Red Blood Cell Transfusion: Decision

Making in Pediatric Intensive Care Units

Jacques Lacroix, MD, FRCPC, FAAP, Pierre Demaret, MD, and Marisa Tucci, MD, FRCPC
The results of the Transfusion Requirements in Pediatric Intensive Care Unit study suggest
that a red blood cell transfusion is not required in stable or stabilized pediatric intensive
care unit children as long as their hemoglobin level is >7 g/dL. Subgroup analyses suggest
that this recommendation is also adequate for stable critically ill children with a high
severity of illness, respiratory dysfunction, acute lung injury, sepsis, neurological dysfunction, severe head trauma, or severe trauma, and during the postoperative period, for
noncyanotic patients older than 28 days. A small randomized clinical trial suggests that a
hemoglobin level of 9 g/dL is safe in the postoperative care of children with single-ventricle
physiology undergoing cavopulmonary connection. Although there is consensus that blood
is clearly indicated for the treatment of hemorrhagic shock, the clinical determinants that
should prompt pediatric intensivists to prescribe a red blood cell transfusion to unstable
PICU children are not well characterized.
Semin Perinatol 36:225-231 2012 Elsevier Inc. All rights reserved.
KEYWORDS erythrocyte, guidelines, hemoglobin, intensive care, pediatrics, transfusion

here are limited published data on the decision processes

that drive or should drive pediatric intensivists to prescribe a red blood cell (RBC) transfusion. In 2003, during a
brain-storming session, several pediatric intensivists elaborated a list of all potential justifications that come to mind
when considering to give an RBC transfusion; the list generated included 27 different items such as young age (1
year old), respiratory problems (respiratory insufficiency,
high serum lactate level, low PaO2, low oxygen [O2] delivery),
cardiovascular problems (cardiovascular dysfunction, cyanotic heart disease, tachycardia), coagulopathy (increased
prothrombin time or international normalized ratio, disseminated intravascular coagulation), bleeding (gastrointestinal
bleeding, other acute blood loss), hematological or transfusion-related problems (low hemoglobin [Hb] level, bone

Division of Pediatric Critical Care, Department of Pediatrics, Sainte-Justine

Hospital, Universit de Montral, Montral, Canada.
Presented in part at the Annual Congress of the Pediatric Academic Societies,
Denver, April 30-May 3, 2011
The Canadian Institutes of Health Research (grants 84300 and 130770) and
the Fonds de la Recherche en Sant du Qubec (grants 3348 and 3568)
supported the TRIPICU study. The research program on blood products
of J.L. and M.T. is supported by the FRSQ (grant 24460)
Address reprint requests to Jacques Lacroix, MD, FRCPC, FAAP, Division of
Pediatric Critical Care, Department of Pediatrics, Sainte-Justine Hospital,
Universite de Montreal, Room 3431, 3175 Cote Sainte-Catherine, Montreal,
Quebec, Canada H3T 1C5. E-mail: jacques_lacroix@ssss.gouv.qc.ca

0146-0005/12/$-see front matter 2012 Elsevier Inc. All rights reserved.

http://dx.doi.org/10.1053/j.semperi.2012.04.002

marrow suppression defined as a white blood cell count

500 cells/mm3, autologous blood, dedicated packed RBC
units), surgery (emergency surgery, elective nontrauma surgery, severe trauma), procedures (line insertion, exchange
transfusion, plasmapheresis, extracorporeal membrane oxygenation, hemodialysis, hemofiltration), and high severity of
illness as measured by predictive scores like the Pediatric
Risk of Mortality (PRISM) score.1 A prospective descriptive
epidemiologic study was subsequently conducted on the
practice of RBC transfusion in 30 North American pediatric
intensive care units (PICU).2 In this study, the attending physician and/or fellow who prescribed an RBC transfusion was
asked within a few hours after a transfusion to choose up to 3
of the items enumerated earlier that might justify their decision to transfuse; a low Hb level was the most important
justification in 42% of cases, followed by acute blood loss
(17%), cardiovascular insufficiency (9%), respiratory insufficiency (7%), and specific technologies (7%).
In this article, we will review the literature to best determine what evidence a pediatric intensivist can use in his
decision making to prescribe an RBC transfusion. The bedside survey described earlier reported that the Hb level is
indeed the most frequently used determinant of RBC transfusion. Thus, we will first find what threshold Hb level can be
advocated as a tool to make a decision with regard to RBC
transfusion in PICU; this will be done firstly in stable critically ill children and, secondly, in unstable patients with or
225

J. Lacroix, P. Demaret, and M. Tucci

226
without acute blood loss. The concept of goal-directed RBC
transfusion therapy will also be briefly discussed.

