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Fluid resuscitation and
early management
Glenn D. Warden
Introduction
Proper fluid management is critical to the survival of the
victim of a major thermal injury. In the 1940s, hypovolemic
shock or shock-induced renal failure was the leading cause
of death after burn injury. Today, with our current knowledge
of the massive fluid shifts and vascular changes that occur
during burn shock, mortality related to burn-induced
volume loss has decreased considerably. Although a vigorous
approach to fluid therapy has ensued in the last 20 years and
fewer deaths are occurring in the first 24–48 h post-burn, the
fact remains that approximately 50% of the deaths occur
within the first 10 days following burn injury from a multi­
tude of causes, one of the most significant being inadequate
fluid resuscitation therapy.1 Knowledge of fluid management
following burn shock resuscitation is also important and is
often overlooked in burn education.
Burn shock resuscitation
The history of burn resuscitation began over a century ago;
however, complete appreciation of the severity of fluid loss
in burns was not apparent until the enlightening studies of
Frank P. Underhill,2 who studied the victims of the Rialto
Theater fire in 1921. His concept that burn shock was due to
intravascular fluid loss was further elucidated by Cope and
Moore,3 who conducted studies on patients from the Coconut
Grove disaster in 1942. They developed the concept of burn
edema and introduced the body-weight burn budget formula
for fluid resuscitation of burn patients. In 1952, Evans devel­
oped a burn surface area–weight formula for computing
fluid replacement in burns which became the first simplified
formula for fluid resuscitation for burn patients.1 Surgeons
at the Brooke Army Medical Center modified the original
Evans formula and this became the standard for the next
15 years.
A number of methods for accomplishing adequate volume
replacement therapy have been advocated in the more than
40 years since the introduction of the Evans’ formula in
1952. This chapter will review the various methods advo­
cated and present the rationale of each. Importantly, pro­
perly utilized, each resuscitation formula can be effective
in the resuscitation of the burn patient in the immediate
post-burn period, provided that close attention is paid to
the individual’s clinical response to therapy and that fluid
replacement therapy is modified according to this response.
The fact that patients respond to a wide variety of resuscita­
tive efforts is testimony to the fact that burn patients are
very resilient and can be overwhelmed only under the most
unfavorable circumstances.4
Pathophysiology of burn injury
Modern fluid resuscitation formulas originate from experi­
mental studies in the pathophysiology of burn shock. Burn
shock is both hypovolemic shock and cellular shock, and is
characterized by specific hemodynamic changes including
decreased cardiac output, extracellular fluid, plasma volume,
and oliguria. As in the treatment of other forms of shock,
the primary goal is to restore and preserve tissue perfusion
in order to avoid ischemia. However, in burn shock, resusci­
tation is complicated by obligatory burn edema, and the
voluminous transvascular fluid shifts which result from a
major burn are unique to thermal trauma.
Although the exact pathophysiology of the post-burn vas­
cular changes and fluid shifts is unknown, one major com­
ponent of burn shock is the increase in total body capillary
permeability. Direct thermal injury results in marked changes
in the microcirculation. Most of the changes occur locally at
the burn site, when maximal edema formation occurs at
about 8–12 h post-injury in smaller burns and 12–24 h
post-injury in major thermal injuries. The rate of progression
of tissue edema is dependent upon the adequacy of
resuscitation.
Multiple mediators have been proposed to explain the
changes in vascular permeability seen post-burn. The media­
tors can produce either an increase in vascular permeability
or an increase in microvascular hydrostatic pressure.5,6 Most
mediators act to increase permeability by altering membrane
integrity in the venules. The early phase of burn edema for­
mation, lasting for minutes to an hour, has been thought by
some investigators to be the result of mediators, particularly
histamine and bradykinin. Other mediators implicated in
the changes in vascular permeability seen post-burn include
vasoactive amines, products of platelet activation and the
complement cascade, hormones, prostaglandins, and leuko­
trienes. Vasoactive substances are also released which may
act primarily by increasing microvascular blood flow or vas­
cular pressures, further accentuating the burn edema.7,8 His­
tamine is released in large quantities from mast cells in
burned skin immediately after injury.9 Histamine has been
©2012 Elsevier Ltd, Inc, BV
DOI: 10.1016/B978-1-4377-2786-9.00009-6
CHAPTER 9 
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Total Burn Care
9
116
demonstrated that in burns of >30% total body surface area
(TBSA), there is a systemic decrease in cell transmembrane
potential, involving non-thermally injured cells as well. This
decrease in cell transmitting potential, as defined by the
Nernst equation, results from an increase in intracellular
sodium concentration. The cause of this is thought to be a
decrease in sodium ATPase activity responsible for main­
taining the intracellular–extracellular ionic gradient. Baxter
further demonstrated that resuscitation only partially restores
the membrane potential and intracellular sodium concentra­
tions to normal levels, demonstrating that hypovolemia with
its attendant ischemia is not totally responsible for the cel­
lular swelling seen in burn shock. In fact, the membrane
potential may not return to normal for many days post-burn
despite adequate resuscitation. If resuscitation is inadequate,
cell membrane potential progressively decreases, resulting
ultimately in cellular death. This may be the final common
denominator in burn shock during the resuscitation period.
