Anemia and blood transfusion in a surgical intensive care unit.
ABSTRACT Studies in intensive care unit (ICU) patients have suggested that anemia and blood transfusions can influence outcomes, but these effects have not been widely investigated specifically in surgical ICU patients.
We retrospectively analyzed the prospectively collected data from all adult patients (>18 years old) admitted to a 50-bed surgical ICU between 1st March 2004 and 30th July 2006.
Of the 5925 patients admitted during the study period, 1833 (30.9%) received a blood transfusion in the ICU. Hemoglobin concentrations were < 9 g/dl on at least one occasion in 57.6% of patients. Lower hemoglobin concentrations were associated with a higher Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score, greater mortality rates, and longer ICU and hospital lengths of stay. Transfused patients had higher ICU (12.5 vs. 3.2%) and hospital (18.3 vs. 6.5%) mortality rates (both p < 0.001) than non-transfused patients. However, ICU and in-hospital mortality rates were similar among transfused and non-transfused matched pairs according to a propensity score (n = 1184 pairs), and after adjustment for possible confounders in a multivariable analysis, higher hemoglobin concentrations (RR 0.97[0.95-0.98], per 1 g/dl, p < 0.001) and blood transfusions (RR 0.96[0.92-0.99], p = 0.031) were independently associated with a lower risk of in-hospital death, especially in patients aged from 66 to 80 years, in patients admitted to the ICU after non-cardiovascular surgery, in patients with higher severity scores, and in patients with severe sepsis.
In this group of surgical ICU patients, anemia was common and was associated with higher morbidity and mortality. Higher hemoglobin concentrations and receipt of a blood transfusion were independently associated with a lower risk of in-hospital death. Randomized control studies are warranted to confirm the potential benefit of blood transfusions in these subpopulations.
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ABSTRACT: IntroductionPrevious research has debated whether red blood cell (RBC) transfusion is associated with decreased or increased mortality in patients admitted to the intensive care unit (ICU). We conducted a systematic review and meta-analysis to assess the relationship of RBC transfusion with in-hospital mortality in ICU patients.Methods We carried out a literature search on Medline (1950 through May 2013), Web of Science (1986 through May 2013) and Embase (1980 through May 2013). We included all prospective and retrospective studies on the association between RBC transfusion and in-hospital mortality in ICU patients. The relative risk for the overall pooled effects was estimated by random effect model. Sensitivity analyses were conducted to assess potential bias.ResultsThe meta-analysis included 28,797 participants from 18 studies. The pooled relative risk for transfused versus non-transfused ICU patients was 1.431 (95% CI, 1.105 to 1.854). In sensitivity analyses, the pooled relative risk was 1.211 (95% CI, 0.975 to 1.505) if excluding studies without adjustment for confounders, 1.178 (95% CI, 0.937 to 1.481) if excluding studies with relative high risk of bias, and 0.901 (95% CI, 0.622 to 1.305) if excluding studies without reporting hazard ratio (HR) or relative risk (RR) as an effect size measure. Subgroup analyses revealed increased risks in studies enrolling patients from all ICU admissions (RR 1.513, 95%CI 1.123 to 2.039), studies without reporting information on leukoreduction (RR 1.851, 95%CI 1.229 to 2.786), studies reporting unadjusted effect estimates (RR 3.933, 95%CI 2.107 to 7.343), and studies using Odds ratio as an effect measure (RR 1.465, 95%CI 1.049 to 2.045). Meta-regression analyses showed that RBC transfusion could decrease risk of mortality in older patients (slope coefficient ¿0.0417, 95%CI ¿0.0680 to ¿0.0154).Conclusions There is lack of strong evidence to support the notion that ICU patients with RBC transfused have an increased risk of in-hospital death. In studies adjusted for confounders, we found that RBC transfusion does not increase the risk of in-hospital mortality in ICU patients. Type of patient, information on leukoreduction, statistical method, mean age of patient enrolled and publication year of the article may account for the disagreement between previous studies.Critical care (London, England) 11/2014; 18(6):515. · 5.04 Impact Factor
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ABSTRACT: IntroductionWe sought to investigate whether treatment of subnormal (<70%) central venous oxygen saturation (ScvO2) with inotropes or red blood cell (RBC) transfusion during early goal-directed therapy (EGDT) for septic shock is independently associated with in-hospital mortality.Methods Retrospective analysis of a prospective EGDT patient database drawn from 21 emergency departments with a single standardized EGDT protocol. Patients were included if, during EGDT, patients concomitantly achieved a central venous pressure (CVP) of ¿8 mm Hg and a mean arterial pressure (MAP) of ¿65 mm Hg while registering a ScvO2¿<¿70%. Treatment propensity scores for either RBC transfusion or inotrope administration were separately determined from independent patient sub-cohorts. Propensity-adjusted logistic regression analyses