Estimated peri-operative blood loss and preopera-tive hemoglobin Hb concentration are critical predictors of the need for blood transfusion.2,3 Cohen and Brecher4 developed a nomogram to
Trang 1The safety of surgical blood
man-agement practices is critically
important because of the potential
risks of transfusion reactions,
im-munosuppression, and disease
transmission associated with use of
allogenic blood One response to
these concerns has been increased
use of autologous blood
Approxi-mately 15 years ago, less than 5% of
patients participated in
preopera-tive autologous donation (PAD)
before elective surgery.1 Today,
50% to 75% of patients opt for PAD,
primarily because of concerns about
transfusion-transmitted human
im-munodeficiency virus (HIV) and
hepatitis Other blood management
techniques have been developed,
including the use of hemostatic
agents, perioperative blood salvage,
and the use of recombinant human
erythropoietin (epoetin alfa) to
stim-ulate erythropoiesis Because of the implications for the effective man-agement and allocation of blood bank resources, making the opti-mum choice requires careful preop-erative decision making Proper preoperative planning also can opti-mize the patient’s perioperative course and recovery
Predictors of Transfusion Risk
A patient’s risk of requiring a trans-fusion during surgery and in the immediate postoperative period is
an important element of effective blood management Estimated peri-operative blood loss and preopera-tive hemoglobin (Hb) concentration are critical predictors of the need for blood transfusion.2,3 Cohen and
Brecher4 developed a nomogram to estimate the volume of surgical blood loss that would trigger a deci-sion to transfuse, based on the patient’s preoperative and mini-mum tolerable postoperative hemat-ocrit (Hct) levels Preoperative Hb concentration itself is readily assess-able and statistically is a powerful predictor of the risk of requiring a transfusion.5 In a study of 9,482 patients who underwent total hip or knee arthroplasty, Bierbaum et al6
demonstrated that the lower the baseline Hb level, the more proba-ble the transfusion of allogenic blood Of the 3,020 patients who met the study entry requirement of baseline Hb >10 but ≤13 g/dL, 864 (29%) needed a transfusion of allo-genic blood compared with 267 (8%) of 3,374 patients with baseline
Hb >14 g/dL Other studies have
Dr Keating is Orthopaedic Surgeon, The Center for Hip and Knee Surgery, Mooresville,
IN Dr Meding is Orthopaedic Surgeon, The Center for Hip and Knee Surgery, Mooresville One or more of the authors or the departments with which they are affiliated has received something of value from a commercial or other party related directly or indirectly to the sub-ject of this article.
Reprint requests: Dr Keating, 1199 Hadley Road, Mooresville, IN 46158.
Copyright 2002 by the American Academy of Orthopaedic Surgeons.
Abstract
Concern about the cost and safety of allogenic blood transfusion, including the
risk of viral infection and immunosuppression, has led to refinements in and
new approaches to blood conservation, including the development of transfusion
practice standards and improvements in surgical practice Preoperative
autolo-gous blood collection, the use of hemostatic agents, perioperative blood salvage,
and the use of recombinant human erythropoietin (epoetin alfa) to stimulate
erythropoiesis have contributed to decreased use of allogenic blood services.
Development of appropriate blood management strategies to help reduce or
eliminate exposure to allogenic blood requires a preoperative assessment of the
likelihood of transfusion and of the risks as well as costs associated with
conser-vation and replacement options The informed selection of alternatives based on
preoperative assessment of hematologic status, estimated blood loss, and sources
for blood replacement may enhance blood management practices in major
elec-tive orthopaedic surgery.
