b u r n s 3 7 ( 2 0 1 1 ) 7 4 2 – 7 5 2

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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, USAbCivico and Benfratelli Hospital Burn Center, Palermo, Italyc Johns Hopkins University School of Medicine, Baltimore, MD, USAdSwedish Medical Center, Denver, CO, USA

a r t i c l e i n f o

Article history:

Accepted 20 January 2011

Keywords:

Blood transfusion

Blood in burn

Blood management

Blood loss

Anemia in burn patients

Unnecessary transfusion

Appropriate transfusion

in burn population

Red blood cells transfusion

in burn patients

Physiologic transfusion trigger

s u m m a r y

A severe burn will significantly alter haematologic parameters, and manifest as anaemia,

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

been the gold standard for the treatment of anaemia for many years.

While there is no consensus on when to transfuse, an increasing number of authors have

expressed that less blood products should be transfused.

Current transfusion protocols use a specific level of haemoglobin or haematocrit, which

dictates when to transfuse packed red blood cells (PRBCs). This level is known as the trigger.

There is no one ‘common trigger’ as values range from 6 g dl�1 to 8 g dl�1 of haemoglobin.

The aim of this study was to analyse the current status of red blood cell (RBC) transfu-

sions in the treatment of burn patients, and address new information regarding burn and

blood transfusion management.

Analysis of existing transfusion literature confirms that individual burn centres trans-

fuse at a lower trigger than in previous years.

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

b u r n s 3 7 ( 2 0 1 1 ) 7 4 2 – 7 5 2 743

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

A severe burn will significantly alter haematologic param-

eters. This manifests as anaemia, which is commonly found in

patients with greater than 10% total body surface area (TBSA)

involvement [1–3]. The aetiology of anaemia in severe burns is

multifactorial (Table 1). This is important because blood

transfusions have potential complications and collateral

effects [4–6]. Despite the potential complications, blood

transfusion remains common, with approximately 12 million

units of packed red blood cells (PRBCs) transfused each year in

the United States [7].

This practice can have an immunomodulatory effect, by

decreasing cell-mediated immunity, increasing a proinflam-

matory state, augmenting the risk of infection, increasing the

risk of acute respiratory distress syndrome (ARDS) and

ultimately causing multi-system organ failure (MOF) [8–10].

Historically, blood is transfused when the haemoglobin

(Hb) level falls below 10 g dl�1 or the haematocrit (Htc) is less

than 30%. Maintaining haemoglobin and haematocrit levels

with blood transfusion has been the gold standard for

treatment of anaemia for many years [11–17]. Multicentre

trials have shown that a restricted blood transfusion protocol

is associated with a lower in-hospital mortality rate, cardiac

complication rate and organ dysfunction compared with a

liberal transfusion group [8,11,13,14]. Similar results were

shown in a cohort of burn patients and in paediatric burn

patients [18,19]. Over the past few years, several studies have

Table 1 – Causes of anaemia in burn patients.

# Production

Delayed decreased erythropoiesis

" Destruction

Thermal injury

Injury related coagulopathy

Hypotermic coagulopathy

Thrombocytopenia

DIC

" External loss

Wounds

Iatrogenic

Initial excision, multiple

debridements

Donor site bleeding

Phlebotomy/lab draw

shown that a restrictive red blood cell (RBC) transfusion policy

reduces complications.

While a consensus on when to transfuse has been elusive

even until today, an increasing number of authors are agreeing

that less blood products should be transfused.

Current transfusion protocols use a specific level of

haemoglobin or haematocrit, which dictates when to trans-

fuse PRBCs. This level is known as the trigger. There is no one

‘common trigger’ as values range from a 6 g dl�1 to 8 g dl�1 of

haemoglobin.

The aim of this article is to analyse the current status of RBC

transfusions in the treatment of burn patients and address

new information regarding burn and blood transfusion

management. 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.