Although the etiology of burn shock is not totally under­
stood, many authors have studied the fluid volume shifts
and hemodynamic changes that accompany burn shock.
Early work by Moyer et al.,21 and Baxter and Shires22 estab­
lished the definitive role of crystalloid solutions in burn
resuscitation and delineated the fluid volume changes in
the early post-burn period. Moyer’s original studies in
196521 demonstrated that burn edema sequestered enor­
mous amounts of fluid, resulting in the hypovolemia of burn
shock. In addition, he described the first crystalloid-only
resuscitation formula used to treat burn shock. He noted that
burn shock recovery occurred in the majority of patients
studied, although hemoconcentration remained unchanged
and the hematocrit was unresponsive to fluid administration
despite adequate resuscitation. This became the first objec­
tive evidence that burn shock is not simply due to hypo­
volemia but is also influenced by extracellular sodium
depletion. Baxter and Shires,22 in 1968, using radioisotope
dilution techniques, defined the fluid volume changes of the
post-burn period in relation to cardiac output. They first
demonstrated that edema fluid in the burn wound is iso­
tonic with respect to plasma fluid and contains protein in
the same proportions as that found in blood. This confirmed
Arturson’s earlier findings that in major burns there is com­
plete disruption of the normal capillary barrier, with free
exchange between plasma and extravascular extracellular
compartments. They measured changes in fluid compart­
ment volumes in burned primates and dogs and demon­
strated that in untreated (unresuscitated) animals, a 30–50%
extracellular fluid (ECF) defect persisted at 18 h post-burn.
Plasma volume decreased 23%, to 27% below controls,
although red cell mass changed only about 10% over the
same 18-hour period. Thus, the greatest volume loss was
functional intravascular extracellular fluid. Cardiac output
was initially depressed very soon after injury to a level of
about 25% of controls at 4 h after a 30% TBSA burn. By
18 h, however, the cardiac output had stabilized at around
40% of control, despite persistent defects in plasma and ECF
volumes. On the basis of studies using different volumes of
resuscitation fluids, they arrived at an optimal response in
terms of cardiac output and restoration of ECF at the end of
24 h in a canine model. Clinical studies using similar sodium
and fluid loads immediately followed, confirming efficacy in
restoring ECF to within 10% of controls within 24 h. This
clearly demonstrated to increase the leakage of fluid and
protein from systemic micro vessels, its major effect being
on venules in which an increase in the intracellular junction
space is characteristically seen.10 However, the increase in
serum histamine levels after burn is transient, peaking in the
first several hours post-injury, indicating that histamine is
only involved in the very early increase in permeability. The
use of H1 receptor inhibitors, e.g. diphenhydramine, has
only limited success in decreasing edema. Recently, the use
of an H2 receptor antagonist has been reported to decrease
burn edema in an animal model.11
Serotonin is released immediately post-burn as a result of
platelet aggregation and acts directly to increase the pulmo­
nary vascular resistance and indirectly to amplify the vaso­
constrictive effect of norepinephrine, histamine, angiotensin
II, and prostaglandin.12 The use of ketanserin, a specific sero­
tonin antagonist, in a porcine burn shock model, improved
cardiac index, decreased pulmonary pressure, and reduced
arteriovenous oxygen content differences compared to a
control group in the early post-burn period. Serotonin antag­
onists should be investigated further as possible adjuvant
therapeutic agents during burn shock resuscitation.13 Pros­
taglandins, vasoactive products of arachidonic acid metabo­
lism, have been reported to be released in burn tissue and
to be at least in part responsible for burn edema. Although
these substances do not directly alter vasopermeability,
increased levels of vasodilator prostaglandins such as pros­
taglandin E2 (PGE2) and prostacyclin (PGI2) result in arterial
dilatation in burned tissue, increased blood flow and intra­
vascular hydrostatic pressure in the injured microcirculation,
and thus accentuate the edema process. Concentrations of
PGI2 and the vasoconstrictor thromboxane A2 (TXA2) have
been demonstrated in burned tissue, burn blister fluid,
lymph, and wound secretion.14,15 However, the use of pros­
taglandin inhibitors has produced variable results in animal
studies. Arturson16 reported a decrease in burn lymph and
protein flow with the use of prostaglandin inhibitor,
indomethacin. Those results have not been corroborated by
other investigators and the role of thromboxane and the
prostaglandins still needs to be elucidated.
