REVIEW
Blood Transfusions in Cardiac Surgery:
Indications, Risks, and Conservation Strategies
Arman Kilic, MD, and Glenn J.R. Whitman, MD
Division of Cardiac Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland
Although red blood cell (RBC) transfusions are
frequently used in cardiac operations, an increasing
amount of data has demonstrated deleterious conse-
quences. Consequently, the appropriate use of this
limited resource is unclear. In this review, we discuss
the relationship between anemia and the outcomes of
cardiac surgical procedures, the risks associated with
RBC transfusion, and the impact of blood transfusions
he discovery of circulation and the first attempted
T blood transfusions performed in animals dates back
to the 1600s, but not until the 1800s was the first suc-
cessful human transfusion performed [1, 2]. In the early
1900s, preservation techniques for storing blood and
blood banking matured, enabling the practice to
become more widespread [3]. Red blood cell (RBC)
transfusions were performed with limited understand-
ing of their complications until the latter half of the 20th
century. In the modern era, however, an increasing
amount of data has demonstrated deleterious conse-
quences of RBC transfusions. As a result of these
recognized transfusion-related risks and the fact that
blood is a limited resource, randomized trials have been
conducted to better define transfusion strategies.
Furthermore, to salvage as much of the patient’s own
native RBCs and to focus attention on critical thinking
regarding transfusion, blood conservation techniques
REVIEW
and protocols have been developed.
Rationale for Review
Although cardiac surgical procedures represent a limited
fraction of overall surgical procedures, they are respon-
sible for approximately 2.5 million, or 20%, of the annual
transfusions in the United States [4]. Although the figure
is variable, approximately 60% of coronary bypass
(CABG) patients receive transfusions [5–7].
Given the significant use of blood products in cardiac
operations, and the wide disparity in transfusion rates
among cardiac surgical centers, it is important to under-
stand the growing evidence regarding the risks and
benefits of transfusions in this specific cohort of patients.
In this literature review, we summarize relevant data
regarding RBC transfusions as they relate to the patient
Address correspondence to Dr Whitman, Division of Cardiac Surgery,
Johns Hopkins Hospital, 1800 Orleans St, Sheikh Zayed Tower Ste 7107,
Baltimore, MD 21287; e-mail: gwhitman@jhmi.edu.
Ó 2014 by The Society of Thoracic Surgeons
Published by Elsevier Inc
on mortality and morbidity after cardiac operations.
The review concludes with a discussion of randomized
trials comparing restrictive versus liberal transfusion
strategies and a consideration of blood conservation
techniques.
(Ann Thorac Surg 2014;97:726–34)
Ó 2014 by The Society of Thoracic Surgeons
undergoing cardiac surgical procedures. Specifically, we
discuss the relationship between preoperative, intra-
operative, and postoperative anemia and the outcomes of
cardiac surgical procedures; the risks associated with RBC
transfusion; and the impact of blood transfusions on
mortality and morbidity after cardiac operations. The
review concludes with a discussion of randomized trials
comparing restrictive versus liberal transfusion strategies
and a consideration of blood conservation techniques.
Patients and Methods
A search was conducted on MEDLINE of studies pub-
lished between January 1, 1980, and February 1, 2013. The
search terms included “anemia,” “red blood cells,”
“blood transfusion,” “blood utilization,” “cardiac sur-
gery,” and “blood conservation” or any combination
thereof. We excluded studies in languages other than
English. Otherwise, there were no exclusion criteria, and
we included all types of articles.
Results
Correlation Between Anemia and Outcomes of Cardiac
Surgical Procedures
PREOPERATIVE OR INTRAOPERATIVE ANEMIA. Multiple studies
have demonstrated a significant correlation between
preoperative anemia and worse outcomes after cardiac
operations (Table 1) [8–11] Two large-cohort, risk-
adjusted analyses demonstrated associations between
preoperative anemia and postoperative mortality [8, 10]
One study of 3,500 patients found a risk-adjusted
twofold increase in in the composite outcome of in-
hospital mortality, stroke, or acute kidney injury in pa-
tients who were anemic preoperatively [9]. A worldwide
study involving 70 institutions and 5,065 CABGs deter-
mined that preoperative anemia was a significant risk
0003-4975/$36.00
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Ann Thorac Surg REVIEW KILIC AND WHITMAN 727
2014;97:726–34 BLOOD TRANSFUSIONS IN CARDIAC SURGERY

