SUBJECTS AND METHODS
Design
A prospective, randomized, double-blind, controlled trial.
Time and setting
This study was completed in the Department of Joint Surgery, Affiliated Hospital of Qingdao University Medical School, China between July 2011 and July 2013.
Subjects
The patients who underwent TKA in the Department of Joint Surgery, Affiliated Hospital of Qingdao University Medical School and fulfilled the inclusion criteria as well as did not meet the exclusion criteria were 324 cases.
The inclusion criteria were as follows: patients who (1) met the diagnostic criteria for osteoarthritis of the knee[8]; (2) initially underwent unilateral TKA; (3) were negative for deep vein thrombosis according to the preoperative color Doppler ultrasonography on the deep veins of both lower extremities; and (4) gave informed consent for the therapeutic schedule.
The exclusion criteria were as follows: patients who (1) had a history of hemorrhagic disease or a bleeding tendency during the preoperative coagulation test; (2) had a past medical history of venous thrombosis; (3) were infused with over 2 000 mL of fluids 24 hours after surgery[9]; (4) underwent knee arthroplasty; or (5) used a combination of other drugs that might impact the findings.
A total of 324 patients were randomized into three groups using a random number table generated by a computer (Microsoft Office Excel 2010; Microsoft Corp., Redmond, USA). Rivaroxaban group comprised 102 patients
(32 males and 70 females) with a mean age of 63.5 years (50 to 82 years). Low-molecular-weight heparin (LMWH) group comprised 112 patients (20 males and 92 females) with a mean age of 65.7 years (54 to 80 years). Aspirin group comprised 110 patients (28 males and 82 females) with a mean age of 62.7 years (47 to 79 years).
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Related drugs were used in this experiment:
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Related drugs
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Source
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Rivaroxaban (Xarelto), Aspirin (Bayaspirin)
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Bayer, Leverkusen, Germany
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LMWH sodium (Clexane)
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Sanofi Corp., Paris, France
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The three groups each received a different postoperative anticoagulant treatment according to the anticoagulation guidelines
[10-11]: 12 hours after the operation, Rivaroxaban group was given oral rivaroxaban at a dose of 10 mg/d, the LMWH group was given subcutaneous LMWH sodium at a dose of 4 000 AxaIU (0.4 mL/d) and the aspirin group was given oral aspirin at a dose of 100 mg/d. All of the groups were treated for 14 days.
Methods
Preoperative management
The patients underwent routine examinations, including routine blood tests, routine anticoagulation measures and color Doppler ultrasonography on the deep veins of both lower extremities. The body mass index, hemoglobin, hematocrit, range of motion and the knee society score[12] were assessed in the patients before surgery.
Operation methods
All of the patients were operated on by a single surgeon using an anterior midline incision via a medial parapatellar approach with a tourniquet (pressure of 260 mm Hg,
1 mm Hg=0.133 kPa)[13]. All of the operations were performed under continuous epidural anesthesia with an epidural catheter in place and the use of intravenous sedation. The operations in the three groups were the same; the cemented Scorpio NRG Knee System (Stryker, Kalamazoo, USA) without patellar resurfacing was used. After surgery, a drainage tube was placed to be connected to an autologous blood transfusion device (Stryker, Kalamazoo) without clipping[14], and a pressure dressing was applied with an elastic bandage before the tourniquet was slowly released.
The rest of postoperative management
The shed blood in the autologous blood transfusion device was measured and was re-transfused through the veins within 6 hours as well as was discarded after 6 hours[15]. The drainage tubes were removed from all patients
24 hours after surgery[14]. The patients who showed clinical manifestations of hypovolemia (such as hypotension < 90 mm Hg that did not respond to crystalloid volume expansion) and tachycardia were given a blood transfusion. The patients were given antibiotics by intravenous drip for 3 days to prevent infections and oral Celecoxib capsules for analgesia after surgery. A pressure dressing was applied to the affected extremities with elastic bandages, and the affected extremities were elevated. Ankle pump exercises began 6 hours after the surgery[16]. The patients left their sickbeds and stood up with the help of physicians and began performing functional rehabilitation exercises at day 1 after surgery, including the straight-leg raise and knee flexion-extension[16]. They practiced walking with walking aids two or three times a day under the guidance of caregivers 2 days after surgery, once for 10-
20 minutes.
Postoperative observation indexes
Routine blood tests were performed 3, 7 and 14 days after surgery, and the hemoglobin, hematocrit, drainage volume, and autologous and heterogeneous blood transfusion volumes were recorded during the removal of the drainage tube. In the 2nd and 4th weeks after surgery, color Doppler ultrasonography was performed on the deep veins of both lower extremities, and thromboses of the common and superficial femoral, popliteal, posterior tibial and muscular calf veins were recorded. All of the patients were followed for 4 weeks, their wound healing and wound complications (including hematoma, superficial wound infection and deep infection requiring another surgery) were observed. Any evidence of wound drainage, erythema or surrounding cellulitis identified by the medical staff was regarded as a wound complication.
The hidden blood losses of the three groups were calculated based on the gross equations[17] according to the method of Sehat[18] and Feldschuh et al [19].
Main outcome measures
The incidence of deep vein thrombosis, hidden blood loss, the incidence of wound complications and the incidences of lower limb subcutaneous ecchymosis and swelling were measured.
Statistical analysis
Measurement data are reported as means and ranges, and the medians and inter-quartile ranges (IQRs) were used when the data were skewed. Enumeration data are expressed as percentage. All of the experimental data were statistically analyzed using SPSS 20.0 software (IBM Corp., Armonk, USA). To compare the data among the three groups, a one-way analysis of variance (ANOVA) test was used for normal distributions and the Kruskal-Wallis test was used for skewed distributions. For pairwise comparisons among the three groups, the Bonferroni test was used. For qualitative comparative parameters, the chi-square test was used. Significant level was set at bilateral α=0.05. Statistical power was reached to 0.8 in the comparison of continuous variables[20].