The activation of the proteolytic cascades, including those
of coagulation, fibrinolysis, the kinins, and the complement
system, has been demonstrated to occur immediately follow­
ing thermal injury. Kinins, specifically bradykinins, are
known to increase vascular permeability, primarily in the
venule. Rocha and co-workers17 report increased kinin levels
in burn edema fluid in the rat. The release of other mediators
and the generalized inflammatory response after burns
favors the activation of the kallikrein–kinin system, with the
release of bradykinin into the circulation.18 Elevation of pro­
teolytic activity has been demonstrated in both animals and
in burn patients.19 Pretreatment with protease inhibitors sig­
nificantly decreases free kinin levels but appears to have little
effect on the edema process.
The end result of the changes in the microvasculature due
to thermal injury is disruption of normal capillary barriers
separating intravascular and interstitial compartments, and
rapid equilibrium of these compartments. This results in
severe depletion of plasma volume with a marked increase
in extracellular fluid clinically manifested as hypovolemia.
In addition to a loss of capillary integrity, thermal injury
also causes changes at the cellular level. Baxter20 has

Fluid resuscitation and early management
117
from it. Further studies by Demling and co-workers24 have
demonstrated that in 50% TBSA burns, one-half of the
initial fluid resuscitation requirement may end up in non-
thermally injured tissues.
Resuscitation from burn shock
Fluid resuscitation is aimed at supporting the patient
throughout the initial 24-hour to 48-hour period of hypovo­
lemia. The primary goal of therapy is to replace the fluid
sequestered as a result of thermal injury. The critical concept
in burn shock is that massive fluid shifts can occur even
though total body water remains unchanged. What actually
changes is the volume of each fluid compartment, intracel­
lular and interstitial volumes increasing at the expense of
plasma volume and blood volume. In light of all the studies
on different fluid regimens, the question still remains: ‘What
is the best formula for resuscitation of the burn patient?’
It is quite clear that the edema process is accentuated by
the resuscitation fluid. The magnitude of edema will be
affected by the amount and type of fluid administered.25 The
National Institutes of Health consensus summary on fluid
resuscitation in 1978 was not in agreement in regard to a
specific formula; however, there was consensus in regard to
two major issues – the guidelines used during the resuscita­
tion process and the type of fluid used. In regard to the
guidelines, the consensus was to give the least amount of
fluid necessary to maintain adequate organ perfusion. The
volume infused should be continually titrated so as to avoid
both under-resuscitation and over-resuscitation.26,27 As for
the optimum type of fluid, there is no question that replace­
ment of the extracellular salt lost into the burned tissue and
into the cell is essential for successful resuscitation.19,21
Crystalloid resuscitation
Crystalloid, in particular lactated Ringer’s solution with a
sodium concentration of 130 mEq/L, is the most popular
resuscitation fluid currently utilized. Proponents of the use
of crystalloid solution alone for resuscitation report that
other solutions, specifically colloids, are no better and are
certainly more expensive than crystalloid for maintaining
intravascular volume following thermal injury.4 The most
common reason given for not using colloids is that even
large proteins leak from the capillary following thermal
injury. However, capillaries in non-burned tissues do con­
tinue to sieve proteins, maintaining relatively normal protein
permeability characteristics.
The quantity of crystalloid needed is in part dependent
upon the parameters used to monitor resuscitation. If a
urinary output of 0.5 cc/kg of body weight/hour is consid­
ered to indicate adequate perfusion, approximately 3 cc/
kg/% burn will be needed in the first 24 h. If 1 cc/kg of body
weight/hour of urine is deemed necessary, then of course
considerably more fluid will be needed and in turn more
edema will result. The Parkland formula recommends 4 cc/
kg/% burn in the first 24 h, with one-half of that amount
administered in the first 8 h9 (Table 9.1). The modified
Brooke formula recommends beginning burn shock resusci­
tation at 2 cc/kg/% burn in the first 24 h (Table 9.1). In
major burns, severe hypoproteinemia usually develops
with these resuscitation regimens. The hypoproteinemia and
became the basis for the Baxter or Parkland formula.20 Mor­
tality was comparable to that obtained with a colloid-
containing resuscitation formula.