2. Definition of anaemia

The World Health Organization (WHO) defines anaemia as a

haemoglobin value of <13 g dl�1 (haematocrit <39%) for an

adult male and <12 g dl�1 (haematocrit <36%) for an adult

non-pregnant female [20]. The haemoglobin concentration or

haematocrit used to define anaemia and classify its severity in

critical care patients is less clear. While this may be a

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 dl�1) of red-cell transfusion

is at least as effective as and possibly superior to a liberal

transfusion strategy (to maintain haemoglobin at 10–12 g dl�1)

in critically ill patients [8,11,13,14,21,22].

Anaemia is also defined as a decrease in the oxygen-carrying

capacity of blood. The oxygen-carrying capacity of blood is a

function of the total volume of circulating RBCs, so anaemia can

be defined as a decrease in the total cell volume [23].

3. Review of the literature

One of the cornerstones of the management of a severe burn

involves resuscitation to restore an adequate vascular volume

for perfusion [24]. An acceptable haemoglobin concentration

is the degree of anaemia that balances the risk of red-cell

b u r n s 3 7 ( 2 0 1 1 ) 7 4 2 – 7 5 2744

transfusion with that of low haemoglobin concentration. An

optimal transfusion protocol has not yet been described.

There is currently little debate about the need for

restricting blood transfusions. Blood products remain a vital

resource and its judicious use in trauma and burn patients has

to be applied.

With the goal of decreasing transfusion-associated morbidi-

ty and mortality, some researchers have focused on safely

reducing the amount of blood transfused [25,26]. Mann et al. [27]

compared the quantity of blood given to burn patients in 1980

(haematocrit greater than 30%) with that given in 1990. In 1980,

133 ml blood was transfused per patient per percent burn

during acute hospitalisation, compared with 20 ml in 1990.

There were no instances of myocardial infarction or congestive

heart failure related to the maintenance of lower haematocrits.

In 1994, Sittig and Deitch [28] compared the results of a

selective transfusion policy in which 14 patients were

transfused when their haemoglobin levels went below 6 g dl�1

1 versus previous routine transfusion policy in which the

haemoglobin levels of 38 patients were routinely maintained

at 10 g dl�1. No differences were found in the length of hospital

stay. The patients treated with the liberal strategy received 3.5

times as much blood as their restrictive counterparts. They

proposed that prophylactic transfusions to increase the

oxygen-carrying capacity of blood are not indicated in

asymptomatic anaemic patients (without coronary artery

disease) with haemoglobin levels greater than 6 g dl�1.

Palmieri et al., in a multicentre study of transfusion among

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-

sodes in patients with major burns even after factoring for

indices of burn severity. The risk of infection was increased by

13% per unit transfused [18].

The haemoglobin transfusion threshold was reported by

the majority of physicians. Mean haemoglobin transfusion

threshold was 8.1 g dl�1. The most frequent reasons for

transfusion were ongoing blood loss (22%), anaemia (20%),

hypoxia (13%) and cardiac disease (12%). Age, TBSA burn, the

need for further operative intervention, the presence of ARDS,

sepsis and evidence of cardiac ischaemia were also deemed

important [29].

Kwan et al. [30] in a retrospective study, evaluated the

effects of a restrictive transfusion strategy in two group of

patients with burns >20%. The restrictive group (REST group

135 patients, Hb transfusion trigger 7.0 g dl�1) received fewer

transfusion than the liberal group (LIB group 37 patients, Hb

transfusion trigger 9.2 g dl�1) and appeared to have signifi-

cantly better organ function. There were no differences

between the groups in the incidence of cardiac disease.

A retrospective study conducted on 1615 patients admitted

to the burn unit showed that patients with small burns or no

comorbidities were also at risk of transfusion, especially if

they required debridement and grafting. This study also

reaffirmed that patients with comorbidities, who required

transfusions, were at a higher risk of mortality [31].

Studies conducted on animal burn models demonstrate

that blood transfusion depresses immune function and

increases the risks of infectious complication [32–35]. Jeschke

et al. [19] performed a retrospective study (252 paediatric

patients) and reported that patients suffering from a 60% TBSA

with inhalation injury had an 8% risk of developing sepsis in

the low group (PRBCs received < 20 U), which increased to 58%

in the high group (PRBCs received > 20 U). This directly

correlated the use of high amounts of blood products with

an increased likelihood to develop sepsis, thus showing that

PRBC transfusion causes an immunocompromising state.