Threshold Hb
Level in Stable Patients
Most data on a given threshold Hb level that should prompt
pediatric intensivists to prescribe an RBC transfusion come
from the Transfusion Requirements in PICU (TRIPICU)
study, a noninferiority randomized clinical trial (RCT) that
enrolled 637 stable or stabilized critically ill children.3 In
TRIPICU, a patient was considered stable or stabilized if the
mean arterial pressure was not 2 standard deviations below
normal mean for age and if the cardiovascular support (pressors/inotropes and fluids) has not been increased for at least
2 hours (note that the respiratory status and the neurological
status were not taken into account in this definition). Participants were allocated to receive an RBC transfusion only if
their Hb level decreased to 7 g/dL in the restrictive group or
below 9.5 g/dL in the liberal group. The primary outcome
measure was the proportion of patients who died during the
first 28 days after randomization or who developed new or
progressive multiple organ dysfunction syndrome (NP/
MODS). A multiple organ dysfunction syndrome (MODS)
was defined as the concurrent observation of 2 or more organ/system dysfunctions as defined by Proulx et al.4 For patients with no organ dysfunction at randomization, new
MODS was the development of 2 or more concurrent organ
dysfunctions at any time during the first 28 days after randomization. For patients with 1 organ dysfunction at randomization, new MODS was the development of at least one
other concurrent organ dysfunction after randomization.
Progressive MODS was defined as the development of at least
one additional concurrent organ dysfunction at any time during the first 28 days after randomization (ie, concurrent dysfunction of 2 or more organ systems) in a patient who already

has MODS at randomization. All deaths were considered progressive MODS. There was no need to be an expert in statistics to understand the results; there were 38 cases of NP/
MODS in the restrictive group and 39 in the liberal group.
Results were also similar for many other secondary outcomes
measures, including 28-day mortality (14 vs 14), highest
number of organ dysfunctions (1.6 1.4 vs 1.5 1.2, P
0.87), and Pediatric Logistic Organ Dysfunction (PELOD)
score (9.8 11.9 vs 8.4 10.9, P 0.16). These results
suggest that a threshold Hb level of 7 g/dL can be safely
applied to stable or stabilized critically ill children. Can we
apply these results to subgroups of patients enrolled in TRIPICU? Table 1 reports the data from subgroup analyses of the
TRIPICU study.

Severity of Illness in Stable Patients

One may hypothesize that sicker PICU patients should receive more RBC transfusions. However, this is not what was
found with TRIPICU in stable critically ill children; a liberal
RBC transfusion strategy was not associated with a lower risk
of NP/MODS, whatever the severity of illness at baseline, as
measured by the PRISM score: the absolute risk reduction
(ARR) and the 95% confidence interval (95% CI) were almost
similar (ARR: 1.5%; 95% CI: 6.3 to 9.4) with PRISM
score of zero (1st quartile) and with a score 8 (4th quartile).

Transfusion Thresholds in Septic Shock

Some cellular dysoxia is observed in severe cases of sepsis.5
Although this cellular respiratory insufficiency is attributable, at least in part, to mitochondrial dysfunction,6 a low O2
delivery is also frequently considered as a significant mechanism.7 This is why giving more RBC transfusions is considered
by many practitioners as an important part of the therapeutic
armamentarium for patients with sepsis. One hundred thirtyseven patients with sepsis were included in TRIPICU: 69 in the
restrictive and 68 in the liberal group. All were stable or stabi-

Table 1 Risk of NP/MODS: Subgroup Analyses of the TRIPICU Study

TRIPICU Subgroup
All patients in TRIPICU
PRISM score
0 (1st quartile)
1-4 (2nd quartile)
5-7 (3rd quartile)
>8 (4th quartile)
Cases of sepsis
Pediatric noncardiac surgery
Cardiac surgery (noncyanotic)
Respiratory dysfunction
Acute lung injury
ARDS
Neurological dysfunction
Severe head trauma
Severe trauma

Planned Analysis

Patients Number

Absolute Risk Reduction

(95% confidence interval)

637

0.4% (4.6 to 5.5)

