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PEDIATRIC CARDIAC
Blood Transfusion After Pediatric Cardiac Surgery
Is Associated With Prolonged Hospital Stay
Joshua W. Salvin, MD, MPH, Mark A. Scheurer, MD, Peter C. Laussen, MBBS,
David Wypij, PhD, Angelo Polito, MD, Emile A. Bacha, MD, Frank A. Pigula, MD,
Francis X. McGowan, MD, John M. Costello, MD, MPH, and
Ravi R. Thiagarajan, MBBS, MPH
Department of Cardiology, Children’s Hospital Boston, and Department of Pediatrics, Harvard Medical School, Boston,
Massachusetts; Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Hospital, Rome, Italy; Department of
Cardiovascular Surgery, Children’s Hospital Boston, and Department of Surgery, Harvard Medical School, Boston, and
Department of Anesthesia, Children’s Hospital Boston, and Department of Anesthesia, Harvard Medical School, Boston,
Massachusetts
Background. Red blood cell transfusion is associated
with morbidity and mortality among adults undergoing
cardiac surgery. We aimed to evaluate the association of
transfusion with morbidity among pediatric cardiac surgical patients.
Methods. Patients discharged after cardiac surgery in
2003 were retrospectively reviewed. The red blood cell
volume administered during the first 48 postoperative
hours was used to classify patients into nonexposure, low
exposure (<15 mL/kg), or high exposure (>15 mL/kg)
groups. Cox proportional hazards modeling was used to
evaluate the association of red blood cell exposure to
length of hospital stay (LOS).
Results. Of 802 discharges, 371 patients (46.2%) required blood transfusion. Demographic differences between the transfusion exposure groups included age,
weight, prematurity, and noncardiac structural abnormalities (all p < 0.001). Distribution of Risk Adjusted
Classification for Congenital Heart Surgery, version 1
(RACHS-1) categories, intraoperative support times, and
postoperative Pediatric Risk of Mortality Score, Version
III (PRISM-III) scores varied among the exposure groups
(p < 0.001). Median duration of mechanical ventilation
(34 hours [0 to 493] versus 27 hours [0 to 621] versus 16
hours [0 to 375]), incidence of infection (21 [14%] versus
29 [13%] versus 17 [4%]), and acute kidney injury (25
[17%] versus 29 [13%] versus 34 [8%]) were highest in the
high transfusion exposure group when compared with
the low or nontransfusion groups (all p < 0.001). In a
multivariable Cox proportional hazards model, both the
low transfusion group (adjusted hazard ratio [HR] 0.80,
95% confidence interval [CI]: 0.66 to 0.97, p ⴝ 0.02) and
high transfusion group (adjusted HR 0.66, 95% CI: 0.53 to
0.82, p < 0.001) were associated with increased LOS. In
subgroup analyses, both low transfusion (adjusted HR
0.81, 95% CI: 0.65 to 1.00, p ⴝ 0.05) and high transfusion
(adjusted HR 0.65, 95% CI: 0.49 to 0.87, p ⴝ 0.004) in the
biventricular group but not in the single ventricle group
was associated with increased LOS.
Conclusions. Blood transfusion is associated with prolonged hospitalization of children after cardiac surgery,
with biventricular patients at highest risk for increased
LOS. Future studies are necessary to explore this association and refine transfusion practices.
(Ann Thorac Surg 2011;91:204 –11)
© 2011 by The Society of Thoracic Surgeons
R
hospital length of stay (LOS), and increased hospital
costs [6].
Because the majority of these patients underwent coronary artery bypass graft surgery, generalization of this
information to children undergoing cardiac surgery is
limited. Lacroix and coworkers [7] recently demonstrated
the safety of a restrictive transfusion strategy compared
with a liberal strategy in a randomized prospective noninferiority trial of general pediatric intensive care unit
patients. While not powered to determine equivalence, a
subgroup analysis of noncyanotic postoperative cardiac
surgical patients from this cohort suggested that a restrictive transfusion strategy was not associated with organ
dysfunction [8]. Children undergoing cardiac surgery are
frequently exposed to blood products, and recent data
support RBC transfusion associations with morbidity and
poor outcome [9 –11].
ed blood cell (RBC) transfusion may benefit a subset
of patients in whom a low hemoglobin concentration contributes to a state of oxygen-supply dependency.
