1. burns 37 (2011) 742–752
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/burns
Review
Red blood cell transfusion following burn
Giuseppe Curinga b,*, Amit Jain c, Michael Feldman a, Mark Prosciak a,
Bradley Phillips d, Stephen Milner a
a
Johns Hopkins Burn Center, MD, Baltimore, USA
b
Civico and Benfratelli Hospital Burn Center, Palermo, Italy
c
Johns Hopkins University School of Medicine, Baltimore, MD, USA
d
Swedish Medical Center, Denver, CO, USA
article info summary
Article history: A severe burn will significantly alter haematologic parameters, and manifest as anaemia,
Accepted 20 January 2011 which is commonly found in patients with greater than 10% total body surface area (TBSA)
involvement. Maintaining haemoglobin and haematocrit levels with blood transfusion has
Keywords: been the gold standard for the treatment of anaemia for many years.
Blood transfusion While there is no consensus on when to transfuse, an increasing number of authors have
Blood in burn expressed that less blood products should be transfused.
Blood management Current transfusion protocols use a specific level of haemoglobin or haematocrit, which
Blood loss dictates when to transfuse packed red blood cells (PRBCs). This level is known as the trigger.
Anemia in burn patients There is no one ‘common trigger’ as values range from 6 g dlÀ1 to 8 g dlÀ1 of haemoglobin.
Unnecessary transfusion The aim of this study was to analyse the current status of red blood cell (RBC) transfu-
Appropriate transfusion sions in the treatment of burn patients, and address new information regarding burn and
in burn population blood transfusion management.
Red blood cells transfusion Analysis of existing transfusion literature confirms that individual burn centres trans-
in burn patients fuse at a lower trigger than in previous years.
Physiologic transfusion trigger The quest for a universal transfusion trigger should be abandoned. All RBC transfusions
should be tailored to the patient’s blood volume status, acuity of blood loss and ongoing
perfusion requirements.
We also focus on the prevention of unnecessary transfusion as well as techniques to
minimise blood loss, optimise red cell production and determine when transfusion is
appropriate.
# 2011 Elsevier Ltd and ISBI. All rights reserved.
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 743
2. Definition of anaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 743
3. Review of the literature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 743
4. Management: treatment and prevention of anaemia in the burn patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 744
4.1. When to transfuse? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 744
* Corresponding author. Tel.: +39 3204748193.
E-mail address: giuseppecuringa@venuslab.it (G. Curinga).
0305-4179/$36.00 # 2011 Elsevier Ltd and ISBI. All rights reserved.
doi:10.1016/j.burns.2011.01.016

2. burns 37 (2011) 742–752 743
4.2. Strategy to minimise blood loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 746
4.2.1. Blood conservation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 746
4.2.2. Estimation of blood loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 746
4.2.3. Reduction of blood loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 746
4.2.4. Optimisation of red cell production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 747
5. Adverse events associated with RBC transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 747
5.1. Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 747
5.2. Immunosuppression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 748
5.3. Transfusion-related acute lung injury (TRALI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 748
5.4. Transfusion errors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 748
6. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 748
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 749
1. Introduction shown that a restrictive red blood cell (RBC) transfusion policy
reduces complications.
A severe burn will significantly alter haematologic param- While a consensus on when to transfuse has been elusive
eters. This manifests as anaemia, which is commonly found in even until today, an increasing number of authors are agreeing
patients with greater than 10% total body surface area (TBSA) that less blood products should be transfused.
involvement [1–3]. The aetiology of anaemia in severe burns is Current transfusion protocols use a specific level of
multifactorial (Table 1). This is important because blood haemoglobin or haematocrit, which dictates when to trans-
transfusions have potential complications and collateral fuse PRBCs. This level is known as the trigger. There is no one
effects [4–6]. Despite the potential complications, blood ‘common trigger’ as values range from a 6 g dlÀ1 to 8 g dlÀ1 of
transfusion remains common, with approximately 12 million haemoglobin.