Baxter went on to demonstrate that during the first 24 h
post-burn, plasma volume changes were independent of
the type of infused fluid, whether crystalloid or colloid, but
at approximately 24 h post-injury, an infused amount of
colloid would increase the plasma volume by the same
amount. His findings prove that colloid-containing solu­
tions are an unnecessary component of fluid resuscitation in
the first 24 h. He recommended their use only after capillary
integrity was restored, to correct the persistent plasma
volume deficit of about 20% as measured externally. While
the fluid shifts were being defined by Baxter in terms of
crystalloid resuscitation, Pruitt and co-workers4 worked to
characterize the hemodynamic alterations that occur in burn
shock with and without fluid resuscitation. Their efforts cul­
minated in the Brooke formula modification which utilized
2 cc/kg/% burn during the first 24 h. Fluid needs were ini­
tially estimated according to the modified Brooke formula,
but the actual volume for resuscitation was based on clinical
response. In their study, resuscitation permitted an average
decrease of about 20% in both extracellular fluid and plasma
volume, but no further loss accrued in the first 24 h. In the
second 24 h post-burn, plasma volume restoration occurred
with the administration of colloid. Blood volume, however,
was only partially restored and an ongoing loss of 9% of the
red cell mass per day was found. Cardiac output, initially
quite low, rose over the first 18 h post-burn, despite plasma
volume and blood volume defects. These results were quite
consistent with those demonstrated by Baxter in his animal
studies. Peripheral vascular resistance during the initial 24 h
was initially very high but decreased as cardiac output
improved, and in fact the changes were reciprocal. Once
plasma volume and blood volume loss ceased, cardiac
output rose to supranormal levels where it remained until
healing or grafting occurred.
Moylan and associates23 in 1973, using a canine model,
defined the relationships between fluid volumes, sodium
concentration, and colloid in restoring cardiac output during
the first 12 h post-injury. No significant colloid effect on
cardiac output was noted in the first 12 h post-injury. In
addition, 1 mEq of sodium was found to exert an effect on
cardiac output equal to 13 times that of 1 mL of salt-free
volume. This experiment established the fact that any com­
bination of sodium and volume within the broad limits of
the study would effectively resuscitate a thermally injured
patient.
Arturson’s landmark studies in 197916 on vascular perme­
ability characterized the nature of the ‘leaky capillary’ in the
post-burn period. He demonstrated in a canine model that
increased capillary permeability is found both locally and
in non-burned tissue at distant sites when the TBSA burn
exceeded 25%. He proposed that the burn wound is charac­
terized by rapid edema formation due to dilatation of
the resistance vessels (precapillary arterioles); increased
extravascular osmotic activity, due to the products of
thermal injury; and increased microvascular permeability to
macromolecules. The increased permeability permits mol­
ecules of up to 350 000 molecular weight to escape from
the microvasculature, a size which allows essentially all ele­
ments of the vascular space except red blood cells to escape

Total Burn Care
9
118
with lactated Ringer’s solution. Urine output was the indica­
tor used during resuscitation. Demling and colleagues31 in
an animal model demonstrated that the net fluid intake was
less if burned animals were resuscitated with hypertonic
saline to the same cardiac output compared with lactated
Ringer’s. Urine output was much higher with hypertonic
solution. Interestingly, soft tissue interstitial edema in
burned and non-burned tissue, as reflected by lymph flow,
was increased with hypertonic saline similar to that of lac­
tated Ringer’s (LR). This can be explained by a shift of intra­
cellular water into extracellular space as the result of the
hyperosmolar solution. Extracellular edema can therefore
occur at the same time as intracellular fluid defect. This
may give the external appearance of less edema. Although
several studies to date have reported that this intracellular
water depletion does not appear to be deleterious, the issue
remains controversial. Shimazaki et al.32 resuscitated 46
patients with either LR or hypertonic saline. The sodium
infusions were equivalent, but the free water load was greater
with LR; 50% of the latter required endotracheal intubation.
The hypertonic serum also delivers a more concentrated
ultrafiltrate within the kidney. This increases urine volume
and salt clearance without marked increases in the required
volume of free water.
There is no consensus regarding the type of osmolarity of
hypertonic resuscitation fluid. Caldwell and Bowser,30 in
1979, reported a series of 37 patients with greater than 30%
burns treated with either LR or hypertonic lactated saline
(HLS), but no colloid. Total sodium balance was the same
but the HLS group received 30% less free water and the
reduced weight gain was maintained for 7 days. Subsequent
reports from this institution reported successful HLS resus­
citation in the elderly and children but no improvement in
late mortality.33–35
Bartolani et al.36 randomized 40 patients to receive LR or
HLS. HLS patients received more sodium, but less total fluid
than the LR group. The observed higher mortality with HLS
was attributed to larger burns in this group.