Table 1. Studies Evaluating Preoperative or Intraoperative Anemia and Outcomes in Cardiac Operations
No. of
Study Patients Outcomes Major Findings

van Straten et al [8] 10,025 Mortality (early: within 30 days; late: after Preoperative anemia significant risk factor for
30 days) early and late mortality
Karkouti et al [9] 3,500 Composite outcome of in-hospital mortality, Preoperative anemia significant risk factor for
stroke, or acute kidney injury composite outcome in multivariable logistic
regression and propensity-matched analyses
Hung et al [10] 2,688 Primary: perioperative red blood cell Preoperative anemia significant risk factor for
transfusion transfusion, in-hospital mortality, and prolonged
Secondary: in-hospital mortality, length intensive care unit stay
of intensive care unit stay, costs of
transfusion
Kulier et al [11] 5,065 In-hospital cardiac and noncardiac Low preoperative hemoglobin significant
morbidity and mortality independent predictor of noncardiac
adverse events
Fang et al [12] 2,738 Postoperative mortality Minimum hematocrit significant risk factor
for postoperative mortality
DeFoe et al [13] 6,980 In-hospital mortality, need for intraaortic Lowest hematocrit significantly associated with
balloon pump, stroke, return to bypass, increased risk of in-hospital mortality, need
reoperation for bleeding for intraaortic balloon pump, and return to
cardiopulmonary bypass
Loor et al [14] 7,957 In-hospital mortality and morbidity, Lowest hematocrit significantly associated with
markers of end-organ dysfunction, use worse renal function, more myocardial injury,
of resources, long-term survival longer ventilator support, longer hospital stay,
and increased mortality
Karkouti et al [15] 10,949 Postoperative stroke Lowest hematocrit associated with increased risk
of postoperative stroke

factor for noncardiac complications, in particular renal
dysfunction or failure [11].
With regard to intraoperative anemia, multiple large-
cohort studies have demonstrated that nadir hematocrit
during cardiopulmonary bypass has a significant impact
on postoperative mortality (Table 1) [12–14]. An analysis
of 7,957 patients demonstrated that lower nadir hemato-
crit during bypass was associated with worse renal
function, more myocardial injury as measured by
troponin levels, longer ventilator support, and longer
for religious reasons found a 0% mortality rate but a 9.4%
morbidity rate in those with a postoperative hemoglobin
of 7.1 to 8.0 g/dL (Table 2) [16]. Progressive decreases in
hemoglobin levels were met with steep increases in mor-
tality risk, with a 34% observed mortality rate for those with
a hemoglobin of 4.1 to 5.0 g/dL. A retrospective analysis of
data from 2,553 patients from the IMAGINE trial, a nega-
tive study designed to look at the benefit of early institution
of angiotensin-converting enzyme inhibition in CABG,
demonstrated that 44% of patients sustained postoperative

hospital stays, in addition to increased mortality [14].
Another study of 10,949 patients found an association
between lower nadir hematocrit during bypass and an
increased risk of postoperative stroke [15].
POSTOPERATIVE ANEMIA. A study of patients undergoing car-
diac surgical procedures who refused blood transfusions
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anemia for more than 50 days after CABG [17]. Decreasing
hemoglobin was associated with significant increases in
adverse cardiovascular events and all-cause mortality.
Another single-institution series of 617 patients found that
lower hemoglobin levels after cardiopulmonary bypass
were associated with higher odds of postoperative stroke

Table 2. Studies Evaluating Postoperative Anemia and Outcomes in Cardiac Operations