128
239
121
149
137
124
125
480
73
48
40
30
40

1.5% (6.3 to 9.4)

0.3% (7.9 to 7.4)
2.2% (13.0 to 8.7)
1.5% (6.3 to 9.4)
0.3% (12 to 14)
1.1% (8.9 to 11)
6.3% (4 to 16.5)
0.1%
6.3%
2.8%
10.6%
2.3%
5.8%

Yes

Yes
Yes
Yes
No
No
No
No
No
Yes

ARDS, acute respiratory distress syndrome; CI, confidence interval; NP/MODS, new or progressive multiple organ dysfunction syndrome;
PRISM, pediatric risk of mortality score;1,5 TRIPICU, transfusion requirements in pediatric intensive care units.3

RBC transfusion in PICU

lized, but some were quite sick: 13 and 21 patients in septic
shock, 19 and 12 with severe sepsis, and 37 versus 35 with
sepsis only were allocated to the restrictive and liberal groups,
respectively. The number of NP/MODS observed in both
groups was exactly the same (13 vs 13; ARR: 0.3%; 95% CI:
12%, 14%). The highest daily PELOD score was 14.9
16.4 versus 12.6 14.2 (P 0.33). PICU mortality (5 vs 2,
P 0.44) and 28-day mortality (7 vs 2, P 0.08) were
higher in the restrictive group, but the number of deaths was
small and the differences were not statistically significant.
These data suggest that a threshold Hb level of 7 g/dL can
probably be safely applied to critically ill children with sepsis
after they are stabilized.8

Transfusion Thresholds
in Noncardiac Surgical Cases
One hundred twenty-four patients were included in TRIPICU
after undergoing surgery that was not cardiac, 60 in the restrictive group and 64 in the liberal group; 6 and 5 NP/MODS were
observed in the restrictive group and the liberal group, respectively (ARR: 1.1%; 95% CI: 8.9%, 11%, P 0.83). No
clinically or statistically significant difference was observed with respect to highest-daily PELOD score (7.4
9.6 vs 7.6 8.8), PICU mortality (1 vs 0), and 28-day
mortality (0 vs 1). A threshold Hb level of 7 g/dL seems
safe in stable critically ill children admitted to PICU after a
noncardiac surgery.9

Transfusion Thresholds
in Respiratory Dysfunction
RBC transfusion is frequently given to improve the O2 delivery in patients with respiratory dysfunction. Murphy et al10
reported that 47% of 249 critically ill adults with acute lung
injury (ALI) received at least 1 RBC transfusion in the intensive care unit; the pretransfusion Hb level was 10 g/dL in
15.4% and 7 g/dL in 69.5% of cases. However, Church et
al11 reported that giving more RBC transfusions did not improve the outcome of children with ALI. Actually, the mortality rate was higher in transfused patients, but this was not
statistically significant for RBCs. Many respiratory adverse
events can be caused by RBC transfusions, including transfusion-related ALI,12-14 transfusion-associated circulatory
overload,15 and many acute respiratory transfusion reactions.16 In the TRIPICU study, a respiratory dysfunction was
observed at randomization in 234 and 246 patients of the
restrictive and liberal group, respectively; the number of NP/
MODS was 33 and 35 in the restrictive group and the liberal
group, respectively(ARR: 0.1%). Among 38 (restrictive
group) and 35 patients (liberal group) with an ALI, 10 and 7,
respectively, developed NP/MODS (ARR: 6.3%). Among
23 (restrictive group) and 25 (liberal group) patients with an
acute respiratory distress syndrome, 8 and 8 in the restrictive
group and the liberal group, respectively, developed an NP/
MODS (ARR: 6.3%). The duration of mechanical ventilation was not different in all these subgroups: 6.4 6.0 versus
6.3 5.3 days (ARR: 0.16; 95% CI: 1.2, 0.9, P 0.75)
in patients with respiratory dysfunction at randomization,

227
7.2 6.5 versus 7.1 6.2 days (ARR: 0.12; 95% CI:
3.1, 2.9, P 0.94) in patients with ALI, and 10.5 9.2
versus 8.5 7.2 days (ARR: 2.0; 95% CI: 6.8, 2.8, P
0.40) in patients with acute respiratory distress syndrome.
More RBC transfusions do not improve the outcome of stable
critically ill children with respiratory problems if their Hb
level is 7 g/dL.

