Pediatric Anesthesia 2005

15: 716726

doi:10.1111/j.1460-9592.2004.01548.x

Review article

Intraoperative pediatric blood transfusion therapy:

a review of common issues. Part I: hematologic and
physiologic differences from adults; metabolic and
infectious risks
S A N D R A L . B A R C E L O N A M D * , A L E X I S A . TH O M P S O N
M D *
M D A N D C H A R LE S J . C O T E
Departments of *Anesthesiology and Pediatrics, The Feinberg School of Medicine at Northwestern
University, Chicago, IL, USA and Departments of Pediatric Anesthesiology and HematologyOncology-Stem Cell Transplantation, Childrens Memorial Hospital, Chicago, IL, USA

Summary
Pediatric intraoperative transfusion therapy, particularly the approach
to massive blood transfusion (blood loss one blood volume) can be
quite complex because of the unique relationship between the
patients blood volume and the volume of the individual blood
product transfused. This paper is divided into two parts: part 1
presents an overview of the physiologic and hematologic differences
between children and adults as well as an overview of the metabolic
consequences of blood transfusions, risks of disease transmission, and
blood compatibility issues.
Keywords: transfusion therapy; massive blood transfusion; hypocalcemia; hypomagnesemia; hyperkalemia; hypothermia; disease
transmission

Hematologic and physiologic differences

from adults
The physiologic and hematologic differences
between adults and children dictate different guidelines regarding perioperative blood transfusions.
The threshold to transfuse a child may be altered
secondary to these physiologic considerations.
Although many of the complications associated with
pediatric blood transfusions are similar to those
encountered in adults, some complications occur
Correspondence to: Sandra L. Barcelona, MD, Department of
Pediatric Anesthesiology, PO Box 19, Childrens Memorial Hospital, 2300 Childrens Plaza, Chicago, IL 60614, USA (email:
s-barcelona@northwestern.edu).

716

more readily and with a greater frequency in

children. Familiarity with the differences between
adult and pediatric transfusion management is
of utmost importance when planning transfusion
strategies.
Children have higher oxygen consumption and a
higher cardiac output to blood volume ratio than
adults (1,2). The neonatal myocardium operates at
near maximum level of performance as a baseline.
Therefore, the newborns heart may be unable to
compensate for a decreased oxygen carrying capacity by increasing cardiac output. The neonatal
myocardium will also suffer a greater degree of
decompensation when exposed to decreased oxygen
delivery; intraoperative cardiac ischemia has been

2005 Blackwell Publishing Ltd

I N T R A O P E R A TI V E P E D I A TR I C B L O O D T R A N S FU S I O N T H E R A P Y

Table 1
Normal hemoglobin values for full-term and premature infants

Birth
0.5 months
1 month
Age at hemoglobin nadir
Mean hemoglobin at nadir
4 months
6 months

Full term
(gdl)1 of blood)

Premature
(gdl)1 of blood)

19.3

Slightly less than

full term
15.4
11.6
610 weeks
9.4
11.7
12.4

16.6
13.9
912 weeks
11.2
12.2
12.5

Modified with permission from Barcelona & Cote (10).

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 716726

100

Fetal hemoglobin
(percent of total)

reported in neonates (3). Therefore the optimal

hemoglobin values in the newborn are generally
higher than those of older patients. The normal term
neonate has hemoglobin values in the 1420 gdl)1
range depending in part upon how long it takes to
clamp the umbilical cord. These elevated hemoglobin levels gradually decrease over the first several
months of life because of decreased erythropoietin
and reduced red blood cell half-life such that the
physiologic nadir for hemoglobin occurs at approximately 23 months of age (Table 1). Term infants
with hemoglobin levels <9 gdl)1 and preterm
infants with hemoglobin values <7 gdl)1 at the time
of this nadir should be investigated for the presence
of hemoglobinopathy or other pathology. If concern
over adequate oxygen carrying capacity exists, an
elective procedure may be postponed pending evaluation and treatment. Raising the hemoglobin level
may be accomplished by transfusion, exogenous
erythropoietin administration, or simply postponing
the case until the childs natural hematopoietic
mechanisms have taken effect. Higher hemoglobin
levels will increase oxygen carrying capacity and in
the premature infant, may protect from postanesthetic apnea of prematurity although transfusion for
this purpose alone is not generally indicated (4).
Transfusions are usually withheld unless clinically
important blood loss is likely to occur.
Fetal hemoglobin (HbF) comprises 70% of full term
and 97% of premature infants total hemoglobin at
birth (5). Red blood cells (RBCs) containing HbF have
a shorter life span (90 days) than those containing
primarily adult hemoglobin (HbA) (120 days). HbF
interacts poorly with 23-diphosphoglycerate (23
DPG). Therefore the P50 (the partial pressure of
oxygen at which hemoglobin is 50% saturated)

7 17

80

60

40

20

0
2

Age (months)
Figure 1
Percent of fetal hemoglobin in infants. The shaded area represents
the range of fetal hemoglobin in infants from preterm to 6 months
of age. [Modified from Brown (5) p. 258.]

decreases from 26 mmHg with HbA to 19 mmHg

with HbF. This leftward displacement of the oxygen
hemoglobin dissociation curve results in decreased
oxygen delivery to tissue because of the high affinity
of HbF for oxygen. HbF production diminishes
during the first few months of life until only a trace
is present at 6 months of age (Fig. 1) (5). In clinical
terms, the younger the infant, the higher the fraction
of HbF and thus the lower the oxygen carrying
capacity. Premature infants have higher percentages
of HbF than their full-term counterparts and decreased erythropoietin production which inhibits
them from responding to anemia appropriately (6).
Another concern in all neonates is that they may have
a decreased ability to oxygenate blood because of lung
disease or congenital heart disease. It is for these
reasons that hemoglobin levels that are adequate for
the older patient may be suboptimal in the younger
infant or neonate. The threshold for transfusing RBCs
to a neonate should be at a higher hemoglobin trigger
than an older child or healthy adult. In the operating
room the decision to initiate RBC transfusion is based
upon a constellation of factors such as the rapidity of
the blood loss, the presence of impaired oxygenation
(pulmonary or cardiac in origin), and the general
medical condition of the patient.