No. of
Study Patients Outcomes Major Findings

Carson et al [16] 300 Primary: in-hospital mortality
within 30 days
Secondary: 30-day mortality or
in-hospital 30-day morbidity
Westenbrink et al [17] 2,553 Adverse cardiovascular events
All-cause mortality
Bahrainwala et al [18] 617 Postoperative stroke
0% mortality and 9.4% morbidity if hemoglobin 7.1–8.0 g/dL
34% mortality if hemoglobin 4.1–5.0 g/dL
Mortality odds increased 2.5 times for each gram
decrease in hemoglobin level below 8 g/dL
Decreasing hemoglobin significantly associated with
increased risk of adverse cardiovascular events and
all-cause mortality
Lower hemoglobin levels significantly associated with
increased risk of postoperative stroke
 728 REVIEW KILIC AND WHITMAN
BLOOD TRANSFUSIONS IN CARDIAC SURGERY
[18]. Although these studies demonstrated significant as-
sociations between postoperative anemia and worse out-
comes, specific hematocrit thresholds below which risk
increased were not collectively well defined.
Risks Associated With RBC Transfusions
Although these studies demonstrate that perioperative
anemia is associated with adverse outcomes, the decision
to transfuse might be more straightforward if not for its
associated risks and for the data demonstrating that
transfusions in and of themselves can be associated with
deleterious consequences. The risks of transfusion
range from the remote but lethal risk of transmitting a
bacterial infection, to transfusion-related acute lung
injury (TRALI), to the more common febrile transfusion
reactions.
TRALI. Acute lung injury is defined by acute onset, lack of
left atrial hypertension, bilateral infiltrates on chest
roentgenogram, and hypoxemia with a PaO2/FiO2 ratio of