were conducted to test for associations between treatments and in-hospital mortality.ResultsOf 2595 EGDT patients, 572 (22.0%) met study inclusion criteria. The overall in-hospital mortality rate was 20.5%. Inotropes or RBC transfusions were administered for an ScvO2¿<¿70% to 51.9% patients. Patients were not statistically more likely to achieve an ScvO2 of ¿70% if they were treated with RBC transfusion alone (29/59, 49.2%, P¿=¿0.19), inotropic therapy alone (104/226, 46.0%, P¿=¿0.15) or both RBC and inotropic therapy (7/12, 58.3%, P¿=¿0.23) as compared to no therapy (108/275, 39.3%). Following adjustment for treatment propensity score, RBC transfusion was associated with a decreased adjusted odds ratio (aOR) of in-hospital mortality among patients with hemoglobin values less than 10 g/dL (aOR 0.42, 95% CI 0.18-0.97, P¿=¿0.04) while inotropic therapy was not associated with in-hospital mortality among patients with hemoglobin values of 10 g/dL or greater (aOR 1.16, 95% CI 0.69 to 1.96, P¿=¿0.57).Conclusions Among patients with septic shock treated with EGDT in the setting of subnormal ScvO2 values despite meeting CVP and MAP target goals, treatment with RBC transfusion may be independently associated with decreased in-hospital mortality.Critical care (London, England) 09/2014; 18(5):496. · 5.04 Impact Factor
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ABSTRACT: IntroductionWhether red blood cell (RBC) transfusion is beneficial remains controversial. In both retrospective and prospective evaluations, transfusion has been associated with adverse, neutral, or protective effects. These varying results likely stem from a complex interplay between transfusion, patient characteristics, and clinical context. The objective was to test whether age, comorbidities, and clinical context modulate the effect of transfusion on survival.Methods Using the multiparameter intelligent monitoring in intensive care II database (v.2.6), a retrospective analysis of 9,809 critically ill patients evaluated the effect of RBC transfusion on 30-day and 1-year mortality. Propensity score modeling and logistic regression adjusted for known confounding and assessed the independent effect of transfusion on 30-day and 1-year mortality. Sensitivity analysis was performed using 3,164 transfused and non-transfused pairs matched according the previously validated propensity model for RBC transfusion.ResultsRBC transfusion did not affect 30-day or 1-year mortality in the overall cohort. Patients <55 years had increased odds of mortality (OR 1.71, P¿<¿0.01) with transfusion. Patients >75 years had lower odds of 30-day and 1-year mortality (OR 0.70, P¿<¿0.01) with transfusion. Transfusion was associated with worse outcome among patients undergoing cardiac surgery (OR 2.1, P¿<¿0.01). The propensity-matched population, corroborated findings identified by regression adjustment.Conclusion There is a complex relationship between RBC transfusion and clinical outcome. Our results show that transfusion is associated with improved outcomes in some cohorts and worse outcome in others depending on comorbidities and patient characteristics. As such, future investigations and clinical decisions evaluating the value of transfusion should account for variations in baseline characteristics and clinical context.Critical care (London, England) 08/2014; 18(4):487. · 5.04 Impact Factor
Sakr et al. Critical Care 2010, 14:R92
Anemia and blood transfusion in a surgical
intensive care unit
© 2010 Sakr et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons At-
tribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Yasser Sakr*1, Suzana Lobo1, Stefanie Knuepfer1, Elizabeth Esser1, Michael Bauer1, Utz Settmacher2, Dagmar Barz3 and
Introduction: Studies in intensive care unit (ICU) patients have suggested that anemia and blood transfusions can
influence outcomes, but these effects have not been widely investigated specifically in surgical ICU patients.
Methods: We retrospectively analyzed the prospectively collected data from all adult patients (>18 years old) admitted
to a 50-bed surgical ICU between 1st March 2004 and 30th July 2006.
Results: Of the 5925 patients admitted during the study period, 1833 (30.9%) received a blood transfusion in the ICU.
Hemoglobin concentrations were < 9 g/dl on at least one occasion in 57.6% of patients. Lower hemoglobin
concentrations were associated with a higher Simplified Acute Physiology Score II and Sequential Organ Failure
Assessment score, greater mortality rates, and longer ICU and hospital lengths of stay. Transfused patients had higher
ICU (12.5 vs. 3.2%) and hospital (18.3 vs. 6.5%) mortality rates (both p < 0.001) than non-transfused patients. However,
ICU and in-hospital mortality rates were similar among transfused and non-transfused matched pairs according to a
propensity score (n = 1184 pairs), and after adjustment for possible confounders in a multivariable analysis, higher
hemoglobin concentrations (RR 0.97[0.95-0.98], per 1 g/dl, p < 0.001) and blood transfusions (RR 0.96[0.92-0.99], p =
0.031) were independently associated with a lower risk of in-hospital death, especially in patients aged from 66 to 80
years, in patients admitted to the ICU after non-cardiovascular surgery, in patients with higher severity scores, and in
patients with severe sepsis.