The RBC transfusion is not without risk, and recent data
suggest an association between transfusion and poor
outcome in critically ill adults [1-4]. The use of leukocytereduced product may limit the activation of the inflammatory cascade during RBC transfusion, and thus reduce
morbidity associated with transfusion of whole blood [5].
However, transfusion of even leukocyte-reduced RBCs in
adult cardiac surgical patients remains associated with
infection, postoperative morbidity, mortality, prolonged
Accepted for publication July 9, 2010.
Address correspondence to Dr Salvin, Department of Cardiology, Cardiac
ICU Office, Bader 600, Children’s Hospital Boston, 300 Longwood Ave,
Boston, MA 02115; e-mail: [email protected].
© 2011 by The Society of Thoracic Surgeons
Published by Elsevier Inc
0003-4975/$36.00
doi:10.1016/j.athoracsur.2010.07.037
Abbreviations and Acronyms
CI
⫽ confidence interval
CICU
⫽ cardiac intensive care unit
CPB
⫽ cardiopulmonary bypass
ECMO
⫽ extracorporeal membrane
oxygenation
HR
⫽ hazard ratio
LOS
⫽ length of stay
POD
⫽ postoperative day
PRISM-III ⫽ Pediatric Risk of Mortality, Version
III
RACHS-1 ⫽ Risk Adjusted Classification for
Congenital Heart Surgery, Version 1
RBC
⫽ red blood cell
The primary aim of this study was to examine the
relationship of RBC transfusion upon hospital LOS in a
large, single center and heterogeneous pediatric cardiac
surgical cohort. We hypothesized that patients requiring
early postoperative blood transfusion would have longer
LOS after adjusting for variables known to influence
duration of hospitalization. The secondary aims were to
compare the demographic, anatomic, and physiologic
characteristics of patients who received RBC transfusion
with those of patients who did not, and to identify a
subset of patients who may warrant future study of a
restrictive transfusion strategy.
Patients and Methods
Study Design
We performed a retrospective review of all patients
admitted to the cardiac intensive care unit (CICU) at
Children’s Hospital Boston after cardiac surgery between
January 1 and December 31, 2003. The Institutional Review Board at the hospital approved the review of patient
records for this study. A comprehensive database including demographic, anatomic, and preoperative, intraoperative, and postoperative physiologic data for all patients
was created. Patients requiring extracorporeal membrane oxygenation (ECMO) were necessarily exposed to
RBC, and were thereby excluded in an attempt to eliminate selection bias. Patients who died were also excluded,
as the majority of nonsurvivors required ECMO before
death. The final study population therefore included all
patients admitted to the CICU after cardiac surgery who
survived to discharge without the need for ECMO.
Demographic and anatomic data were collected from
the electronic medical record. Cardiac surgical procedures were categorized using the Risk Adjusted Classification for Congenital Heart Surgery, Version 1
(RACHS-1) method [12]. Patients were classified as either
single ventricle circulation (including shunted single
ventricle physiology and all cavopulmonary connections)
or biventricular circulation based upon their physiology
at the time of postoperative admission to the CICU.
Intraoperative variables including cardiopulmonary by-
SALVIN ET AL
TRANSFUSION AFTER PEDIATRIC HEART SURGERY
205
pass time (CPB [minutes]), aortic cross-clamp time (minutes), and use of deep hypothermic circulatory arrest
were collected. Operative lactate (mmol/L) was defined
as the peak reported value in the operating room after
cardiopulmonary bypass. Vital signs and laboratory values obtained during the first 24 hours after admission to
the CICU were used to calculate the postoperative Pediatric Risk of Mortality, Version III (PRISM-III) score [13,
14]. Peak CICU lactate (mmol/L), defined as the highest
lactate value within the first 24 hours after CICU admission, was also collected. Reoperation was defined as the
need for surgical revision of the original cardiac repair
before hospital discharge. Acute kidney injury was defined as either a 50% rise in serum creatinine compared
with admission baseline, or an absolute rise in serum
creatinine of 0.3 mg/dL [15] during the CICU stay for all
age groups. Infection was defined as a positive blood or
endotracheal tube aspirate culture per the Center for
Disease Control and Prevention’s National Healthcare
Safety Network surveillance criteria in use during the
study time period [16]. Duration of mechanical ventilation was defined as the number of hours from admission
to the CICU from the operating room until the date and
time of the first attempted trial of extubation. Inotropic
score for the first 48 postoperative hours was calculated
using a previously described formula: (dopamine ⫹ dobutamine ⫹ [milrinone*10] ⫹ [epinephrine*100]), using
peak infusion rates measured in micrograms per kilogram per minute [17, 18]. The need for temporary pacing
was recorded for any patient requiring an external pacing
device for longer than 24 hours after surgery. Weight,
CPB time, aortic cross-clamp time, PRISM-III score, and
inotrope scores were divided by interquartile range to
facilitate interpretation of regression modeling.
