Prospective, Randomized Trial to Evaluate Efficacy of a Thrombin-Based Hemostatic Agent in Total Knee Arthroplasty Juan C. Suarez MD, Eric M. Slotkin DO, Andres M. Alvarez MD, Caleb R. Szubski BA, Wael Barsoum MD, Preetesh Patel MD PII: DOI: Reference:

S0883-5403(14)00393-3 doi: 10.1016/j.arth.2014.05.025 YARTH 54021

To appear in:

Journal of Arthroplasty

Received date: Revised date: Accepted date:

13 February 2014 8 May 2014 29 May 2014

Please cite this article as: Suarez Juan C., Slotkin Eric M., Alvarez Andres M., Szubski Caleb R., Barsoum Wael, Patel Preetesh, Prospective, Randomized Trial to Evaluate Efficacy of a Thrombin-Based Hemostatic Agent in Total Knee Arthroplasty, Journal of Arthroplasty (2014), doi: 10.1016/j.arth.2014.05.025

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Prospective, Randomized Trial to Evaluate Efficacy of a Thrombin-Based Hemostatic Agent in Total Knee Arthroplasty Juan C Suarez1, MD, Eric M Slotkin1, DO, Andres M Alvarez1, MD, Caleb R Szubski2, BA, Wael Barsoum2, MD, Preetesh Patel1, MD Affiliations: 1. Cleveland Clinic Florida, Department of Orthopedic Surgery, 2950 Cleveland Clinic Blvd, Weston, FL 33331 2. Cleveland Clinic, Department of Orthopedic Surgery, 9500 Euclid Avenue, Cleveland, OH 44195 Cooresponding Author: Eric M. Slotkin, DO Clinical Fellow Department of Orthopedic Surgery Cleveland Clinic Florida 2950 Cleveland Clinic Blvd Weston, FL 33331 856-265-9094 [email protected]

ACCEPTED MANUSCRIPT Prospective, Randomized Trial to Evaluate Efficacy of a Thrombin-Based Hemostatic Agent

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in Total Knee Arthroplasty

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ABSTRACT: Total knee arthroplasty (TKA) can be associated with substantial blood loss, leading to increased morbidity and need for blood transfusions. The study objective was to evaluate

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routine use of a thrombin-based topical hemostatic matrix sealant in reducing blood loss and

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transfusion requirements in primary TKA. 108 patients were enrolled in a prospective, randomized, single-center trial. Patients who received the hemostatic agent demonstrated a

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lower mean calculated blood loss (1325.2±464.8 mL vs. control, 1509.3±432.8 mL; p=0.02), drain output (415.6±202.0 mL vs. control, 579.9±306.7 mL; p=0.008), and length of stay (3.3±0.8 days

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vs. control, 3.7±1.1 days; p=0.03), without a statistically significant difference in mean hemoglobin

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loss or transfusion requirements. The clinical utility of this hemostatic agent to reduce

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transfusions after uncomplicated, primary TKA continues to remain unclear.

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Keywords: Total knee arthroplasty, Floseal, blood conservation, hemostatic agent, blood management, transfusion

ACCEPTED MANUSCRIPT INTRODUCTION

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Total knee arthroplasty (TKA) can be associated with significant blood loss due to soft tissue

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releases and bone cuts. Increased blood loss may lead to unanticipated postoperative morbidity, including excessive pain, decreased knee motion, increased transfusion requirements, and, often,

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increased convalescence times1. Although transfusion-associated risks have decreased, the use of

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blood products following knee arthroplasty is frequently necessary. Allogeneic transfusion carries with it the potential for increased hospital length of stay, overall cost, disease transmission, and

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systemic immune immodulation and reaction2-4. Therefore, it is important to minimize intraoperative blood loss and the need for allogeneic transfusions in order to improve system

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wide outcomes in TKA.

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Strategies to limit the use of allogeneic blood products in orthopaedic surgery center on the immediate perioperative time period5. Preoperative management involves the evaluation and

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optimization of the patient’s circulating blood volume prior to a procedure with recognition of atrisk patients and treatment with agents specifically designed to boost circulating blood levels5,6. Intraoperative surgical techniques designed to improve hemostasis have been demonstrated to decrease intraoperative blood loss, thereby potentially decreasing postoperative need for allogeneic transfusion5. Examples include the use of manufactured devices specifically designed to prevent and treat hemostasis, such as radiofrequency controlled tissue sealers, drugs designed specifically to decrease bleeding at the capillary bed, and the use of direct hemostatic agents. The use of locally applied hemostatic agents at the time of surgery may help to reduce blood loss and

ACCEPTED MANUSCRIPT to improve surgical outcomes6. Postoperative methods include the use of reinfusion drains and

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lowering the transfusion triggers.