Transfusion Thresholds in
Central Nervous System Trauma Cases
The brain can be injured within a few minutes if exposed to
severe hypoxemia. Thus, many intensivists believe that anemia is a greater risk in patients with brain injury, and that
more RBC transfusions must be given to these patients. Zygun et al17 studied 30 adults with severe traumatic brain
injury; after an RBC transfusion, the PbtO2 (brain tissue PO2)
increased in 57%, whereas it did not change or it decreased in
43%. The observed response to RBC transfusion of PbtO2 and
of lactate/pyruvate ratio was not modulated by baseline Hb
concentration or low baseline PbtO2. The authors concluded
that Transfusion of packed RBCs acutely results in improved
PbtO2 without appreciable effect on cerebral metabolism.
Figaji et al18 studied 17 children with severe traumatic brain
injury who received an RBC transfusion while their PbtO2 was
monitored. The PbtO2 increased transiently after 79% of
transfusions and decreased transiently after 21%. In most
instances, the overall change was small, and the PbtO2 returned to baseline within 24 hours. They concluded that, in
these patients, Reliable predictors of PbtO2 response to blood
transfusion remain elusive. Only 40 patients with a neurological dysfunction and 30 cases of severe head trauma were
enrolled in TRIPICU; the number of patients with NP/MODS
was 6 versus 3 in the former and 2 versus 3 in the latter. These
numbers are too small to allow for any conclusion. However,
the data reported earlier do not support the point of view that
giving more RBC transfusions to stable patients with a neurological condition is mandatory if their Hb level is 7 g/dL.

Severe Trauma
Forty cases of severe trauma were enrolled in the TRIPICU
study. The number of cases of NP/MODS was 2 and 1 in the
restrictive and the liberal group, respectively. It remains to be
determined whether stable critically ill children with severe
trauma should receive more RBC transfusions if their Hb
level is 7 g/dL.

RBC Transfusion
in Unstable Children
Transfusion Thresholds After Hemorrhage
There is consensus that RBC transfusions are mandatory in
cases of hemorrhagic shock. What is not so clear is how much
blood must be given. In theory, the goal should be blood loss
replacement; the problem is that the volume of bleeding can
be difficult to estimate. The Hb level is unreliable because it
takes several hours for the Hb to decrease after an acute

228
hemorrhage. Moreover, some blood losses, such as chest
drainage, chylous effusion, and bleeding in the abdomen, are
difficult to measure. There are methods to estimate blood loss
from bleeding, such as the World Health Organization bleeding score19 and the GEMINA bleeding score,20 but these are
not validated in PICU. However, it is accepted that a rapid
loss of at least 30% of the blood volume is required before
seeing a blood pressure drop.21 Thus, a patient in hemorrhagic shock should probably initially receive at least this
amount of volume in blood products, which could include
RBC units, and then continue to be transfused to compensate
for ongoing blood loss.

Transfusion Thresholds in Septic Shock

There are some data on RBC transfusion therapy in septic
patients. In 2001, Rivers et al22 published a landmark RCT
that was completed in 1 emergency department: 266 adults
with severe sepsis or septic shock were allocated to be monitored goal-directed therapy or not monitored by continuous central venous O2 saturation (ScvO2). In monitored patients, a bundle of treatments were advocated aiming to keep
the ScvO2 70%. This early protocolized therapy (6 hours
of presentation) included mechanical ventilation, up to 80
mL/kg of fluid, dobutamine and vasoconstrictive therapy;
RBC transfusion was given if all these treatments failed to
bring the ScvO2 70% and if the hematocrit level was lower
than 30% (10 g/dL). The rationale of this early goal-directed
therapy was to provide enough O2 delivery (DO2) to prevent
more cellular insult. The short-term mortality was 30.5%
with early goal-directed therapy versus 46.5% in controls. A
quite similar study was conducted in the emergency department and the PICU of 2 Brazilian hospitals: de Oliveira et al23
randomized 102 children in severe sepsis or fluid refractory
shock to the same interventions and the same bundle of
treatments. During the first 6 hours of treatment, the children
allocated to the ScvO2-driven therapy received more crystalloid (28 [20-40] vs 5 [0-20] mL/kg, P 0.0001), more
inotropic drugs (29.4% vs 7.8%, P 0.01), and more RBC
transfusions (45.1% vs 15.7%, P 0.002). The mortality was
11.8% with ScvO2-driven early goal-directed therapy versus
39.2% in controls. These 2 studies were well conducted, but
their generalizability can be questioned. Moreover, it remains
to be determined whether the better outcome observed in
monitored patients is attributable to more RBC transfusions.
At least 2 large RCTs are underway to address these limitations. The Australasian Resuscitation in Sepsis Evaluation
RCT (NCT00975793) will compare early goal-directed therapy with ScvO2 to standard care in 1600 patients with severe
sepsis presenting to the emergency department. The Protocolized Care for Early Septic Shock study (NCT00510835)
will enroll 1935 patients with severe sepsis presenting to the
emergency department; participants will be allocated to 1 of
3 arms: (1) early goal-directed therapy (ScvO2); (2) early
structured treatment based on the subjects systolic blood
pressure and the study doctors judgment of fluid status and
perfusion status; and (3) routine care (study measurements
and treatments are based on the physicians and/or sites stan-