units of packed red blood cells (PRBCs) transfused each year in The aim of this article is to analyse the current status of RBC
the United States [7]. transfusions in the treatment of burn patients and address
This practice can have an immunomodulatory effect, by new information regarding burn and blood transfusion
decreasing cell-mediated immunity, increasing a proinflam- management. We also focus on the prevention of unnecessary
matory state, augmenting the risk of infection, increasing the transfusion as well as techniques to minimise blood loss,
risk of acute respiratory distress syndrome (ARDS) and optimise red cell production and determine when transfusion
ultimately causing multi-system organ failure (MOF) [8–10]. is appropriate.
Historically, blood is transfused when the haemoglobin
(Hb) level falls below 10 g dlÀ1 or the haematocrit (Htc) is less
than 30%. Maintaining haemoglobin and haematocrit levels 2. Definition of anaemia
with blood transfusion has been the gold standard for
treatment of anaemia for many years [11–17]. Multicentre The World Health Organization (WHO) defines anaemia as a
trials have shown that a restricted blood transfusion protocol haemoglobin value of <13 g dlÀ1 (haematocrit <39%) for an
is associated with a lower in-hospital mortality rate, cardiac adult male and <12 g dlÀ1 (haematocrit <36%) for an adult
complication rate and organ dysfunction compared with a non-pregnant female [20]. The haemoglobin concentration or
liberal transfusion group [8,11,13,14]. Similar results were haematocrit used to define anaemia and classify its severity in
shown in a cohort of burn patients and in paediatric burn critical care patients is less clear. While this may be a
patients [18,19]. Over the past few years, several studies have convenient and useful parameter in the non-injured, euvo-
lemic patient, it is not a reliable indicator of anaemia in trauma
or burn patients. Furthermore, the restrictive strategy (to
maintain the haemoglobin at 7–9 g dlÀ1) of red-cell transfusion
Table 1 – Causes of anaemia in burn patients. is at least as effective as and possibly superior to a liberal
transfusion strategy (to maintain haemoglobin at 10–12 g dlÀ1)
# Production
Delayed decreased erythropoiesis
in critically ill patients [8,11,13,14,21,22].
" Destruction Anaemia is also defined as a decrease in the oxygen-carrying
Thermal injury capacity of blood. The oxygen-carrying capacity of blood is a
Injury related coagulopathy function of the total volume of circulating RBCs, so anaemia can
Hypotermic coagulopathy be defined as a decrease in the total cell volume [23].
Thrombocytopenia
DIC
" External loss 3. Review of the literature
Wounds
Iatrogenic
Initial excision, multiple One of the cornerstones of the management of a severe burn
debridements involves resuscitation to restore an adequate vascular volume
Donor site bleeding for perfusion [24]. An acceptable haemoglobin concentration
Phlebotomy/lab draw
is the degree of anaemia that balances the risk of red-cell

3. 744 burns 37 (2011) 742–752
transfusion with that of low haemoglobin concentration. An patients) and reported that patients suffering from a 60% TBSA
optimal transfusion protocol has not yet been described. with inhalation injury had an 8% risk of developing sepsis in
There is currently little debate about the need for the low group (PRBCs received < 20 U), which increased to 58%
restricting blood transfusions. Blood products remain a vital in the high group (PRBCs received > 20 U). This directly
resource and its judicious use in trauma and burn patients has correlated the use of high amounts of blood products with
to be applied. an increased likelihood to develop sepsis, thus showing that
With the goal of decreasing transfusion-associated morbidi- PRBC transfusion causes an immunocompromising state.
