Background
Total knee arthroplasty (TKA), as one of the most common surgeries in
orthopaedics, is routinely applied to treat end-stage knee diseases. It
has been proven to be tolerable in correctly selected patients and can
effectively alleviate pain, ameliorate function, and improve the quality
of life of patients (1). As the proportion of aging adults increases in
the general population so does the demand for TKA. It is estimated that
the demand for primary TKA will grow to 3.48 million procedures by 2030
in the United States (2). Although the procedure has potential in
facilitating the patient’s functional recovery, substantial
intraoperative and postoperative blood loss and consequential acute
anaemia and transfusion are major concerns for orthopaedic surgeons. The
TKA procedure is associated with substantial blood loss, leading to a
high prevalence (82.5% in males and 84.3% in females) of postoperative
anaemia (3), which may therefore cause the relatively high rate (nearly
45%) of postoperative allogeneic blood transfusion (4). In addition,
most patients undergoing TKA are elderly and have a high prevalence
(25.3-30.2%) of preoperative anaemia, which is widely accepted as a
predictive factor of postoperative allogeneic transfusion. Allogeneic
transfusion carries a substantial risk of transfusion-associated
complications requiring additional treatment and increased length of
stay (5).
To reduce blood loss and allogeneic blood transfusion requirements while
accelerating haemoglobin and function recovery, many blood-saving
strategies have been reported, of which
recombinant human erythropoietin
(rhEPO) has demonstrated effectiveness in perioperative autologous blood
donation, reducing haemoglobin (Hb) level drop and blood transfusion
requirements according to numerous randomized controlled trials (6-10).
Currently, there are two main plans for the perioperative application of
rhEPO in patients who are scheduled for total joint arthroplasty (TJA).
One is the weekly administration
of large-dose rhEPO for 2-4 weeks before surgery, which is called the
long-term dosing schedule (10). The other is the daily administration of
small-dose rhEPO from 0-5 days preoperatively to a few days (less than a
week) postoperatively, which is called the short-term dosing schedule
(6-9). However, the weekly dosing schedule has some known drawbacks; for
instance, patients receiving the
long-term dosing schedule and who had not undergone TKA are not allowed
to visit the hospital for weekly injections, which is very inconvenient
to the patients and will increase the preoperative waiting time and
medical costs. The implementation of the dosing schedule is difficult in
patients with poor compliance. In addition, initial high peak levels of
erythropoietin caused by high weekly doses are likely considered to be
wasteful, as erythropoietin receptors on progenitor cells in bone marrow
may become saturated; when these receptors are again free for binding,
the level of serum erythropoietin will fall (11). Compared with the
weekly protocol, the short-term daily dosing schedule with small amounts
of rhEPO could maintain a more constant low but relatively more
effective level of serum erythropoietin without causing inconvenience or
other potential risk to the patient (11). In addition, previous studies
also reported that repeated administration of rhEPO is more effective in
stimulating the reticulocyte response than the weekly large dose of the
same total amount of rhEPO (12).
It has been reported that one daily dose (150 IU/kg) of rhEPO, starting
from 3 days before arthroplasty, is more effective in increasing Hb
levels and reducing blood loss without causing additional complications
than starting on the day of surgery. In the same study, researchers also
concluded that the initial application of rhEPO on the surgery day
neither significantly reduced blood loss nor increased Hb level after
arthroplasty when compared with the blank control group (7). In
contrast, Na et al (9) administered 3000 IU of rhEPO subcutaneously to
patients, starting on the surgery day through the postoperative period,
and found that compared with the placebo group, starting rhEPO on the
surgery day could effectively attenuate anaemia and decrease transfusion
requirements in patients undergoing arthroplasty, which was comparable
with the conclusion of a study by Bernabeu-Wittel et al (6) with a
similar rhEPO dosing schedule. Moreover, in another study (8),
researchers suggested that each patient undergoing arthroplasty receive
a dosing schedule involving 10,000 IU of rhEPO daily subcutaneously from
preoperative day 5 to postoperative day 3, which is also the same dosing
schedule as our centre. Under this dosing schedule of rhEPO, researchers
found a significant reduction of 94% in the need for allogeneic blood
transfusion in patients.
As a result, the optimal
short-term daily dosing schedule of rhEPO for TKA patients still needs
to be investigated. This
prospective double-blinded
randomized placebo-controlled trial was conducted to compare three
different types of short-term
rhEPO-based treatment plans for perioperative autologous blood donation
in TKA.