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Floseal Matrix Hemostatic Sealant (Baxter, Deerfield, Illinois) possesses distinct characteristics that make it a desirable alternative to other products used for hemostasis in the operating room7.

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The United States Food and Drug Administration (FDA) approval of Floseal was based on a

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multicenter, multispecialty, prospective, randomized clinical trial proving the safety and efficacy of its use as a hemostatic agent in spinal surgery8. Since then, multiple surgical specialties have

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also tested and proven the efficacy of Floseal in other elective orthopedic, cardiac, and general

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been limited to spinal procedures.

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surgical procedures. However, to date most studies on Floseal for use in orthopedic surgery have

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The solution is prepared by mixing together a gelatin matrix with thrombin just prior to its use. These components interact synergistically to form a clot that adheres to the bleeding site7. The

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gelatin matrix is made up of specially designed gelatin granules mixed with topical thrombin that allow the matrix to conform to irregular wound geometries. Supporters believe this will aid the surgeon in achieving hemostasis in challenging procedures with difficult to reach locations8,9. Additionally, the gelatin matrix component conforms to and swells at the bleeding site creating a tamponade effect that helps barricade aggressive bleeding while activating the clotting cascade. The thrombin component of Floseal serves to activate this coagulation cascade. In particular, it enzymatically converts fibrinogen into fibrin to form a fibrin clot. Hence, Floseal does not rely on the presence of functional platelets or other coagulation factors besides fibrinogen. In theory, this

ACCEPTED MANUSCRIPT may make this sealant less susceptible to coagulopathies due to clotting factor deficiencies or

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platelet malfunction8.

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We performed a prospective, randomized controlled, single-center clinical trial evaluating the efficacy of Floseal in blood conservation in unilateral, primary TKA. We hypothesized that the

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application of a thrombin-based hemostatic sealant at the completion of a cemented TKA would

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decrease intraoperative and postoperative bleeding and lead to lower transfusion rates.

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MATERIALS AND METHODS

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The study received approval by the institutional review board. All patients were enrolled after

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informed consent was obtained. Enrollment was both voluntary and proceeded in a consecutive

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Participants

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manner.

All patients undergoing unilateral, primary TKA with two enrolling adult reconstruction fellowship-trained surgeons were approached (Figure 1). Strict inclusion and exclusion criteria were employed and are outlined in Table 1. Computer-generated and sealed randomization envelopes with equal numbers in each treatment arm were developed with use of SAS Version 9.1 (SAS Institute, Cary, North Carolina). Two patients were moved from the control arm to the treatment arm based on intraoperative surgical decision to use the treating agent. No individual

ACCEPTED MANUSCRIPT involved in the surgery or postoperative assessment was involved in the randomization process. Additionally, personnel blinded to the randomization process prospectively collected all data.

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Intervention

All patients received a fully cemented, either posterior stabilized or cruciate retaining, TKA with

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patellar resurfacing. An above-the-knee tourniquet was inflated prior to surgical incision and

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deflated after the cement had procured and prior to the wound closure in every case. Randomization to either study arm was announced only after the cementing of components and

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prior to any application of the sealant. For the control arm, hemostasis was achieved with standard electrocautery after tourniquet deflation followed by wound closure. For the treatment

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arm, hemostasis of the soft tissues was achieved with electrocautery followed by application of the

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hemostatic agent to all exposed bone and soft tissue surfaces. A 10-mL vial of the product was used. The matrix remained in place for two minutes, and then any excess product was gently

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rinsed from the knee. A medium sized hemovac drain was placed in each knee prior to closure.

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Fascial layers were closed with a running QuillTM suture (QUILL, Surgical Specialties Corporation, Vancouver, British Columbia, Canada),10 the subcutaneous tissue with interrupted 2-0 Vicryl suture, and the skin with a subcuticular 3-0 monocryl suture. A compressive bandage was applied to the limb following closure and remained in place for 48 hrs. The hemovac drain was connected to a vacuum container and removed at 24 hours after completion of surgery regardless of drain output. The type of surgical anesthetic used remained at the discretion of the anesthesiologist and the patient. Prophylaxis for VTE was achieved with renal-dose Enoxaparin initiated 24 hours after surgery along with sequential pneumatic compression devices and early ambulation. Daily

ACCEPTED MANUSCRIPT complete blood counts and basic metabolic panels were obtained until the third postoperative

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day, unless the patient was discharged earlier.