ty and mortality, some researchers have focused on safely RBCs can be minimised using a clear protocol of haemos-
reducing the amount of blood transfused [25,26]. Mann et al. [27] tasis. O’Mara et al. [36] analysed two 3-year periods before and
compared the quantity of blood given to burn patients in 1980 after institution of a protocol to reduce blood loss and blood
(haematocrit greater than 30%) with that given in 1990. In 1980, use. In early period, methods of excision and grafting were
133 ml blood was transfused per patient per percent burn more variable. In the later period, a protocol to reduce blood
during acute hospitalisation, compared with 20 ml in 1990. loss was implemented. All patients were transfused for a
There were no instances of myocardial infarction or congestive haemoglobin below 8.0 g dlÀ1. Overall unit transfused per
heart failure related to the maintenance of lower haematocrits. operation decreased from 1.56 to 1.25 units after instituting
In 1994, Sittig and Deitch [28] compared the results of a the protocol. They concluded that when using a clear protocol
selective transfusion policy in which 14 patients were of haemostasis, technique and transfusion trigger, it is
transfused when their haemoglobin levels went below 6 g dlÀ1 possible to decrease overall use of blood for burn patients,
1 versus previous routine transfusion policy in which the and in particular to eliminate transfusion requirements in a
haemoglobin levels of 38 patients were routinely maintained great part of the burn population.
at 10 g dlÀ1. No differences were found in the length of hospital Another protocol was proposed by Losee et al. [37] for
stay. The patients treated with the liberal strategy received 3.5 treating the paediatric burn population. Using electrocautery
times as much blood as their restrictive counterparts. They for the debridement of full-thickness burns, and dermabra-
proposed that prophylactic transfusions to increase the sion for the partial thickness burns, treated immediately with
oxygen-carrying capacity of blood are not indicated in epinephrine solution, they showed that intra-operative blood
asymptomatic anaemic patients (without coronary artery loss requiring transfusion can be minimised or eliminated.
disease) with haemoglobin levels greater than 6 g dlÀ1. Table 2 summarises the literature on burn patients on RBC
Palmieri et al., in a multicentre study of transfusion among transfusion.
666 patients in 21 North American Burn Centers with 20% or
greater TBSA showed that the number of transfusions
received was associated with mortality and infectious epi- 4. Management: treatment and prevention of
sodes in patients with major burns even after factoring for anaemia in the burn patient
indices of burn severity. The risk of infection was increased by
13% per unit transfused [18]. Criteria for the optimal management of anaemia in trauma
The haemoglobin transfusion threshold was reported by and burn patients are poorly defined. The management of
the majority of physicians. Mean haemoglobin transfusion anaemia in burn patients must follow a two-pronged
threshold was 8.1 g dlÀ1. The most frequent reasons for approach: treatment and prevention.
transfusion were ongoing blood loss (22%), anaemia (20%),
hypoxia (13%) and cardiac disease (12%). Age, TBSA burn, the 4.1. When to transfuse?
need for further operative intervention, the presence of ARDS,
sepsis and evidence of cardiac ischaemia were also deemed The concept of an appropriate ‘transfusion trigger’ for RBC
important [29]. transfusion in burns is not well described in the literature. As
Kwan et al. [30] in a retrospective study, evaluated the shown in Table 1, the trigger most often cited is haemoglobin
effects of a restrictive transfusion strategy in two group of or haematocrit. The reason for this may be that there is no one
patients with burns >20%. The restrictive group (REST group discrete ‘transfusion trigger’.
