1. Transfusion and Apheresis Science 45 (2011) 299–303
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Transfusion and Apheresis Science
journal homepage: www.elsevier.com/ locate/ transci
Effects of red blood cell transfusions on exercise tolerance
and rehabilitation time after cardiac surgery
Marco Ranucci a,⇑, Maria Teresa La Rovere b, Serenella Castelvecchio a, Roberto Maestri b,
Andrea Maria D’Armini c
a Department of Cardiothoracic – Vascular Anesthesia, Intensive Care and Cardiac Surgery, IRCCS Policlinico San Donato, Milan, Italy
b Department of Cardiology and Biomedical Engineering, Fondazione Salvatore Maugeri, IRCCS Istituto Scientifico di Montescano, Montescano, Italy
c Division of Cardiac Surgery, Foundation IRCCS San Matteo Hospital, Pavia, Italy
a r t i c l e i n f o
Article history:
a b s t r a c t
Transfusions in cardiac surgery are associated with an increased morbidity and mortality
rate. However, no information is available with respect to the recovery process of trans-fused
patients after discharge from the hospital. Two-hundred-seventeen patients who
underwent cardiac surgery operations requiring packed red cells transfusions were studied
during the rehabilitation stay. The exercise tolerance (6-min walk test) was not dependent
on the number of packed red cells units transfused. Conversely, the length of stay in the
rehabilitation hospital was independently associated (P = 0.004) with the number of
packed red cells transfused, with an increase of 0.6 days per each unit transfused.
2011 Elsevier Ltd. All rights reserved.
1. Introduction
Transfusions in cardiac surgery are associated with in-creased
morbidity and mortality [1–4]. Due to this reason
and given the costs and resources involved in transfusion
practice and the shortage in blood donors [5], restrictive
transfusion strategies have been proposed [6,7]. Recently
[8], a study comparing a liberal vs. restrictive transfusion
policy in cardiac surgery demonstrated that a restrictive
transfusion policy is not associated with increased morbid-ity
or mortality.
However, assessing the effects of transfusions in terms
of patient outcome should not be limited to the investiga-tion
of mortality or morbidity. The quality of life is an
important issue and within this issue the ability of the pa-tient
to sustain a physical exercise is a relevant part of the
recovery process after discharge from the hospital.
In a recent study [9], we could investigate the exercise
tolerance at the 6-min walk test (6-MWT) in a population
of patients who did not receive allogeneic blood products
during the cardiac surgery procedure, therefore facing dif-ferent
levels of postoperative anemia. Our results demon-strated
that hemoglobin (Hb) values 10 g/dL were
accompanied by a reduced exercise tolerance; however,
this gap was totally recovered during a 3-weeks period of
rehabilitation.
The present study investigates a population of patients
who received packed red cells (PRC) during or after cardiac
operations. The endpoints of this study are (a) exploring
the exercise tolerance in this subset of patients, with spe-cific
respect to the Hb value and (b) exploring the relation-ship
between numbers of units transfused the exercise
tolerance and the length of stay in the rehabilitation
hospital.
2. Material and methods
This is a retrospective study based on prospectively col-lected
data. The Local Ethics Committee approved the
study design and waived the need for an informed consent.
The study started on January 2010 and ended on May 2010.
⇑ Corresponding author. Address: Department of Anesthesia and
Intensive Care, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San
Donato Milanese, Milan, Italy. Tel.: +39 02 52774320; fax: +39 02
55602262.
E-mail address: cardioanestesia@virgilio.it (M. Ranucci).
1473-0502/$ - see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.transci.2011.10.012

2. 300 M. Ranucci et al. / Transfusion and Apheresis Science 45 (2011) 299–303
One rehabilitation hospital (Fondazione Salvatore Mau-geri,
IRCCS Istituto Scientifico di Montescano, Montescano,
Italy) and two cardiac surgery Hospital (IRCCS Policlinico
San Donato and IRCCS Policlinico San Matteo) participated
in the study.
2.1. Patient population
The patient dataset comprised all the patients admitted
at the IRCCS Fondazione Maugeri Montescano for post-car-diac
surgery rehabilitation in the period 2008–2010 oper-ated
in the participating cardiac surgical hospitals and
being transfused with PRC before admission in the rehabil-itation
hospital.