Irradiated, leukocyte-reduced RBCs were administered to all patients per institutional blood bank protocol.
The CICU patients were transfused with the oldest available matched unit of RBC per institutional protocol. The
RBC transfusion was given with the goal of improving
oxygen delivery or blood volume at the discretion of the
bedside CICU physician or cardiac surgeon. Early postoperative RBC transfusion volume was defined as the
total volume of RBCs (mL/kg) administered in the CICU
during the initial 48 hours after cardiac surgery (postoperative day [POD] 1 or 2). The RBC transfusion volume
administered in the operating room was excluded from
this analysis because indications for RBC transfusion
were considered different when compared with the
CICU. Additionally, electronic recording of intraoperative RBC transfusion during the study period was inconsistent and precluded accurate data collection.
Three exposure groups were defined based on the
volume of RBC administered in the CICU during the first
48 postoperative hours. Patients requiring no blood on
POD 1 or 2 were categorized as the nontransfusion
group. The low transfusion group contained transfused
patients receiving a total of 15 mL/kg or less RBC, while
the high transfusion group contained transfused patients
receiving a total of more than 15 mL/kg RBC on POD 1 or
2. Nadir hemoglobin in the low and high transfusion
PEDIATRIC CARDIAC
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PEDIATRIC CARDIAC
groups was defined as the lowest hemoglobin concentration before first transfusion on POD 1 or 2. In the
nontransfused cohort, nadir hemoglobin was defined as
the lowest hemoglobin concentration on POD 1 or 2.
Hospital LOS was chosen as the primary outcome
variable as it incorporated the cumulative effect of postoperative morbidities previously associated with RBC
transfusion in the literature [6, 19 –21], including time of
mechanical ventilation, renal failure, infection, and endorgan injury.
Statistical Analysis
Continuous variables were summarized as median
(range) or mean (SD) as appropriate. The ␹2 test, and
when appropriate, Fisher’s exact test were used to test for
differences in proportions between the exposure groups.
Normally distributed continuous variables were compared by analysis of variance techniques, while nonnormally distributed continuous variables were compared
using the Mann-Whitney U nonparametric method.
The association of preoperative and intraoperative
factors with the need for RBC transfusion was assessed in
a univariate logistic regression model. All covariates
reaching statistical significance in univariate modeling
were entered into a forward selection multivariable logistic regression model designed to assess the independent association of preoperative and intraoperative factors with the need for transfusion.
An independent association of transfusion group to the
primary outcome variable (LOS) was assessed using a
Cox proportional hazards survival model owing to the
nonnormal distribution for LOS. Each candidate covariate for inclusion in the Cox multivariable model was
chosen from univariate regression of the variable with
LOS. Covariates independently associated with the need
for transfusion were also included in final multivariable
analysis. Eligible covariates were entered into a forward
selection multivariable Cox proportional hazards model.
The multivariable Cox proportional hazard analysis
modeled an instantaneous risk of discharge from the
hospital. Thus, a hazard ratio (HR) of less than 1 predicted a lower probability of discharge and implied
longer LOS. Secondary subgroup analysis of the relationship between transfusion and LOS was performed in an
identical fashion for both the biventricular and single
ventricle cohorts.
