Clinical effectiveness of 3 days preoperative treatment with recombinant human erythropoietin in total knee arthroplasty surgery: a clinical trial

Abstract

Aims The purpose of study is to evaluate the effect and complication of preoperative short-term daily recombinant human erythropoietin (rhEPO) treatment for blood-saving in patients undergoing unilateral primary total knee arthroplasty (TKA). Methods This three-arm randomized clinical trial compared three different rhEPO-based treatment protocols for unilateral primary TKA. Group A: application of daily doses of rhEPO combined with iron supplement starting 3 days before surgery; Group B: application of daily doses of rhEPO combined with iron supplement starting the day of surgery; Group C: iron supplement alone. Perioperative hemoglobin (Hb) level gaps, total perioperative blood loss, reticulocyte levels and treatment-related complications were studied. Results A total of 102 patients were included (35, 35 and 32 patients in Groups A, B and C, respectively). Total blood loss (TBL) in Groups A, B and C was 490.84, 806.76 and 924.21 ml, respectively. Patients in Group A had a significant lower TBL than Groups B and C (A vs. B: P = 0.010; A vs. C: P < 0.001). There was no difference as for TBL between Groups B and C (P = 0.377). Group A patients had significant smaller Hb decline than Group C on the third and fifth postoperative day (P = 0.049, P = 0.037), as well as than Group B on the fifth postoperative day (P = 0.048). There was no difference as for Hb decline between Groups B and C. No difference was shown in levels of inflammatory biomarkers or blood-saving protocol-related complications among three groups. Conclusions Daily dose of rhEPO combined with iron supplement administered 3 days before TKA procedures could significantly decrease perioperative blood loss and improve postoperative Hb levels, without significantly elevating risks of complication, when compared with admission of rhEPO on the day of surgery and iron supplement alone. Preoperative daily rhEPO treatment could be a more effective blood-saving protocol in TKA procedures.

Comparison of Blood Loss between Open‐Box Prosthesis and Closed‐Box Prosthesis after Primary Total Knee Arthroplasty

“…A sample size analysis was performed to calculate the minimum number of patients necessary for this study. Based on our pilot study and previous literature 10 , the standard deviation of hemoglobin was assumed to be 15.0 g/L and a difference of >10.0 g/L in hemoglobin concentration was considered the minimal clinical difference. With the test of significant level as 0.05 and the power of test as 80%, the minimal sample size was calculated to be 35 per group (2‐tailed), which indicated that the number of patients enrolled in each group was sufficient for this study.…”

“…Numerous trials were performed to find out risk factors contributing to bleeding after procedure of TKA, and corresponding interventions were carried out to prevent further blood loss and avoid postoperative transfusion. For example, the erythropoietin taken before surgery could effectively stimulate erythropoiesis and improve preoperative and postoperative hemoglobin levels and decrease transfusion rate when combined with iron therapy, helping patients get over anemia 10 . According to our protocol, if the open‐box prosthesis is proved to cause more blood loss than the closed‐box prosthesis in patients undergoing unilateral or one‐stage bilateral TKA, the uncovered areas in the intercondylar fossa in the open‐box one should be regarded as a risk factor related with further postoperative bleeding, which benefits patients by informing surgeon's selection for knee prosthesis, such as not implanting open‐box prosthesis in patient with some other risk factors of bleeding or transfusion.…”

Finding the optimal regimen for short-term daily recombinant human erythropoietin treatment for blood-saving purpose in patients undergoing unilateral primary total hip arthroplasty: a double-blinded randomized placebo-controlled trial

“…Allogeneic transfusion carries a substantial risk of transfusion-associated complications requiring additional treatment and increased length of stay [ 4 ]. Many blood-saving strategies have been reported, of which recombinant human erythropoietin (rhEPO) has demonstrated effectiveness in reducing hemoglobin (Hb) level drop and blood transfusion requirements according to numerous randomized controlled trials [ 5 , 6 , 7 , 8 , 9 ].…”

“…One is weekly application of large-dose rhEPO for 2–4 weeks before surgery, which is called the long-term regimen [ 9 ]. The other one is daily application of small-dose rhEPO from 0–5 days preoperatively to a few days (less than a week) postoperatively, which is called the short-term regimen [ 5 , 6 , 7 , 8 ]. However, the weekly protocol has some obvious drawbacks: The long-term of treatment requested the patients to come back to hospital weekly for injections, which would therefore cause inconvenience to the patients and it would also increase the preoperative waiting interval.…”

“…Cao et al [ 6 ] advocated that a daily dose (150 IU/kg) of rhEPO started from 3 days before arthroplasty is more effective than being applied from the day of surgery in increasing Hb level, reducing blood loss without additional complications, they also concluded that the application of rhEPO since the day of surgery cannot significantly reduce the blood loss or increase the Hb level after arthroplasty compared with no application of rhEPO. On the contrary, Na et al [ 8 ] applied 3000 IU of rhEPO subcutaneously during the operation and the postoperative period, they found that compared with the control (placebo) group, application of rhEPO since the day of surgery could effectively attenuated anemia and decreased transfusion requirements in patients undergoing arthroplasty, which was coincident with the conclusion of Bernabeu-Wittel et al [ 5 ] with the similar rhEPO regimen.…”