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Outcome Measures

The primary outcome measure of the study was calculated blood loss. Secondary outcome

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measures included transfusion requirements, hemoglobin loss, drain output, and length of stay. The decision to postoperatively transfuse patients was made by the non-operating surgeon,

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blinded to the randomization and using a threshold of hemoglobin < 8.0 g/dL. Several other

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secondary outcome measures were assessed, including drop in hemoglobin values, drop in hematocrit values, and wound complications. Hemoglobin loss was calculated based on

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modification of the method established by Good and colleagues11,12 to reflect the lowest

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hemoglobin during admission, therefore eliminating transfused blood from the equation. Thus,

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we set calculated hemoglobin loss to:

Total Hemoglobin Loss (g) = blood volume * (preoperative Hb – lowest Hb) * 0.001.

Sample Size

The sample size was developed using an alpha of 0.05, a beta of 0.80, and the standard deviation from a similar study by Bloomfield et al.13, to estimate a cohort which would provide in excess of 80% statistical power to detect less than a 100 ml difference13 in blood loss between the two

ACCEPTED MANUSCRIPT groups. Assuming 10% exclusion from analysis due to ineligibility, and 10% loss to follow-up, a

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total of 108 patients were enrolled.

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Statistical Analysis

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Data were analyzed using JMP Version 10.0 (SAS Institute, Cary, North Carolina). Univariate

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analysis was conducted using the Wilcoxon rank-sum test for continuous variables to account for potentially non-normal data distributions and the Pearson’s chi-square test and Fisher’s exact test

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for categorical variables. Differences were considered significant at p≤0.05.

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Source of Funding

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RESULTS

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No external source of funding was utilized.

The study enrollment period started in August 2011 and culminated March 2013 in order to reach the sample size needed from our a priori power calculation. During this time period, 300 TKA surgeries were performed. From these, and a total of 108 patients met the inclusion criteria and provided consent for participation. Of the 108 patients enrolled in this prospective, single-center, randomized, double-blinded trial, 56 were randomized to the hemostatic matrix treatment group and 52 to the control group. Demographic data is listed in Table 2 and all operative details are found in Table 3. Amongst all these variables, there was a notable difference in pre-operative BMI

ACCEPTED MANUSCRIPT among the treatment groups, with a lower mean BMI in the hemostatic agent group (29.8 kg/m2

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vs. control, 33.7 kg/m2; p=0.007).

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Analysis of the perioperative blood data (Table 4) demonstrated a statistically significant difference in calculated blood loss (hemostatic agent, 1325.2 ± 464.8 mL; control, 1509.3 ± 432.8

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mL; p=0.02) and drain output (hemostatic agent, 415.6 ± 202.0 mL; control, 579.9 ± 306.7 mL;

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p=0.008) among the study groups, favoring the hemostatic agent group. However, this did not translate to a statistically significant difference in transfusion requirements (hemostatic agent,

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n=3, 5.4%; control, n=4, 7.7%; p=0.71) nor mean hemoglobin loss (p=0.09). Additionally, there was no significant difference between the two study groups in terms of hemoglobin or hematocrit

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drop, postoperative fluids, or hidden blood loss. Finally, patients treated with the hemostatic

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agent had a slightly shorter length of stay (3.3 ± 0.8 days; control, 3.7 ± 1.1 days; p=0.03).

The hemostatic agent appeared to reduce high blood loss outliers, as evidence by the graphed

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distributions presented in Figures 2-4. A substantially larger percentage of patients in the control group had drain outputs postoperatively greater than 750 mL (n=15, 28.8%; hemostatic agent, n=4, 7.1%). Likewise, the hemostatic agent patients had a higher percentage of patients with drain outputs less than 600 mL (n=47, 83.9%; control, n=31, 59.6%) (Figure 2). In Figures 3 and 4, there remain a higher percentage of patients in the control group with increased hemoglobin loss (i.e., greater than 250 g) (n=12, 23.1%; hemostatic agent, n=6, 10.7%) and calculated blood loss (i.e., greater than 1750 mL) (n=13, 25.0%; hemostatic agent, n=7, 12.5%). While these figures are not significant alone, they do help demonstrate a greater number of clinical outliers with increased blood loss within the control group for these outcomes.