RBCs can be minimised using a clear protocol of haemos-

tasis. O’Mara et al. [36] analysed two 3-year periods before and

after institution of a protocol to reduce blood loss and blood

use. In early period, methods of excision and grafting were

more variable. In the later period, a protocol to reduce blood

loss was implemented. All patients were transfused for a

haemoglobin below 8.0 g dl�1. Overall unit transfused per

operation decreased from 1.56 to 1.25 units after instituting

the protocol. They concluded that when using a clear protocol

of haemostasis, technique and transfusion trigger, it is

possible to decrease overall use of blood for burn patients,

and in particular to eliminate transfusion requirements in a

great part of the burn population.

Another protocol was proposed by Losee et al. [37] for

treating the paediatric burn population. Using electrocautery

for the debridement of full-thickness burns, and dermabra-

sion for the partial thickness burns, treated immediately with

epinephrine solution, they showed that intra-operative blood

loss requiring transfusion can be minimised or eliminated.

Table 2 summarises the literature on burn patients on RBC

transfusion.

4. Management: treatment and prevention ofanaemia in the burn patient

Criteria for the optimal management of anaemia in trauma

and burn patients are poorly defined. The management of

anaemia in burn patients must follow a two-pronged

approach: treatment and prevention.

4.1. When to transfuse?

The concept of an appropriate ‘transfusion trigger’ for RBC

transfusion in burns is not well described in the literature. As

shown in Table 1, the trigger most often cited is haemoglobin

or haematocrit. The reason for this may be that there is no one

discrete ‘transfusion trigger’.

Since the late 1980s, haemoglobin and haematocrit levels of

8–10 g dl�1 and 32–35%, respectively, have generally been

accepted as being adequate in most patients. More recently,

this threshold has been lowered even further to 7 g dl�1 in

response to compelling large trials conducted in medical and

surgical intensive care unit (ICU) patients. The Transfusion

Requirements in Critical Care (TRICC) trial is the most cited

clinical trial evaluating RBC transfusion threshold. The TRICC

investigators allocated 838 critically ill patients who had

baseline haemoglobin concentrations of less than 9 g dl�1 to

two transfusion groups. The ‘liberal’ strategy allowed transfu-

sions if the haemoglobin concentration decreased below

10 g dl�1, with a target haemoglobin concentration of 10–

12 g dl�1. The ‘restrictive’ strategy allowed transfusions only if

the haemoglobin concentration decreased below 7 g dl�1, and

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

single operation 15% < Ht < 20%

1980 group received 1321 � 154 ml

– Healthy with multiple operations

Ht < 25%

1990 group 207 � 62 ml

– 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

threshold

Multicentre survey of North American Centers

Criswell et al. [25] 107 1.78 U PRBCs were transfused

for 1000 cm2

excised to maintain 25%

< Ht < 31%

Retrospective chart review with TBSA > 20%, to evaluate

as the estimation of excision area can predict transfusion need

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

currently bleeding patients

Retrospective review. Patients with small burns or no comorbidities

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.

b u r n s 3 7 ( 2 0 1 1 ) 7 4 2 – 7 5 2 745

the target haemoglobin concentration was 7–9 g dl�1 [38]. The

30-day mortality rates were similar for these groups (81% with

the restrictive strategy and 77% with the liberal strategy).

In 2007, results were published on a trial in children in the

ICU. The authors compared a 7 g dl�1 threshold on the rate of

multiple-organ dysfunctions with a 9.5 g dl�1 threshold [39].

The TRICC trial outcomes were very similar in patients

allocated to liberal transfusion threshold and restrictive

transfusion and were associated with a 44% drop in the

number of RBC transfusions.

These combined findings, showed in critically ill patients

and in-burn patients, suggest that many patients are receiving

more RBCs than is necessary.