J Am Acad Orthop Surg 2002;10:393-400 Elective Orthopaedic Surgery
E Michael Keating, MD, and John B Meding, MD
Trang 2shown that surgical morbidity and
mortality are inversely correlated
with preoperative Hb levels.3,7
Although the transfusion
thresh-old of Hb 10 g/dL and Hct 30% (the
10/30 rule) is no longer common
practice, using lower transfusion
thresholds has not resulted in
deter-mination of an optimal threshold
for all patients.8 Instead, the
deci-sion for blood transfudeci-sion should be
based on a patient’s overall clinical
status and the nature of the anemia
(eg, acute or chronic) once other
measures of red blood cell repletion
have failed.9,10
Effect of Anemia on
Surgical Outcomes
The primary purpose of transfusion
is to reduce the risks associated with
anemia, which is common in
pa-tients undergoing elective
ortho-paedic surgery Of the 8,561
pa-tients in the Bierbaum study6for
whom the baseline Hb level was
known, 35% (3,020) had a level ≤13
g/dL Furthermore, the mean Hb
level decreased from a mean
base-line value of 13.8 to 12.8 g/dL before
admission in patients who
predonat-ed blood In another study11
assess-ing the prevalence of anemia in
elec-tive orthopaedic surgery patients, 34
(21%) of 162 patients who
predonat-ed autologous blood were anemic
(Hct ≤39%) at initial donation
Sub-sequently, 35% of these anemic
donors required allogenic blood
transfusion, indicating a need for
early identification and treatment of
anemia Furthermore, the incidence
of anemia by numeric criteria in
elderly patients (≥65 years) is four to
six times greater than can be
predict-ed by the presence of clinical
symp-toms.12 The incidence of anemia
increases with age12and is of
partic-ular concern because the elderly
constitute a large proportion of
pa-tients undergoing elective
ortho-paedic surgery
Morbidity and Mortality
Anemia has an adverse effect on morbidity and mortality Morbidi-ties associated with both acute and chronic severe anemia (Hb <6 g/dL), especially in older patients, include fatigue, tachycardia, hypotension, dyspnea, and impaired levels of consciousness.13,14 Anemia and the associated need for transfusion also can lengthen the duration of hospi-talization after elective orthopaedic surgery In the Bierbaum study,6
patients who received a transfusion
of only allogenic blood had the longest mean duration of hospital-ization (6.6 days), compared with patients who were transfused with autologous blood (5.6 days) or had
no transfusion (5.4 days) (P ≤ 0.01).
Severe preoperative anemia is associated with an increased risk of postoperative mortality Carson et al8
reported that the 30-day mortality rate in cardiovascular patients with preoperative Hb levels <6 g/dL was 33.3% compared with 1.3% for those with levels ≥12 g/dL (The patients with low Hb levels refused transfu-sion because of religious convic-tions.) In an earlier study,7a higher surgical mortality rate was reported for patients with Hb levels <6 g/dL (61.5%) compared with those with levels >10 g/dL (7.1%)
Patient Vigor and Quality of Life
Another potential complication
of anemia is decreased vigor, which can have implications for recovery, prolonging length of hospitalization and affecting quality of life Early inpatient rehabilitation after surgery decreases the length and cost of hospitalization and enhances short-term functional recovery.15 Assess-ments of the patient’s preoperative and postoperative vigor could, therefore, play an important role in initiating and monitoring the early rehabilitation program
A correlation (r = 0.4) between
muscle strength (a surrogate mea-sure of vigor) and Hct levels
sug-gests that Hct may be a valuable objective measure of vigor in pa-tients undergoing major elective or-thopaedic surgery.16 Furthermore, improving vigor in this population
by increasing Hb and Hct levels could facilitate recovery and im-prove overall quality of life Studies assessing the effect of increases in
Hb on quality of life after adminis-tration of epoetin alfa in anemic cancer patients demonstrated a direct correlation between Hb level and quality of life.17,18 The largest improvement in quality of life in these patients occurred when Hb levels were increased from 11 to 12 g/dL.17 However, a similar correla-tion between increases in Hb and improved quality of life in ortho-paedic surgery patients remains to
be established
Perioperative Blood Management
Allogenic Blood Transfusion
Historically, allogenic blood transfusion has been the mainstay
in perioperative blood manage-ment However, the association of allogenic blood transfusions with numerous risks—including trans-mission of HIV, hepatitis B and C viruses, and human T-cell lym-photropic virus types I and II—has diminished its utility19,20 (Table 1) The institution of various measures