135 patients, Hb transfusion trigger 7.0 g dlÀ1) received fewer Since the late 1980s, haemoglobin and haematocrit levels of
transfusion than the liberal group (LIB group 37 patients, Hb 8–10 g dlÀ1 and 32–35%, respectively, have generally been
transfusion trigger 9.2 g dlÀ1) and appeared to have signifi- accepted as being adequate in most patients. More recently,
cantly better organ function. There were no differences this threshold has been lowered even further to 7 g dlÀ1 in
between the groups in the incidence of cardiac disease. response to compelling large trials conducted in medical and
A retrospective study conducted on 1615 patients admitted surgical intensive care unit (ICU) patients. The Transfusion
to the burn unit showed that patients with small burns or no Requirements in Critical Care (TRICC) trial is the most cited
comorbidities were also at risk of transfusion, especially if clinical trial evaluating RBC transfusion threshold. The TRICC
they required debridement and grafting. This study also investigators allocated 838 critically ill patients who had
reaffirmed that patients with comorbidities, who required baseline haemoglobin concentrations of less than 9 g dlÀ1 to
transfusions, were at a higher risk of mortality [31]. two transfusion groups. The ‘liberal’ strategy allowed transfu-
Studies conducted on animal burn models demonstrate sions if the haemoglobin concentration decreased below
that blood transfusion depresses immune function and 10 g dlÀ1, with a target haemoglobin concentration of 10–
increases the risks of infectious complication [32–35]. Jeschke 12 g dlÀ1. The ‘restrictive’ strategy allowed transfusions only if
et al. [19] performed a retrospective study (252 paediatric the haemoglobin concentration decreased below 7 g dlÀ1, and

4. burns 37 (2011) 742–752 745
Table 2 – Red blood cells transfusion in burn patients: review of the literature.
Author Pt Transfusion trigger Study
Graves et al. [5] 594 A cross-tabulation of predicted mortality, no of transfusions, and
infectious complications revealed a significant positive correlation
between transfusion number and infectious
complications
Mann et al. [27] 79 Guidelines suggested: Comparative study between two group (41 patients in 1980,
38 patients in 1990)
– Healthy Pt who will undergo a 1980 group received 1321 Æ 154 ml
single operation 15% < Ht < 20%
– Healthy with multiple operations 1990 group 207 Æ 62 ml
Ht < 25%
– Critically ill patient or with limited
cardiovascular reserve Ht < 30%
Sittig et al. [28] 14 Hb < 6 g/dl Retrospective comparative study. The length of hospital stay
was similar
Prophylactic transfusion to increase oxygen carrying capacity
of blood are not indicated in asymptomatic anaemic patients
38 Hb > 9.5–10 g/dl
Palmieri et al. [29] Hb 8.1 g/dl, mean transfusion Multicentre survey of North American Centers
threshold
Criswell et al. [25] 107 1.78 U PRBCs were transfused Retrospective chart review with TBSA > 20%, to evaluate
for 1000 cm2 as the estimation of excision area can predict transfusion need
excised to maintain 25%
< Ht < 31%
O’Mara et al. [36] Hb < 8 g/dl Two 3-year time periods were analyzed, before and after
implementation of intraoperative protocol to reduce blood loss
Kwan et al. [30] 37 Liberal group Retrospective comparison of adults with >20% TBSA
Hb 9.2 g/dl Restrictive group appeared to have significantly better
organ function
135 Restrictive group
Hb 7 g/dl
Palmieri et al. [18] 666 Mean Hb 9.2 g/dl Multicentre retrospective cohort analysis; TBSA > 20%; infections
per patient increased with each unit of blood transfused
Palmieri et al. [26] 584 Traditional policy Retrospective study on paediatric population
Hb < 10 g/dl Twice number of pulmonary complications in traditional group
556 Restrictive group Restrictive transfusion policy in children decrease in
transfusion-related costs
Hb < 7 g/dl
Jeschke et al. [19] 252 Hb < 8 g/dl Retrospective, cohort study in paediatric burn population. Patients
with TBSA > 60% and concomitant inhalation injury are more likely
to develop sepsis if they are given high amount of blood
Boral et al. [31] 1615 – Hypovolemic shock in Retrospective review. Patients with small burns or no comorbidities
currently bleeding patients were also at risk of transfusion, especially if they required
debridment and grafting. Patients with comorbidities,
who required transfusions, were at higher risk for mortality
– Preoperative Hb
< 8 g/dl or Ht < 24%
Pt, number of patients; Hb, haemoglobin; Ht, haematocrit.