J. Lacroix, P. Demaret, and M. Tucci

dard practices). No strong recommendation can be advocated before we get the results of these RCTs. Meanwhile, it
makes sense to maintain the Hb level to 10 g/dL in unstable
children with severe sepsis and in septic shock if their ScvO2
is 70%, once they are mechanically ventilated and have
received fluids and inotropic drugs.
There are also almost no hard data on what must be done
with respect to RBC transfusion therapy in unstable critically
ill children without hemorrhagic or septic shock. Intensivists
believe that a higher threshold may be required in unstable
patients,24,25 but no hard data support this. Presently, the
only recommendation that can be made with respect to RBC
transfusion in unstable critically ill children without hemorrhagic or septic shock is to use clinical judgment.

RBC Transfusion
in Cardiac Patients
The coping capacity of myocardial cells to anemia is minimal
because their O2 extraction rate is almost maximal, even at
rest. The adaptive mechanisms of these cells to anemia are
even more challenged in cases of pediatric cardiac surgery
because the ventricular function is impaired and the heart
rate is elevated.
There is evidence in the medical literature that cardiac
patients do not tolerate anemia as well as other severely ill
patients. Carson et al26 studied 1958 adult Jehovahs Witnesses who declined RBC transfusion after surgery. The odds
ratio (OR) of death in noncardiac patients increased from 1
with an Hb level of 12 g/dL to 2.5 in those with an Hb of 6
g/dL; mortality started to increase steadily after the Hb level
decreased to 12 g/dL in patients with ischemic heart disease, reaching about 17 in those with an Hb of 6 g/dL. Sabatine et al27 studied the relationship between anemia and the
outcome of 39,922 patients with acute coronary syndrome
who were enrolled in 16 RCTs. In patients with ST elevation
on the electrocardiogram, cardiovascular mortality increased
as Hb levels decreased to 14 g/dL (adjusted OR: 1.21 for
each 1 g/dL decrement in Hb level; 95% CI: 1.12-1.30, P
0.001). In patients with no ST elevation, the likelihood of
cardiovascular death, myocardial infarction, or recurrent
ischemia increased as the Hb decreased to 11 g/dL (adjusted OR: 1.45 for each 1 g/dL decrement in Hb; 95% CI:
1.33-1.58, P 0.001). There is clearly an association between anemia and the risk of death in adults with cardiac
problems. There are no hard data in children with cardiac
problems on the relationship between anemia and outcome,
but it is noteworthy that the pretransfusion Hb concentration
is higher during the postoperative period of pediatric cardiac
surgery cases than in other PICU patients.28
The data reported earlier suggest that an RBC transfusion
should be given to cardiac patients with Hb level 11 or 12
g/dL if these transfusions are completely safe; this is not the
case. Actually, there are data suggesting that RBC transfusion
can be harmful in cardiac patients. For example, Murphy et
al29 reported a statistically and clinically significant association between RBC transfusions and ischemia in 8518 adults

RBC transfusion in PICU

transfused during postoperative care after cardiac surgery
(adjusted OR: 3.35; 95% CI: 2.68-4.35).
What determinants of RBC transfusion should be used in
the postoperative care of pediatric cardiac surgery patients
and whether they are useful clues in the decision-making
process to give an RBC transfusion are matters of debate.
However, there is consensus that the need for RBC transfusion during the postoperative period must be addressed separately in cyanotic and noncyanotic patients.