2.2. Transfusion therapy
The participating surgical institution followed an inter-nal
protocol in adherence with the existing guidelines [10].
2.3. Rehabilitation program
The patients followed a rehabilitation program with
functional assessment using the 6-MWT. The test was per-formed
within the fourth day of hospital admission and at
pre-discharge according to a well standardized procedure
[11]. Reference values have been used to personalize the
physical component of the comprehensive rehabilitation
program [12] which also included stabilization of the
underlying disease, optimization of therapy and control
of modifiable risk factors. Specifically, physical training in-cluded
aerobic exercise at cycle-ergometer or treadmill,
targeted on 65–75% of the maximal heart rate, gentle
low-level (around 25 watts) and short-lasting (1–2 min)
calisthenic exercises and gentle passive stretching involv-ing
all major joints.
2.4. Data collection
For each patient the following variables were recorded:
(a) Preoperative data: demographics.
(b) Operative data: type of operation (isolated coronary
operation; valve operation; coronary + valve opera-tion
or other operations).
(c) Rehabilitation hospital data: albumin (g/dL), blood
urea nitrogen (BUN, mg/dL) and hemoglobin (g/dL)
values at the admission; left ventricular ejection
fraction; performance at the admission 6-MWT
(meters) and length of stay in the rehabilitation
hospital.
Parametric (paired and unpaired Student’s t test, linear
regression analysis) and non-parametric (Mann–Whitney)
tests were used according to the normality of distribution
for assessing the relationship between independent vari-ables
and the 6-MWT performance. The role of potential
confounders was explored using a multivariable analysis
(stepwise forward multivariable linear regression). The pa-tient
population was divided into deciles according to the
Hb value.
Table 1
Demographics and clinical variables of the patient population (N = 217).
Variable Mean ± SD
Age (years) 67.8 ± 10.7
Weight (kgs) 72.4 ± 13.4
Body surface area (m2) 1.80 ± 0.18
Left ventricular EF 52.3 ± 11.3
Hemoglobin (mg/dL) 10.2 ± 1.2
Albumin (mg/dL) 3.8 ± 0.4
Blood urea nitrogen (mg/dL) 48.2 ± 28
6-MWT admission (mts) 248 ± 100
Median (range)
Rehabilitation length (days) 28 (14–83)
Packed red cells (units) 3 (1–13)
Number (%)
Gender male 138 (64)
Isolated coronary operation 137 (63)
Isolated valve operation 56 (27)
Combined operation 24 (11)
6-MWT: six-minutes walk test; EF: ejection fraction.
SD: standard deviation.
The level of significance was settled at 0.05 or less. All
the analyses were conducted using computer statistical
software (SPSS 13.0, SPSS Inc., Chicago, IL).
3. Results
Two-hundred-seventeen patients constituted the pa-tient
population. The characteristics of the patient popula-tion
are shown in Table 1.
The exercise tolerance at the admission was not depen-dent
on the number of PRC transfused (Fig. 1) neither on
the Hb value at the admission (Fig. 2). Factors determining
a worse exercise tolerance where age (P = 0.001) and BUN
(P = 0.045).
At univariate analysis (Table 2) the factors being associ-ated
with the length of the rehabilitation stay were the
type of surgery (isolated coronary operation vs. other oper-ations),
the 6-MWT at the admission, the BUN value at the
admission, the left ventricular ejection fraction and the
number of PRC transfused. The relationship between PRC
transfused and length of rehabilitation hospital stay is
shown in Fig. 3.
At the multivariable regression analysis (Table 2), left
ventricular ejection fraction (P = 0.008), BUN (P = 0.044)
and number of PRC transfused (P = 0.004) remained inde-pendent
predictors for length of rehabilitation hospital
stay. Per each PRC unit transfused, there is an increase in
rehabilitation stay of 0.6 days (95% confidence interval
0.2–0.9).
4. Discussion
The main findings of our study are: (i) exercise toler-ance
after cardiac operations in transfused patients does
not depend on the Hb level at the admission in the rehabil-itation
hospital; (ii) the number of PRC units transfused
does not determine exercise tolerance; and (iii) the num-ber
of PRC units transfused is an independent predictor
of the length of the rehabilitation hospital stay.