Reserve colloid for the second 24 h in cases where the
patient remains poorly perfused after large infusions of
crystalloid. Griswold et al.37 reported resuscitation of 47
patients with HLS resuscitation. Of these, 29 were also given
colloid as albumin or fresh frozen plasma based on burn
severity, premorbid state, or poor response to HLS resuscita­
tion. This group had larger burns, greater mean age, and
higher incidence of inhalation injury, but required only 57%
of the fluid volume predicted by the Parkland formula, com­
pared to 75% of predicted volume in the HLS alone group.
Both groups maintained urine volumes of 1 mL/kg/h with
no significant difference in hematocrit or serum sodium
levels. Jelenko et al.38 also reported in a small series that
patients given HLS and albumin required fewer escharoto­
mies, fewer days of mechanical ventilation, and less total
fluid than patients resuscitated with LR or HLS alone. Gunn
et al.39 in a series of 51 randomized patients found no differ­
ence in fluid requirements or weight gain if they were
given LR or hypertonic saline, if fresh frozen plasma was
administered to maintain serum albumin levels above 2 g/
dL, but all patients received hypotonic enteral feedings
during resuscitation.
Yoshioka et al.40 reviewed 53 patients treated with greater
than 30% burns resuscitated with LR, LR and colloid, or
interstitial protein depletion may result in more edema
formation.
Hypertonic saline
Hypertonic salt solutions have been known for many years
to be effective in treating burn shock.28,29 Rapid infusion
produces serum hyperosmolarity and hypernatremia with
two potentially positive effects.28,30 The hypertonic serum
reduces the shift into the extracellular space of intravascular
water. Proposed benefits include decreased tissue edema and
fewer attendant complications, including escharotomies for
vascular compromise or endotracheal intubation to protect
the airway. Monafo28 reported that the resuscitation of burn
patients with salt solution of 240–300 mEq/L resulted in less
edema because of the smaller total fluid requirements than
Table 9.1  Formulas for estimating adult burn patient
resuscitation fluid needs
Colloid
formulas
Electrolyte
Colloid
D5W
Evans
Normal saline
1.0 cc/kg/%
burn
1.0 cc/kg/%
burn
2000 cc
Brooke
Lactated
Ringer’s 1.5 cc/
kg/% burn
0.5 cc/kg
2000 cc
Slater
Lactated
Ringer’s
2 L/24 h
Fresh frozen
plasma
75 cc/kg/24 h
Crystalloid
formulas
  Parkland
Lactated
Ringer’s
4 cc/kg/% burn
  Modified
Brooke
Lactated
Ringer’s
2 cc/kg/% burn
Hypertonic
saline formulas
  Hypertonic
saline solution
(Monafo)
Volume to maintain urine output at 30 cc/h
Fluid contains 250 mEq Na/L
  Modified
hypertonic
(Warden)
Lactated Ringer’s + 50 mEq NaHCO3 (180 mEq
Na/L) for 8 h to maintain urine output at
30–50 cc/h
Lactated Ringer’s to maintain urine output at
30–50 cc/h beginning 8 h post-burn
Dextran formula
(Demling)
Dextran 40 in saline – 2 cc/kg/h for 8 h
Lactated Ringer’s – volume to maintain urine
output at 30 cc/h
Fresh frozen plasma – 0.5 cc/kg/h for 18 h
beginning 8 h post-burn
Reproduced from: Warden GD. Burn shock resuscitation. World J Surg 1992;
16:21–23. With kind permission of Springer Science and Business Media.53

Fluid resuscitation and early management
119
2. Proteins, specifically albumin, should be given from
the beginning of resuscitation along with crystalloid;
it should usually be added to salt water.
3. Protein should be given between 8 and 12 h post-burn
using strictly crystalloid in the first 8–12 h because of
the massive fluid shifts during this period. Demling
demonstrated experimentally that restoration and
maintenance of plasma protein contents were not
effective until 8 h post-burn, after which adequate
levels can be maintained with infusion.47 Because
non-burned tissues appear to regain normal
permeability very shortly after injury and because
hypoproteinemia may accentuate the edema, the action
advocated by the first school appears to be least
appropriate.
The choice of the type of protein solution can be confus­
ing. Heat-fixed protein solutions, e.g. Plasmanate, are known
to contain some denatured and aggregated protein, which
decreases the oncotic effect. Albumin solutions would clearly
be the most oncotically active solutions. Fresh frozen plasma,
however, contains all the protein fractions that exert both
the oncotic and the non-oncotic actions. The optimal
amount of protein to infuse remains undefined. Demling47
uses between 0.5 and 1 cc/kg/% burn of fresh frozen plasma
during the first 24 h, beginning at 8–10 h post-burn.48,49 He
emphasizes that all major burns require large amounts of
fluid, but notes that older patients with burns, patients with
burns and concomitant inhalation injury, and patients with
burns in excess of 50% TBSA not only develop less edema
but also better maintain hemodynamic stability with the
addition of protein.