Conclusions: In this group of surgical ICU patients, anemia was common and was associated with higher morbidity
and mortality. Higher hemoglobin concentrations and receipt of a blood transfusion were independently associated
with a lower risk of in-hospital death. Randomized control studies are warranted to confirm the potential benefit of
blood transfusions in these subpopulations.
Anemia is common in critically ill patients [1-4] and is
associated with considerable morbidity and worse out-
come [1,3]. Conversely, several studies [1,3] have indi-
cated a potential association between blood transfusion
and poor outcome from critical illness. Large observa-
tional European  and North American  cohort stud-
ies on blood transfusion practices in critically ill patients
reported that blood transfusion was independently asso-
ciated with an increased risk of death. This association
was confirmed in propensity score-matched groups.
Studies in trauma patients , in patients with burns ,
in patients undergoing cardiac surgery , and in patients
with acute coronary syndromes  have also suggested
increased mortality rates associated with blood transfu-
A landmark study by Hébert and colleagues , the
transfusion requirements in critically ill patients (TRICC)
study, demonstrated that a restrictive strategy of red
blood cell (RBC) transfusion was as effective as a liberal
strategy. Moreover, these authors  reported a survival
benefit with the restrictive strategy in patients younger
than 55 years and those with acute physiology and
chronic health evaluation (APACHE) II scores of 20 or
less. Similarly, in a recent study in pediatric critically ill
patients, Lacroix and colleagues  reported that
restricting transfusions to patients with a hemoglobin
* Correspondence: Yasser.Sakr@med.uni-jena.de
1 Department of Anesthesiology and Intensive Care, Friedrich Schiller
University Hospital, Erlanger Allee 103, Jena, 07743, Germany
Full list of author information is available at the end of the article
Sakr et al. Critical Care 2010, 14:R92
Page 2 of 10
threshold of 7 g/dl was not associated with an increase in
adverse events compared with patients transfused
according to a trigger of 9.5 g/dl.
Heightened awareness of the possible risks of blood
transfusion has led to changes in blood preparation so
that blood transfusions may be safer today than they were
a decade ago, not only in terms of viral transmission
[11,12], but also in terms of transfusion related immuno-
suppression (TRIM) [12-14]. In particular, leukoreduc-
tion, which may reduce some of the negative
immunosuppressive effects of transfusions, has been
widely implemented [12,15,16]. A recent observational
study , the sepsis occurrence in acutely ill patients
(SOAP) study, showed that in 821 pairs of patients
matched according to a propensity score, the 30-day sur-
vival rate was higher in the transfusion group than in
patients who were not transfused. The effects of blood
transfusion need, therefore, to be reassessed following
these changes in transfusion preparation and practice.
The aim of our study was to investigate the epidemiol-
ogy and associated outcome of anemia and blood transfu-
sion in a large cohort of surgical ICU patients.
Materials and methods
The study was approved by the institutional review board
of Friedrich Schiller University Hospital, Jena, Germany.
Informed consent was waived due to the retrospective,
anonymous nature of the analysis. We retrospectively
included all adult (>18 years old) patients admitted to our
50-bed surgical ICU between 1 March 2004 and 30 July
2006. For patients admitted more than once to the ICU
only the first admission was considered.
Data were collected from vital sign monitors, ventilators
and infusion pumps, and automatically recorded by a
clinical information system (Copra System GmbH, Sas-
bachwalden, Germany). The clinical information system
provides staff with complete electronic documentation,
order entry (e.g., medications), and direct access to labo-
ratory results. Data recorded prospectively on admission
included age, gender, referring facility, primary and sec-
ondary admission diagnoses, and surgical procedures.
Admission diagnosis was categorized retrospectively on
the basis of prospectively recorded codes from the Inter-
national Classification of Diseases-10 and electronic
The simplified acute physiology score (SAPS) II 
was calculated on admission and the sequential organ
failure assessment (SOFA) score  calculated daily by
the physician in charge of the patient using a special
sheet. A plausibility check of the automatically transmit-
ted data was performed by the attending physician before
calculating the final scores. In sedated patients, Glasgow
Coma Scale prior to initiation of sedation was considered.
Hospital mortality and hospital discharge dates were
available for all patients from the electronic hospital
Blood transfusion was registered electronically in the
clinical information system as part of standard procedure
in our ICU. Each blood transfusion unit was recorded
separately using identification codes that allow tracing in
case of suspected or confirmed adverse events. According
to our local standards, hemoglobin concentrations should
be kept above 7 g/dl in all patients unless blood transfu-
sion is explicitly refused by patients or their next of kin.
Hemoglobin concentrations are targeted between 7 to 9
g/dl by administration of one unit of blood at a time fol-
lowed by determination of hemoglobin concentration.
The attending physician may decide to target hemoglobin
concentrations above 9 g/dl in the presence of multiple
comorbidities, ischemic heart disease, cardiovascular
instability, or evidence of tissue hypoperfusion such as
increased blood lactate levels or decreased central or
mixed venous oxygen saturation. Blood transfusion is dis-
couraged when hemoglobin concentrations are above 10
g/dl. Pre-storage leukodepletion was performed as a stan-
dard procedure. Regular quality control checks are per-
formed by the transfusion authorities in our hospital and
regular training is given by special personnel.