As reported by several authors in the recent literature

[40,41] transfusion for a set transfusion trigger is ill-advised,

and that purported cardiac risks with anaemia have been

overemphasised. Although cardiovascular disease could in-

crease the risk of anaemia because of restricted oxygen

delivery to the myocardium [42], a more recent article showed

that a restrictive RBC transfusion strategy seemed safe in most

critically ill patients with cardiovascular disease, with the

possible exception of patients with acute myocardial infarcts

and unstable angina [43].

Regardless, an important consideration for any decision to

give blood is the acuity of the blood loss. Patients with acute,

massive haemorrhage show signs of haemodynamic instabil-

ity early in their presentation. The clinical picture depends on

the amount of blood loss. Loss of about 20% of blood volume

elicits compensatory increases in heart rate and cardiac

output, as well as a rise in vasoactive hormones, redistribution

b u r n s 3 7 ( 2 0 1 1 ) 7 4 2 – 7 5 2746

of blood flow and influx of extravascular fluid to the

intravascular compartment [44–47].

Therefore, with anaemia, oxygen delivery is maintained

through a series of complex interactions and compensatory

mechanisms.

Blood volume evaluation should be estimated to restore

adequately the circulatory system, preventing complications

of inadequate or overload fluid resuscitation, which can

aggravate the anaemic status.

Clinical signs at the bedside have been proven insensitive

and nonspecific markers of hypoxia; blood pressure, heart

rate, changes in mental status and urine output, suffer

confounding factors in their interpretation, and may not

accurately predict the clinical status [48,49].

Base deficit, a surrogate marker for lactic acidosis, reflects

failing tissue oxygenation, is easily measured but is confounded

by a range of conditions as well as resuscitative efforts [48]. The

measurement of serum lactate has also been proposed as a test

toestimate and monitor the extent of bleeding and shock [50]. In

fact, the clearance of serum lactate to normal levels within 24 h

is a powerful predictor of mortality in the critically ill patient.

The amount of lactate produced by anaerobic glycolysis is an

indirect marker of oxygen debt, tissue hypoperfusion and the

severity of haemorrhagic shock [51–54].

Therefore, serum lactate adds another variable to decide

when to transfuse.

Mixed venous oxygen saturation should be the best guide to

need transfusion, but is limited by the need for invasive

monitoring using a pulmonary artery catheter or right atrial

central line [55,56]. Central venous oxygen saturation, a more

easily measured approximation of mixed venous saturation,

and currently a marker used to guide early goal-directed

therapy in the adult septic shock patients, can be misleading

[56].

Tissue-specific markers of hypoxia are ST segment changes

on electrocardiogram and P300 latency on electroencephalo-

gram.

Myocardial insufficient tissue oxygenation can be detected

by continuous five-lead ECG monitoring as new ST-depression

>0.1 mV or as new ST-segment elevation >0.2 mV for more

than a minute [57]. Although authors reported that ST-

segment change is a physiological transfusion trigger [58,59]

it cannot be used to signal the need for transfusion. There are

no evidence literature data to support these findings.

Current monitoring techniques that assess the heart for

development of myocardial ischaemia are electrocardiogram

and transoesophageal echocardiography. Weiskopf et al. [60]

have opened the ‘window to the brain’ with respect to

monitoring the adequacy of cerebral oxygenation during acute

anaemia. The P300 latency above a certain threshold might

serve as a monitorof inadequatecerebral oxygenation and as an

organ-specific transfusion trigger in the future [49,61]. Blood

transfusion should be based on a comprehensive assessment of

the patient, including vital signs, estimation of the amount of

blood loss and evaluation of blood volume, as well as clinical

and laboratory evaluation of end-organ perfusion.

The conclusion of the National Institutes of Health

Consensus Conference remains the extremely valid one today:

no single measurement can replace good clinical judgement

concerning the need for red-cell transfusion [62].

4.2. Strategy to minimise blood loss

4.2.1. Blood conservationIn attempts to lower the rate of complications reported with

the use of PRBCs in burn patients, some authors examined the

use of autologous blood transfusion [63,64].

Samuelsson et al. [63] used auto transfusion in four cases

ranging from 8% to 30% TBSA. The study was limited by and

abandoned due to the high risk of bacterial contamination of

blood collected intra-operatively.