300 [19]. TRALI is defined as an acute lung injury that
occurs within 6 hours of transfusion. Although there are
approximately 150,000 cases of acute lung injury in the
United States each year, the estimated incidence of
TRALI is roughly 1 per 1,000 transfusions [20]. Impor-
tantly, this incidence is not well established, with a recent
study demonstrating a TRALI rate of 2.4% specifically in
patients undergoing cardiac surgical procedures [21].
This may in part be due to an incomplete understanding
of this complication by providers and therefore a resul-
tant underreporting of its occurrence.
The central feature of acute lung injury is increased
permeability in the pulmonary microvasculature with
protein-rich edema fluid. In TRALI, the presence of donor
antibodies to recipient leukocytes is thought to be
responsible for the ensuing lung damage and capillary
leak [20]. Another proposed mechanism of TRALI in-
volves a predisposing patient condition, such as sepsis or
a surgical procedure, that causes neutrophil sequestration
REVIEW
in the lungs. Exposure to biologically active substances,
which occurs with blood transfusions, activates these
neutrophils, again leading to lung injury [22]. Patients
with TRALI typically improve clinically within 48 to 96
hours after onset, with resolution of pulmonary infiltrates
within days, and no long-term adverse effects [23].
Nevertheless, almost certainly because of associated un-
derlying conditions, the mortality rate associated with
TRALI is 5% to 15% [21, 23].
IMMUNOMODULATION. The concept of immunomodulation
related to transfusions was sparked by the observation
that renal transplant patients had improved graft
survival if they underwent transfusion before trans-
plantation [24]. Despite this beneficial effect, additional
observational studies demonstrated an increased risk of
postoperative bacterial infections and higher rates of
cancer recurrence in patients receiving blood trans-
fusions, all of which supported the notion that trans-
fusions induce immunosuppression [25]. Although the
mechanisms remain incompletely understood, proposed
causes of transfusion-related immunomodulation involve
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2014;97:726–34
immunologically active donor white blood cells, soluble
white blood cell—derived immune mediators in stored
blood, and soluble human leukocyte antigen peptides
circulating in allogeneic plasma [26]. Perhaps most
convincing of this complication was a randomized trial
demonstrating that patients undergoing cardiac surgical
procedures had reduced multiorgan failure and mor-
tality when receiving only leukoreduced transfusions,
compared with nonreduced transfusions—a finding that
was not entirely explained by lower infection rates in the
cohort receiving leukoreduced transfusions [27].
TRANSFUSION REACTIONS. Simple allergic reactions occur in
approximately 1 of 100 transfusions, typically manifest
immediately after transfusion, and are the result of a type
I hypersensitivity reaction [28]. Antihistamines are the
treatment of choice. Anaphylactic transfusion reactions
usually occur as a result of antiimmunoglobulin A anti-
bodies in the recipient [28]. Patients with a history of
anaphylactic reactions to RBC transfusions should
therefore be screened for the presence of these antibodies
in their own blood before undergoing transfusion, and
they should receive saline-washed RBCs or immuno-
globulin A–deficient products.
Febrile nonhemolytic transfusion reactions are thought
to be due to transfusion of leukocyte antigens or pyro-
genic cytokines that accumulate in stored blood [29]. In
one study, leukoreduction decreased the incidence of
febrile nonhemolytic reactions from 0.33% to 0.19% [30].
Acute hemolytic transfusion reactions are most
commonly the result of inadvertently transfusing RBCs
that are incompatible with antibodies present in the
recipient. This reaction occurs in approximately 1 in 6,000
to 20,000 transfusions, with hallmark symptoms including
fevers, chills, rigors, hypotension, hemoglobinuria, renal
failure, back or flank pain, and disseminated intravas-
cular coagulation [31, 32]. Delayed transfusion reactions
can also occur, generally 1 to 3 weeks after transfusion.
Most commonly, delayed transfusion reactions are due to
antibodies to minor blood group antigens, such as anti-
Duffy or anti-Kidd antibodies, which are frequently
stimulated by previous transfusion or pregnancy [33, 34].
Very rarely, transfusion-associated graft-versus-host-
disease can occur, usually a week after transfusion.
Generally, it is characterized by a rapid downward course
that can lead to death within 1 to 3 weeks after the initial
presence of symptoms [32]. This complication develops
after the transfusion of immunocompetent T-lymphocytes
into an immunocompromised host. The transfused lym-
phocytes can proliferate, activate, and reject host tissue.
Gamma irradiation of transfused blood products is
essential to preventing the occurrence of this serious
complication [35].
INFECTIOUS COMPLICATIONS OF TRANSFUSIONS. The estimated
transmission risks of human immunodeficiency virus (1
in 2.3 million), hepatitis B (1 in 300,000), hepatitis C (1 in
1.8 million), and human T-lymphotrophic virus (1 in 2.9
million) are extremely low with transfusions [36]. Human
herpesvirus-8, Epstein-Barr virus, West Nile virus, and
the other hepatitides are also rarely transmitted. On the
Ann Thorac Surg
2014;97:726–34
other hand, more than 50% of blood donors are thought
to be cytomegalovirus positive, and the transmission of
cytomegalovirus can cause significant morbidity in
immunocompromised recipients [36].
Bacterial contamination of RBCs occurs in approxi-
mately 1 in 38,000 units, with septic reactions occurring in
1 in 250,000 units transfused—rates that are, interestingly,