All statistical tests were two-sided, and type I error was
controlled at 0.05. Analyses were performed using SAS
version 9.1 (SAS Institute, Cary, NC) and SPSS version
16.0.2 for Macintosh (SPSS, Chicago, IL).
Ann Thorac Surg
2011;91:204 –11
analysis. Thus, the final study cohort contained 802
postoperative admissions to the CICU. When characterized by age, there were 147 neonates (18%), 276 patients
(34%) aged 1 month to 1 year, and 379 (47%) more than 1
year of age. Thirty-eight infants (5%) were born prematurely (ⱕ36 weeks’ gestation), and 57 (7%) had noncardiac structural abnormalities. The most common cardiac
diagnoses were atrial septal defect (n ⫽ 104), hypoplastic
left heart syndrome (n ⫽ 83), tetralogy of Fallot with
pulmonary stenosis (n ⫽ 69), D-transposition of the great
arteries (n ⫽ 51), complete common atrioventricular
canal (n ⫽ 46), ventricular septal defect (n ⫽ 45), and
coarctation of the aorta (n ⫽ 45). There were 173 patients
(22%) who had single ventricle physiology at the time of
postoperative admission.
Transfusion Exposure Groups
Four hundred and nineteen patients (52%) were exposed
to blood while in the CICU. Figure 1 demonstrates the
proportion of patients who received transfusion for each
POD. Within the transfused group, 371 patients (89%)
were exposed on POD 1 or 2, the median volume administered was 14.7 mL/kg, and the mean admission hemoglobin concentration was 14.6 ⫾ 2.3 g/dL. There were 222
patients in the low transfusion volume group (ⱕ15 mL/
kg) and 149 patients in the high transfusion volume
group (⬎15 mL/kg). Characteristics of the nontransfusion, low transfusion, and high transfusion groups are
compared in Table 1. There was significant variation in
age, weight, single ventricle physiology, and RACHS-1
and PRISM-III scores across the transfusion groups.
There was no significant difference in sex, prematurity, or
the presence major noncardiac structural abnormality
among the transfusion exposure groups.
Intraoperative and CICU characteristics for the RBC
transfusion exposure groups are described in Table 2.
Results
Demographics
Eight hundred and thirty-three patients were admitted to
the CICU after cardiac surgery. Twenty-three patients
(3%) required postoperative ECMO, and 20 patients (2%)
died in the postoperative period (including 12 patients
who died after ECMO) and were therefore excluded from
Fig 1. This graph demonstrates the proportion of all patients exposed to a red blood cell transfusion (black bars) on each postoperative day. Among patients requiring red blood cells, the majority
(89%) received their first transfusion within the first 48 postoperative hours. (Gray bars ⫽ no transfusion.)
Ann Thorac Surg
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Table 1. Demographic Characteristics of Red Blood Cell Transfusion Exposure Groups
Median (range) age, years
Median weight (range), kg
Male
Prematurity, ⱕ36 weeks EGA
Single ventricle
Major noncardiac structural anomaly
Mean (SD) admission PRISM-III score
RACHS-1 category
1
2
3
4
6
EGA ⫽ estimated gestational age;
Heart Surgery, Version 1.
No Transfusion
n ⫽ 431
Low Transfusion
n ⫽ 222
High Transfusion
n ⫽ 149
1.95 (0–47.3)
10.0 (1.4–110)
236 (54.8%)
17 (3.9%)
45 (10.4%)
31 (7.2%)
6.7 ⫾ 4.1
0.59 (0–47.3)
6.1 (1.5–105.0)
123 (54.9%)
9 (4.0%)
61 (27.6%)
16 (7.1%)
8.5 ⫾ 4.3
0.416 (0–46.4)
5.0 (0.7–77.5)
80 (54.4%)
12 (31.6%)
67 (45.0%)
10 (6.8%)
10.4 ⫾ 5.2
85 (20.6%)
156 (37.9%)
143 (34.7%)
22 (5.3%)
6 (1.5%)
15 (7.1%)
73 (34.6%)
89 (42.2%)
21 (10.0%)
13 (6.2%)
PRISM-III ⫽ Pediatric Risk of Mortality, Version III;
The CPB and aortic cross-clamp times were longer, and
postbypass lactate levels were higher in patients who
received high transfusion volumes. Patients in the high
transfusion volume group had higher inotropic scores
and peak lactate values, required more frequent temporary pacing, and had lower nadir hemoglobin concentrations when compared with the other transfusion exposure groups. Median duration of mechanical ventilation,
CICU LOS, and hospital LOS were longest in the high
transfusion group. Similarly, the incidence of infection
and acute kidney injury were higher in the high transfusion group compared with the other groups. In a multivariable logistic regression model, lower weight, single
ventricle physiology, higher PRISM-III score, longer CPB
time, and lower admission hemoglobin concentration
p Value
⬍0.001
⬍0.001
0.996
0.096
⬍0.001
0.987
⬍0.001
⬍0.001
1 (0.7%)
44 (31.9%)
60 (43.5%)
14 (10.1%)
19 (13.8%)
RACHS-1 ⫽ Risk Adjusted Classification for Congenital
were the preoperative and intraoperative variables associated with the need for RBC transfusion (Table 3).