Comorbidities were defined according to the definitions
provided in the original SAPS II paper . SOFAmax
was defined as the maximum SOFA score recorded dur-
ing the ICU stay and SOFAmean as the mean value dur-
ing the ICU stay . Sepsis syndromes were defined
according to consensus conference definitions  and
their presence was recorded daily by the attending physi-
cian in a specific section of the electronic records.
Planned admission was defined as an admission after
elective surgery that was planned 24 hours before the sur-
gical procedure was conducted.
A priori subgroups were defined arbitrarily according to
admission characteristics and included age (18 to 50
years, 51 to 65 years, 66 to 80 years, and more than 80
years), SAPS II score (< 24, 25 to 50, 51 to 75, and more
than 75), SOFA score (0 to 4, 5 to 8, 9 to 12, and more
than 12), surgical procedures (cardiovascular vs. non-car-
diovascular surgery), and the occurrence of severe sepsis.
Data were analyzed using SPSS 13.0 for windows (SPSS
Inc, Chicago, IL, USA) and SAS version 9.1.3 software
(SAS Institute Inc., Cary, NC, USA). Difference testing
between groups was performed using a Wilcoxon test,
Mann-Whitney U test, chi-square test and Fisher's exact
Sakr et al. Critical Care 2010, 14:R92
Page 3 of 10
test as appropriate. A Bonferroni correction was used for
multiple comparisons. Analysis of variance was used to
assess progression of SOFA score within and among sub-
To determine the relative risk of hospital death we
developed a multivariable Cox proportional hazard
model in the overall population. Variables considered for
the Cox regression analysis included age, gender,
mechanical ventilation, hemofiltration, referring facility,
comorbid diseases, SAPS II and SOFA scores and SOFA
subscores on admission, the type of admission (planned
or unplanned), the type of surgery, the presence of sepsis
during the ICU stay, hemoglobin concentration on
admission to the ICU, the minimum hemoglobin concen-
tration during ICU stay, the number of transfused blood
units in the ICU, and the maximum number of transfused
units within 24 hours during the ICU stay. Colinearity
between variables was excluded before modeling. Vari-
ables were introduced into this model if significantly
associated with a higher risk of in-hospital death on a
univariate basis at a P less than 0.2 or if clinically relevant
variables. To avoid bias related to longer ICU stay in
transfused patients, we adjusted for the ICU length of
stay (in non-transfused patients) and the time to the first
transfusion (in transfused patients). Blood transfusion
was introduced in the final model as a time-dependent
variable. Another similar Cox regression analysis was
performed to evaluate the effects of blood transfusion on
in-hospital mortality in subgroups of patients according
to gender, age, type of surgery, presence of severe sepsis,
and for the different strata of the severity scores.
Propensity scores  were obtained through logistic
regression of patient characteristics on blood transfusion
status, that is, need for blood transfusion as the depen-
dent factor. The propensity score was calculated as the
probability based on the final model. A greedy matching
technique was used to match individual patients who
received a blood transfusion at any time with individual
patients who did not, based on propensity scores. The
best-matched propensity score was five digits long. Once
a match was made, the control patient was removed from
the pool. This process was then repeated using four-digit
matching, then three-digit matching, and so on. The pro-
cess proceeded sequentially to a single-digit match on
propensity score. If a match was not obtained at this
point, the patient who had received a blood transfusion
All statistics were two-tailed, and a P less than 0.05 was
considered to be significant. Continuous variables are
presented as mean ± standard deviation or median (25 to
75% interquartile range (IQR)) and categorical variables
as number and percentage, unless otherwise indicated.
A total of 5,925 patients were admitted to our ICU during
the study period. The characteristics of the study group
are presented in Table 1.
Hemoglobin concentrations and outcome
On ICU admission, hemoglobin concentrations were less
than 7 g/dl in 18.7% of patients and between 7 and 9 g/dl
in 29.5% of patients (mean 9.9 g/dl). During the ICU stay,
hemoglobin concentrations were less than 9 g/dl on at
least one occasion in 57.6% of patients. Mean hemoglobin
concentrations decreased or increased towards median
levels of 10 g/dl throughout the first two weeks in the
ICU (Figure 1). Patients with hemoglobin concentrations
less than 9 g/dl on admission to the ICU had higher SAPS
II and SOFA scores than those with higher hemoglobin
concentrations [see Table S1 in Additional file 1]. ICU
and hospital mortality rates were higher and ICU and
hospital lengths of stay were longer in patients with lower
hemoglobin concentrations (Table 2). In patients dis-
charged from the ICU (n = 5,564), in-hospital mortality
rates were lower in those with higher hemoglobin con-
centrations on ICU discharge (< 7, 7 to 9, 9.1 to 11, >11 g/
dl; 7.3, 7.8, 4.0, and 3.8%, respectively, P < 0.001) than
those with lower haemoglobin concentrations. SOFA
scores increased during the first week in the ICU in all
patients [see Figure S1 in Additional file 1]. Patients with
hemoglobin concentrations of more than 11 g/dl had the
lowest SOFA scores during the first week in the ICU.