much lower than those reported with platelet trans-
fusions [32]. The clinical presentation of high fever, rigors,
and hypotension shortly after transfusion raises clinical
suspicion for bacterial contamination. The mortality
associated with transfusion of RBCs contaminated
with bacteria is over 60%, even higher if it is due to
gram-negative organisms [36, 37].
Correlation Between RBC Transfusions and Outcomes of
Cardiac Surgical Procedures
IMPACT OF BLOOD TRANSFUSIONS ON MORTALITY AFTER CARDIAC
OPERATIONS. All studies examining the effect of trans-
fusions on mortality after cardiac operations suffer from
the criticism that someone who needs blood post-
operatively is quite likely not to be doing as well as
someone who does not need blood. Multivariate risk
analyses and propensity analyses have attempted to
address that study limitation, and all have found that
transfusion is an independent risk factor for morbidity
and mortality (Table 3). A study of 10,425 patients found
that RBC transfusion was an independent and dose-
dependent risk factor for early mortality after CABG
[38]. Another study of 3,024 CABG patients similarly
found that blood transfusions were associated with
significantly increased 30-day and 1-year mortality, even
after baseline risk, reoperations for bleeding, periopera-
tive blood loss, and postoperative complications were
accounted for [39].
Of importance is that even if short-term survival is
disregarded, long-term survival after cardiac operations
is negatively affected by perioperative RBC transfusions
[40–43]. A study of 8,598 patients found that even after
the exclusion of deaths within 1 year of operation,
there remained a significant impact of perioperative
Table 3. Studies Evaluating the Impact of Blood Transfusions on Mortality After Cardiac Operations
No. of
Study Patients Outcomes
van Straten et al [38] 10,425 Mortality (early: within 30 days;
late: after 30 days)
Kuduvalli et al [39] 3,024 30-day and 1-year mortality
Engoren et al [41] 1,915 Long-term mortality
Koch et al [42] 10,289 All-cause mortality
Surgenor et al [43] 9,079 Long-term mortality
RBC ¼ red blood cell(s).
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BLOOD TRANSFUSIONS IN CARDIAC SURGERY
transfusions on increased subsequent mortality [40].
Similarly, a single-institution series involving 1,915 CABG
patients demonstrated that the negative effect of trans-
fusions on survival persisted when 1-year to 5-year
mortality was specifically examined [41]. Another anal-
ysis of 10,289 patients found an increased risk-adjusted
odds of mortality occurring at least 6 months from
CABG in patients undergoing transfusion [42]. As a
follow-up to a prior study that demonstrated worse out-
comes in anemic patients but did not examine trans-
fusions in that setting [13], a study of over 9,000 patients
demonstrated a 16% increased risk of long-term mortality
in patients undergoing transfusion [43].
The age of RBCs is another important concept. A
propensity-matched analysis demonstrated that trans-
fusion of RBCs that had been stored for more than 2
weeks was associated with an increased risk of post-
operative complications and with short-term and long-
term mortality [44]. An ongoing trial, the Red Cell
Storage Duration Study (RECESS) randomizes patients to
receive RBCs stored less than 10 days versus 21 or more
days, with the primary outcome being change in the
Multiple Organ Dysfunction Score by day 7 [45].
IMPACT OF BLOOD TRANSFUSIONS ON MORBIDITY AFTER CARDIAC
OPERATIONS. Along with increased mortality, perioperative
blood transfusions have been associated with increased
morbidity. Perioperative RBC transfusions have been
identified as an independent risk factor for postoperative
atrial fibrillation after cardiac operations [46–48]. The rate
of infectious complications after cardiac operations,
including bacteremia, sternal wound infections, and
Clostridium difficile–associated diarrhea, has also been
shown to be increased in those receiving blood trans-
fusions [7, 49–53] With regard to pulmonary morbidity,
higher risk-adjusted rates of postoperative respiratory
distress, respiratory failure, acute respiratory distress
syndrome, and reintubation, and longer times on the
ventilator, have been demonstrated in patients undergo-
ing transfusion [54, 55]
REVIEW
In an analysis of 11,963 CABG patients, the risk-
adjusted rates of postoperative renal failure and
Major Findings
Number of transfused RBCs predictor of early mortality
Compared to expected survival, receiving no RBC
improved long-term survival whereas receiving
3 RBC decreased survival
Transfusion significantly associated with 30-day
and 1-year mortality
Patients undergoing transfusion had a 70% increased
risk of long-term mortality
Patients undergoing transfusion had higher risk-adjusted
odds of early and late mortality
Patients receiving transfusions of 1 or 2 RBC units
had 16% higher odds of long-term mortality
compared with patients not receiving transfusions
 730 REVIEW KILIC AND WHITMAN
BLOOD TRANSFUSIONS IN CARDIAC SURGERY
neurologic events were higher in patients undergoing
transfusion [56]. An analysis of 12,388 patients undergo-
ing cardiac surgical procedures found that the risk of
acute kidney injury increased proportionally with the
number of RBCs transfused [57]. A study of gastrointes-
tinal complications in patients undergoing cardiac surgi-
cal procedures found a low rate of such complications
(0.5%), but nonetheless blood transfusions were found to
be an independent risk factor for their occurrence [58]. An
important study that used propensity matching found
that Jehovah’s witnesses undergoing cardiac surgical
procedures had fewer acute complications, including
myocardial infarctions, reoperations for bleeding, pro-