to improve the detection and elimi-nation of tainted blood supplies has substantially reduced the estimated risks of transfusion-transmitted dis-eases.21 The implementation of HIV-antibody testing in 1985 reduced the rate of transfusion-associated HIV infection reported to the Centers for Disease Control and Prevention from 714 cases in 1984 to only about
5 cases per year during the subse-quent 5 years.21 Similarly, screening tests for hepatitis B and C viruses also have decreased the number of cases of posttransfusion hepatitis.21
Trang 3Nevertheless, the risk of infection
or other adverse reactions still
exists Observational retrospective
reports22and prospective studies23
both have described an association
between exposure to allogenic
blood and increased rates of
postop-erative infection and early
recur-rence of cancer Although exposure
to leukocytes in allogenic blood and
subsequent sensitization can trigger
an immunosuppressive reaction, the
clinical importance of this
immuno-suppression has yet to be clearly
defined.21 Other risks include
bac-terial contamination and
transfu-sion-related acute lung injury
Finally, despite advances in the
understanding of red blood cell
antigens, allogenic transfusions are
known to cause fatal acute hemolytic
reaction (albeit rarely)
Directed donation of allogenic
blood increased in the early 1990s,
presumably because the practice
allayed the fears of some patients of
contracting disease from unknown
donors Nevertheless, directed donations accounted for only 2% to 3% of all blood collected between
1989 and 1994 in the United States and have since declined.1 Although the use of blood from directed do-nations potentially can accelerate surgery compared with the time required for donation of autologous blood or for epoetin alfa therapy, no evidence suggests that directed donations lessen the risks associated with allogenic blood transfusion
Preoperative Autologous Blood Donation
The use of PAD has increased sub-stantially in recent years although it has been associated with such risks
as preoperative anemia, ischemic events, and complications severe enough to require hospitalization.24-27
Furthermore, the magnitude and rate
of patient response to compensatory erythropoiesis to replace donated red blood cells generally has been overes-timated.1 In one study,27
preopera-tive donation between 42 and 7 days before surgery still resulted in an average decrease of 1 g/dL for every unit of autologous blood donated, suggesting an absence of adequate compensatory erythropoiesis Au-thors of a recent study of 225 adults estimated that compensatory eryth-ropoiesis resulted in preoperative mean red blood cell production of
351 mL compared with a mean loss
of 522 mL from weekly donations of autologous blood.28 In another study
of patients undergoing aggressive autologous blood phlebotomy, the administration of erythropoietin increased preoperative red blood cell production from 568 mL (placebo group) to 911 mL.29 Adequate iron supplementation is important for patients with low iron stores while they undergo erythropoietin treat-ment.30 The degree of compensatory erythropoiesis depends on initial iron status but not on patient age and sex.31
Overcollection of blood also is a problem associated with PAD As much as 50% of autologous blood is unused in patients undergoing joint replacement or radical prostatec-tomy.1 PAD is often used to cover the need for a range (up to 90%) of patients who might need blood, a practice that results in the routine collection of more blood than is needed for the average patient (Some patients who have blood col-lected do not require it; other pa-tients have more blood collected than is needed.) Other reasons for the possible overuse of PAD include perceptions that PAD is associated with no or few adverse events, pa-tients’ fears of contracting transfu-sion-transmitted diseases, and po-tential legal issues associated with allogenic blood transfusions
In addition to weighing the risks
of anemia and the cost of medical resources associated with overcollec-tion, clinicians considering PAD for elective surgeries should review published guidelines for the
appro-Table 1
Estimated Risks of Allogenic Blood Transfusion 19,20,22,23
Unit of Blood Transfused Viral infection
HTLV I and II 1:200,000
CMV and bacterial contamination Varies; 1:2,500
Immunosuppression
Infection Increased after surgery
Transfusion reaction
Fatal hemolytic reaction <1:600,000
Nonfatal hemolytic reaction 1:6,000
Fever or urticaria 1:100
Allergic reaction 1:100
Graft-versus-host disease Rare
Alloimmunization Common
HIV = human immunodeficiency virus; HBV = hepatitis B virus; HCV = hepatitis C
virus; HTLV = human T-cell lymphotropic virus; CMV = cytomegalovirus.