Metabolic consequences and infectious

disease risks of transfusion therapy
The anesthesiologist must be well versed in the
infectious disease risks and metabolic consequences

S.L. BARCELONA ET AL.

Metabolic implications
Hypocalcemia
Ionized calcium is essential for the successful initiation of the coagulation cascade (7). Citrate is
present in stored blood as a chelating agent for
calcium to prevent clot formation. However, upon
transfusion, the deleterious effect of citrate is in vivo
ionized hypocalcemia. All blood products contain
some citrate but the resulting degree of ionized
hypocalcemia depends upon the blood product
transfused, the rate of transfusion, and hepatic blood
flow/function (811). Hypocalcemia is most often
seen during transfusion of fresh frozen plasma (FFP)
and whole blood because these components contain
the greatest concentration of citrate per unit volume.
Patients with hepatic dysfunction and neonates are
at high risk secondary to their decreased ability to
metabolize citrate (911). As the neonates heart has
reduced sarcoplasmic reticulum, it is greatly
dependent on ionized calcium (calcium flux) for
normal contraction and relaxation. Therefore the
neonatal heart is particularly vulnerable to myocardial dysfunction in the presence of citrateinduced ionized hypocalcemia. This is further confounded by the concomitant administration of
potent inhalational anesthetic agents because all of
the potent inhalation agents cause myocardial
depression secondary to blocking of calcium channels (Figure 2) (9,1214).
Severe cardiac dysfunction may be prevented by
slowing the rate of infusion of citrate containing
products to <1 mlkgmin)1, prophylactically infusing calcium during the transfusion, and by reducing the concentration of inhaled potent anesthetic
agent. If a patient becomes hemodynamically

0.2
0
0.0
10
0.2
20

0.4

30

40

MAP deep halothane (1.5% expired)

MAP light halothane (0.85 expired)
Ionized calcium - deep
Ionized calcium - light

0.6

50

Ionized calcium reduction (mmoll1)

of blood transfusions. The common metabolic consequences of transfusion include: hypocalcemia,

hyperkalemia, hypomagnesemia, hypothermia,
changes in acidbase status, and shifts in the
oxygenhemoglobin dissociation curve. These metabolic disturbances may occur to a greater degree in
children than with adults because of the larger
transfusion to blood volume ratio. For example, a
unit of whole blood may represent the entire
circulating blood volume of an infant whereas that
same unit of blood transfused into an adult represents only one-tenth of the circulating blood volume.

MAP reduction (mmHg)

7 18

0.8
0

10

12

Time (min) citrate infusion

Figure 2
The effects of an infusion of citrate on ionized calcium and mean
arterial pressure (MAP) in a dog model. Note that with the higher
expired concentration of halothane there is a greater fall in ionized
calcium and MAP. This suggests that the calcium channel
blocking properties of inhalation agents are potentiated by the
reduced ionized calcium while at the same time the reduced MAP
decreases citrate metabolism by reducing hepatic blood flow.
Although this study examined halothane, the interaction between
ionized hypocalcemia and any potent anesthetic agent would be
similar as all potent anesthetics depress cardiac function through
calcium channel blocking activity. [Modified from data in Cote
(13)].

unstable during rapid blood transfusion, and the

circulating blood volume has been maintained, then
ionized hypocalcemia is the most likely cause of the
hypotension. The treatment for ionized hypocalcemia is administration of exogenous calcium.
There is no difference in the rate of ionization or the
change in blood ionized calcium concentrations if
equivalent doses of calcium chloride vs calcium
gluconate are administered. Generally three times
more calcium gluconate is required than calcium
chloride,
e.g.
2.5 mgkg)1
calcium
chlor)1
ide 7.5 mgkg
calcium gluconate (Figure 3)
(15). Calcium should not be administered in the
blood container or even in the same intravenous line
because this will rapidly allow clot formation. A
reasonable starting dose for calcium chloride is 5
10 mgkg)1 or 1530 mgkg)1 for calcium gluconate
to treat ionized hypocalcemia during rapid infusions
of FFP or whole blood (>1 mlkg)1min)1). Alternatively, with blood loss that is moderate but continuing over an extended period of time, e.g. redo liver
transplantation, a baseline infusion of calcium particularly during the anhepative phase may be useful.
Our practice in this situation is to begin calcium

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 716726

I N T R A O P E R A TI V E P E D I A TR I C B L O O D T R A N S FU S I O N T H E R A P Y

calcium chloride (1520 mgkg)1) or calcium gluconate (4560 mgkg)1) should be administered at
12-min intervals until the arrhythmia is resolved. It
should be noted that the calcium therapy only
opposes the electrophysiologic effects of hyperkalemia. Other measures to reduce circulating potassium
values such as administration of glucose and insulin,
hyperventilation, administration of albuterol, and
Kayexalate will be needed to correct the hyperkalemia. Standard cardiopulmonary resuscitation (CPR
measures) should be initiated as indicated.

