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Blood Transfusions in Cardiac Surgery .pdf



Nom original: Blood Transfusions in Cardiac Surgery.pdf
Titre: Blood Transfusions in Cardiac Surgery: Indications, Risks, and Conservation Strategies
Auteur: Arman Kilic MD

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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 consequences. 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

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.

he discovery of circulation and the first attempted
blood transfusions performed in animals dates back
to the 1600s, but not until the 1800s was the first successful 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 understanding of their complications until the latter half of the 20th
century. In the modern era, however, an increasing
amount of data has demonstrated deleterious consequences 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
and protocols have been developed.

undergoing cardiac surgical procedures. Specifically, we
discuss the relationship between preoperative, intraoperative, 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.

T

(Ann Thorac Surg 2014;97:726–34)
Ó 2014 by The Society of Thoracic Surgeons

Patients and Methods

REVIEW

A search was conducted on MEDLINE of studies published between January 1, 1980, and February 1, 2013. The
search terms included “anemia,” “red blood cells,”
“blood transfusion,” “blood utilization,” “cardiac surgery,” 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.

Rationale for Review
Although cardiac surgical procedures represent a limited
fraction of overall surgical procedures, they are responsible 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 understand 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

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, riskadjusted 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 inhospital mortality, stroke, or acute kidney injury in patients who were anemic preoperatively [9]. A worldwide
study involving 70 institutions and 5,065 CABGs determined that preoperative anemia was a significant risk

0003-4975/$36.00
http://dx.doi.org/10.1016/j.athoracsur.2013.08.016

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KILIC AND WHITMAN
BLOOD TRANSFUSIONS IN CARDIAC SURGERY

727

Table 1. Studies Evaluating Preoperative or Intraoperative Anemia and Outcomes in Cardiac Operations

van Straten et al [8]

No. of
Patients
10,025

Outcomes

Major Findings

Mortality (early: within 30 days; late: after
30 days)
Composite outcome of in-hospital mortality,
stroke, or acute kidney injury

Preoperative anemia significant risk factor for
early and late mortality
Preoperative anemia significant risk factor for
composite outcome in multivariable logistic
regression and propensity-matched analyses
Preoperative anemia significant risk factor for
transfusion, in-hospital mortality, and prolonged
intensive care unit stay

Karkouti et al [9]

3,500

Hung et al [10]

2,688

Kulier et al [11]

5,065

Fang et al [12]

2,738

Postoperative mortality

DeFoe et al [13]

6,980

In-hospital mortality, need for intraaortic
balloon pump, stroke, return to bypass,
reoperation for bleeding

Loor et al [14]

7,957

In-hospital mortality and morbidity,
markers of end-organ dysfunction, use
of resources, long-term survival

Karkouti et al [15]

10,949

Primary: perioperative red blood cell
transfusion
Secondary: in-hospital mortality, length
of intensive care unit stay, costs of
transfusion
In-hospital cardiac and noncardiac
morbidity and mortality

Postoperative stroke

factor for noncardiac complications, in particular renal
dysfunction or failure [11].
With regard to intraoperative anemia, multiple largecohort 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 hematocrit during bypass was associated with worse renal
function, more myocardial injury as measured by
troponin levels, longer ventilator support, and longer
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 cardiac surgical procedures who refused blood transfusions

Low preoperative hemoglobin significant
independent predictor of noncardiac
adverse events
Minimum hematocrit significant risk factor
for postoperative mortality
Lowest hematocrit significantly associated with
increased risk of in-hospital mortality, need
for intraaortic balloon pump, and return to
cardiopulmonary bypass
Lowest hematocrit significantly associated with
worse renal function, more myocardial injury,
longer ventilator support, longer hospital stay,
and increased mortality
Lowest hematocrit associated with increased risk
of postoperative stroke

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 mortality 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 negative study designed to look at the benefit of early institution
of angiotensin-converting enzyme inhibition in CABG,
demonstrated that 44% of patients sustained postoperative
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
Study
Carson et al [16]

No. of
Patients
300

Westenbrink et al [17]

2,553

Bahrainwala et al [18]

617

Outcomes

Major Findings

Primary: in-hospital mortality
within 30 days
Secondary: 30-day mortality or
in-hospital 30-day morbidity
Adverse cardiovascular events
All-cause mortality

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

Postoperative stroke

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Study

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[18]. Although these studies demonstrated significant associations between postoperative anemia and worse outcomes, specific hematocrit thresholds below which risk
increased were not collectively well defined.

Risks Associated With RBC Transfusions

REVIEW

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]. Importantly, 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 resultant 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 involves a predisposing patient condition, such as sepsis or
a surgical procedure, that causes neutrophil sequestration
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 underlying 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 transplantation [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 transfusions, all of which supported the notion that transfusions induce immunosuppression [25]. Although the
mechanisms remain incompletely understood, proposed
causes of transfusion-related immunomodulation involve

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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 mortality 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 antibodies 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 immunoglobulin A–deficient products.
Febrile nonhemolytic transfusion reactions are thought
to be due to transfusion of leukocyte antigens or pyrogenic 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 intravascular 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 antiDuffy or anti-Kidd antibodies, which are frequently
stimulated by previous transfusion or pregnancy [33, 34].
Very rarely, transfusion-associated graft-versus-hostdisease 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 lymphocytes 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