Trang 4priate use of PAD.32 Patients should
be stratified according to risk of
requiring a transfusion This
stratifi-cation is based on preoperative Hb
levels and the estimated blood loss
associated with the scheduled
proce-dure As mentioned, preoperative
Hb levels are a practical means of
estimating the risk of requiring a
transfusion.5 However, algorithms
that determine low and high risk for
transfusion based on estimated
blood loss and preoperative Hct
level may have limited usefulness
because of the difficulty in
predict-ing actual blood loss for a given
pro-cedure and patient According to
the British consensus guidelines,32
PAD should be considered only if
the likelihood of transfusion exceeds
50% In the United States, this
per-centage is much lower because laws
in some states require that the
possi-bility of autologous transfusion be
presented to patients even though
the likelihood of transfusion is low
Patients being considered for PAD
should receive supplemental oral
iron therapy (eg, 325 mg ferrous
sul-fate 3 times a day) Autologous
blood donation generally should
begin 3 to 5 weeks before the
sched-uled surgery
PAD allows patients to fulfill
blood requirements for planned
sur-gical procedures with minimal risk
of transfusion-transmitted diseases
Predominantly the risk is that of
clerical error, similar to that of
allo-genic transfusion In addition, PAD
is sometimes wasteful and should
be used only in the context of
care-ful preoperative planning
Acute Normovolemic
Hemodilution
Acute normovolemic
hemodilu-tion (ANH) involves simultaneous
removal of whole blood from a
patient immediately before
begin-ning surgery and replacement with
acellular fluids, such as crystalloid
and colloid, to maintain
normovol-emia.1 The blood is collected in an
anticoagulant-containing bag and stored in the operating room, to be reinfused after any major loss of blood Guidelines for ANH recom-mend that this approach be consid-ered when the potential surgical blood loss is likely to exceed 20% of blood volume in patients with a preoperative Hb level >10 g/dL.1
In contrast with PAD, ANH does not require testing to screen for transfusion-transmitted viral dis-eases and therefore is less costly
Furthermore, there is virtually no risk of bacterial contamination or of
an administrative error that could lead to an ABO-incompatible blood transfusion ANH also does not require the additional investment of time from patients to donate blood before surgery, nor does it prolong the duration of surgery and anes-thesia.33 However, ANH is con-traindicated in patients with coro-nary artery, renal, pulmocoro-nary, or severe hepatic disease.10 Also, because the precision required to implement the technique is time consuming, the use of ANH is often impractical in many orthopaedic procedures of short duration.10
Epoetin Alfa
The main regulator for erythro-poiesis is erythropoietin, a glycopro-tein hormone synthesized predomi-nantly in the kidney and secreted by renal cortical interstitial cells in response to tissue hypoxia Erythro-poietin functions in the recruitment and differentiation of erythroid progenitor cells, aids in their mainte-nance and survival, and stimulates the synthesis of Hb Epoetin alfa is identical to endogenous erythropoi-etin in its amino acid sequence and biologic activity Like endogenous erythropoietin, epoetin alfa effec-tively and safely stimulates synthe-sis of Hb and thus has clinical value
in the treatment of anemia Epoetin alfa has been available for more than
10 years and has been used to treat anemia in patients with chronic
renal failure, in patients with non-myeloid malignancies (in which anemia results from concomitantly administered chemotherapy), and in HIV-infected patients with anemia related to treatment with zidovu-dine Epoetin alfa also has been used preoperatively in patients undergoing elective noncardiac, nonvascular surgery Research is ongoing in other patient popula-tions, including critical care patients Although epoetin alfa can be administered both intravenously and subcutaneously, subcutaneous administration generally is pre-ferred because slow release from subcutaneous depots provides more sustained plasma levels.34 For sur-gical patients, these sustained
plas-ma levels allow for weekly dosing
of epoetin alfa Adequate iron sta-tus must be maintained through supplementation in patients receiv-ing epoetin alfa.35