longed ventilation, and shorter length of hospitalization,
in addition to improved 1-year survival, than did
well-matched patients receiving transfusions [59].
Randomized Trials of Restrictive Versus Liberal
Transfusion Strategies
These published studies have increased our awareness
that blood transfusions are not benign but rather are
associated with increased morbidity, mortality, and cost
and, in fact, may be causative. Specifically addressing the
issue of an appropriate transfusion strategy, four ran-
domized trials have been conducted to better define the
risks and benefits of a restrictive transfusion trigger,
although only one has addressed the postoperative car-
diac operation population specifically (Table 4). In 1999, a
multicenter randomized trial of Transfusion Re-
quirements in Critical Care (TRICC) enrolled 838 criti-
cally ill patients and randomized them to a restrictive
(transfuse if hemoglobin <7 g/dL) versus a liberal
(transfuse if hemoglobin <10 g/dL) strategy [60]. The
30-day mortality rates, though better in the restrictive
strategy group, did not reach statistical significance (p ¼
0.11). However, myocardial infarction and pulmonary
edema occurred less frequently with the restrictive
strategy. A subgroup analysis, which looked at younger
patients (age <55) and patients who were less acutely ill
REVIEW
(APACHE <20) showed significantly lower mortality rates
with the restrictive strategy. Patients with known, signif-
icant cardiac disease had comparable mortality rates
regardless of the transfusion strategy.
A more recent randomized trial, Functional Outcomes
in Cardiovascular Patients Undergoing Surgical Hip
Fracture Repair (FOCUS), randomizing 2,016 patients
with a history of, or with, risk factors for cardiovascular
disease to a restrictive (transfuse with symptoms of ane-
mia, or hemoglobin <8.0 g/dL) versus a liberal (transfuse
if hemoglobin <10.0 g/dL) strategy [61]. The average age
of the study population was 81.6 years. Both strategies
were found to have comparable morbidity, mortality, and
ability to walk independently at 30-day and 60-day
follow-up.
Another recent randomized trial compared a restrictive
(transfuse when hemoglobin <7 g/dL) with a liberal
(transfuse when hemoglobin <9 g/dL) strategy in 921
patients with acute upper gastrointestinal bleeding [62].
The principal finding was that 6-week survival was
significantly better in the restrictive cohort. The rates of
Ann Thorac Surg
2014;97:726–34
adverse events and further bleeding were also signifi-
cantly lower with the restrictive strategy.
Finally, only one randomized trial in cardiac surgical
procedures has looked at appropriate hemoglobin trig-
gers for transfusions. The Transfusion Requirements Af-
ter Cardiac Surgery (TRACS) trial randomized 502
patients who had undergone cardiac surgical procedures
with the use of cardiopulmonary bypass to a restrictive
(maintain hematocrit 24%) versus a liberal (maintain
hematocrit 30%) strategy [63]. The primary outcome of
30-day mortality and in-hospital major morbidity was
comparable between transfusion strategies. In the
restrictive strategy group, there was a 60% diminution in
the number of transfused units. Furthermore, RBC
transfusions were again found to be an independent risk
factor for mortality.
HEMOGLOBIN DRIFT. A single-institution study of 199 cardiac
surgical patients not receiving postoperative transfusions
demonstrated that all patients’ hemoglobin levels initially
dropped, with the average difference between minimum
and maximum hemoglobin level being 1.8 g/dL, occur-
ring on postoperative day 3 to day 4 [64]. The majority of
patients (79%) recovered close to 40% of the initial drop,
or an average of 0.7 g/dL, by discharge on postoperative
day 7 through day 10. The almost universal upward he-
moglobin trend before discharge is an important finding
for those attempting to implement a restrictive trans-
fusion strategy.
BLOOD CONSERVATION. In 2007, the Society of Thoracic
Surgeons and the Society of Cardiovascular Anesthesi-
ologists released a clinical practice guideline that high-
lighted five techniques for blood conservation [65]. These
included (1) drugs that increase preoperative blood vol-
ume or decrease postoperative bleeding, including
erythropoietin or preoperative autologous donation, (2)
devices that conserve blood such as the cell-saving de-
vice, (3) interventions that protect patients’ blood from
operative stress, (4) the use of institution-specific trans-
fusion algorithms, and (5) a multimodality approach to
blood conservation. The utility of these conservation
techniques was postulated to be most productive in high-
risk patients, with high-risk criteria including older age,
preoperative anemia, and redo or emergency procedures
[65].
An update in 2011 added even more specific recom-
mendations for blood conservation, including the use of
minicircuits or modified ultrafiltration [66]. Minicircuits
can reduce by 70% the priming volume needed; thus,
they markedly decrease the amount of hemodilution that
occurs on institution of cardiopulmonary bypass. A ran-
domized study of 60 CABG patients found that mini-
circuits were associated with a 38% reduction in blood
product use, reducing not only transfused volume but
postoperative bleeding as well [67]. Minicircuits may also
offer logistic advantages with reduced tubing length and
fewer components compared with conventional circuits.
Despite these national guidelines, institutions continue
to vary significantly in their blood use during cardiac
surgical procedures. A multicenter study involving 17,252
 2014;97:726–34
Ann Thorac Surg
Table 4. Randomized Controlled Trials Comparing Restrictive Versus Liberal Transfusion Strategies
No. of
Patients
Trial Enrolled Cohorts (Transfusion Triggers) Outcomes Major Findings