A total of 1,833 patients (30.9%) received a blood transfu-
sion in the ICU within a median of 1 (IQR 1 to 2) days.
The initial blood transfusion was given on the first day in
the ICU in 69% of transfused patients (n = 1,209). Trans-
fused patients were older, were more commonly
unplanned admissions, had greater SAPS II and SOFA
scores, and had a higher incidence of comorbid condi-
tions than patients who were not transfused [see Table S2
in Additional file 1]. The mean hemoglobin concentra-
tion prior to transfusion was 8.2 ± 1.4 g/dl (24% at < 7 g/
dl, 46.6% at 7 to 9 g/dl, 29.4% at >9 g/dl). Characteristics
of patients according to the number of transfused units
are presented in Table S3 in Additional file 1.
Transfused patients had higher ICU and in-hospital
mortality rates (12.5 vs. 3.2 and 18.3 vs. 6.5%, respectively,
both P < 0.001 pairwise) and longer ICU and hospital
lengths of stay (4 (2 to 11) vs. 1 (1 to 2) and 15 (11 to 26)
vs. 11 (8 to 16) days, respectively, both P < 0.001 pairwise)
than non-transfused patients. There was a relation
between the number of transfused units of blood and the
degree of organ dysfunction/failure during the ICU stay,
as assessed by SOFA scores, length of stay in the ICU, and
mortality rates (Table 3). About 50% of patients who
Sakr et al. Critical Care 2010, 14:R92
Page 4 of 10
received more than eight units of blood died in the hospi-
tal. Patients who were transfused later in the ICU stay
had higher mortality rates than those who were trans-
fused earlier during the ICU stay (see Figure S2 in the
Additional file 1).
In the multivariable Cox regression analysis with in-hos-
pital death as the dependent variable, higher hemoglobin
concentrations (relative risk (RR) = 0.97, 95% confidence
interval (CI) = 0.95 to 0.98, per 1 g/dl, P≤0.001) and
receipt of a blood transfusion (RR = 0.96, 95% CI = 0.92 to
0.99, P = 0.031) were independently associated with a
lower risk of in-hospital death [see Table S4 in Additional
Propensity score matching
A total of 1,184 pairs were matched according to their
propensity score [see Table S5 and Figure S3 in Addi-
tional file 1]. Transfused patients for whom propensity
score-matched pairs were found had a higher incidence
of chronic renal failure and cirrhosis, were more com-
monly unplanned admissions, had greater SAPS II and
SOFA scores and lower hemoglobin concentrations on
admission to the ICU, had higher mortality rates, and
longer ICU and hospital lengths of stay than those for
whom no matched pairs were found (n = 649) [see Table
S6 in Additional file 1]. However, there were no differ-
ences in baseline characteristics or outcomes between the
propensity score-matched patients (Table 4). The mean
hemoglobin concentration prior to transfusion was 8.3 ±
1.8 g/dl in this subgroup. ICU and in-hospital mortality
rates were similar (6.3 vs. 7.3% and 11.8 vs. 12.2%, respec-
tively, P > 0.2 pairwise) among transfused and non-trans-
The results of univariate and multivariable Cox regres-
sion analysis in the a priori defined subgroups are pre-
sented in Figure 2. Blood transfusion was associated with
a lower risk of in-hospital death in patients aged from 66
to 80 years, in patients admitted to the ICU after non-car-
diovascular surgery, in patients with SAPS II score
greater than 50 and SOFA score more than four on
admission to the ICU, and in patients with severe sepsis.
In this large cohort of surgical ICU patients, hemoglobin
concentrations were less than 9 g/dl on at least one occa-
sion in 57.6% of patients. Lower hemoglobin concentra-
tions were associated with higher morbidity and
mortality. In a multivariable analysis, higher hemoglobin
concentrations and blood transfusions were indepen-
dently associated with a lower risk of in-hospital death,
especially in patients aged from 66 to 80 years, in patients
admitted to the ICU after non-cardiovascular surgery, in
patients with higher severity scores, and in patients with
In this study, we demonstrate that anemia is common
in surgical intensive care patients. The cause of anemia in
Table 1: Characteristics of the study group on admission to
Age, years, mean ± SD 62.2 ± 15.2
Gender, male (%)3,748 (63.3)
Operating/recovery room4,482 (75.7 )
Emergency room 393 (6.6)
Other hospital30 (0.5)
Other ICU455 (7.6)
Diabetes mellitus1,316 (22.2)
Chronic renal failure700 (11.9)
COPD 143 (2.4)
Cirrhosis 133 (2.2)
Heart failure (NYHA III to IV) 75 (1.3)
Hematologic cancer 8 (0.1)
Mechanical ventilation (%)3,248 (54.8)
Severity scores, mean ± SD
SAPS II score36.7 ± 18.2
SOFA score5.9 ± 3.9
Surgery within 24 hours
Cardiovascular surgery2,210 (37.3)
General surgery1,130 (19.1)
Neurosurgery 831 (14.0)
Trauma 342 (5.8 )
Thoracic surgery260 (4.4)
Others 1,152 (19.4)
Unplanned admissions (%)1,495 (25.2)
Hemoglobin concentration, g/dl, mean ± SD 9.9 ± 2.3
ICU mortality rate (%) 361 (6.1)
Hospital mortality rate (%)601 (10.1)
ICU LOS, days, median (IQR) 1 (1-4)
Hospital LOS, days, median (IQR)12 (9-19)
COPD: chronic obstructive pulmonary disease; IQR: interquartile
range; LOS: length of stay; NYHA: New York Heart Association;
SAPS: simplified acute physiology score; SD: standard deviation;
SOFA: sequential organ failure assessment.