Epoetin alfa is useful in the peri-operative treatment of anemia in patients undergoing elective, non-cardiac, nonvascular surgery.36
Studies in anemic (Hb ≥10 to ≤13 g/dL) patients undergoing elective orthopaedic surgery have shown that treatment with epoetin alfa (300 IU/kg/day for 15 days periopera-tively, or 600 IU/kg in four weekly doses beginning 3 weeks before surgery) increases preoperative Hb concentrations and reduces the need for perioperative allogenic blood transfusions.37-40 Figure 1 is a treat-ment algorithm for the use of epoetin alfa in anemic patients Normal pa-tients with Hb <10 g/dL should be worked up by a hematologist Pa-tients with a chronic disease such as rheumatoid arthritis and Hb <10 g/dL should receive epoetin alfa for
a longer duration
No significant safety issues have been noted in studies of epoetin alfa
in surgical patients Incidence of thrombotic/vascular events, blood pressure changes, pain, bruising, and stinging at the injection site did
Trang 5not differ significantly from those of
placebo groups.37,38
Intraoperative Blood
Management
Optimal intraoperative blood
man-agement reduces the need for
allo-genic blood transfusion through
modifications in surgical technique,
use of hemostatic agents, and blood
salvage strategies Approximately
two thirds of transfusions in the
United States are related to surgical
procedures;10orthopaedic surgeons,
therefore, should be aware of the
blood conservation strategies as
well as the relevant pharmaceutical
agents available (Fig 2)
Surgical Technique
Blood loss can be minimized
through careful adherence to
pre-scribed guidelines for maintaining
hemostasis.41 Techniques such as
electrocautery and argon-beam
coagulation can reduce blood loss
safely and effectively Hypotensive
anesthesia is an effective option for blood management for procedures such as spine surgery and arthro-plasty In patients undergoing pri-mary total hip arthroplasty, a differ-ence in mean arterial blood pressure
of 10 mm Hg (from 60 to 50 mm Hg)
significantly (P = 0.004) reduced
mean intraoperative blood loss from
263 to 179 mL.42 In addition, an arterial line is necessary for this technique
Hemostatic Agents
Pharmacologic agents available
or under investigation for mainte-nance of perioperative hemostasis include topically active agents and antifibrinolytics.10 Topically or locally active agents include throm-bin, collagen, and fibrin glue A proprietary gelatin matrix contain-ing thrombin was shown to stop bleeding in cardiac surgery within
10 minutes in 94% of patients.43
Collagen-based topical hemostatic agents also controlled bleeding Fibrin glue, made with highly con-centrated human fibrinogen and clotting factors, does not depend on platelet or clotting factor levels to be effective The use of a fibrin tissue
adhesive significantly (P < 0.001)
reduced mean postoperative blood loss from 878 to 360 mL in a study
of 58 patients undergoing total knee arthroplasty.44 The fibrin tissue adhesive was sprayed on the inter-nal aspects of the operating field before skin closure
Although the use of antifibri-nolytic drugs to maintain periopera-tive hemostasis has increased, they remain controversial because of high cost and the risk of thromboembolic complications.45 Desmopressin has been widely used to prevent bleed-ing in other types of surgery,46but several studies have shown that it failed to decrease blood loss or
Pretreatment Hb
≤ 10 or >13 g/dL
>10 to ≤ 13 g/dL
Not a candidate for epoetin alfa therapy
If the preoperative
period is <3 wk,
treat with epoetin alfa
20,000 U* (300 U/kg)
10 d preoperatively, on
the day of surgery, and
4 d postoperatively
If the preoperative period is ≥ 3 wk, treat with epoetin alfa 40,000 U* (600 U/kg)
on days − 21, − 14, and − 7, and the day
of surgery
Figure 1 Treatment algorithm for use of
epoetin alfa in anemic patients scheduled
for elective, noncardiac, nonvascular
sur-gery at high risk for transfusion because of
anticipated blood loss.
* Based on patient weight of 70 kg.
Decision for orthopaedic surgery
Measure Hb
>10 to ≤ 13 g/dL*
Predict Hb drop
Transfusion risk <10% Transfusion risk ≥ 10%
Surgery Surgery
Donate autologous blood Treat anemia with oral
iron supplementation and epoetin alfa
Transfusion risk <10% Transfusion risk ≥ 10%
>13 g/dL
Predict Hb drop
Figure 2 Algorithm for optimizing blood management strategies in orthopaedic surgery.