Length of Stay Analysis
The median length of stay was 6 days (range, 1 to 394).
The univariate association between median hospital LOS
and transfusion exposure group is represented in Figure
2 (p ⬍ 0.001, Mann-Whitney U statistic). Many covariates
had statistically significant univariate associations with
hospital LOS. These included older age, lower weight,
prematurity, structural anomalies, PRISM-III score, single ventricle physiology, longer CPB and aortic crossclamp times, use of deep hypothermic circulatory arrest,
higher operating room lactate, and higher inotrope score.
Mutivariable associations of preoperative, intraoperative,
Table 2. Intraoperative and Cardiac Intensive Care Unit (CICU) Characteristics of Transfusion Exposure Groups
Variable
CPB time, minutes
AXC time, minutes
DHCA use
OR lactate, mmol/L
ICU lactate, mmol/L
Admission Hgb, g/dL
Nadir CICU Hgb, g/dL
Peak CICU Hgb, g/dL
Inotropic score
Paced at admission
Duration mechanical ventilation, hours (range)
Acute kidney injury
Infection
Reoperation
Hospital LOS, days (range)
No Transfusion
n ⫽ 431
Low Transfusion
n ⫽ 222
High Transfusion
n ⫽ 149
p Value
78.4 ⫾ 47.2
39.1 ⫾ 29.5
64 (14.8%)
2.4 ⫾ 1.4
2.0 ⫾ 1.3
14.7 ⫾ 2.7
12.1 ⫾ 1.8
14.3 ⫾ 2.4
4.9 ⫾ 7.1
37 (8.6%)
17 (0–374)
34 (7.9%)
17 (3.9%)
9 (2.1%)
5 (2–61)
98.11 ⫾ 53.2
48.5 ⫾ 41.0
46 (20.5%)
2.7 ⫾ 1.8
1.9 ⫾ 1.6
15.0 ⫾ 2.2
11.9 ⫾ 1.6
15.2 ⫾ 2.2
9.1 ⫾ 8.0
28 (12.5%)
26 (0–621)
29 (12.9%)
30 (13.4%)
4 (1.8%)
8 (2–142)
110.5 ⫾ 61.4
50.1 ⫾ 42.8
36 (24.5%)
3.5 ⫾ 2.2
3.7 ⫾ 3.6
14.1 ⫾ 2.3
11.5 ⫾ 1.8
15.7 ⫾ 1.9
12.1 ⫾ 8.6
28 (19.0%)
34 (0–493)
25 (17.0%)
20 (13.6%)
7 (4.7%)
11 (3–92)
⬍0.001
⬍0.001
0.19
⬍0.001
0.002
⬍0.001
0.003
⬍0.001
⬍0.001
0.003
⬍0.001
0.005
⬍0.001
0.157
⬍0.001
AXC ⫽ aortic cross-clamp;
CPB ⫽ cardiopulmonary bypass;
DHCA ⫽ deep hypothermic circulatory arrest;
intensive care unit;
LOS ⫽ length of stay;
OR ⫽ operating room.