Du and co-workers44 have recently utilized fresh frozen
plasma during burn shock. They use lactated Ringer’s, 2 L
for 24 h, and fresh frozen plasma, 75 cc/kg/24 h (Table 9.1).
Although the volume of fresh frozen plasma is calculated,
the volume infused is titrated to maintain an adequate urine
output. Although the authors are utilizing colloid early in
the burn shock period, they emphasize that most burn
patients have received LR in significant volumes during field
management.
The use of albumin in burns and critically ill patients has
recently been challenged by the Cochrane Central Register
of Controlled Trials, which demonstrated in critical hypovo­
lemia that there was no evidence that albumin reduces mor­
tality when compared with cheaper alternatives such as
saline.50 Others using a meta-analysis of randomized, con­
trolled trials found no effect of albumin on mortality and
could not find a deleterious effect of albumin.51 Most burn
surgeons agree that in burn patients who have a very low
serum albumin during burn shock albumin supplementa­
tion is warranted to maintain oncotic pressure.
Dextran resuscitation solutions
Dextran is a colloid consisting of glucose molecules which
have been polymerized into chains to form high molecular
weight polysaccharides.49 This compound is commercially
available in a number of molecular sizes. Dextran, which has
an average molecular weight of 40 000 Da, is referred to as
low molecular weight dextran. British dextran has a mean
molecular weight of 150 000, whereas the dextran used
HLS. Fluid requirements were 4.8 mL/kg/% TBSA with LR,
3.3 mL/kg/% TBSA with LR and colloid, and 2.2 mL/kg/%
TBSA with HLS. The total sodium requirements were
increased 30% with LR compared to the other groups.
Oxygen extraction, measured as A-VO2 difference, was
improved with HLS, but reduced with LR–colloid, perhaps
because of protein leak across the alveoli.
Vigorous administration of hypertonic saline solutions
can produce a serum sodium above 160 mEq/dL or serum
osmolarity greater than 340 mOsm/dL, followed by a rapid
fall in urine output.41 Bowser-Wallace et al.33 and Crum
et al.42 have reported 40–50% of patients treated with HLS
developed hypernatremia with serum sodium greater than
160 mEq/L requiring switch to hypotonic fluids. Huang
et al.43 reported a series of deaths associated with hyper­
natremia and hyperosmolarity following hypertonic saline
resuscitation. Serial determinations of serum sodium and
serum osmolarity are required to prevent complications
including sudden anuria, brain shrinkage with tearing of
intracranial vessels, or excessive brain swelling following
rapid correction of serum hyperosmolarity. Current recom­
mendations are that the serum sodium levels should not be
allowed to exceed 160 mEq/dL during its use. Of interest,
Gunn and associates,39 in a prospective randomized study of
patients with 20% TBSA burns evaluating HSL versus LR
solution, were not able to demonstrate decreased fluid
requirements, improved nutritional tolerance, or decreased
percent weight gain.
A modified hypertonic solution has been utilized in chil­
dren with major thermal injuries >40% TBSA burn. The
resuscitation fluid contains 180 mEq Na+ (lactated Ringer’s
+50 mEq NaHCO3). The solution is utilized until the reversal
of metabolic acidosis has occurred, usually by 8 h post-burn.
The volume administered is begun at a rate calculated by the
Parkland formula (4 cc/kg/% burn); however, volume is
titrated to maintain urine output at 30–50 cc/h. After 8 h the
resuscitation is completed utilizing LR to maintain urine
output at 30–50 cc/h. This hypertonic formula can be used
in infants and in the elderly without the accompanying risk
of hypernatremia.44,45
Colloid resuscitation
Plasma proteins are extremely important in the circulation
since they generate the inward oncotic force that counteracts
the outward capillary hydrostatic force. Without protein,
plasma volume could not be maintained and massive edema
would result. Protein replacement was an important compo­
nent of early formulas for burn management. The Evans
formula, advocated in 1952, used 1 cc/kg of body weight/%
burn each for colloid and LR over the first 24 h. The Brooke
formula was clearly based on estimate rather than deter­
mined scientifically, but the formula used 0.5 /kg/% burn as
colloid and 1.5 cc/kg/% burn as LR. The burn budget of
Moore similarly used a substantial amount of colloids.3 Con­
siderable confusion exists concerning the role of protein in
a resuscitation formula. There are three schools of thought:
1. Protein solutions should not be given in the first 24 h
because during this period they are no more effective
than salt water in maintaining intravascular volume
and they promote accumulation of lung water when
edema fluid is being absorbed from the burn wound.46

Total Burn Care
9
120
Support (PALS), which recommends volume resuscitation
begin with a fluid bolus of 20 mL/kg of isotonic crystalloid
administered over 5 to 20 min – this amount is repeated if
urine output is not adequate.57 This regimen can lead to
over-resuscitation. PALS actually recommends a modifica­
tion of this fluid bolus resuscitation for burns utilizing
2–4 mL/kg/% of body surface area burned per 24 h.57 Educa­
tion of first responders on the differences between these two
fluid regimens is imperative.