Ionized calcium (mmoll1) mean SD

1.5
Calcium gluconate (7.5 mgkg1)
Calcium chloride (2.5 mgkg1)

1.4

7 19

1.3

1.2

1.1

1.0

0.9
0

Time (min)

Figure 3
Changes in ionized calcium values following equi-ionizable doses
of calcium chloride and calcium gluconate in 10 children who
were undergoing burn wound excision and grafting. Note that
there was no difference at any time point between 30 s and 5 min
following administration. Thus both forms of calcium dissociate
with equal rapidity and are interchangeable provided equiionizable doses are administered. [Abstracted from data from
Cote et al. (15)].

chloride at 1015 mgkg)1h)1 with frequent measurement of ionized calcium values and appropriate
titration of the infusion to the desired value.
Hyperkalemia
Transfusion associated hyperkalemia also occurs
during specific conditions in pediatric patients. Neonates and infants have experienced fatal cardiac
arrhythmias during large volume or exchange transfusions as a result of hyperkalemia (1619). The rate of
rise of serum potassium values occurs quickly in
children with small blood volumes (20). Blood components with the highest levels of potassium include
whole blood, irradiated units and units approaching
their expiration date (9,10,2024). Washing of erythrocytes has been shown to markedly reduce the
potassium concentration (16,25). As potassium leaks
from older RBC as their cell membranes deteriorate, it
may be advisable to use fresh or newer (i.e. <7-day
old) units, and to avoid the use of whole blood when
transfusing neonates and small infants (16,20,26). It
should be noted however that life-threatening hyperkalemia may occur even with packed RBC if large
quantities of blood are rapidly infused (18,20,27).
Should a life-threatening arrhythmia such as ventricular tachycardia develop, then higher doses of

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 716726

Hypomagnesemia
Decreased ionized magnesium levels occur with
massive blood transfusion. Similar to hypocalcemia,
hypomagnesemia is the result of citrate toxicity and
is seen with its greatest severity during the anhepatic
phase of liver transplantation. Magnesium is essential in stabilizing resting membrane potential and
thus is very important in maintaining cardiovascular
stability, particularly from an electrophysiologic
standpoint (2830). Should a life-threatening
arrhythmia such as ventricular tachycardia or ventricular fibrillation develop that does not respond to
exogenous calcium therapy, then intravenous
magnesium sulfate (2550 mgkg)1) may be administered followed by an infusion of 3060 mg
kg)124 h)1.
Acidbase changes
The typical unit of donated whole blood contains
approximately 450 ml of whole blood and about
50 ml of anticoagulant for a final volume of approximately 500 ml. After donation, the RBC continue to
undergo metabolism and can elevate dissolved
carbon dioxide to 180210 mmHg within several
hours (31). Once the available oxygen is utilized, the
RBC change to anaerobic metabolism thus increasing the lactic acid content. Therefore, the rapid
transfusion of whole blood may initially cause a
transient combined respiratory and metabolic acidosis. However, the carbon dioxide is rapidly
excreted through the lungs and the small amount
of lactic acid is generally rapidly buffered so that
there is no net effect upon acidbase status (32).
Thus there is no need for exogenous bicarbonate
therapy as long as the patient is adequately volume
resuscitated. The development of a metabolic acidosis during massive blood transfusion generally

7 20

S.L. BARCELONA ET AL.

indicates inadequate perfusion, severe hypovolemia

prior to initiation of transfusion therapy, or an
underlying issue such as systemic infection or
hypoxemia. In general, patients who experience
massive blood transfusion will later develop a
metabolic alkalosis secondary to the metabolism of
citrate. This is another good reason to limit exogenous sodium bicarbonate therapy to treatment of
measured acidbase abnormalities rather than by
administering bicarbonate empirically.
Hypothermia
Children are predisposed to heat loss because of
their large surface area to weight ratio and relatively
large head size. The normal shift in heat distribution
from core to periphery from general anesthesia,
evaporative losses through ventilation and surgical
incisions, use of irrigation solutions, and cold operating rooms further contribute to the development of
hypothermia (33). Maintenance of normothermia is
often challenging even without the administration of
cold blood products.
The deleterious effects of hypothermia include
apnea, hypoglycemia and decreased drug metabolism which can lead to prolonged effects of
anesthesia and delayed emergence (34,35). A drop
in patient temperature also leads to a leftward
displacement of the oxyhemoglobin dissociation
curve, resulting in decreased oxygen delivery to
tissues (31,32). Hypothermia increases oxygen consumption (secondary to shivering and nonshivering
thermogenesis), worsens coagulopathy, and may
even increase mortality (3638). The warming of
blood products transfused to children may require
specific equipment and different techniques than
used in adults. When priming any fluid warmer
with blood products to be transfused to an infant or
small child, it is important to disconnect the system
from the patient so as to avoid a concomitant
massive infusion of crystalloid. A standard heating
plate type blood warmer has a large dead space and
high resistance to flow caused by the coiled tubing
through which the blood must travel while traversing the heating plates. These devices can be used in
most situations where blood loss is slow and a
syringe can be used to both quantitate the volume
transfused and facilitate flow of blood. For patients
in whom blood loss is rapid, more sophisticated
warming devices are often needed. Recent genera-