Average Hb drop: single total knee replacement, 3.85 ± 1.4 g/dL; bilateral total knee replacement, 5.42 ± 1.8 g/dL; single total hip replacement, 4.07 ± 1.74 g/dL.
* Normal patients with Hb <10 g/dL should be worked up by a hematologist.
Trang 6transfusion requirements in patients
undergoing total hip or knee
arthro-plasty.47,48 Aprotinin has had mixed
results In one study49of 40 patients
who underwent total hip
arthroplas-ty, those given aprotonin showed a
significant (P < 0.05) reduction in
blood loss from 1,943 to 1,446 mL
and a decrease in mean blood
trans-fusions from 3.4 to 1.8 units Another
study50of aprotonin showed no
effect on blood loss or transfusion
requirement Tranexamic acid has
been shown to reduce both
postop-erative blood loss and transfusion
requirements in patients undergoing
total knee arthroplasty.51,52
Blood Salvage
Despite advances in surgical
technique and the effective use of
hemostatic agents, blood loss
dur-ing orthopaedic procedures can be
extensive Blood salvage returns to
the patient washed or unwashed
autologous blood lost in surgery
The blood is collected by aspiration
or drainage, filtered, and
centri-fuged before transfusion.10 Blood
salvage can be applied both
intraop-eratively and postopintraop-eratively
Intraoperative Blood Recovery
Intraoperative recovery of
autolo-gous blood requires special
equip-ment and trained personnel
Cell-washing devices can provide the
equivalent of 10 units of banked
blood per hour.1 However, because
cell-washing does not completely
remove bacteria from recovered
blood, this technique should not be
used if the surgical field has gross
bacterial contamination.53 Other
contraindications for intraoperative blood recovery include the potential for aspiration of malignant cells, the presence of infection, or the presence
of contaminants such as amniotic or ascitic fluid.1 Deaths related to intraoperative blood recovery have been reported; estimated risk is 1 per 35,000 procedures Interestingly, studies of patients undergoing either cardiothoracic surgery54 or repair
of abdominal aortic aneurysms55
showed that intraoperative blood recovery did not result in fewer blood transfusions However, intra-operative recovery still may be of value in patients with substantial blood loss during major ortho-paedic surgery because it provides less costly, immediately available blood.1 At least 2 units need to be recovered for the method to be cost effective.1
Postoperative Blood Recovery
Postoperative recovery involves collecting blood from surgical drains followed by reinfusion, with or with-out processing Because the recov-ered blood is diluted, defibrinated, and partially hemolyzed, and is likely
to contain cytokines, there is gener-ally a threshold for the volume of unprocessed blood that can be rein-fused This technique has been used most commonly after cardiac surgery.1 The value of postoperative blood recovery in these patients is controversial; some studies demon-strate a benefit,56while others show
no efficacy.57 The safety and useful-ness of postoperative blood recovery after orthopaedic surgery also re-mains controversial.58,59 Because of
the high cost and questionable bene-fit of this technique, postoperative blood recovery should be limited to cases in which large postoperative blood losses are anticipated, such as
in bilateral joint replacement sur-gery.1
Summary
Concern about the safety of allo-genic blood transfusion has led to notable refinements and new ap-proaches to blood conservation.10
These efforts include the develop-ment of transfusion practice stan-dards, promotion of PAD, the clini-cal use of epoetin alfa to stimulate erythropoiesis, improvements in surgical practice, the use of hemo-static agents, and perioperative blood salvage Despite these ad-vances, awareness must be raised regarding the significance of preop-erative Hb levels in predicting and reducing transfusion requirements
in major orthopaedic surgery A strategy for managing perioperative blood loss can minimize or elimi-nate the need for allogenic blood The preoperative assessment of estimated blood loss and transfu-sion risk, and careful evaluation of alternative sources for replacement
of blood, are key to optimizing blood management strategies Sur-geons must be discriminating in their use of PAD, blood salvage, and epoetin alfa by carefully consid-ering the clinical status of individ-ual patients, specific surgical pro-cedures, potential adverse effects, and outcomes
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