Children With Noncyanotic Heart Disease

Some experts in pediatric cardiology and transfusion medicine recommend maintaining the Hb levels 12-13 g/dL in
noncyanotic cardiac children,30 whereas others advocate
thresholds as low as 7-8 g/dL.31,32 In 4 surveys on their stated
practice pattern, pediatric intensivists reported that they
would tolerate an Hb level of 7-10 g/dL in stable noncyanotic
cardiac children.24,25,33,34 Their transfusion threshold increased if the patient was unstable, if he required extracorporeal membrane oxygenation, if active bleeding occurred,
or if the ScvO2 or the systemic blood pressure dropped suddenly. In the TRIPICU study, 63 children older than 28 days
with noncyanotic cardiac disease were randomized to a restrictive group (RBC transfusion if Hb 7 g/dL) and 62 to a
liberal group (RBC if Hb 9.5 g/dL).35 NP/MODS was observed in 8 patients in the former group and 4 patients in the
latter group (P 0.36); there were 2 deaths in each group at
28 days post randomization. This subgroup analysis suggests
that an Hb level of 7 g/dL is safe for stable critically ill
children with noncyanotic heart disease. A higher threshold
Hb level is probably required in unstable patients.

Children With Cyanotic Heart Disease

Hb concentrations as high as 16-20 g/dL are frequently observed in children with cyanotic heart disease. In a scenariobased survey,33 respondents replied that they would prescribe an RBC transfusion to stable children with cyanotic
heart disease if the Hb level drops below 12 g/dL; the threshold Hb level increased if the patient became unstable, if an
active bleeding appeared, if the ScvO2 dropped suddenly, or if
the lactate level was high. Few clinical studies have addressed
this question. Experience with bloodless surgery for complex
cyanotic defects suggests that cardiac surgery can be safely
performed with an Hb level as low as 7 g/dL without evidence
of increased risk.36,37 Cholette et al38 published an RCT that
included 60 children with univentricular physiology (33
Glenn and 27 Fontan procedures): 30 patients were allocated
to a restrictive strategy (RBC transfusion if Hb 9 g/dL) and
30 to a liberal group (threshold of 13 g/dL). One death was
observed in the liberal group. The O2 extraction rate was
slightly higher in the restrictive group (31% 7% vs 26%
6%, P 0.013), but median lactate blood level (1.4 0.05
in both groups) and peak blood lactate (3.1 1.5 vs 3.2
1.3 mmol/L) were quite similar. Although the number of
patients is small in this RCT, these results suggest that it is
safe not to give an RBC transfusion to patients with cyanotic
cardiac disease as long as their Hb level is 9 g/dL.

229

RBC Transfusion in
Cardiac Children: Conclusion
The evidence that RBC transfusions improve the outcome of
pediatric cardiac surgery is weak. Some data in adults suggest
that RBC transfusion may be detrimental in some patients
with cardiac conditions. Practitioners believe that a higher
Hb threshold is required in cyanotic cases, but the right
threshold Hb is unknown in these cases. One can suggest that
an Hb level of 7 g/dL is safe in stable noncyanotic cardiac
children, an Hb level of 9 g/dL appears to be safe in cyanotic
cardiac children, and a higher Hb level is probably safer in
unstable cardiac children. Clearly, more studies are needed
to better characterize the determinants of RBC transfusion in
cardiac children.

Goal-Directed
RBC Transfusion Therapy
In theory, a goal-directed RBC transfusion therapy can be the
best approach. Based on this concept, an RBC transfusion
would be given to attain a given physiological goal and not
only to attain a given Hb level. The previously described
RCTs by Rivers et al22 and de Oliveira et al23 illustrate the
concept well: in both RCTs, the goal was to maintain the
ScvO2 70% and the bundle advocated by the investigators
to maintain the ScvO2 70% includes not only mechanical
ventilation, fluid load, and inotropes/vasoactive drugs, but
also RBC transfusion. The concept of goal-directed transfusion therapy is appealing because it suggests that an RBC
transfusion should be given only in response to some symptoms and/or clinical signs that are associated with adverse
outcomes, and that should respond positively to an RBC
transfusion. Many goals have been suggested. Some are systemic markers of DO2 and/or O2 consumption (VO2), like
measurements of global DO2 and/or VO2,7 blood lactate,39,40
SvO2 (mixed venous O2 saturation) and ScvO2,22,23 and O2
extraction rate.41 Others are markers of regional (tissular)
DO2 and/or VO2, such as near-infrared spectroscopy (NIRS),42
and tissular SO2 (StO2).43 Even heart rate variability, plethysmographic variability, and vascular endothelial growth factor
may be markers of interest for tissue hypoxia and transfusion
in some anemic children.44,45
Goal-directed RBC transfusion therapy is an attractive approach. There are good data supporting the use of ScvO2 as a
goal in unstable septic patients, but the role of RBC transfusion to maintain the ScvO2 70% in these patients is unclear.
There are no strong data supporting the use of any other
possible goal. Not surprisingly, there is no consensus on what
should be the first choice goal (other than ScvO2 in severe
sepsis) that should drive goal-directed transfusion therapy
nor any consensus on what threshold should be used for
these goals. Presently, the best available hard data are regarding the 3 determinants discussed earlier: hemodynamic stability (stable or unstable patients), threshold Hb, and case
mix (cardiac or noncardiac patients).