tions of blood warmers have taken advantage of

counter current heat exchange (tube within a tube of
hot water). For discussion purposes we will present
information on systems available in the USA recognizing that other systems are available in other
countries.
The Hot Line fluid warmer (Level-1 Technologies,
Rockland, MA, USA) utilizes a circulating warm
water bath and a simple system which has much less
dead space and resistance to blood flow than heating
plate type warmers (39). However, air bubbles have
been observed in the transfusate raising concerns
regarding the potential for air embolization (40).
This system is not designed for rapid blood transfusions.
Level-1 system also uses counter current technology but with an automatic pressurization system that
squeezes the blood or crystalloid containers (10,41).
However, fatal air embolism has occurred with the
use of Level-1 when intravenous fluid bags were not
properly evacuated of air (42,43). Level-1 has now
developed a new air detection system with further
refinements in the air detection and flow cutoff that
may be added on to the currently available systems. A
recently released model of Level-1 technology is now
equipped with an automatic air purging system with
an alarm with flow cutoff should air bypass the air
eliminator. Level-1 has also developed upgraded
disposable blood administration systems (D-100 and
D-300) which are capable of more rapid transfusion
and superior heating of fluids compared with the
original D-50 disposable blood administration system
(44).
The Rapid Infusion System (RIS; Haemonetics,
Inc., Braintree, MA, USA) has a much greater
capacity and is based upon cardiotomy reservoir
technology (41,4547). The RIS has many safety
features, including superior air elimination and
warming capabilities compared with Level-1, but
this device is large, expensive and too powerful for
most pediatric cases. In addition, this system is quite
difficult to set-up for the occasional user (41).
Haemonetics Inc. is no longer producing this
machine but will continue to service it until 2005.
The replacement for the RIS is the FMS 2000
(Belmont Inc., Billerica, MA, USA). It uses magnetic
induction for heating of fluids between 10 and
500 mlmin)1 (an upgraded system with the capacity
to heat up to 750 mlmin)1 is in development). This

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 716726

I N T R A O P E R A TI V E P E D I A TR I C B L O O D T R A N S FU S I O N T H E R A P Y

7 21

Table 2
Comparison of fluid warming devices
Warming device
Level-1

Rapid Infusion System

Manufacturer

Level-1 Technologies,
Rockland, MA, USA

Haemonetics, Inc.,
Braintree, MA, USA

Cost of unit (USD)

Without air detector, 5500

With air detector,
8947
D-50,
26
D-100,
65
D-300,
88
32 (including i.v. pole)
Medium
Stand alone system mounted on separate i.v. pole

51 700

Cost of disposable
(USD)
Weight (kg)
Footprint
Set up

Air detection
Ease of fluid
loading
Ease of set-up
Other

Improved with new model or

retrofit add on device
Requires venting of air
from i.v. bags to prevent
air embolization
Easiest
No available reservoir for
blood mixing

FMS 2000

Buddy

Belmont Instrument
Corp., Billerica, MA,
USA
19 900

500

Without reservoir,
With reservoir,

118
Largest
Stand alone
system with
built in wheels
Two detectors

11.8
Medium
Mounted on i.v. pole

No air venting
required

No air venting
required

Most difficult
Being phased out

Relatively easy
Does not heat at flow
<10 mlmin)1

Two detectors

Belmont Instrument Corp.,

Billerica, MA, USA
1595
108
201

15

4.43 (unit on i.v. 105 g)

Small
Power module mounted on i.v.
pole, warming unit
mounted on i.v. tubing
Pressure regulating valve
and venting membrane
No air venting required
but not designed to
deliver fluid under pressure
Very easy
Unclear effectiveness with rapid
transfusion of blood

USD, United States dollars (costs may vary with multiple purchases).

device is smaller and easier to set up than the RIS,

has excellent air detection and elimination capabilities, and may provide a middle ground between
Level-1 and RIS for bigger pediatric patients. The
disadvantage of the FMS for smaller pediatric
patients is its inability to heat fluids at flows
<10 mlmin)1. At present the FMS seems to have
superior blood warming and air detection compared
with Level-1, however a new add-on air detector for
the Level-1 will likely correct the air detection
problem (48).
Recently Belmont has introduced a new fluid
warmer (Buddy) that heats fluids and blood just
prior to entering the patient using the same magnetic
induction heating method. This system mounts on
an i.v. pole but the disposable 3 11 cm cartridge
and warming unit are interfaced with the patients
i.v. system close to entry to the patient. This plate is
equipped with a pressure regulating valve and a
venting membrane that the manufacturer purports
to automatically remove air from crystalloid solutions. This heating unit only weighs 105 g. Having
the blood warmer so close to the patient eliminates
the usual long distance between warmer and patient

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 716726

whereby warmed fluids cool to room temperature

prior to entering the patient. The manufacturer
states that room temperature crystalloid solutions
can be warmed to 38C at flow rates up to
100 mlmin)1. This device is not designed to administer blood products under pressure.
Each of these fluid-warming devices has advantages and disadvantages in terms of ease of setup,
cost per setup, cost per device, and footprint in the
operating room where space can be at a premium
(Table 2).

Infectious disease transmission risk

Infectious risks of transfusion have decreased dramatically thanks to improved screening, detection of
infected units and advances in pathogen inactivation
(Table 3). The incidence of infectious complications
is now smaller than that of metabolic or immunologic consequences. Further improvements in safety
are likely in the future with the more widespread
use of viral RNA detection by means of nucleic acid
amplification but this will not occur until the cost of
this test is markedly reduced (49,50). Nonetheless,

7 22

S.L. BARCELONA ET AL.

