study clinic. Mr. Tiwari will assign these envelopes in sequential order, by envelope number and surgeon, to eligible /consenting patients. . During the process, Dr. Jason Wong and Mr. Andrew Schwartz will be blinded and will have no access to the randomization assignment. Preoperative blood work including hematocrit and hemoglobin will be performed, a standard for patients undergoing joint arthroplasty. On the day of surgery, the patients will be seen in the preoperative holding area, and again be asked if they consent to take part in the study. Total knee arthroplasty will then be performed with a standard medial parapatellar approach using a 350 mm Hg pneumatic tourniquet on the operative leg. All surgeons will use Zimmer implants. After patient is put to sleep, attending surgeon will inform the operating team that whether the patient is randomized into the treatment or control group. If the patient is part of the treatment group, they will receive a 10 mg/kg dose of tranexamic acid prior to tourniquet inflation. After removal of trial implants and irrigation/thorough drying, 2 mL of Evicel® will be sprayed (under 15-25 psi of CO2) into the posterior joint capsule (via the gap between femur and tibia). Once the implants are in place and the methylmethacrylate cement is cured, the joints will be irrigated copiously and dried thoroughly for the final time. 2 mL of Evicel® will be dripped into pinholes, another 2 mL of Evicel® will be dripped along the exposed edges of bony tissue, and an additional 2 mL of Evicel® will be sprayed on all remaining soft tissue. After 2 minutes, the tourniquet will be released and a second dose of 10 mg/kg tranexamic acid will be given as electrocautery is being performed. After joint capsule closure, a final 2 mL of Evicel® will be sprayed along the arthrotomy incision and on subcutaneous soft tissue. On top of the treatment protocol mentioned above, patient will also receive the standard tourniquet protocol and electrocautery. If the patient is in the control group, the standard tourniquet protocol and electrocautery alone will be used for hemostasis. In both groups, an auto transfusion drain will then be placed within the deep layer of the knee. The joint will then be closed and dressed in standard fashion. The patient will then be taken to the postoperative anesthesia care unit. Immediate postoperative hemoglobin and hematocrit levels will be recorded, a standard practice at our institution. The drain output will be recorded over a 24-hour period. As is standard, hemoglobin and hematocrit levels will be recorded for the three days postoperatively. Any transfusions and/or complications (pulmonary embolism, deep vein thrombosis, and wound complications requiring a return to the operating room) and length of stay will be monitored (according to standard protocol) and recorded. Pain scores utilizing the WOMAC, SF-36, and VAS scales will be recorded during postoperative follow up in the clinic. Range of motion will be compared to preoperative values at two and six weeks postoperatively.