TRICC [60] 838 Restrictive: hemoglobin <7.0 g/dL
Liberal: hemoglobin <10.0 g/dL
FOCUS [61] 2,016 Restrictive: symptoms of anemia,
or physician discretion if
hemoglobin <8.0 g/dL
Liberal: hemoglobin <10.0 g/dL
Acute gastrointestinal 921 Restrictive: hemoglobin <7.0 g/dL
bleeding [62] Liberal: hemoglobin <9.0 g/dL
Primary: 30-day mortality
Secondary: 60-day mortality, intensive
care unit mortality, in-hospital mortality
Primary: mortality or inability to
walk 10 feet independently at
60-day follow-up
Secondary: in-hospital myocardial
infarction, unstable angina, or mortality
Tertiary: in-hospital morbidity at 30 days
Primary: mortality within 45 days
Secondary: in-hospital complications
Restrictive and liberal 30-day mortality comparable
(18.7% vs 23.3%; p ¼0.11)
30-day mortality lower with restrictive strategy in
less acutely ill and patients younger than 55 years
In-hospital mortality rate lower in restrictive group
(22.2% vs 28.1%; p ¼ 0.05)
Primary outcome (34.7% vs 35.2%), in-hospital acute
coronary syndrome and mortality, and 60-day mortality
and morbidity each comparable between restrictive and
liberal cohorts, respectively
Improved 45-day survival, lower complication and further
bleeding rates with restrictive strategy