the target haemoglobin concentration was 7–9 g dlÀ1 [38]. The and that purported cardiac risks with anaemia have been
30-day mortality rates were similar for these groups (81% with overemphasised. Although cardiovascular disease could in-
the restrictive strategy and 77% with the liberal strategy). crease the risk of anaemia because of restricted oxygen
In 2007, results were published on a trial in children in the delivery to the myocardium [42], a more recent article showed
ICU. The authors compared a 7 g dlÀ1 threshold on the rate of that a restrictive RBC transfusion strategy seemed safe in most
multiple-organ dysfunctions with a 9.5 g dlÀ1 threshold [39]. critically ill patients with cardiovascular disease, with the
The TRICC trial outcomes were very similar in patients possible exception of patients with acute myocardial infarcts
allocated to liberal transfusion threshold and restrictive and unstable angina [43].
transfusion and were associated with a 44% drop in the Regardless, an important consideration for any decision to
number of RBC transfusions. give blood is the acuity of the blood loss. Patients with acute,
These combined findings, showed in critically ill patients massive haemorrhage show signs of haemodynamic instabil-
and in-burn patients, suggest that many patients are receiving ity early in their presentation. The clinical picture depends on
more RBCs than is necessary. the amount of blood loss. Loss of about 20% of blood volume
As reported by several authors in the recent literature elicits compensatory increases in heart rate and cardiac
[40,41] transfusion for a set transfusion trigger is ill-advised, output, as well as a rise in vasoactive hormones, redistribution

5. 746 burns 37 (2011) 742–752
of blood flow and influx of extravascular fluid to the 4.2. Strategy to minimise blood loss
intravascular compartment [44–47].
Therefore, with anaemia, oxygen delivery is maintained 4.2.1. Blood conservation
through a series of complex interactions and compensatory In attempts to lower the rate of complications reported with
mechanisms. the use of PRBCs in burn patients, some authors examined the
Blood volume evaluation should be estimated to restore use of autologous blood transfusion [63,64].
adequately the circulatory system, preventing complications Samuelsson et al. [63] used auto transfusion in four cases
of inadequate or overload fluid resuscitation, which can ranging from 8% to 30% TBSA. The study was limited by and
aggravate the anaemic status. abandoned due to the high risk of bacterial contamination of
Clinical signs at the bedside have been proven insensitive blood collected intra-operatively.
and nonspecific markers of hypoxia; blood pressure, heart Imai et al., in 2007 [64], reported treatment with periopera-
rate, changes in mental status and urine output, suffer tive haemodilutional autologous blood transfusion of seven
confounding factors in their interpretation, and may not cases in burn patients. Patients ranged from 33 to 79 years of
accurately predict the clinical status [48,49]. age and TBSA ranged from 5.5% to 20%. One patient required
Base deficit, a surrogate marker for lactic acidosis, reflects allogenic blood transfusion. The main disadvantage of this
failing tissue oxygenation, is easily measured but is confounded method was the limitation of the amount of blood that could
by a range of conditions as well as resuscitative efforts [48]. The be withdrawn and transfused. They concluded that this
measurement of serum lactate has also been proposed as a test technique avoids or minimises the risks of allogenic transfu-
to estimate and monitor the extent of bleeding and shock [50]. In sion in burn surgery involving less than 20% TBSA.
fact, the clearance of serum lactate to normal levels within 24 h
is a powerful predictor of mortality in the critically ill patient. 4.2.2. Estimation of blood loss
The amount of lactate produced by anaerobic glycolysis is an In the burn unit, it is essential to be able to estimate the
indirect marker of oxygen debt, tissue hypoperfusion and the probable blood requirements of surgery prior to burns
severity of haemorrhagic shock [51–54]. excision. This can reduce wasting of blood products.
Therefore, serum lactate adds another variable to decide Several authors have proposed different and various
when to transfuse. systems to estimate blood loss during the surgery [65–69].