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DISCUSSION

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This study demonstrated no significant differences in demographic characteristics, operative details, or perioperative blood management. There were significant differences in drain output

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and calculated blood loss in the hemostatic agent treatment group, however these differences

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were relatively small and likely did not correlate to any clinical significance. The data presented in this study demonstrate that the intraoperative use of this hemostatic agent did decrease both

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the amount of blood loss perioperatively and overall length of stay, though its clinical impact to

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reduce transfusion requirements in this patient population is inconclusive.

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The difference in calculated blood loss observed during this study without a difference in hidden

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blood loss or total hemoglobin loss may be explained by the difference in drain output as presented in Table 4. Overall, the control group had a statistically significant higher drain output

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than the hemostatic agent treatment group (p=0.008). Therefore, with a similar hidden blood loss it may be concluded that both groups have similar interstitial bleeding, yet less blood loss in the joint space with treatment group patients (i.e. location of the drain and closest to the location of hemostat application).

A number of studies examining a variety of blood preserving agents and devices during total joint arthroplasty exist14-19. Marulanda et al.14 compared the use of a bipolar sealer during primary, unilateral TKA with conventional electrocautery for hemostasis and found a significant reduction in blood loss in the group using the bipolar sealer, as well as a decreased need for autologous

ACCEPTED MANUSCRIPT blood transfusion. Everts et al.15 examined the use of an autologous platelet gel during TKA. They concluded that the perioperative use of the platelet gel and fibrin sealant reduced the need for

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blood transfusions after surgery. In a study evaluating outcomes, Gardner et al.16 demonstrated

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improved hemostasis, better pain control, and shorter lengths of stay after TKA through the use of autologous platelet gel during surgery. Wang et al.17 and Levy et al.18 studied the use of fibrin-

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based hemostatic agents during TKA and demonstrated similar positive results, reporting less

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drain output and measured blood loss as well as lower hemoglobin drops in patients treated with

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the hemostatic agent.

A recent examination by Kim et al.19 with 196 patients compared the same thrombin-based

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hemostatic agent we analyzed, and found no differences in mean drain output at 24 hours (Floseal,

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711.3 mL; control, 701.6 mL; p=0.82), estimated blood loss (Floseal, 205.7; control, 205.4; p=0.97),

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and transfused units per patient (autologous, p=0.81; allogeneic, p=0.34) between hemostatic agent and control groups. Their study population had a large percentage of patients that

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predonated blood (Floseal, n=58, 59.8%; control, n=63, 63.6%), which caused high transfusion rates and lower preoperative hemoglobin values in their study.

Our prospective, randomized controlled study expands and confirms many of the conclusions made by Kim et al. We are unaware of any study designed to strictly examine calculated blood loss as a final endpoint to determine its effect on blood conservation. Further strengths of our study include standardized VTE prophylaxis, a limited number of patients that predonated blood, and a similar cohort of treatment and control groups.

ACCEPTED MANUSCRIPT A critical analysis of this study reveals that within both the treatment and control group there remain uncontrolled variables that need to be accounted for. One such variable is the differing

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type of total knee implant design used between the two participating surgeons (cruciate retaining

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and posterior stabilized). Additionally, our analyses did not control for anesthesia type, which is debated to affect perioperative blood loss20, 21. However, we found no statistically significant

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differences in calculated blood loss (p=0.71), transfusion rate (0.99), or drain output (0.69)

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between patients that received spinal and general endotracheal anesthesia. Also, the participants in this study adhered to strict inclusion and exclusion criteria. Through this process, a relatively

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healthier population of patients was enrolled who would otherwise be expected to have a lower natural risk for transfusion. It may be necessary to include more patients in order to detect any

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significant clinical implications on transfusion rates. Finally, during the study period, the surgeons’

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threshold for transfusion was hemoglobin < 8.0 g/dL. There is significant variability regarding

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optimal transfusion guidelines in the total joint population, and at our institution, we now

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individualize transfusion requirements.

In conclusion, the use of this hemostatic agent led to decreased calculated blood loss and drain output during primary TKA in our study population. Based on the data presented, it appears that the hemostatic agent can minimize upper bound outliers with regards to drain output, hemoglobin loss, and calculated blood loss. However, in this healthy population, the product did not lead to a reduction in transfusion requirements. Future research powered for transfusion rate should be explored to further evaluate the clinical significance of this product and efforts should be directed at studying such agents in more complex surgical patients at increased risk of bleeding.