Inhalation injury
The presence of inhalation injury increases the fluid require­
ments for resuscitation from burn shock after thermal
injury.58,59 We have demonstrated that patients with docu­
mented inhalation injury require 5.7 cc/kg/% burn, as com­
pared to 3.98 cc/kg/% burn in patients without inhalation
injury. These data confirm and quantitate that inhalation
injury accompanying thermal trauma increases the magni­
tude of total body injury and requires increased volumes of
fluid and sodium to achieve resuscitation from early burn
shock.
Choice of fluids and rate of administration
It is clear that all the solutions reviewed are effective in
restoring tissue perfusion. However, it makes no more sense
to use one particular fluid for all patients than it does to use
one antibiotic for all infections. Most patients with burns of
<40% TBSA and patients with no pulmonary injury can be
resuscitated with isotonic crystalloid fluid. In patients with
burns of >40% TBSA and in patients with pulmonary injury,
hypertonic saline can be utilized in the first 8 h post-burn,
following which lactated Ringer’s is infused to complete
burn shock resuscitation. In the pediatric and elderly burn
patient population, utilizing a lower but still hypertonic con­
centration of sodium, i.e. 180 mEq/L, still gives the benefits
of hypertonic resuscitation without the potential complica­
tions of excessive sodium retention and hypernatremia.
In patients with massive burns, young pediatric patients,
and burns complicated by severe inhalation injury, a
predominantly in Sweden has a molecular weight of 70 000.
Dextran is excreted at the kidneys, with 40% removed within
24 h. The remainder is slowly metabolized. Demling and
associates have utilized dextran 70 in a 6% solution to
prevent edema in non-burned tissues. Dextran 70 carries
some risk of allergic reaction and can interfere with blood
typing. Dextran 40 actually improves the microcirculatory
flow by decreasing red cell aggregation.52 Demling and col­
leagues49 demonstrated that the net requirements to main­
tain vascular pressure at the baseline levels with dextran 40
were about half those seen with LR alone during the first
24 h post-burn. These authors have used an infusion rate
of dextran 40 and saline of 2 cc/kg/h along with sufficient
LR to maintain adequate perfusion. At 8 h an infusion of
fresh frozen plasma at 0.5–1.0 cc/kg/% TBSA burn over
18 h is instituted along with necessary additional crystalloid
(Table 9.1).
In the young pediatric burn patient with major burn
injury, colloid replacement is frequently required as serum
protein concentration rapidly decreases during burn shock.
The Shriners Hospitals for Children in Cincinnati and Galve­
ston both routinely utilize colloid during resuscitation of
children with major thermal injuries.53,54
Special considerations in burn
shock resuscitation
Fluid resuscitation in the thermally injured
pediatric patient
The burned child continues to represent a special challenge,
since resuscitation therapy must be more precise than that
for an adult with a similar burn. In addition, children have
a limited physiological reserve. We have demonstrated that
children require more fluid for burn shock resuscitation than
adults with similar thermal injury; fluid requirements for
children averaged 5.8 cc/kg/% burn.55 In addition, children
commonly require intravenous resuscitation for relatively
small burns of 10–20% TBSA. Baxter45 found similar resus­
citation requirements in the pediatric age group. Graves and
associates56 substantiated that children received 6.3 ± 2 cc/
kg/% TBSA burn. At the Shriners Burns Hospital, Cincinnati,
we have utilized the Parkland formula with the addition of
maintenance fluid, to the resuscitation fluid volume, 4 mL/
kg × % TBSA burn per 24 h + 1500 cc/m2 BSA per 24 h. This
is the formula used to begin burn shock resuscitation and to
compare the amount of fluid needed by a particular pediatric
burn patient with that needed by an unburned pediatric
patient (Table 9.2). This is similar to the results reported by
Graves and co-workers56 who found that if maintenance
fluids were subtracted from the resuscitation fluid require­
ments, the resulting resuscitation volumes would approach
4 cc/kg/% burn. At the Shriners Burns Hospital in Galveston,
fluid requirements are estimated according to a formula
based on total BSA and BSA burned in square meters.54
Total fluid requirements for the first day are estimated as
follows: 5000 mL/m2 BSA burned per 24 h + 2000 mL/m2
BSA per 24 h.