Imai et al., in 2007 [64], reported treatment with periopera-

tive haemodilutional autologous blood transfusion of seven

cases in burn patients. Patients ranged from 33 to 79 years of

age and TBSA ranged from 5.5% to 20%. One patient required

allogenic blood transfusion. The main disadvantage of this

method was the limitation of the amount of blood that could

be withdrawn and transfused. They concluded that this

technique avoids or minimises the risks of allogenic transfu-

sion in burn surgery involving less than 20% TBSA.

4.2.2. Estimation of blood lossIn the burn unit, it is essential to be able to estimate the

probable blood requirements of surgery prior to burns

excision. This can reduce wasting of blood products.

Several authors have proposed different and various

systems to estimate blood loss during the surgery [65–69].

It is commonly estimated that 117 ml of the blood volume is

lost for every 1% of body surface area excised and grafted [66].

Desai et al., in 1990, calculated that blood losses in burns of

more than 30% TBSA were 0.75 ml cm�2 between 2 and 16 days

after the burn [69].

4.2.3. Reduction of blood lossA significant amount of blood can be lost with repeated

phlebotomy in the ICU. A policy of obtaining laboratory results

only when clinically indicated should be followed. This issue

may be addressed by drawing a smaller sample using paediatric

collection tubes. Another way of reducing blood loss from

laboratory draws is by sending a single sample for multiple tests

(batching of requests for laboratory tests) [70]. Early wound

excisionminimises the lossof bloodbecausehyperaemiahasnot

yet occurred [69]. Blood loss in large burns (more than 30% TBSA)

significantly decreased when surgical excision was performed

within the first 24 h after injury compared to those performed

between the second and sixteenth days after injury [69].

Based on these findings, early wound excision may

decrease the loss of blood. Burn wound excision to fascia,

when performed, has been shown to decrease blood loss,

although tangential excision can result in better cosmetic and

functional outcomes [71].

New intra-operative techniques and approaches have been

developed to reduce blood loss and limit the need for allogenic

blood transfusions. These approaches include the use of

surgical instruments that minimise bleeding, and minimally

invasive surgical procedures [72].

Several techniques that use warm saline-soaked pads,

tourniquet and topical epinephrine (1:100,000–1:200,000), have

been described to minimise blood loss during burn excision

[73–77]. Subdermal clysis with epinephrine can be used almost

everywhere except the extremities.

Table 3 – Estimated risks in transfusions per unittransfused.

Adverse effect Estimated risk

Urticaria or other cutaneous reaction 1 in 33–100

Febrile reaction 1 in 18–300

TRALI 1 in 5000

Haemolytic reaction 1 in 6000–70,000

Mistransfusion 1 in 14,000–18,000

Anaphylaxis 1 in 20,000–50,000

Bacterial infections 1 in 5,000,000

HTLV I and II 1 in 641,000

Hepatitis B 1 in 50,000–150,000

Fatal haemolysis 1 in 1,000,000

Hepatitis C 1 in 1,600,000

HIV 1 in 1,900,000

TRALI, transfusion-related acute lung injury; HTLV, human T-

lymphotropic virus; HIV, human immunodeficiency virus (Ref.

[84]).

b u r n s 3 7 ( 2 0 1 1 ) 7 4 2 – 7 5 2 747

Upper and lower extremity use of a tourniquet allows for

bloodless debridement. This practice requires close attention to

detail and experience to recognise adequacy of debridement.

Even on more difficult sites like the torso and on the graft

donor sites, blood loss can be reduced dramatically with the

use of a haemostatic agent (such as recombinant thrombin)

[78–80]. All fascial excisions should be performed with

electrocautery such that perforating vessels can be immedi-

ately coagulated [81].

It is a crucial and often overlooked point to maintain

euthermia, principally through operating room heating. These

patients are particularly susceptible to intra-operative hypo-

thermia as massive evaporative heat loss can occur through

their wounds. The heat loss rate is related to TBSA and the

temperature gradient between body and the environment.