Sakr et al. Critical Care 2010, 14:R92
Page 5 of 10
these patients is likely to be multifactorial [4,21]. The ret-
rospective design of our study does not allow us to elabo-
rate on the exact cause of the low hemoglobin
concentrations. Nevertheless, we found that lower hemo-
globin concentrations were associated with poor out-
come even after adjustment for possible confounding
factors. Our data confirm the results of previous studies
in mixed populations of medical and surgical critically ill
patients [1,3], in surgical patients who declined blood
transfusions [22,23], and in patients with ischemic heart
disease [24,25]. We additionally demonstrate a correla-
tion between hemoglobin concentrations and organ dys-
function/failure as assessed by the SOFA scores in these
Blood transfusion has also been thought to increase the
risk of death in ICU patients [1,3]. Indeed, transfused
patients in our study had higher ICU and in-hospital
mortality rates; however, after adjustment for possible
confounders and severity of illness, blood transfusion was
associated with a lower risk of in-hospital death. The dis-
crepancy between our results and those of previous
observational studies [1,3] may be related to the imple-
mentation of leukoreduction in our institution. Hébert
and colleagues  reported reduced in-hospital mortal-
ity rates after implementation of leukoreduction in a large
Canadian multicenter study compared with the control
period. van de Watering and colleagues  showed
increased survival rates in post-cardiac surgery patients
transfused with packed RBCs filtered to remove leuko-
cytes compared with those transfused with blood just
treated to remove buffy coats. Another possible explana-
tion may be the different case-mix in our study from
those of the previous observational cohort studies [1,3],
which included mixed medical and surgical ICU patients.
Nevertheless, our data support those of the recently pub-
lished analysis from the SOAP study , in which blood
transfusion, mostly with leukoreduced blood, was associ-
ated with a lower RR of death.
In-hospital mortality was the primary end point in our
study. This was also the primary end point for previous
prospective randomized  and observational studies
[1,3]. Possible deleterious effects of blood transfusions,
especially immunosuppression, are expected to occur
later in the course of the disease. The relatively short ICU
length of stay in our study may, therefore, render the ICU
mortality inadequate in this context.
The results of propensity score matching in our study
do not exclude beneficial effects of blood transfusion
despite similar outcomes between the matched groups.
Severely ill patients were not included in this analysis due
to the absence of suitable matched pairs. These patients
may be more likely to benefit from blood transfusion, a
hypothesis supported by the subgroup analysis in our
study. The optimal transfusion trigger in ICU patients has
been a matter of controversy. Although randomized con-
trolled trials would be the most appropriate means to
Table 2: Outcomes according to hemoglobin concentration
Length of stay, days
ICUHospital ICU LOSHospital LOS
< 7 g/dl (n = 1109) 120 (10.8)171 (15.4) 2 (1-5)12 (9-21)
7-9 g/dl (n = 1748)114 (6.5)* 196 (11.2)**2 (1-4) 13 (10-19)
9-11 g/dl (n =
85 (4.2)*158 (6.8)* 1(1-3)*12 (9-19)
>11 g/dl (n =
42 (4.0)*76 (7.3)*1(1-3)*11 (7-16)*
< 7 g/dl (n = 1483)189 (12.7)259 (17.5)3(1-9)14 (10-25)
7-9 g/dl (n = 1928)104 (5.4)* 200 (10.4)*2 (1-5)*13 (10-20)*
9-11 g/dl (n =
45 (2.7)*99 (5.8)* 1 (1-2)*11 (8-16)*
>11 g/dl (n = 821)23 (2.8)* 43 (5.2)*1 (1-1)* 10 (7-14)*
Statistics were performed for columns between categories for initial or minimum hemoglobin concentrations, respectively.
† P < 0.001 between groups; * P < 0.001 vs < 7 g/dl; ** P < 0.05 vs 7 g/dl. IQR, interquartile range; LOS, length of stay.