J. Lacroix, P. Demaret, and M. Tucci

230

Hemorrhagic shock:
RBC transfusion
must be given.

Unstable: clinical judgment*.

Not a case with
cardiac disease

Critically ill
children
No hemorrhagic
shock.

Stable: if Hb > 7 g/dL, no RBC; RBC

can be useful if Hb < 7 g/dL.
Unstable (cyanotic and non-cyanotic):
clinical judgment*.

Patient with a
cardiac disease
or postoperative care
of a cardiac
surgery

Stable, non-cyanotic:
a) < 28 days of age: clinical judgment*.
b) > 28 days: no RBC if Hb > 7 g/dL?
Stable, cyanotic:
a) < 28 days: clinical judgment*.
b) > 28 days: no RBC if Hb > 9 g/dL?

Figure 1 Decision tree for RBC transfusion in PICU. *Hb level and other determinants of RBC transfusion may play a
role, like acute blood loss, NIRS, and ScvO2 (70%), but the usefulness of these markers to drive goal-directed
transfusion therapy remains to be determined. Definition of stable derived from the TRIPICU study: mean arterial
pressure is not 2 standard deviations below normal mean for age and cardiovascular support (vasopressors/inotropes
and fluids) has not been increased in the past 2 hours.3 Hb, hemoglobin; NIRS, near infrared spectroscopy; PICU,
pediatric intensive care unit; RBC, red blood cell; ScvO2, central venous oxygen saturation; TRIPICU, transfusion
requirements in PICU. (Color version of figure is available online.)

Conclusions
The same trends are observed in all planned and unplanned
subgroup analyses of the TRIPICU study described in Table
1: the outcome of stable patients who received an RBC transfusion only once their Hb level decreased to 7 g/dL was not
worse than those who received more transfusions. Interpretation of these results warrants caution; there are multiple
comparisons, and the number of subjects is small in many of
these subgroup analyses. Moreover, experts in clinical epidemiology consider that subgroup analyses should be used only
to generate hypotheses.46 However, the consistency of all the
comparisons is striking and supports the point of view that
the main recommendation of the TRIPICU studyto consider RBC transfusions in stable critically ill children only if
their Hb is 7 g/dLis applicable to several subgroups of
stable critically ill children (Table 1). In other words, there is
no justification to use a threshold Hb level higher than 7 g/dL
in stable critically ill children, unless they have a cyanotic
cardiac disease.
Figure 1 suggests a decision tree for RBC transfusion in
PICU. A threshold Hb level of 9 g/dL is suggested in children
who have a cyanotic heart disease and 7 g/dL in all other
stable critically ill children. The most appropriate determinants of RBC transfusion for unstable PICU patients are presently not ascertained, but maintaining the ScvO2 70%
could be a fair goal to direct RBC transfusion in the first 6
hours of treatment in children with severe sepsis and in septic
shock. All patients in hemorrhagic shock must receive RBC
transfusions.
More studies are needed on RBC transfusion in critically ill
children. For example, RCTs must be done in patients with

hemorrhagic shock, in unstable children, in children with

cardiac issues, in PICU cases with neurological problems,
and in patients in the operating room and in the emergency
department. Finding the right goal to drive RBC transfusion
therapy would be of great interest in all these clinical contexts.

References
1. Pollack MM, Ruttimann UE, Getson PR: Pediatric risk of mortality
(PRISM) score. Crit Care Med 16:1110-1116, 1988
2. Bateman ST, Lacroix J, Boven K, et al: Anemia, blood loss and blood
transfusions in North American children in the intensive care unit. Am J
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