Table 3
Current blood screening tests used on donated blood in the
United States
Screening tests
Hepatitis B surface antigen (HBsAg)
Hepatitis B core antigen (anti-HBc)
Hepatitis C virus antibody (anti-HCV)
HIV-1 antibody (anti-HIV-1)
HIV-2 antibody (anti-HIV-2)
HTLV-I antibody (anti-HTLV-I)
HTLV-II antibody (anti-HTLV-II)
Nucleic acid amplification testing (NAT) for HIV-1 and HCV
Serologic test for syphilis
Nucleic acid amplification for West Nile virus
Abstracted from data in: http://www.aabb.org/All_About_
Blood/FAQs/aabb_faqs.htm.

the risk of infection, especially of human immunodeficiency virus and hepatitis C, is often the primary
concern of parents whose child may need a blood
transfusion. As the incidence data will vary from
country to country, the anesthesiologist should be
familiar with the most recent statistics in their
country in order to have meaningful discussions
with concerned parents (Table 4). Clearly the incidence of these viral pathogens in the blood pool is
also dependent upon the prevalence of these infections within the donor community and the resources
used to screen the blood products; unfortunately
some less advantaged countries cannot afford to
carry out all the necessary testing (5159). In these
settings it is likely that anemia (Hb u 5 gdl)1) is a
better alternative than transfusion with contaminated blood provided that a stable cardiovascular and
acidbase status can be maintained.
Table 4
Risk of transfusion related viral transmission and viral window
for a negative screening test

Virus
Hepatitis A
Hepatitis B
Hepatitis C
Human
T-lymphotrophic
virus I and II
HIV

Risk

Days possible to
transmit disease, i.e.
false negative screen

?
1 per 137 000
1 per 1 000 000
1 per 641 000 or less

Occasional cases
59
82
51

1 per 1 900 000

22

Abstracted from data in: http://www.aabb.org/All_About_

Blood/FAQs/aabb_faqs.htm

Besides the viral pathogens included in Table 4,

the anesthesiologist should be aware that bacterial
contamination may also occur, and is most common with platelets (6063). Standards for testing of
platelets for bacterial growth prior to release for
administration are now being developed by the
American Association of Blood Banks. Various
other infectious diseases are potentially transmittable by transfusion including HTLV, West Nile
virus, Babesiosis, Chagas disease, Lyme disease,
malaria and CreutzfeldtJakob disease (6470).
Although no specific nucleic acid testing or antigen testing for many of these rare diseases exist,
donor screening and deferral of those with potential symptoms helps to prevent transfusion-related
transmission.
Another recent concern is the possibility of transmission of severe acute respiratory syndrome
(SARS) through blood transfusion. The position of
the American Association of Blood Banks (http://
www.aabb.org/All_About_Blood/FAQs/aabb_faqs.
htm) is that as live virus could be in the blood of a
potential symptom free donor, they will ask if the
donor has traveled to a SARS-affected region. They
also inquire if the donor has had contact with a
SARS-infected individual, and if so, they will not
collect blood from that person.

Incompatibility and other immunologic

considerations
While transfusions of blood products can be highly
beneficial in many clinical settings, side effects and
other hazards may be associated with their use.
Compatibility tests are standard procedures which
are routinely performed to prevent hemolytic transfusion reactions which can be life-threatening.
Table 5 displays the common blood types (USA)
and Table 6 displays typical compatibilities for
cross-match. Clerical error is the most common
cause for a mismatched transfusion. These reactions
can be decreased by scrupulous vigilance by the
anesthesiologists and nurses responsible for checking blood products prior to patient administration
(7174). The most common clerical error we have
observed is a careful check of the name on the unit
and the name on the paperwork from the blood bank
but not a cross check that the patient for whom it is
intended is in fact the patient receiving it which then

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 716726

I N T R A O P E R A TI V E P E D I A TR I C B L O O D T R A N S FU S I O N T H E R A P Y

Transfusion-related graft vs host disease

occurs when lymphocytes contained in a transfused
blood component proliferate and cause host tissue
destruction (8,76,77). This is primarily a problem in
immunocompromised patients who cannot mount a
response to foreign lymphocytes before this lethal
proliferation occurs. Immunosuppression of this
degree has been reported in premature infants,
children suffering from cancer or severe systemic
illness, children experiencing rapid acute blood loss,
and those undergoing cardiopulmonary bypass
(8,7779). More important however is that graft vs
host disease may also occur in immunocompetent
children who receive directed donor transfusion
from a biological relative (8). The lymphocytes
present in these units may not be recognized as
foreign by the recipient secondary to the similarity of
haplotypes between relatives (77,79). Therefore, the
recipient does not mount an immune response to the
lymphocytes which may then proliferate and destroy host tissue. This is a critically important
consideration when families are considering directed donor blood as ultimately safe for administration
to their children.
Graft vs host disease may be prevented by
effectively reducing lymphocyte counts in transfused blood. Irradiation of directed donor units and
those cross-matched for transfusion to immunocompromised patients has been shown to effectively
inhibit the lymphocytes from proliferating and
decreases the likelihood of graft vs host disease
(8,77,78). Thus it is vitally important that the anesthesiologist assures that these units have been

Table 5
Blood group distribution within the United States
Blood type

Percent United States population

O Rh-positive
O Rh-negative
A Rh-positive
A Rh-negative
B Rh-positive
B Rh-negative
AB Rh-positive
AB Rh-negative

7 23

38
7
34
6
9
2
3
1

Abstracted from data in: http://www.aabb.org/All_About_

Blood/FAQs/aabb_faqs.htm.

results in administration of blood to the wrong

recipient.
Severe acute hemolytic reactions most often
result from immunologic destruction of red cells
because of ABO incompatibility. Less frequently,
serologic incompatibilities not detectable by standard antibody screens can cause an acute hemolytic
reaction. Symptoms in the anesthetized patient
include fever, tachycardia, hypotension and abnormal bleeding. If suspected, treatment should include immediate cessation of transfusion, measures
to maintain or correct arterial blood pressure, and
attention to the maintenance of good urine output.
Anaphylactoid reactions with bronchospasm, laryngeal edema and urticaria are dangerous but rare
and typically occur in IgA-deficient individuals.
Treatment includes corticosteroids, antihistamines
and epinephrine (75).