BLOOD TRANSFUSIONS IN CARDIAC SURGERY

and further bleeding
TRACS [63] 502 Restrictive: hematocrit <24% Primary: composite of 30-day
Liberal: hematocrit <30% mortality and in-hospital severe morbidity
Secondary: complications,
intensive care unit and hospital lengths
Primary outcome met in 11% and 10% of restrictive and
liberal cohorts, respectively (p ¼ 0.85)
Number of transfused units independent risk factor for
complications or death at 30 days

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of stay

FOCUS ¼ Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair; TRACS ¼ Transfusion Requirements After Cardiac Surgery; TRICC ¼ Transfusion Requirements
in Critical Care.

KILIC AND WHITMAN

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 732 REVIEW KILIC AND WHITMAN
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CABGs noted significant variability in institutional RBC
transfusion rates (0% to 85.7%) [68]. Similarly, an analysis
of 102,470 CABGs performed at 798 centers revealed an
unexplained variability between hospitals in blood
transfusion rates (8% to 93%), with hospital characteristics
and case mix accounting for only 11% and 20% of the
variation, respectively [69].
These data point out a lack of standardization and a
need for the use of evidence-driven algorithms guiding
blood transfusions in each cardiac surgery program.
Attempting to systemize the approach to transfusions in
CABG, 23 Ontario hospitals emphasized conservation
education, preoperative autologous donation, erythro-
poietin use, and cell salvage, experiencing a significant
23% reduction in transfusion rates [70]. At a single insti-
tution, a multifaceted blood conservation strategy in
cardiac surgical procedures involving restrictive trans-
fusion triggers, algorithm-driven decisions, point-of-care
testing, and use of low prime perfusion circuits reduced
blood component use by 40%, with no detrimental effect
on outcomes [71]. Yet another study compared trans-
fusion rates and outcomes after CABG at an institution
with a well-established blood conservation program
compared with a propensity-matched cohort at other
hospitals in which there were no identifiable, systematic
approaches to blood conservation [72]. A significant ab-
solute reduction in transfusion rates of 32% was observed
at the institution with the conservation program, with
transfusion again being identified as a risk factor for
adverse outcomes in both cohorts. A recent analysis of
14,000 CABG patients from a statewide dataset demon-
strated that the implementation of transfusion guidelines
was associated with significant reductions in morbidity,
mortality, and use of resources [73].
Part of the issue may relate to effective delivery of
evidence-based guidelines to providers and programs.
One survey-based study found that only 20% of re-
spondents reported having an institutional discussion after
publication of the aforementioned 2007 guidelines [74].
REVIEW
These guidelines and the updates can be found online on
the Society of Thoracic Surgeons website (http://www.sts.
org/resources-publications/clinical-practice-credentiali
ng-guidelines/blood-conservation-guidelines). A blood
conservation webinar was also presented (http://www.sts.
org/webinars/blood_conservation_webinar).
Summary
Over the past decade, an increasing amount of evidence
points to the significant disadvantages associated with
blood transfusions in all patients. In cardiac surgical
procedures, the data are convincing that there are im-
mediate and long-term negative consequences of trans-
fusion. The randomized trials demonstrating the lack of
benefit to a liberal transfusion strategy are very persua-
sive, but they have not yet appeared to have significantly
changed the transfusion behavior within our specialty.
As our review highlights, both anemia and transfusion
are each independently associated with adverse out-
comes; yet, at a critical level of anemia, transfusion is
Ann Thorac Surg
2014;97:726–34
lifesaving. Our deficit in identifying this critical level has
undoubtedly contributed to the wide variability in
transfusion practices. Although hemoglobin levels have
been used as triggers in prior trials, oxygen extraction,
oxygen content, and oxygen delivery are important
measurements that may reflect the need for increased
hemoglobin content. Citing lack of evidence, our prefer-
ence is to transfuse at a hemoglobin of 8 g/dL, with ex-
ceptions including (1) a mixed venous saturation that
cannot be made to go over 50% by increasing cardiac
output safely, inasmuch as below 50% the PO2 is less than
27, and the driving force for oxygen and its availability
and the capillary level may be too low to support aerobic
energy production, (2) end-organ ischemia, (3) ongoing
bleeding, and (4) hypotension recalcitrant to low-dose
pressors after adrenal insufficiency has been ruled out.
Recent developments have significantly improved our
techniques of blood conservation in cardiac operations
and could help us substantially decrease the number of
transfusions our patients receive. As the major user of
blood in most hospitals, cardiac surgeons should lead the
way implementing protocol-driven blood transfusion al-
gorithms within their institutions in an effort to stan-
dardize transfusion behavior. In the near future, it is very
likely that transfusions will be regarded as a quality
measure in cardiac surgical procedures [69]. Improving
the evidence associated with the indications for blood
transfusions, and addressing the barriers within our
specialty to widespread adoption of evidence-based
guidelines, should be recognized as crucial elements in
providing high-quality care to our patients. It is our hope
that this review article will provide a knowledge base that
lays the groundwork for improved transfusion practices
that would benefit all of our patients.
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