Hgb ⫽ hemoglobin;
ICU ⫽
PEDIATRIC CARDIAC
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TRANSFUSION AFTER PEDIATRIC HEART SURGERY
Table 3. Preoperative and Intraoperative Characteristics
Associated With Early Postoperative Red Blood Cell
Transfusion
PEDIATRIC CARDIAC
Unadjusted Odds
Ratio (95%
Confidence
Interval)
Neonate
Weight
Single ventricle
PRISM-III score
RACHS-1 category ⬎3
Cardiopulmonary
bypass time
Aortic cross-clamp time
Operating room lactate
Admission hemoglobin
Nadir CICU hemoglobin
1.77 (1.23, 2.54)
0.75 (0.67, 0.84)
4.54 (3.12, 6.61)
2.15 (1.76, 2.64)
3.26 (2.04, 5.20)
1.74 (1.47, 2.05)
1.42 (1.19, 1.69)
1.23 (1.13, 1.35)
0.85 (0.79, 0.91)
0.90 (0.83, 0.98)
Adjusted Odds
Ratio (95%
Confidence
Interval)
0.62 (0.54, 0.71)
4.82 (3.02, 7.70)
2.12 (1.63, 2.76)
1.84 (1.50, 2.26)
0.65 (0.60,0.71)
CICU ⫽ cardiac intensive care unit;
PRISM-III ⫽ Pediatric Risk of
Mortality, Version III;
RACHS-1 ⫽ Risk Adjusted Classification for
Congenital Heart Surgery, Version 1.
Interquartile range for cardiopulmonary bypass ⫽ 56 minutes;
PRISM-III ⫽ 6;
weight ⫽ 14.4 kg; and aortic cross-clamp time, 42
minutes.
and postoperative variables with hospital LOS are shown
in Table 4. All covariates that were significantly associated with LOS (neonatal age category, lower weight,
structural anomalies, prematurity, single ventricle, CPB
time, operating room lactate, PRISM-III score, inotrope
score, and transfusion exposure category) were entered
into a forward selection multivariable Cox proportional
hazards model. The instantaneous risk for hospital discharge was lower in both the low transfusion group
(adjusted HR 0.80, 95% confidence interval [CI]: 0.66 to
0.97, p ⫽ 0.02) and high transfusion group (adjusted HR
Fig 2. This box plot demonstrates the median hospital length of stay
(LOS) for patients across the red blood cell transfusion exposure
groups. Patients in the high transfusion group had longer median
length of stay than did patients in the low transfusion group or nontransfusion group (Mann-Whitney U p ⬍ 0.001).
Ann Thorac Surg
2011;91:204 –11
Table 4. Multivariable Cox Proportional Hazards Model
Showing Association of Length of Hospitalization and Red
Blood Cell Transfusion
Variable
Total transfusion volume
None
Low, ⬍15 mL/kg
High, ⬎15 mL/kg
Age ⬍28 days
Weight
Prematurity
Structural anomalies
Postoperative 24-hour
PRISM-III
Single ventricle
Cardiopulmonary bypass
time
Operating room lactate
Inotrope score
Admission hemoglobin
Hazard Ratio
(95%
Confidence
Interval)
Adjusted Hazard
Ratio (95%
Confidence
Interval)
Reference
0.60 (0.51, 0.71)
0.46 (0.38, 0.55)
0.60 (0.50, 0.72)
1.01 (1.06, 1.15)
0.49 (0.35, 0.68)
0.48 (0.36, 0.64)
0.50 (0.46, 0.56)
Reference
0.72 (0.60, 0.86)
0.53 (0.42, 0.67)
0.47 (0.32, 0.68)
0.35 (0.26, 0.48)
0.93 (0.91, 0.94)
0.61 (0.51, 0.72)
0.75 (0.70, 0.81)
0.81 (0.75, 0.88)
0.83 (0.80, 0.87)
0.93 (0.92, 0.95)
0.94 (0.92, 0.97)
0.96 (0.95, 0.98)
0.94 (0.90, 0.97)
Covariates entered into forward selection Cox proportional hazards
model include neonatal age category, weight, structural anomalies, prematurity, single ventricle, cardiopulmonary bypass time, operating room
lactate, Pediatric Risk of Mortality, Version III (PRISM-III) score, inotrope
score, and transfusion exposure group. A hazard ratio of less than 1
predicted a lower probability of discharge and implied longer length of
stay.