The induction of anaesthesia results in relative ablation of

thermoregulatory mechanism and puts the patient at further

risk for developing hypothermia. Actions such as maintaining

higher ambient air temperature, covering extremities and

head, applying warm blankets, utilising radiant heaters and

forced air warming gases are usually effective in maintaining

core temperature if applied aggressively. Body temperature

should be maintained at or above 37 8C in burn patients.

Hypothermia is a contributing factor to platelet and coagula-

tion factor dysfunction; patients should be aggressively

warmed during surgery [82].

By keeping the patient euthermic, we can minimise the

need to transfuse blood products.

Optimal timing and quantity of RBCs, plasma and platelets

in the treatment of hypothermia is unclear. It is unclear if

current component therapy is equivalent to whole blood

transfusion. In fact, data from the current war in Iraq and

Afghanistan suggest otherwise [83].

Timely use of FFP, prevention of hypothermia and correction

of acidosis through PRBC resuscitation are important strategies

in preventing coagulopathy. Transfusing FFP and PRBC in an 1:1

strategy may prevent some of the coagulopathic effects [84].

4.2.4. Optimisation of red cell productionTo promote haematopoiesis, supplementation with vitamin

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

experimental evidence that iron therapy in the critically ill

patient mayenhance the riskof infectionsand the productionof

free radicals [87,88]. Iron is required for microbial growth.

Inflammatory cytokines increase the synthesis of ferritin,

which may serve as a protective function by binding iron and

reducing its availability for microbial growth [89]. Iron appears

to stimulate bacterial virulence, and impair cellular immunity

via inhibition of phagocytosis by neutrophils [90]. Before

routinely supplementing anaemic burn patients with iron, we

need additional studies to clarify the risk of infection.

Recombinant human erythropoietin (r-HuEPO) in acutely

burned patients did not prevent the development of postburn

anaemia or decrease transfusion requirements. Several

studies reported a statistically significant increase of reticu-

locytosis, but no change in the haemoglobin, haematocrit or

RBC count [90–94]. In a prospective randomised placebo-

controlled trial [95], the use of epoetin alfa does not reduce the

incidence of red-cell transfusion among critically ill patients,

but it may reduce mortality in patients with trauma. At day 29,

the increase in the haemoglobin concentration from baseline

was greater in the epoetin alfa group than in the placebo

group. Treatment with epoetin alfa was associated with an

increase in the incidence of thrombotic events.

Contrarily, two previous trials involving critically ill

patients showed that treatment with epoetin alfa reduced

the number of red-cell transfusions and raised the haemo-

globin concentration [96,97].

A randomised, double-blind, placebo-controlled, multi-

centre trial in anaemic critically ill patients demonstrated a

29-day survival benefit in the trauma subgroup receiving

epoetin alfa [98].

It has also been reported that EPO administration exerts

protective effects on apoptosis induced by ischaemic reperfu-

sion injury, in the brain, spinal cord, skeletal muscle and the

myocardium [99–103].

5. Adverse events associated with RBCtransfusion

The transfusion of blood and blood products is associated with

several well-documented adverse effects, which can be divided

into transfusion-associated infections, immunological risks,

metabolic complications and transfusion errors (Table 3) [84].

5.1. Infections

Estimated risks of transfusion–transmitted disease for immu-

nocompetent patients are lower than ever before. Since 1999,

the risks have been declining substantially with the imple-

mentation of NAT (nucleid acid testing), which has shortened

infectious periods and dramatically reduced the current

estimated risks of post-transfusion hepatitis C virus (HCV)

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

[104–106]. In contrast to the reduction of infection for HIV and

HCV, the risk of hepatitis B virus remains approximately

b u r n s 3 7 ( 2 0 1 1 ) 7 4 2 – 7 5 2748

1:50,000–1:150,000 in the Western countries [106]. Bacterial

contamination of red blood occurs 1:500,000. The most

commonly implicated organism in bacterial contamination

is Yersinia enterocolitica [106].

5.2. Immunosuppression

There is also evidence that red-cell transfusions are associated

with an immunomodulatory effect. Transfusion-related

immunomodulation has been noted to be clinically important

in renal transplantation patients and in women with multiple

miscarriages [107,108].