Mixed venous oxygen saturation should be the best guide to It is commonly estimated that 117 ml of the blood volume is
need transfusion, but is limited by the need for invasive lost for every 1% of body surface area excised and grafted [66].
monitoring using a pulmonary artery catheter or right atrial Desai et al., in 1990, calculated that blood losses in burns of
central line [55,56]. Central venous oxygen saturation, a more more than 30% TBSA were 0.75 ml cmÀ2 between 2 and 16 days
easily measured approximation of mixed venous saturation, after the burn [69].
and currently a marker used to guide early goal-directed
therapy in the adult septic shock patients, can be misleading 4.2.3. Reduction of blood loss
[56]. A significant amount of blood can be lost with repeated
Tissue-specific markers of hypoxia are ST segment changes phlebotomy in the ICU. A policy of obtaining laboratory results
on electrocardiogram and P300 latency on electroencephalo- only when clinically indicated should be followed. This issue
gram. may be addressed by drawing a smaller sample using paediatric
Myocardial insufficient tissue oxygenation can be detected collection tubes. Another way of reducing blood loss from
by continuous five-lead ECG monitoring as new ST-depression laboratory draws is by sending a single sample for multiple tests
>0.1 mV or as new ST-segment elevation >0.2 mV for more (batching of requests for laboratory tests) [70]. Early wound
than a minute [57]. Although authors reported that ST- excision minimises the loss of blood because hyperaemia has not
segment change is a physiological transfusion trigger [58,59] yet occurred [69]. Blood loss in large burns (more than 30% TBSA)
it cannot be used to signal the need for transfusion. There are significantly decreased when surgical excision was performed
no evidence literature data to support these findings. within the first 24 h after injury compared to those performed
Current monitoring techniques that assess the heart for between the second and sixteenth days after injury [69].
development of myocardial ischaemia are electrocardiogram Based on these findings, early wound excision may
and transoesophageal echocardiography. Weiskopf et al. [60] decrease the loss of blood. Burn wound excision to fascia,
have opened the ‘window to the brain’ with respect to when performed, has been shown to decrease blood loss,
monitoring the adequacy of cerebral oxygenation during acute although tangential excision can result in better cosmetic and
anaemia. The P300 latency above a certain threshold might functional outcomes [71].
serve as a monitor of inadequate cerebral oxygenation and as an New intra-operative techniques and approaches have been
organ-specific transfusion trigger in the future [49,61]. Blood developed to reduce blood loss and limit the need for allogenic
transfusion should be based on a comprehensive assessment of blood transfusions. These approaches include the use of
the patient, including vital signs, estimation of the amount of surgical instruments that minimise bleeding, and minimally
blood loss and evaluation of blood volume, as well as clinical invasive surgical procedures [72].
and laboratory evaluation of end-organ perfusion. Several techniques that use warm saline-soaked pads,
The conclusion of the National Institutes of Health tourniquet and topical epinephrine (1:100,000–1:200,000), have
Consensus Conference remains the extremely valid one today: been described to minimise blood loss during burn excision
no single measurement can replace good clinical judgement [73–77]. Subdermal clysis with epinephrine can be used almost
concerning the need for red-cell transfusion [62]. everywhere except the extremities.

6. burns 37 (2011) 742–752 747
Upper and lower extremity use of a tourniquet allows for incidence of red-cell transfusion among critically ill patients,
bloodless debridement. This practice requires close attention to but it may reduce mortality in patients with trauma. At day 29,
detail and experience to recognise adequacy of debridement. the increase in the haemoglobin concentration from baseline
Even on more difficult sites like the torso and on the graft was greater in the epoetin alfa group than in the placebo
donor sites, blood loss can be reduced dramatically with the group. Treatment with epoetin alfa was associated with an
use of a haemostatic agent (such as recombinant thrombin) increase in the incidence of thrombotic events.