0.66, 95% CI: 0.53 to 0.82, p ⬍ 0.001) when compared with
the nontransfusion group. A hazard ratio of less than 1
predicted a lower probability of discharge and implied
longer LOS.
Subgroup Analysis for Single Versus
Biventricular Circulation
Among 174 patients with single ventricle physiology, 128
(74%) received a blood transfusion as compared with biventricular patients (n ⫽ 629), of whom 242 (38%) received
blood transfusion (p ⬍ 0.001). Single ventricle patients
required high transfusion volume in 67 cases (39%), low
transfusion in 61 (35%), and none in 45 (26%). Biventricular
patients required high transfusion in 82 cases (13%), low
transfusion in 160 (26%), and none in 386 (61%). The median
hemoglobin concentration at the time of first transfusion for
single ventricle patients was 12.5 ⫾ 1.7 g/dL compared with
11.3 ⫾ 1.5 g/dL in biventricular circulation patients. The
subgroup multivariable Cox proportional hazards models
considered all significant covariates from the initial modeling (RBC exposure, structural anomalies, mechanical ventilation, CPB time, acute kidney injury, infection PRISM-III
score, and inotrope score). Among patients in the single
ventricle subgroup, the instantaneous risk for hospital discharge did not differ among the low transfusion group
(adjusted HR 1.02, 95% CI: 0.64 to 1.63, p ⫽ 0.92) or high
transfusion groups (adjusted HR 0.82, 95% CI: 0.51 to 1.30, p
⫽ 0.40) when compared with the nontransfusion group.
Among patients in the biventricular subgroup, the instan-
taneous risk for hospital discharge was lower among both
the low transfusion group (adjusted HR 0.81, 95% CI: 0.65 to
1.00, p ⫽ 0.05) and the high transfusion group (adjusted HR
0.65, 95% CI: 0.49 to 0.87, p ⫽ 0.004) when compared with the
nontransfusion group.
Comment
In this study of 802 postoperative admissions to the CICU,
we found that 46% received RBC transfusion within the first
48 postoperative hours. Patients requiring RBC transfusion
were younger, more likely to have single ventricle physiology, required more complicated cardiac surgery, and were
more acutely ill than those in the low transfusion or nontransfusion groups. In a multivariable model adjusting for
univariate associations, RBC transfusion was associated
with longer hospital LOS, and the strongest association was
found in the high transfusion group. Single ventricle patients were more likely to require RBC transfusion, and
were transfused at a higher hemoglobin concentration. In
contrast to a transfused single ventricle patient, low or high
RBC transfusion requirement in the biventricular circulation patient was associated with a longer hospital LOS.
Significant variability in blood transfusion practice
exists among adult intensive care units [22, 23]. Recent
studies support the notion that RBC transfusion does not
improve outcome in critically ill adults, and may be an
independent risk factor for increased morbidity and
mortality [1– 4]. A randomized controlled trial of more
than 800 adult intensive care unit patients established
that a restrictive RBC transfusion strategy is safe, and
may be superior to liberal transfusion practices [24]. In
subgroup analysis of this trial, Hebert and colleagues [25]
demonstrated this restrictive strategy was safe in all
patients with cardiovascular disease except those with
acute myocardial infarction. Analyses of adults undergoing coronary artery bypass surgery have identified transfusion as an important independent risk factor for mortality, renal failure, infection, prolonged ventilation,
neurologic events, and hospital costs, with each unit of
blood incrementally increasing the risk of poor outcome
[6, 20, 21]. In patients requiring large-volume transfusion,
leukocyte depletion has been shown to reduce postoperative mortality, suggesting that exposure to donor white
blood cells may a mechanism for increased mortality [26].
Transfusion occurs in nearly half of pediatric intensive
care unit patients [19]. Children with cardiac disease are
more likely to require RBC transfusion when compared
with noncardiac pediatric intensive care unit patients [27].