Table 6
Compatibilities of various blood products
Acceptable donor
Recipient

Whole blood

Packed RBCa

FFP

Plateletsb

AB+
AB)
A+
A)
B+
B)
O+
O)

AB+, AB)
AB)
A+, A)
A)
B+, B)
B)
O+, O)
O)

AB+, AB), A+, A), B+, B), O), O+

AB), A), B), O)
A+, A), O), O+
A), O),
B+, B), O), O+
B), O)
O), O+
O)

AB
AB
A, AB
A, AB
B, AB
B, AB
O, A, B, AB
O, A, B, AB

AB+, AB) (A+, A), B+, B), O+, O) if hyper-concentrated)

AB) (A), B), O) if hyper-concentrated)
A+, A), AB+, AB) (B+, B), O+, O) if hyper-concentrated)
A), AB) (B), O) if hyper-concentrated)
B+, B), AB+, AB) (A+, A), O+, O) if hyper-concentrated)
B), AB) (A), O) if hyper-concentrated)
O+, O), A+, A), B+, B), AB+, AB)
O), A), B), AB)

Rh) patients should not receive Rh+ RBC unless in emergency, particularly in females to avoid Rh sensitization.
Platelets have a minute amount of RBC that might potentially cause Rh sensitization in Rh) patients. If giving Rh+ platelets is necessary,
Rh immunoglobulin should be considered (Rh+ patients can always receive any Rh) products).
b

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 716726

7 24

S.L. BARCELONA ET AL.

irradiated prior to administration and to return

nonirradiated units to the blood bank. The anesthesiologist should take note that irradiated units contain higher concentrations of potassium than
nonirradiated units. It is vital to maintain a high
degree of vigilance for the development of hyperkalemia when administering irradiated units
(8,23,24,80).

Acknowledgements
We wish to thank the Blood Bank of Childrens
Memorial Hospital, Chicago IL, USA for assembling
Table 6.

References
1 Cross KW, Tizard JP, Trythall DA. The gaseous metabolism of
the newborn infant breathing 15% oxygen. Acta Paediatr 1958;
47: 217237.
2 Cross KW, Flynn DM, Hill JR. Oxygen consumption in normal
newborn infants during moderate hypoxia in warm and cool
environments. Pediatrics 1966; 37: 565576.
3 Bell C, Rimar S, Barash P. Intraoperative ST-segment changes
consistent with myocardial ischemia in the neonate: a report of
three cases. Anesthesiology 1989; 71: 601604.
4 Cote CJ, Zaslavsky A, Downes JJ et al. Postoperative apnea in
former preterm infants after inguinal herniorrhaphy. A combined analysis. Anesthesiology 1995; 82: 809822.
5 Brown MS. Physiologic anemia of infancy: Normal red-cell
values and physiology of neonatal erythropoiesis. In: Stockman JA III, Pochedly C, eds. Developmental and Neonatal Hematology. New York: Raven Press, 1988: 249274.
6 Roseff SD, Luban NL, Manno CS. Guidelines for assessing
appropriateness of pediatric transfusion. Transfusion 2002; 42:
13981413.
7 Butenas S, Mann KG. Blood coagulation. Biochemistry (Mosc)
2002; 67: 312.
8 Manno CS. Whats new in transfusion medicine? Pediatr Clin
North Am 1996; 43: 793808.
9 Cote CJ. Blood, colloid, and crystalloid therapy. Anesth Clin
North Am 1991; 9: 865884.
10 Barcelona SL, Cote CJ. Pediatric resuscitation in the operating
room. Anesthesiol Clin North Am 2001; 19: 339365.
11 Borland LM, Roule M, Cook DR. Anesthesia for pediatric orthotopic liver transplantation. Anesth Analg 1985; 64: 117124.
12 Cote CJ, Drop LJ, Hoaglin DC et al. Ionized hypocalcemia after
fresh frozen plasma administration to thermally injured children: effects of infusion rate, duration, and treatment with
calcium chloride. Anesth Analg 1988; 67: 152160.
13 Cote CJ. Depth of halothane anesthesia potentiates citrate-induced ionized hypocalcemia and adverse cardiovascular
events in dogs. Anesthesiology 1987; 67: 676680.
14 Stulz PM, Scheidegger D, Drop LJ et al. Ventricular pump
performance during hypocalcemia. Clinical and experimental
studies. J Thorac Cardiovasc Surg 1979; 78: 185194.