Sakr et al. Critical Care 2010, 14:R92
Page 6 of 10
Figure 1 Time course of hemoglobin concentration during the first two weeks in the ICU. This was classified according to hemoglobin concen-
trations on admission (categories with increments of 1 g/dl). Mean values are displayed.
n: 5925 2490 1739 1355 1078 913 773 669 608 555 516 477 437 397
1 2 3 4 5 6 7 8 9 10 11 12
Table 3: Outcome according to the number of transfused blood units
(n = 381)
(n = 683)
(n = 378)
(n = 224)
(n = 167)
SOFA scores in the ICU, mean ± SD
SOFAmax †7.5 ± 3.37.9 ± 3.6*9.7 ± 3.4*12.4 ± 3.7*14.9 ± 3.0*
SOFAmean †6.3 ± 2.9 6.5 ± 3.2*7.5 ± 3.1* 8.6 ± 3.6*9.8 ± 3.3*
ICU LOS, days, median (IQR) ‡ 2 (1-5)3 (1-5)*4 (2-9)* 13 (6-21)*28 (15-41)*
Hospital LOS, days, median (IQR) 14 (10-20) 13 (10-22)15 (11-25)*20 (13-30)*34 (20-59)*
Death in ICU (%) †16 (4.2%)45 (6.6%) 37 (9.8%)*58 (25.9%)* 73 (43.7%)*
Death in hospital (%) †37 (9.7%) 88 (12.9%) 58 (15.3%)*69 (30.8%)* 84 (50.3%)*
† P < 0.001 between groups; ‡ P < 0.05 between groups; * P < 0.001 vs. patients transfused with one unit of blood. IQR: interquartile range;
LOS: length of stay; SD: standard deviation; SOFA: sequential organ failure assessment.
Sakr et al. Critical Care 2010, 14:R92
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Table 4: Basic characteristics and outcome among propensity score matched groups
Age, years, mean ± SD64.2 ± 15.1 64.9 ±14.2 0.255
Gender, male (%) 717 (60.6)709 (59.9) 0.737
Severity scores on admission mean ± SD
SAPS II score41.8 ± 16.242.2 ± 17.8 0.370
SOFA score7.1 ± 3.37.3 ± 3.5 0.259
Operating/recovery room914 (77.2)886 (74.8)
Emergency room55 (4.6)88 (7.4)
Other hospital5 (0.4) 5 (0.4)
Other ICU101 (8.5)88 (7.4)
Others109 (9.2)117 (9.9)
Diabetes mellitus307 (25.9) 327 (27.6)0.353
Chronic renal failure 187 (15.8)178 (15.0) 0.645
Cancer181 (15.3) 166 (14.0) 0.384
Cirrhosis28 (2.4)27 (2.3) 0.892
COPD 31 (2.6)34 (2.9)0.706
Heart failure (NYHA III-IV)18 (1.5)17 (1.4)0.865
Hematologic cancer3 (0.3)2 (0.2)0.654
Surgery within 24 hours (%)0.460
Cardiovascular surgery 563 (47.6) 593 (50.1)
General surgery 174 (14.7) 133 (11.2)
Neurosurgery 125 (10.6)141 (11.9)
Trauma 94 (7.9)52 (4.4)
Thoracic surgery33 (2.8)33 (2.8)
Others195 (16.5) 232 (19.6)
Unplanned admissions (%)357 (30.2)337 (28.5)0.367
Hemoglobin concentration on admission to the ICU, mean ± SD8.4 ± 1.9 8.3 ± 1.70.165
Minimum hemoglobin concentration during ICU stay, mean ± SD8.4 ± 1.98.3 ± 1.70.219
Severity scores, mean ± SD
SOFAmean6.4 ± 3.06.5 ± 3.3 0.217
SOFAmax7.7 ± 3.5 7.5 ± 3.6 0.537
ICU mortality rate (%) 74 (6.3 ) 87 (7.3)0.289
Hospital mortality rate (%) 140 (11.8) 144 (12.2) 0.800
ICU LOS*, median (IQR)1 (0-3) 1 (1-4)0.276
Hospital LOS, median (IQR) 12 (9-29)12 (9-17)0.201
* ICU LOS in patients who did not receive blood transfusion and the time to the first blood transfusion in transfused patients.
COPD: chronic obstructive pulmonary disease; IQR: interquartile range; LOS: length of stay; NYHA: New York Heart Association; SAPS:
simplified acute physiology score; SD: standard deviation; SOFA: sequential organ failure assessment.
Sakr et al. Critical Care 2010, 14:R92
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investigate this issue, observational studies such as ours
can provide insight, generate hypotheses, and comple-
ment the results of randomized studies. Randomized
controlled studies in which subjects are randomized to
two different therapeutic strategies, independent of their
needs, are at risk of therapeutic misassignment .
Exclusion of subgroups of patients according to study
protocol, dropout of others due to declined consent or
non-compliance of physicians, and failure of recruitment
are all factors that hinder extrapolation of the results of
randomized controlled trials to other patient populations
with different case mixes. Changes in practice and quality
of care over time may be another important factor that
necessitates reassessment of current treatment strategies.
