J.Orthopaedics 2007;4(4)e5
index.htm
Introduction:
Joint prosthetic surgery, particularly of the hip and knee, is
one of the most common orthopedic procedures performed today.
The increase in life expectancy and an aging population
demanding an increasingly higher quality of life are factors
that have contributed to this phenomenon. This type of surgery
is known to cause a loss of blood that often requires a blood
transfusion,1 which is not without potential risks
and complications such as transmission of infectious diseases
(mainly hepatitis and AIDS),2,3 manipulation errors,
fever, increased rate of infections, etc., without forgetting
that a proportion of the population refuses to have a blood
transfusion because of religious beliefs.4 In order
to palliate these problems, it is attempted to reduce blood
transfusion needs as much as possible by various procedures,
including preoperative autologous blood donation, the use of
blood recovery systems, agents that reduce bleeding, minimally
invasive surgery and stimulation of erythrocyte production with
erythropoietin (EPO) among others.
The present study analyzed the reduction in
transfusion requirements achieved by preoperative administration
of EPO in patients undergoing primary hip and knee arthroplasty.
Material and Methods :
From December 1, 2001 to July 31, 2005, 717
primary total prostheses (426 total knee and 291 total hip
prostheses) were implanted in our Orthopedics Department (Figure
1). Of these, 93 implanted patients (12.9%) had preoperative
hemoglobin (Hb) levels less than or equal to 13 g/dl, and were
included initially in the study. These patients
were applied the exclusion criteria for treatment with EPO
listed in Table 1.
Four patients were excluded for poorly controlled
hypertension, 1 for acute medical disease, 11 for cardiovascular
disease, 2 for blood disease, and 8 for concomitant
immunosuppressant medication (high-dose corticosteroids and/or
immunosuppressants).
The remaining 67 patients received treatment with EPO
on days -21, -14 and -7 prior to surgery at a dose of 40,000 IU
epoetin alpha. On day 0 (24 hours before surgery), a new blood
test was done and if Hb levels were lower than 15 g/dl patients
received a fourth dose. All patients received oral supplements
of 200 mg iron/day.
In order to harmonize the
transfusion criteria on an objective and statistically
quantifiable basis, the indication to perform blood transfusion
was considered to be Hb levels <8.5 g/dl, as these levels are
widely accepted in the literature5-7 as
indication for transfusion. The patients receiving transfusion
with Hb>8.5 g/dl were excluded from the study. Patients meeting
the exclusion criteria indicated by Salido8 (Table 2)
were also excluded, as this removes possible causes of Hb
reduction other than surgery itself. In this way,
2 patients who had liver cirrhosis and 4 patients who were
transfused during resuscitation in the operating room with Hb
levels > 8.5 g/dl were excluded from the study.
A total of 61 patients met all the above requirements and were
included in the study.
All patients received antithrombotic prophylaxis with
calcium nadroparin (Sanofi Winthrop) from 12 hours before to 2
months after surgery.
The study was approved by our Institutional Review Board and the
subjects gave informed consent to participate in the study.
Pre- and postoperative Hb levels, the increase in Hb levels
after administration of EPO, and the rate of blood transfusion
were analyzed.
TABLE 1:Exclusion
criteria for treatment with recombinant human erythropoietin.
Allergy to epoetin alpha |
Significant bleeding or hemolysis |
Uncontrolled hypertension |
Acute infection or medical disease |
Cardiovascular or blood disease |
Need for concomitant administration of
medication that may suppress erythropoiesis (eg, cytotoxic
agents) |
Patients in whom adequate antithrombotic
prophylaxis cannot be performed |
Pregnancy |
TABLE 2 :Exclusion
criteria used by Salido8.
Fractures |
Prior anticoagulant treatment |
Chronic hematological or liver disease |
Postoperative hemorrhagic complications not attributable to
surgery |
Patients who were transfused with a postoperative hemoglobin
>8.5 g/dl |
TABLE 3 : Demographic data
Sex
|
Women |
Men |
Number of
patients |
58 |
3 |
Mean age |
69 years (range
30-85) |
71 years (range
67-75) |
Knee prosthesis |
43 |
1 |
Hip prosthesis |
15 |
2 |
Mean preoperative
Hb* (g/dl) |
12.3 (range 10.2-13) |
12.4 (range
12.2-12.8) |
Mean Hb on
admission (g/dl)** |
14.3 (range
11.3-15.9) |
14.6 (range
13.9-15.3) |
Mean
postoperative Hb (g/dl)*** |
11.3 (range
8.4-13.5) |
11.6 (range
11.6-11.6) |
Transfusion |
3 |
0 |
*Mean
preoperative Hb = mean Hb of the patients before starting
treatment with EPO.