[78–80]. All fascial excisions should be performed with Contrarily, two previous trials involving critically ill
electrocautery such that perforating vessels can be immedi- patients showed that treatment with epoetin alfa reduced
ately coagulated [81]. the number of red-cell transfusions and raised the haemo-
It is a crucial and often overlooked point to maintain globin concentration [96,97].
euthermia, principally through operating room heating. These A randomised, double-blind, placebo-controlled, multi-
patients are particularly susceptible to intra-operative hypo- centre trial in anaemic critically ill patients demonstrated a
thermia as massive evaporative heat loss can occur through 29-day survival benefit in the trauma subgroup receiving
their wounds. The heat loss rate is related to TBSA and the epoetin alfa [98].
temperature gradient between body and the environment. It has also been reported that EPO administration exerts
The induction of anaesthesia results in relative ablation of protective effects on apoptosis induced by ischaemic reperfu-
thermoregulatory mechanism and puts the patient at further sion injury, in the brain, spinal cord, skeletal muscle and the
risk for developing hypothermia. Actions such as maintaining myocardium [99–103].
higher ambient air temperature, covering extremities and
head, applying warm blankets, utilising radiant heaters and
forced air warming gases are usually effective in maintaining 5. Adverse events associated with RBC
core temperature if applied aggressively. Body temperature transfusion
should be maintained at or above 37 8C in burn patients.
Hypothermia is a contributing factor to platelet and coagula- The transfusion of blood and blood products is associated with
tion factor dysfunction; patients should be aggressively several well-documented adverse effects, which can be divided
warmed during surgery [82]. into transfusion-associated infections, immunological risks,
By keeping the patient euthermic, we can minimise the metabolic complications and transfusion errors (Table 3) [84].
need to transfuse blood products.
Optimal timing and quantity of RBCs, plasma and platelets 5.1. Infections
in the treatment of hypothermia is unclear. It is unclear if
current component therapy is equivalent to whole blood Estimated risks of transfusion–transmitted disease for immu-
transfusion. In fact, data from the current war in Iraq and nocompetent patients are lower than ever before. Since 1999,
Afghanistan suggest otherwise [83]. the risks have been declining substantially with the imple-
Timely use of FFP, prevention of hypothermia and correction mentation of NAT (nucleid acid testing), which has shortened
of acidosis through PRBC resuscitation are important strategies infectious periods and dramatically reduced the current
in preventing coagulopathy. Transfusing FFP and PRBC in an 1:1 estimated risks of post-transfusion hepatitis C virus (HCV)
strategy may prevent some of the coagulopathic effects [84]. and HIV. Current estimates of the risk per unit of blood are
approximately 1:1,900,000 for HIV and 1:1,600,000 for HCV
4.2.4. Optimisation of red cell production [104–106]. In contrast to the reduction of infection for HIV and
To promote haematopoiesis, supplementation with vitamin HCV, the risk of hepatitis B virus remains approximately
B12 and folate should be considered as part of routine
perioperative care of burn patients. Iron supplementation has
been proposed as adjuvant treatment [85,86]. However, there is
Table 3 – Estimated risks in transfusions per unit
experimental evidence that iron therapy in the critically ill
transfused.
patient may enhance the risk of infections and the production of
free radicals [87,88]. Iron is required for microbial growth. Adverse effect Estimated risk
Inflammatory cytokines increase the synthesis of ferritin, Urticaria or other cutaneous reaction 1 in 33–100
which may serve as a protective function by binding iron and Febrile reaction 1 in 18–300
reducing its availability for microbial growth [89]. Iron appears TRALI 1 in 5000
Haemolytic reaction 1 in 6000–70,000
to stimulate bacterial virulence, and impair cellular immunity
Mistransfusion 1 in 14,000–18,000
via inhibition of phagocytosis by neutrophils [90]. Before Anaphylaxis 1 in 20,000–50,000
routinely supplementing anaemic burn patients with iron, we Bacterial infections 1 in 5,000,000
need additional studies to clarify the risk of infection. HTLV I and II 1 in 641,000
Recombinant human erythropoietin (r-HuEPO) in acutely Hepatitis B 1 in 50,000–150,000
burned patients did not prevent the development of postburn Fatal haemolysis 1 in 1,000,000
Hepatitis C 1 in 1,600,000
anaemia or decrease transfusion requirements. Several
HIV 1 in 1,900,000
studies reported a statistically significant increase of reticu-
locytosis, but no change in the haemoglobin, haematocrit or TRALI, transfusion-related acute lung injury; HTLV, human T-
lymphotropic virus; HIV, human immunodeficiency virus (Ref.
