After this study was approved by the regional ethics committee, we prospectively randomized 80 patients 50 years or older who underwent cemented THA for primary osteoarthritis between March and June 2008. During that same time, we treated a total of 104 patients with primary cemented THAs for osteoarthritis. Exclusion criteria were allergy to LMWH, bleeding disorders, renal failure, hepatic disease, active treatment for malignancy, ongoing antithrombotic treatment, history of DVT or PE, and patients experiencing major operations, traumas, stroke, or cardiac infarction the last 3 months before surgery. All patients were routinely hospitalized the day before surgery. We excluded 10 patients from enrollment owing to antithrombotic treatment, five patients with a history of DVT or PE, and two patients with liver disease. Seven patients refused to participate in the study. This left 80 patients for study. None of the 80 patients was lost to followup 6 months after surgery, and data collection was completed for all participants.
We performed a power analysis based on two earlier studies in which a significant reduction in the number of patients who had transfusions showed a 30% reduction in total blood loss [3
]. We considered this reduction clinically relevant. The effect size was based on blood loss and transfusion requirements in two earlier studies [3
]. In a prospective controlled study on patients who had THAs, Johansson et al. [15
], found a 27% reduction in total blood loss (355 mL) reduced (p = 0.009) the number of patients who had transfusions. In a retrospective study [3
], we found a 30% reduction in total blood loss (370 mL) reduced (p = 0.006) the number of patients who received transfusions by 28%. We believe a reduced risk for being exposed to blood transfusions is clinically relevant. With 80% power (alpha = 0.05), at least 37 patients were required in each group. We randomized a total of 80 patients to compensate for patients who might withdraw consent.
There were no differences between patients who received preoperative or postoperative start of thromboprophylaxis in terms of demographics (Table ). We found no difference in operative times and length of hospitalization (Table ), and preoperative laboratory values also were similar (Table ).
Surgery time, blood loss, and days of hospitalization in preoperative and postoperative groups
Preoperative and postoperative hemoglobin and hematocrit values
In the hospital’s written patient information, patients are advised to stop antiplatelet medication (ie, NSAIDs and high-dose aspirin) 1 week before surgery. A complete record of the patients’ medications during the study period was recorded.
We assigned patients to either 5000 IU dalteparin (Fragmin®; Pharmacia and Upjohn, Stockholm, Sweden) subcutaneously or placebo (saline) injected 12 hours before surgery. All patients had 5000 IU dalteparin subcutaneously 6 hours after surgery and each day until the 35th postoperative day. Randomization was prepared in blocks of 20. Treatment group assignment was concealed by the hospital staff. The syringes with 5000 IU dalteparin and placebo with the same volume in each syringe were prepared by a study nurse who otherwise was not engaged in the study, according to randomized strata. The injection was blinded to the investigator, hospital staff, and the patient. The study blinding was broken after all patients had completed 6 months of followup.
All patients received spinal anesthesia without hypotensive effect with 5 mg/mL bupivacaine (Marcain®; AstraZeneca, Södertälje, Sweden) injected at the lumbar level. Cephalothin (Keflin®; EuroCept Pharmaceuticals BV, Kortenhoef, The Netherlands) 2 g was administered within 30 minutes of the arthroplasty. An equivalent dose subsequently was given 3 hours, 9 hours, and 15 hours after surgery as prophylaxis against infection. Voluven® and Ringer’s acetate (Fresenius KABI, Bad Homburg, Germany) were used as plasma substitutes.
The operation was performed with the patient in the lateral position, using a standardized posterior approach where only the piriformis muscle was detached and with capsular repair at the end of the procedure. All procedures were performed by two surgeons with at least one being experienced in performing THAs. All patients received stem and cups (Exeter®; Stryker Orthopaedics, Mahwah, NJ, USA) embedded in Simplex® tobramycin bone cement (Stryker Howmedica, Limerick, UK).
Postoperative analgesia was administered according to a standard protocol consisting of paracetamol + codeine sulfate (Paralgin forte®; Weifa AS, Oslo, Norway) and ketobemidone (Ketorax®; Jenahexal Pharma, Jena, Germany). Closed postoperative drainage was used for 24 hours. All patients were mobilized on the first postoperative day, and a program for simple self-administrated exercises was provided by the physiotherapists during hospitalization. Walking with the use of crutches was advised 6 to 8 weeks after surgery. Regular outpatient physiotherapy was not recommended until 2 months after surgery. We did not allow concomitant mechanical prophylaxis against DVT.
Hemoglobin and hematocrit were measured during surgery, before the first postoperative injection of dalteparin, and on postoperative Days 1, 3, and 6. We recorded the number of blood transfusions and plasma substitutes. The primary outcome was the volume of blood loss measured by weighing sponges and drapes (1 mg = 1 mL), volume in suction drains during surgery, and wound drains until removal 24 hours postoperatively [20
]. We also recorded the number of patients who received transfusions, consumption of units of allogeneic leukodepleted erythrocyte concentrate, and decrease in hemoglobin concentration postoperatively in the two groups. We used a standard protocol with transfusion thresholds where a hemoglobin level less than 8 g/dL triggered transfusion and patients with a level greater than 10 g/dL did not receive a transfusion. Hemoglobin level on its own may be a poor indicator of tissue hypoxia, and the decision to transfuse patients with hemoglobin between 8 and 10 g/dL will, to some extent, be influenced by other parameters such as concomitant disease, weight, age, and others [1
]. RBCs were given in 300-mL units, and autologous blood was not used. We evaluated all patients on a daily basis during hospitalization for possible bleeding events, such as hematoma, ongoing excessive bleeding, prolonged wound drainage (greater than 7 days), infections, and other complications. Overall surgical complications were classified according to Dindo et al. [8
If patients showed any clinical sign of thromboembolic events, such as respiratory distress, chest pain, unstable hemodynamics, and a swollen, red, painful leg, we performed objective tests, including ECG, blood gases, plain chest radiography, venography, and spiral CT, after a clinical examination. Routine ultrasound screening, venography, or CT was not performed. A clinical research file (CRF) (Appendix 1; supplemental materials are available with the online version of CORR) was completed on a daily basis during hospitalization and at 6 months’ followup.
The data are presented as mean, range, and 1 SD or 95% CI. Patient characteristics, blood loss, hemoglobin, hematocrit, fluid volume, and operation time were compared between the two groups using Student’s t-test. We used the Mann-Whitney U test to compare the number of blood transfusions. Chi-square and Fisher’s exact tests were used to compare frequencies. We used SPSS Statistics Version 17 (IBM Inc, Chicago, IL, USA) for all analyses.