**Mean Hb on admission=mean Hb 24 hours before
surgery.
***Mean post-operative Hb = mean Hb at 12 hours following
surgery
Results :
A total of 61 patients were studied (Table
3), 44 with total knee prostheses (TKP) and 17 with total hip
prostheses (THP). Mean age was 70 years (range 30-85).
There were 58 women and 3 men. The affected side was the right
in 32 and the left in 29. The femoral component was cemented in
6 and the tibial component in 39 of the TKP, while all the THP
were cementless. Initial mean preoperative hemoglobin (Hb) was
12.3 g/dl (range 10.2-13). Mean Hb after administering 3 doses
of EPO rose to 14.3 g/dl (range 11.3-15.9). Forty-one patients
(67.2%) received a fourth dose of EPO on admission. Mean
postoperative Hb, measured 12 hours after the procedure,
decreased to 11.4 (range 8.5-13.5). Three
patients (4.9%) were transfused, 2 undergoing TKP and 1 THP,
with Hb of 8.4, 7.7 and 8.2 g/dl, respectively. Iron supplements
were well tolerated in all patients and of the possible
complications where EPO can act as a risk factor, there was only
1 case of postoperative deep venous thrombosis (1.6%) confirmed
by echo-Doppler.
Discussion:
There is a current consensus that preoperative Hb levels are a
predictive factor for the need for blood transfusion after
primary hip and knee arthroplasty.8-14 . Salido8
reported that 69% of patients with a preoperative Hb level less
than 13 g/dl were transfused and that they had 4 times greater
risk of blood transfusion than those with a preoperative Hb
level between 13-15 g/dl and 15.3 times greater risk than those
with a Hb level greater than 15 g/dl.
These conclusions, together with the already known
risks of blood transfusion, 2, 4,8, 15,16 have led to
attempts to minimize this problem through the use of measures
such as blood recovery, controlled hypotension,4
fibrin spray,17 aprotinin,18 and
particularly autologous blood donation and EPO,19 the
latter two sometimes used in combination, among others.
Autologous blood donation has been and is one of the most widely
used alternatives both in orthopedic surgery3,16,20-22
and other types of surgery that involve large blood losses such
as thoracic or cardiac surgery,23 etc.
However, we consider that though autologous
donation removes the risk of transmission of contagious diseases
its use is associated with other negative factors such as a
greater number of transfusions,4,20 which, although
less than with allogenic blood transfusion,21 is not
free of risks, such as immunosuppression and increased risk of
infection, and generating a longer hospital stay.4,23,24
Cohen20 reported that surgeons tended to
transfuse patients included in autologous blood programs earlier
and more frequently, and not only this, but also the waste of
resources it implies in those cases where the blood is finally
not used.4,15 Bierbaum15 reported that up
to 45% of autologous blood was not used. On the other
hand, patient donating autologous blood suffer a decrease in Hb
prior to surgery,20 which also increases the
likelihood of transfusion. In addition, some patients with low
baseline Hb levels cannot be included in autologous blood
programs, and others may have anemia, medical problems or a poor
response to erythropoietin.19 It is for this that
some surgeons19,24 tend to favor the combined use of
autologous blood donation and EPO, arguing that in this way the
need for allogenic blood transfusion is reduced.
Our results with the use of EPO (4.9% rate of
blood transfusion in patients with a preoperative Hb <13 g/dl)
versus those obtained in our department without EPO8
(69% rate of blood transfusion in patients with a preoperative
Hb <13 g/dl), though both samples are not comparable for several
reasons (one prospective and another retrospective, added
inclusion/exclusion criteria of EPO, higher number of cemented
tibial components, different model in hip prosthesis, and a
higher prevalence of the female sex attributable in part to
several factors25,26) are agree with the
effectiveness of EPO treatment shown by other authors such as
Pierson,27 who reported that the rate of blood
transfusion was 2.1% in the group of patients treated with EPO
versus 16.4% in untreated patients.
In addition, based on the studies by Cheung28
and Golberg29, we consider that the weekly dose is
as effective as the daily dose. On the other hand, the weekly
use of a standard weight-independent dose of 40,000 IU, that
would correspond to the “high dose” used by Feagan7 ,
provides more advantages than a dose adjusted for weight30
as it simplifies the treatment and no significant
complications were observed (only one case of venous
thrombosis). We also advocate the administration of a fourth
dose of EPO in the immediate pre-operative period to patients
with Hb levels <15 g/dl, based on the experience of other
authors such as Andrade31 and on pharmacodynamic
studies 28,32.
In conclusion, we think that use of EPO alone for transfusion
prophylaxis in prosthetic hip and knee surgery is effective and
efficient, has a low complexity of use and a low rate of
complications.
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