3. M. Ranucci et al. / Transfusion and Apheresis Science 45 (2011) 299–303 301
Fig. 1. Six-minutes walk test (6-MWT) performance as a function of the number of packed red cells (PRC) units transfused before the test.
Fig. 2. Six-minutes walk test (6-MWT) performance as a function of the hemoglobin (hb) value at the admission in the rehabilitation hospital.
Exercise tolerance depends on the maximum oxygen
consumption, which in turn depends on the oxygen deliv-ery.
Oxygen delivery derives from cardiac output and arte-rial
oxygen content and the Hb concentration is a
determinant of the oxygen content. Therefore, it is reason-able
to hypothesize that the exercise tolerance should de-pend
at least in part on the Hb concentration. In a previous
study, we could demonstrate that in non-transfused

4. 302 M. Ranucci et al. / Transfusion and Apheresis Science 45 (2011) 299–303
patients this relationship is preserved, for Hb value below
10 g/dL [9]. Conversely, there is no Hb-dependency of the
exercise tolerance in this series of transfused patients.
Our interpretation of this finding is that bank blood Hb
may be less effective in delivering oxygen to the tissues,
since its oxygen transport rate is affected by a number of
donor-related factors (age, gender, weight and cholesterol
level) [13] and may change according to the storage time
[14,15]. In our population of transfused patients the Hb va-lue
at the admission in the rehabilitation hospital repre-sents
a mixture of natural and bank-blood Hb. It is
therefore possible that the same Hb values may result in
totally different oxygen transport rates. This may justify
the absence of association between Hb value and exercise
tolerance.
The number of PRC transfused does not affect the exer-cise
tolerance, but is a strong predictor of the rehabilitation
stay even in a multivariable model. Therefore, we must in-clude
a prolonged rehabilitation time within the PRC-asso-ciated
complications already found in other studies
focused on cardiac surgery [1–4].
Our series of transfused patients, if compared with the
previous series of non-transfused patients [9], demon-strates
a significantly lower exercise tolerance at the 6-
MWT (248 ± 100 vs. 292 ± 105 m, P = 0.001) and a longer
rehabilitation stay (median 28 days vs. 23 days,
P = 0.001). Of course, the two patient populations are very
different and it is likely that transfused patients may have
a worse clinical pattern (older age, more complex opera-tion,
more frail patients, more comorbidities) that justifies
the observed differences in exercise tolerance and rehabil-itation
stay. However, the evidence of a prolongation of the
rehabilitation stay that is dose-related with the PRC trans-fusion
suggests that transfusions may be per se a determi-nant
of a poor postoperative recovery. Moreover, the
independency of the exercise tolerance on the Hb value
suggests that allogeneic PRC transfusions may not increase
the functional ability of the patient, opposite to what
Table 2
Factors associated with rehabilitation hospital length of stay.
Factor Regression coefficient 95% Confidence interval P value
Univariate analysis
Isolated CABG 3.1 5.5/0.6 0.013
Admission 6-MWT 0.027 0.039/0.015 0.001
BUN 0.062 0.019/0.105 0.005
LVEF 0.207 0.309/0.105 0.001
PRC units number 0.71 0.32/1.1 0.001
Multivariable analysis
BUN 0.044 0.001/0.087 0.044
LVEF 0.144 0.25/0.037 0.008
PRC units number 0.57 0.18/0.95 0.004
6-MWT: six minutes walk test; BUN: blood urea nitrogen; CABG: coronary artery bypass graft; LVEF: left ventricular ejection
fraction; PRC: packed red cells.
Fig. 3. Length of stay in the rehabilitation hospital as a function of the packed red cells (PRC) units transfused.

5. M. Ranucci et al. / Transfusion and Apheresis Science 45 (2011) 299–303 303
observed in sport physiology for homologous PRC transfu-sions
[16].
In conclusion, our study raises further concerns on the
use of liberal transfusion strategies in cardiac surgery, pro-viding
a novel estimate of the PRC transfusion-induced
impairment of the postoperative recovery.
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