Allogenic blood transfusions have also been associated

with a reduction of cell-mediated immunity, increased rates of

postoperative infection and early recurrences of malignancy

[109–111].

5.3. Transfusion-related acute lung injury (TRALI)

Presenting signs and symptoms of TRALI include dyspnoea,

hypotension and fever, caused by noncardiogenic pulmonary

oedema. Symptoms begin during, or shortly after transfusion,

typically within 4 h after receiving blood.

The mechanism of transfusion-related acute lung injury

(TRALI) is not completely understood, but it appears to involve

localisation of antibody-coated leucocytes to pulmonary

vasculature resulting in increased permeability and oedema

[112]. Its estimated frequency is approximately 1 in 5000

transfusions, and it is fatal in 5–10% of cases [113]. The actual

reported mortalities underscores the fact that this complica-

tion evades clinical recognition, it may be responsible for more

serious adverse events and fatalities than are reported [114].

[()TD$FIG]

Fig. 1 – Limit and prevent unnecessary transfusion in burn pati

conserving techniques, optimization of red blood cell productio

anaemic status of the patient. *R-HuEPO = recombinant human

5.4. Transfusion errors

Human errors are responsible for more than half of all

transfusion-related fatalities [115]. They have been estimated

to be one in 14,000 units in the United States, and one in 18,000

in the United Kingdom [116]. Mistransfusion, defined as an

ABO-incompatible reaction owing to an error, is a leading

cause of morbidity and mortality from transfusion because it

can lead to a major haemolytic reaction. Non-ABO acute

haemolytic reactions and febrile nonhaemolytic reactions are

much more common but are generally mild and self-limiting

in nature. Mistransfusion may lead to an acute haemolytic

reaction, which is characterised by fever, chills, pain, nausea,

vomiting, hypotension, tachycardia, renal failure and dissem-

inated intravascular coagulation [113].

6. Conclusion

Blood transfusion is not a benign therapy. Patients who receive

PRBCs have an increased incidence of complications. The

optimal transfusion strategy for burn patients has not yet been

definitively determined, and additional clinical research is

needed.

The most important physiologic consequence of anaemia

is a reduction in the oxygen-carrying capacity of blood. These

changes are accompanied by increased cardiac output, a shift

of the oxyhaemoglobin dissociation curve and increased

oxygen extraction.

Anaemia is well tolerated as long as intravascular volume

is maintained. Blood volume evaluation should be evaluated

and corrected based on the length and severity of the anaemia.

ent reduce the RBC exposure: uniform application of blood

n, and an adequate and ‘‘physiologic’’ evaluation of the

erythropoietin.

b u r n s 3 7 ( 2 0 1 1 ) 7 4 2 – 7 5 2 749

Analysis of existing transfusion literature confirms

that individual burn centres transfuse at a lower trigger

than in previous years. However, the quest for a universal

transfusion trigger should be abandoned. All RBC transfu-

sions should be tailored to the patient’s blood volume

status, acuity of blood loss and ongoing perfusion require-

ments.

The indication for and the degree of urgency of RBC

transfusions cannot be defined only on the basis of the values

of Hb or the Htc, but must be based on a complete evaluation of

the patient’s clinical condition and the possible presence of

mechanisms compensating for anaemia. A systematic analy-

sis of clinical status should be made in conjunction with an

analysis of volume status, pulmonary function, cardiovascular

status, duration of anaemia and the need for further surgical

intervention.

Uniform application of blood-conserving techniques, opti-

misation of RBC production and an adequate and ‘physiologic’

evaluation of the anaemic status of the patient can be used to

reduce the RBC exposure (Fig. 1).

The ‘physiologic’ transfusion trigger could be based on

signs and symptoms of impaired global (lactate, SvO2 or ScvO2)

parameters. No standard care exists despite current literature

implying the efficacy of minimising transfusions to critically ill

patients. Complication rates and costs associated with blood

transfusion should be reduced with a comprehensive strategy

of blood conservation.

Conflict of interest

Dr. Giuseppe Curinga was supported in part from ISBI

Travelling Fellowship. Dr. Giuseppe Curinga wants to dedicate

this article in memory of his father.

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