ACCEPTED MANUSCRIPT REFERENCES 1. Birkmeyer JD, Goodnough LT, AuBuchon JP, Noorsij PG, Littenberg B. The cost effectiveness of

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preoperative autologous blood donation for total hip and knee replacement. Transfusion. 1993;33(7):544-51.

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2. Sculco TP, Baldini A, Keating EM. Blood management in total joint arthroplasty. Instr Course

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Lect. 2005;54:51-66.

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3. Keating EM, Ritter MA. Transfusion options in total joint arthroplasty. J Arthroplasty. 2002; 17(4 Suppl 1):125-8.

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4. Spence RK. Current concepts and issues in blood management. Orthopedics. 2004; 27(6

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Suppl):s643-51.

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5. Krebs V, Higuera C, Barsoum W, Helfand R. Blood Management in Joint Arthroplasty: What’s In

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and What’s Out. Orthopedics. 2006: 29(9). 6. Bierbaum BE, Callaghan JJ, Galante JO, Rubash HE, Tooms RE, Welch RB. An analysis of blood management in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am. 1999; 81: 210. 7. Floseal Hemostatic Matrix (2011). Retrieved July 4, 2013, from http://www.floseal.com/us/ 8. Keating EM, Meding JB. Perioperative blood management practices in elective orthopaedic surgery. J Am Acad Orthop Surg. 2002: 10: 393-400.

ACCEPTED MANUSCRIPT 9. Tobias JD. Strategies for minimizing blood loss in orthopedic surgery. Semin Hematol. 2004; 41(suppl 1):145-56.

arthroplasty wounds. Orthopedics. 2011;34(9):e473-5.

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10. Levine BR, Ting N, Della Valle CJ. Use of a barbed suture in the closure of hip and knee

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11. Good L, Peterson E, and Lisander B. Tranexamic acid decreases blood loss but not hidden

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blood loss in total knee replacement. Br J Anaesth. 2003;90(5):596-9. 12. Kalairajah Y, Simpson D, Cossey AD, Verrall GM, Spriggins AJ. Blood loss after total knee

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replacement: effects of computer assisted surgery. J Bone Joint Surg Am. 2005; 87(11):1480-

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13. Bloomfield MR, Klika AK, Molloy RM, Froimson MI, Krebs VE, Barsoum WK. Prospective

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Randomized Evaluation of a Collagen/Thrombin and Autologous Platelet Hemostatic Agent

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During Total Knee Arthroplasty. J Arthroplasty. 2012; 27(5):695-701.

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14. Marulanda GA, Krebs VE, Bierbaum BE, et al. Hemostasis using a bipolar sealer in primary unilateral total knee arthroplasty. Am J Orthopt. 2009;38:E179-83. 15. Everts PA, Devilee RJ, Brown M. Platelet gel and fibrin sealant reduce allogeneic blood transfusions in total knee arthroplasty. Acta Anaesthesiol Scand. 2006;50:593. 16. Gardner MJ, Demetrakopoulos D, Klepchick PR. The efficacy of autologous platelet gel in pain control and blood loss in total knee arthroplasty. Int Orthop. 2007;31:309.

ACCEPTED MANUSCRIPT 17. Wang GJ, Hungerford DS, Savory CG, Rosenberg AG. Use of Fibrin Sealant to Reduce Bloody Drainage and Hemoglobin Loss After Total Knee Arthroplasty: A Brief Note on a Randomized

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Prospective Trial. J Bone Joint Surg Am. 2001;83:1503-05. 18. Levy O, Martinowitz U, Oran A, Tauber C, Horoszowski H. The use of fibrin tissue adhesive to

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reduce blood loss and the need for blood transfusion after total knee arthroplasty, A

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prospective, randomized, multicenter study. J Bone Joint Surg Am. 1999;81(11):1580-8. 19. Kim H, Fraser R, Kahm B, Lyman S, Figgle M. Efficacy of a Thrombin Based Hemostatic Agent

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in Unilateral Total Knee Arthroplasty: A Randomized Controlled Study. J Bone Joint Surg Am. 2012;94(13):1160-65.