RBC count [90–94]. In a prospective randomised placebo-
[84]).
controlled trial [95], the use of epoetin alfa does not reduce the

7. 748 burns 37 (2011) 742–752
1:50,000–1:150,000 in the Western countries [106]. Bacterial 5.4. Transfusion errors
contamination of red blood occurs 1:500,000. The most
commonly implicated organism in bacterial contamination Human errors are responsible for more than half of all
is Yersinia enterocolitica [106]. transfusion-related fatalities [115]. They have been estimated
to be one in 14,000 units in the United States, and one in 18,000
5.2. Immunosuppression in the United Kingdom [116]. Mistransfusion, defined as an
ABO-incompatible reaction owing to an error, is a leading
There is also evidence that red-cell transfusions are associated cause of morbidity and mortality from transfusion because it
with an immunomodulatory effect. Transfusion-related can lead to a major haemolytic reaction. Non-ABO acute
immunomodulation has been noted to be clinically important haemolytic reactions and febrile nonhaemolytic reactions are
in renal transplantation patients and in women with multiple much more common but are generally mild and self-limiting
miscarriages [107,108]. in nature. Mistransfusion may lead to an acute haemolytic
Allogenic blood transfusions have also been associated reaction, which is characterised by fever, chills, pain, nausea,
with a reduction of cell-mediated immunity, increased rates of vomiting, hypotension, tachycardia, renal failure and dissem-
postoperative infection and early recurrences of malignancy inated intravascular coagulation [113].
[109–111].
5.3. Transfusion-related acute lung injury (TRALI) 6. Conclusion
Presenting signs and symptoms of TRALI include dyspnoea, Blood transfusion is not a benign therapy. Patients who receive
hypotension and fever, caused by noncardiogenic pulmonary PRBCs have an increased incidence of complications. The
oedema. Symptoms begin during, or shortly after transfusion, optimal transfusion strategy for burn patients has not yet been
typically within 4 h after receiving blood. definitively determined, and additional clinical research is
The mechanism of transfusion-related acute lung injury needed.
(TRALI) is not completely understood, but it appears to involve The most important physiologic consequence of anaemia
localisation of antibody-coated leucocytes to pulmonary is a reduction in the oxygen-carrying capacity of blood. These
vasculature resulting in increased permeability and oedema changes are accompanied by increased cardiac output, a shift
[112]. Its estimated frequency is approximately 1 in 5000 of the oxyhaemoglobin dissociation curve and increased
transfusions, and it is fatal in 5–10% of cases [113]. The actual oxygen extraction.
reported mortalities underscores the fact that this complica- Anaemia is well tolerated as long as intravascular volume
tion evades clinical recognition, it may be responsible for more is maintained. Blood volume evaluation should be evaluated
serious adverse events and fatalities than are reported [114]. and corrected based on the length and severity of the anaemia.
[()TD$FIG]
Fig. 1 – Limit and prevent unnecessary transfusion in burn patient reduce the RBC exposure: uniform application of blood
conserving techniques, optimization of red blood cell production, and an adequate and ‘‘physiologic’’ evaluation of the
anaemic status of the patient. *R-HuEPO = recombinant human erythropoietin.

8. burns 37 (2011) 742–752 749
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