15 Cote CJ, Drop LJ, Daniels AL et al. Calcium chloride versus

calcium gluconate: comparison of ionization and cardiovascular
effects in children and dogs. Anesthesiology 1987; 66: 465470.
16 Baz EM, Kanazi GE, Mahfouz RA et al. An unusual case of
hyperkalaemia-induced cardiac arrest in a paediatric patient
during transfusion of a fresh 6-day-old blood unit. Transfus
Med 2002; 12: 383386.
17 Phillips GR III, Kauder DR, Schwab CW. Massive blood loss in
trauma patients. The benefits and dangers of transfusion
therapy. Postgrad Med 1994; 95: 6172.
18 Brown KA, Bissonnette B, McIntyre B. Hyperkalaemia during
rapid blood transfusion and hypovolaemic cardiac arrest in
children. Can J Anaesth 1990; 37: 747754.
19 Scanlon JW, Krakaur R. Hyperkalemia following exchange
transfusion. J Pediatr 1980; 96: 108110.
20 Brown KA, Bissonnette B, MacDonald M et al. Hyperkalaemia
during massive blood transfusion in paediatric craniofacial
surgery. Can J Anaesth 1990; 37: 401408.
21 Chen CH, Hong CL, Kau YC et al. Fatal hyperkalemia during
rapid and massive blood transfusion in a child undergoing hip
surgery a case report. Acta Anaesthesiol Sin 1999; 37: 163166.
22 Buntain SG, Pabari M. Massive transfusion and hyperkalaemic
cardiac arrest in craniofacial surgery in a child. Anaesth Intensive Care 1999; 27: 530533.
23 Fukuoka Y, Ishiyama T, Oguchi T et al. Hyperkalemia after
irradiated blood transfusion. Masui 1999; 48: 192194.
24 Thorp JA, Plapp FV, Cohen GR et al. Hyperkalemia after
irradiation of packed red blood cells: possible effects with intravascular fetal transfusion. Am J Obstet Gynecol 1990; 163:
607609.
25 Knichwitz G, Zahl M, Van Aken H et al. Intraoperative
washing of long-stored packed red blood cells by using an
autotransfusion device prevents hyperkalemia. Anesth Analg
2002; 95: 324325.
26 Ratcliffe JM, Elliott MJ, Wyse RK et al. The metabolic load of
stored blood. Implications for major transfusions in infants.
Arch Dis Child 1986; 61: 12081214.
27 Jameson LC, Popic PM, Harms BA. Hyperkalemic death during use of a high-capacity fluid warmer for massive transfusion. Anesthesiology 1990; 73: 10501052.
28 Elin RJ. Magnesium metabolism in health and disease. Dis Mon
1988; 34: 161218.
29 Meikle A, Milne B. Management of prolonged QT interval
during a massive transfusion: calcium, magnesium or both?
Can J Anaesth 2000; 47: 792795.
30 Scott VL, De Wolf AM, Kang Y et al. Ionized hypomagnesemia
in patients undergoing orthotopic liver transplantation: a
complication of citrate intoxication. Liver Transplantation and
Surgery 1996; 2: 343347.
31 Miller RD. Complications of massive blood transfusions.
Anesthesiology 1973; 39: 8293.
32 Miller RD, Tong MJ, Robbins TO. Effects of massive transfusion of blood on acid-base balance. JAMA 1971; 216: 17621765.
33 Bissonnette B. Thermoregulation and paediatric anaesthesia.
Curr Op Anaesth 1993; 6: 537542.
34 Heier T, Caldwell JE, Sessler DI et al. Mild intraoperative
hypothermia increases duration of action and recovery time of
vecuronium. Anesth Analg 1999; 70: S153.
35 Koren G, Barker C, Goresky G. The influence of hypothermia
on the disposition of fentanyl, human and animal studies. Eur J
Clin Pharmacol 1987; 32: 373.

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 716726

I N T R A O P E R A TI V E P E D I A TR I C B L O O D T R A N S FU S I O N T H E R A P Y

36 Johnston TD, Chen Y, Reed RL. Functional equivalence of

hypothermia to specific clotting factor deficiencies. J Trauma
1994; 37: 413417.
37 Patt A, McCroskey BL, Moore EE. Hypothermia-induced
coagulopathies in trauma. Surg Clin North Am 1988; 68: 775
785.
38 Jurkovich GJ, Greiser WB, Luterman A et al. Hypothermia in
trauma victims: an ominous predictor of survival. J Trauma
1987; 27: 10191024.
39 Smallman JM, Morgan M. Evaluation of the Level 1 Hotline
blood warmer. Anaesthesia 1992; 47: 869871.
40 Stevenson GW, Tobin M, Cote CJ. Potential air embolus with
the use of a blood/fluid warming set. Anesth Analg 1994; 79:
610611.
41 Barcelona SL, Vilich F, Cote CJ. A comparison of flow rates and
warming capabilities of the Level 1 and Rapid Infusion System
with various-size intravenous catheters. Anesth Analg 2003; 97:
358363.
42 Adhikary GS, Massey SR. Massive air embolism: a case report.
J Clin Anesth 1998; 10: 7072.
43 Hartsmannsgruber WB. Very limited air elimination capability
of the Level 1 fluid warmer. J Clin Anesth 1997; 9: 233235.
44 Eaton MP, Dhillon AK. Relative performance of the level 1 and
ranger pressure infusion devices 3. Anesth Analg 2003; 97:
10741077.
45 Dunham CM, Belzberg H, Lyles R et al. The rapid infusion
system: a superior method for the resuscitation of hypovolemic trauma patients. Resuscitation 1991; 21: 207227.
46 Rothen HU, Lauber R, Mosimann M. An evaluation of the
Rapid Infusion System. Anaesthesia 1992; 47: 597600.
47 Haglund MM, Grady MS, Kanev PM et al. Rapid infusion
system for neurosurgical treatment of massive intraoperative
hemorrhage. J Neurotrauma 1994; 11: 623627.
48 Comunale ME. A laboratory evaluation of the level 1 rapid
infuser (H1025) and the Belmont instrument fluid management system (FMS 2000) for rapid transfusion. Anesth Analg
2003; 97: 10641069.
49 Stramer SL, Glynn SA, Kleinman SH et al. Detection of HIV-1 and
HCV infections among antibody-negative blood donors by
nucleic acid-amplification testing. N Engl J Med 2004; 351: 760
768.
50 Goodman JL. The safety and availability of blood and tissues
progress and challenges. N Engl J Med 2004; 351: 819822.
51 AuBuchon JP, Birkmeyer JD, Busch MP. Cost-effectiveness of
expanded human immunodeficiency virus- testing protocols
for donated blood. Transfusion 1997; 37: 4551.
52 Chao A, Bulterys M, Musanganire F et al., National University of Rwanda-Johns Hopkins University AIDS Research
Team. Risk factors associated with prevalent HIV-1 infection
among pregnant women in Rwanda. Int J Epidemiol 1994; 23:
371380.
53 Consten EC, van der Meer JT, de Wolf F et al. Risk of iatrogenic
human immunodeficiency virus infection through transfusion
of blood tested by inappropriately stored or expired rapid
antibody assays in a Zambian hospital. Transfusion 1997; 37:
930934.
54 Fang CT, Field SP, Busch MP et al. Human immunodeficiency
virus-1 and hepatitis C virus RNA among South African blood
donors: estimation of residual transfusion risk and yield of
nucleic acid testing. Vox Sang 2003; 85: 919.
55 Foster S, Buve A. Benefits of HIV screening of blood transfusions in Zambia. Lancet 1995; 346: 225227.