In analyses of primarily noncardiac pediatric intensive care
unit patients, RBC transfusion in the critically ill child was
independently associated with increased mortality, prolonged duration of mechanical ventilation, and inotrope
requirements [19, 28]. Our findings in children recovering
from cardiac surgery are consistent with these data. In the
only randomly controlled pediatric trial of transfusion practice, the Transfusion Requirements in Pediatric ICUs (TRIPICU) group reported the safety of a restrictive compared
with a liberal strategy [7]. This study contained a minority of
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209
cardiac patients (20%) admitted after cardiac surgery, and
there was no secondary analysis of this subset reported.
In the operating room under the low-flow conditions of
CPB, a recent study from our institution found that a
hematocrit of 35% compared with 25% did not impact
postoperative hemodynamics or short-term neurologic outcome [29]. After cardiopulmonary bypass, patients admitted to the CICU present a unique challenge in terms of
blood transfusion strategy. The RBC transfusion improves
oxygen-carrying capacity and thus oxygen delivery; however, this benefit may be countered by the risk of transfusion-associated lung injury, immune modulation, cellular
hypoxia, and other unknown factors. Prolonged LOS may
serve as composite outcome that incorporates the cumulative effects of these morbidities, consistent with reported
poor outcomes in adult cardiac surgical patients receiving
RBC transfusion. Furthermore, our findings are consistent
with the reported increased mortality and morbidity in
transfused noncardiac surgical pediatric patients [1]. The
retrospective nature of our study precluded evaluation of
the mechanisms related to RBC transfusion that may lead to
morbidity in children undergoing cardiac surgery. However, we hypothesize that these potential effects may in part
underlie the independent association between volume of
RBC transfusion and prolonged LOS.
We found that the association of blood transfusion and
LOS was limited to patients with a biventricular circulation.
The mechanism for this observation is uncertain. Improving oxygen delivery in single ventricle physiology increases
the mixed venous oxygen saturation, and therefore, the
systemic arterial saturation. That, in turn, may create a
more favorable oxygen balance at the cellular level. We
speculate that this physiologic advantage may mitigate the
potentially harmful effects of transfusion and its association
with LOS. In contrast, we suspect that increasing oxygen
carrying capacity above a critical level in a biventricular
circulation is less likely to improve the ratio of oxygen
consumption to delivery; thus, there may be less therapeutic benefit and more negative effects of transfusion on
patient outcomes.
This analysis has several limitations, many related to the
retrospective nature of the study design. The associations
we found between RBC transfusion and longer LOS do not
prove causality. Variables influencing LOS, and hence our
conclusions, may not have been collected for adjustment in
the multivariable model. While only a small, experienced
group of cardiac surgeons and intensivists cared for all 802
patients, transfusion practice and patient management in
our CICU were not specifically standardized. The retrospective nature of the data collection also precluded accurate assessment of the indication for blood transfusion,
which could influence the interpretation of our data. Longer
duration of red cell storage has been associated with greater
postoperative morbidity and mortality [21, 30]; however,
data regarding the age of transfused RBCs were not available for use in this study. Despite these limitations, our
results are consistent with other published information in
both children and adults describing the association of poor
outcomes with RBC transfusion. The information presented
here may serve as important preliminary data in the plan-
PEDIATRIC CARDIAC
Ann Thorac Surg
2011;91:204 –11
210
SALVIN ET AL
TRANSFUSION AFTER PEDIATRIC HEART SURGERY
PEDIATRIC CARDIAC
ning of future studies to evaluate the influence of RBC
transfusion on patient outcomes.
In conclusion, we show that the volume of RBC transfusion is associated with increased length of hospitalization for children undergoing cardiac surgery, particularly
for children with biventricular circulation. Further prospective studies are required to confirm this association
and optimize transfusion practice.
The Rochelle E. Rose Research Fund of the Cardiac Intensive Care
Unit at the Children’s Hospital Boston supported this study.
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INVITED COMMENTARY
Salvin and coworkers [1] have presented a retrospective
study showing an association between red blood cell
transfusion and hospital length of stay (LOS) in pediatric
cardiac surgical patients. They conclude that changing
© 2011 by The Society of Thoracic Surgeons
Published by Elsevier Inc
transfusion practices may shorten LOS in this population. Although transfusion has well established risks and
can definitely cause excess LOS, the authors’ ability to
add evidence to this fact is hampered by the weaknesses
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doi:10.1016/j.athoracsur.2010.08.044