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20. Hu S, Zhang ZY, Hua YQ, Li J, Cai ZD. A comparison of regional and general anaesthesia for total

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replacement of the hip or knee: a meta-analysis. J Bone Joint Surg Br. 2009;91(7):935-42.

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21. Macfarlane AJ, Prasad GA, Chan VW, Brull R. Does regional anesthesia improve outcome after

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total knee arthroplasty? Clin Orthop Relat Res. 2009;467(9):2379-402.

ACCEPTED MANUSCRIPT Figure 1. Consolidated Standards of Reporting Trials Flow Diagram

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Enrollment Assessed for eligibility (n=300)

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Excluded (n=192)  Not meeting inclusion criteria (n=138)  Declined to participate (n=54)

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Randomized (n= 108)

Allocated to Control group (n=54)  Received allocated intervention (n=52)  Did not receive allocated intervention (n=2) (Intraoperative decision)

Follow-Up

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Allocated to Hemostatic agent (n=54)  Received allocated intervention (n=56)  Did not receive allocated intervention (n=0)

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Allocation

Lost to follow-up (n=0) Discontinued intervention (n=0)

Lost to follow-up (n=0) Discontinued intervention (n=0)

Analysis Analysed (n=56)  Excluded from analysis (n=0)

Analysed (n=52)  Excluded from analysis (n=0)

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Figure 2. Distribution of Drain Output by Treatment Arm (bin size 150 mL)

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Figure 3. Distribution of Hemoglobin Loss by Treatment Arm (bin size 50 g)

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Figure 4: Distribution of Calculated Blood Loss by Treatment Arm (bin size 250mL)

ACCEPTED MANUSCRIPT Table 1. Inclusion and Exclusion Criteria

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Exclusion Known allergy to material of bovine origin Patients undergoing revision or bilateral TKA Patients pre-donating autologous blood Patients with preoperative platelet count below 100,000 Patients with preoperative hemoglobin below 10 mg/dL Previous history of DVT/VTE History of hypercoagulable disorder Prior history of medical condition requiring anticoagulation with warfarin Prior evidence of bleeding or metabolic disorder History of Heparin or Lovenox induced thrombocytopenic disorder Patient with peripheral vascular disease Patients with history of liver disease Patients with history of renal disease, diabetic nephropathy, or decreased creatinine clearance Patient with uncontrolled hypertension Patient with addiction to illegal drugs, solvents, or alcohol who are currently using or previously attempted or failed a treatment program Patients with bacteremia, systemic infection, or infection at surgical site Prisoners Patients pregnant or nursing Patients with personal beliefs prohibiting the use of blood products

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Inclusion Patient Scheduled for Primary TKA Age between 18-85 years old Willing and able to provide informed consent for the study

ACCEPTED MANUSCRIPT Table 2. Demographic Data Hemostatic Matrix Group (N = 56) 65.9 ± 9.2 (47.4 – 84.0)

Control Group (N = 52) 65.1 ± 9.1 (37.3 – 81.9)

0.62 41 (38.0%) 20 (35.7%) 21 (40.4%) 67 (62.0%) 36 (64.3%) 31 (59.6%) 31.7 ± 7.2 29.8 ± 6.3 33.7 ± 7.6 0.007* (18.4 – 54.5) (18.4 – 47.8) (21.1 – 54.5) a Result values are expressed as mean ± standard deviation (range); P value calculation made using Wilcoxon rank-sum test

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Gender b Male Female BMI (kg/m2) a

P-Value c 0.73

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Age (yr)

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Entire Cohort (N = 108) 65.5 ± 9.1 (37.3 – 84.0)

values are expressed as number of cases (percentage of column header population); P value calculation made using Pearson’s chi-square test

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Comparison between Hemostatic agent and Control groups

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c

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b Result

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Tourniquet Time (min) b

53 (94.6%) 2 (3.6%) 1 (1.8%)

49 (94.2%) 1 (1.9%) 2 (3.8%)

31 (55.4%) 25 (44.6%)

18 (34.6%) 34 (65.4%)

27 (48.2%) 29 (51.8%)

23 (44.2%) 29 (55.8%)

45 (80.4%) 11 (19.6%) 92.2 ± 18.5 (50 – 140) 59.8 ± 14.0 (41 – 109)

41 (78.8%) 11 (21.2%) 91.2 ± 16.6 (55 – 135) 57.4 ± 11.5 (31 – 88)

P-Value 0.85

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Control Group (N = 52)

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0.03*

Intraoperative EBL (mL) a