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 716726

7 25

56 Lackritz EM. Prevention of HIV transmission by blood transfusion in the developing world: achievements and continuing
challenges. AIDS 1998; 12: S81S86.
57 Whyte GS, Savoia HF. The risk of transmitting HCV, HBV or
HIV by blood transfusion in Victoria. Med J Aust 1997; 166:
584586.
58 Luban NL. An update on transfusion-transmitted viruses. Curr
Opin Pediatr 1998; 10: 5359.
59 Dodd RY. Bacterial contamination and transfusion safety:
experience in the United States. Transfus Clin Biol 2003; 10:
69.
60 Smith LA, Wright-Kanuth MS. Bacterial contamination of
blood components. Clin Lab Sci 2003; 16: 230238.
61 Bell CE, Botteman MF, Gao X et al. Cost-effectiveness of
transfusion of platelet components prepared with pathogen
inactivation treatment in the United States. Clin Ther 2003; 25:
24642486.
62 Goodnough LT, Kuter D, McCullough J et al. Apheresis
platelets: emerging issues related to donor platelet count,
apheresis platelet yield, and platelet transfusion dose. J Clin
Apheresis 1998; 13: 114119.
63 McCullough J. Progress toward a pathogen-free blood supply.
Clin Infect Dis 2003; 37: 8895.
64 Shulman IA, Saxena S, Nelson JM et al. Neonatal exchange
transfusions complicated by transfusion-induced malaria.
Pediatrics 1984; 73: 330332.
65 Cable RG, Leiby DA. Risk and prevention of transfusiontransmitted babesiosis and other tick-borne diseases. Curr Opin
Hematol 2003; 10: 405411.
66 Gerber MA, Shapiro ED, Krause PJ et al. The risk of acquiring
Lyme disease or babesiosis from a blood transfusion. J Infect
Dis 1994; 170: 231234.
67 Becker JL. Vector-borne illnesses and the safety of the blood
supply. Curr Hematol Rep 2003; 2: 511517.
68 Pealer LN, Marfin AA, Petersen LR et al. Transmission of West
Nile virus through blood transfusion in the United States in
2002. N Engl J Med 2003; 349: 12361245.
69 Sabino EC, Goncalez TT, Salles NA et al. Trends in the prevalence of Chagas disease among first-time blood donors in
Sao Paulo, Brazil. Transfusion 2003; 43: 853856.
70 Busch MP, Kleinman SH, Nemo GJ. Current and emerging
infectious risks of blood transfusions. JAMA 2003; 289: 959962.
71 Linden JV, Paul B, Dressler KP. A report of 104 transfusion
errors in New York State. Transfusion 1992; 32: 601606.
72 Linden JV. Errors in transfusion medicine. Scope of the problem. Arch Pathol Lab Med 1999; 123: 563565.
73 McClelland DB, McMenamin JJ, Moores HM et al. Reducing
risks in blood transfusion: process and outcome. Transfus Med
1996; 6: 110.
74 Mercuriali F, Inghilleri G, Colotti MT et al. Bedside transfusion
errors: analysis of 2 years use of a system to monitor and
prevent transfusion errors. Vox Sang 1996; 70: 1620.
75 Jenner PW, Holland PV. Diagnosis and management of
transfusion reactions. In: Petz LD, Kleinman S, Swisher SN,
Spence RK, Strauss RG, eds. Clinical Practice of Blood Transfusion, 3rd edn. New York: Churchill Livingtone, 1996: 905
929.
76 Cohen A, Manno C. Transfusion practices in infants receiving
assisted ventilation. Clin Perinatol 1998; 25: 97111.
77 Warren LJ, Simmer K, Roxby D et al. DNA polymorphism
analysis in transfusion-associated graft-versus-host disease.
Journal of Paediatrics and Child Health 1999; 35: 98101.

7 26

S.L. BARCELONA ET AL.

78 DePalma L, Yu M, McIntosh CL et al. Changes in lymphocyte

subpopulations as a result of cardiopulmonary bypass. The
effect of blood transfusion. J Thorac Cardiovasc Surg 1991; 101:
240244.
79 Ohto H, Anderson KC. Posttransfusion graft-versus-host disease in Japanese newborns. Transfusion 1996; 36: 117123.

80 Hall TL, Barnes A, Miller JR et al. Neonatal mortality following

transfusion of red cells with high plasma potassium levels.
Transfusion 1993; 33: 606609.

Accepted 23 September 2004

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 716726