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KILIC AND WHITMAN
BLOOD TRANSFUSIONS IN CARDIAC SURGERY

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 transfusions on mortality after cardiac operations suffer from
the criticism that someone who needs blood postoperatively 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 dosedependent 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, perioperative 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

transfusions on increased subsequent mortality [40].
Similarly, a single-institution series involving 1,915 CABG
patients demonstrated that the negative effect of transfusions on survival persisted when 1-year to 5-year
mortality was specifically examined [41]. Another analysis 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 outcomes in anemic patients but did not examine transfusions 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 transfusion of RBCs that had been stored for more than 2
weeks was associated with an increased risk of postoperative complications and with short-term and longterm 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 transfusions [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 undergoing transfusion [54, 55]
In an analysis of 11,963 CABG patients, the riskadjusted rates of postoperative renal failure and

Table 3. Studies Evaluating the Impact of Blood Transfusions on Mortality After Cardiac Operations
Study
van Straten et al [38]

No. of
Patients
10,425

Outcomes

Major Findings

Mortality (early: within 30 days;
late: after 30 days)

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

Kuduvalli et al [39]

3,024

30-day and 1-year mortality

Engoren et al [41]

1,915

Long-term mortality

10,289

All-cause mortality

9,079

Long-term mortality

Koch et al [42]
Surgenor et al [43]

RBC ¼ red blood cell(s).

REVIEW

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 approximately 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 transfusions [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].

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neurologic events were higher in patients undergoing
transfusion [56]. An analysis of 12,388 patients undergoing cardiac surgical procedures found that the risk of
acute kidney injury increased proportionally with the
number of RBCs transfused [57]. A study of gastrointestinal complications in patients undergoing cardiac surgical 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, prolonged 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

REVIEW

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 randomized trials have been conducted to better define the
risks and benefits of a restrictive transfusion trigger,
although only one has addressed the postoperative cardiac operation population specifically (Table 4). In 1999, a
multicenter randomized trial of Transfusion Requirements in Critical Care (TRICC) enrolled 838 critically 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
(APACHE <20) showed significantly lower mortality rates
with the restrictive strategy. Patients with known, significant 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 anemia, 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
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adverse events and further bleeding were also significantly lower with the restrictive strategy.
Finally, only one randomized trial in cardiac surgical
procedures has looked at appropriate hemoglobin triggers for transfusions. The Transfusion Requirements After 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, occurring 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 hemoglobin trend before discharge is an important finding
for those attempting to implement a restrictive transfusion strategy.
BLOOD CONSERVATION. In 2007, the Society of Thoracic
Surgeons and the Society of Cardiovascular Anesthesiologists released a clinical practice guideline that highlighted five techniques for blood conservation [65]. These
included (1) drugs that increase preoperative blood volume or decrease postoperative bleeding, including
erythropoietin or preoperative autologous donation, (2)
devices that conserve blood such as the cell-saving device, (3) interventions that protect patients’ blood from
operative stress, (4) the use of institution-specific transfusion algorithms, and (5) a multimodality approach to
blood conservation. The utility of these conservation
techniques was postulated to be most productive in highrisk patients, with high-risk criteria including older age,
preoperative anemia, and redo or emergency procedures
[65].
An update in 2011 added even more specific recommendations 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 randomized study of 60 CABG patients found that minicircuits 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

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Table 4. Randomized Controlled Trials Comparing Restrictive Versus Liberal Transfusion Strategies

Trial
TRICC [60]

FOCUS [61]

No. of
Patients
Enrolled
838

2,016

Cohorts (Transfusion Triggers)

Outcomes
Primary: 30-day mortality
Secondary: 60-day mortality, intensive
care unit mortality, in-hospital mortality

Restrictive: symptoms of anemia,
or physician discretion if
hemoglobin <8.0 g/dL
Liberal: hemoglobin <10.0 g/dL

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
and further bleeding
Primary: composite of 30-day
mortality and in-hospital severe morbidity
Secondary: complications,
intensive care unit and hospital lengths
of stay

Acute gastrointestinal
bleeding [62]

921

Restrictive: hemoglobin <7.0 g/dL
Liberal: hemoglobin <9.0 g/dL

TRACS [63]

502

Restrictive: hematocrit <24%
Liberal: hematocrit <30%

FOCUS ¼ Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair;
in Critical Care.

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
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

TRACS ¼ Transfusion Requirements After Cardiac Surgery;

TRICC ¼ Transfusion Requirements

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Restrictive: hemoglobin <7.0 g/dL
Liberal: hemoglobin <10.0 g/dL

Major Findings

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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, erythropoietin use, and cell salvage, experiencing a significant
23% reduction in transfusion rates [70]. At a single institution, a multifaceted blood conservation strategy in
cardiac surgical procedures involving restrictive transfusion 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 transfusion 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 absolute 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 demonstrated 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 respondents reported having an institutional discussion after
publication of the aforementioned 2007 guidelines [74].
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 immediate and long-term negative consequences of transfusion. The randomized trials demonstrating the lack of
benefit to a liberal transfusion strategy are very persuasive, 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 outcomes; 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 preference is to transfuse at a hemoglobin of 8 g/dL, with exceptions 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 algorithms within their institutions in an effort to standardize 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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