Although the TRICC study  demonstrated that a
restrictive strategy of blood transfusion was as effective
as a liberal strategy, leukoreduction was not implemented
at the time that study was performed. Whether or not the
results of the TRICC study have changed transfusion
practice in ICUs is unclear. The mean pre-transfusion
hemoglobin concentration in our study was 8.2 g/dl,
which is similar to a large multicenter observational study
 performed after the results of the TRICC study were
published  and the evolution of hemoglobin concen-
trations in our study was also similar to that reported in
this study. This could be explained by the limitations of
the TRICC study  that may hinder the adoption of the
restrictive transfusion strategy in all ICU patients.
We also identified subgroups of patients that are more
likely to benefit from blood transfusion, including
patients with higher severity of illness and more organ
dysfunction. These data may help in guiding transfusion
practice in surgical ICU patients, until the results of rele-
vant randomized trials are available.
To the best of our knowledge, our study is the largest to
date investigating the impact of anemia and possible risks
of blood transfusion in surgical intensive care patients.
However, some limitations should be considered. First,
our analysis is retrospective in nature and our results are
only hypothesis generating. A randomized controlled
Figure 2 Relative risk of in-hospital death due to blood transfusion in selected subgroups of ICU patients. Left panel demonstrates non-ad-
justed relative risks (RR). Right panel demonstrates relative risks adjusted to age, gender, comorbidities, severity scores on admission to the ICU, refer-
ring facility, type of surgery, the presence of sepsis syndromes, hemoglobin concentration on admission to the ICU, and the number of transfused
units of blood. Blood transfusion was introduced in the model as a time-dependent variable in relation to the day on which blood transfusion was
carried out. CI: confidence interval; SAPS: simplified acute physiology score; SOFA: sequential organ failure assessment.
Sakr et al. Critical Care 2010, 14:R92
Page 9 of 10
trial is warranted to clarify this issue. Second, the multi-
variable analysis does not take into account unmeasured
variables and can not establish a cause-effect relation.
The confounding effect of unmeasured variables can not
be excluded. Nevertheless, many relevant variables were
considered. Third, similar to previous observational [1-3]
and interventional studies [9,10], the impact of blood
transfusions given before and after the ICU stay on out-
come was not evaluated and the indication for blood
transfusion was not identified. Fourth, the indication for
blood transfusion was not considered in our analysis and
may have been an important confounding factor. How-
ever, indication for blood transfusion is usually influ-
enced by hemoglobin concentrations, comorbidities, and
severity of illness, all of which are factors that were con-
sidered in our analysis. Finally, the results of our study
may not be extrapolated to patients with other case
mixes, such as medical patients.
In this large cohort of surgical intensive care patients,
anemia was common and was associated with higher
morbidity and mortality. Higher hemoglobin concentra-
tions and blood transfusions were independently associ-
ated with a lower risk of in-hospital death, especially in
patients aged from 66 to 80 years, in patients admitted to
the ICU after non-cardiovascular surgery, in patients
with severe sepsis, and in patients with higher SAPS II
and SOFA scores on admission to the ICU. Randomized
controlled studies are warranted to confirm the potential
benefit of blood transfusion in these subpopulations.
• Anemia is common in surgical ICU patients and is
associated with higher morbidity and mortality
• Blood transfusions may be potentially beneficial in
patients with higher severity scores, in patients aged
from 66 to 80 years, in patients admitted to the ICU
after non-cardiovascular surgery, and in patients with
• Our data should be regarded as being hypothesis-
generating and randomized controlled studies are
warranted to reassess transfusion practice in the ICU.
APACHE: acute physiology and chronic health evaluation; IQR: interquartile;
RBC: red blood cell; RR: relative risk; SAPS: simplified acute physiology score;
SOAP: sepsis occurrence in acutely ill patients; SOFA: sequential organ failure
assessment; TRICC: transfusion requirements in critically ill patients; TRIM: trans-
The authors declare that they have no competing interests.
All authors participated in the design of the study. YS, SL, and SK contributed to
data collection. YS analyzed the data. YS and SL drafted the manuscript. EE, MB,
US, DB, and KR revised the article. All authors read and approved the final man-
1Department of Anesthesiology and Intensive Care, Friedrich Schiller University
Hospital, Erlanger Allee 103, Jena, 07743, Germany, 2Department of General
and Vascular Surgery, Friedrich Schiller University Hospital, Erlanger Allee 103,
Jena, 07743, Germany and 3Institution of Transfusion Medicine, Friedrich
Schiller University Hospital, Erlanger Allee 103, Jena, 07743, Germany
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Received: 26 December 2009 Revised: 14 March 2010
Accepted: 24 May 2010 Published: 24 May 2010
This article is available from: http://ccforum.com/content/14/3/R92© 2010 Sakr et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Cite this article as: Sakr et al., Anemia and blood transfusion in a surgical
intensive care unit Critical Care 2010, 14:R92