Recently pediatric burn surgeons have seen a problem
of over-resuscitation and a ‘saw-tooth resuscitation.’ This
appears to be due to first responders using the volume resus­
citation formula as suggested by Pediatric Advanced Life
Table 9.2  Formulas for estimating pediatric resuscitation needs
Cincinnati
Shriners Burns
Hospital
4 mL × kg × %
TBSA burn
1st 8 h
Lactated
Ringer’s + 50 mg
NaHCO3
+
1500 cc × m2
BSA
2nd 8 h
Lactated
Ringer’s
3rd 8 h
Lactated
Ringer’s + 12.5 g
albumin
Galveston
Shriners Burns
Hospital
5000 mL/m2
BSA burn
Ringer’s
lactate
+
+
2000 mL/m2
BSA
12.5 g
albumin

Fluid resuscitation and early management
121
should be repeated, or the effect of frequent laboratory
testing on the success of resuscitation.
Invasive hemodynamic monitoring permits the direct, and
sometimes continuous, measurement of central venous pres­
sure (CVP), pulmonary capillary wedge pressure (PCWP),
and pulmonary vascular hemodynamics as well as the cal­
culation of cardiac output (CO), systemic vascular resistance
(SVR), oxygen delivery (DO2), and oxygen consumption
(VO2). The decision to perform such monitoring requires
consideration of risks, cost-effectiveness, and impact on
clinical outcome. The Swan-Ganz catheter is most com­
monly utilized in patients in whom routine monitoring is
felt to be ineffective, when there is a history of preexisting
cardiac disease, or when there are other complicating factors.
PAC-guided therapy has been studied most extensively in
trauma and critically ill surgical patients. Kirton and Civetta62
performed a critical literature review to determine if the
use of the PAC in trauma patients altered outcome. They
concluded that hemodynamic data derived from the PAC
appeared to be beneficial to ascertain cardiovascular per­
formance, to direct therapy when non-invasive monitoring
was felt to be inadequate, or when the endpoints of resusci­
tation were difficult to define. These findings were echoed at
the 1997 Pulmonary Artery Catheter Consensus Conference;
however; there was no unanimity that PAC-guided therapy
altered mortality in trauma patients.63
Studies of PAC use for monitoring burn shock resuscita­
tion are limited. Retrospective analyses of adult patients with
extensive burn injuries have concluded that PCWP is a more
reliable indicator of circulatory volume than CVP,64 and that
CO is more accurate in assessing the efficacy of resuscitation
than hourly urine output.65 These findings were supported
by Dries and Waxman66 who noted that urine output and
vital signs monitoring did not correlate with PCWP, cardiac
index (CI), SVR, DO2, or VO2. They concluded that PAC
monitoring may be beneficial in patients at high risk for
adverse outcomes due to suboptimal resuscitation. Most
recently, Schiller and Bay have reported their retrospective
experience in 95 patients treated over a 4-year period during
which an attempt was made to maximize circulatory end­
points.67 They concluded that early invasive monitoring
facilitated more aggressive resuscitation and resulted in
increased survival, and that the inability to achieve hyper­
dynamic endpoints predicted resuscitation failure.
PAC-guided monitoring has also been used to aid in
achieving predetermined therapeutic endpoints during the
resuscitation and management of trauma and critically ill
patients. In a series of prospective randomized class II trials,
it was demonstrated that patients resuscitated to hyper­
dynamic endpoints (i.e. increased CI, DO2I, VO2I) had
decreased mortality, ICU stay, and ventilator days compared
to patients who were resuscitated to normal hemodynamic
values. Studies by Fleming et al.68 and Bishop et al.69 have
not only supported these conclusions but also demonstrated
a decreased incidence of organ failures.
While the data supporting hyperdynamic resuscitation are
impressive, there is also strong evidence that such therapeu­
tic goals are not associated with improved outcome. Two
trials in critically ill patients70,71 were unable to demonstrate
any benefit of PAC monitoring on patient outcome. These
studies were supported by prospective randomized trials72,73
which demonstrated no statistical differences in survival,
combination of fluids may be utilized to achieve the desired
goal of tissue perfusion while minimizing edema. In treating
such patients, we have utilized the regimen of modified
hypertonic (lactated Ringer’s +50 mEq NaHCO3) saline fluid
containing 180 mEq Na/L for the first 8 h. After correction
of the metabolic acidosis, which generally requires 8 h, the
patients are given LR only for the second 8 h. In the last 8 h,
a 5% albumin in LR is utilized to complete resuscitation. The
resuscitation solution used in Galveston for pediatric patients
is an isotonic glucose-containing solution to which a moder­
ate amount of colloid (human serum albumin) is added.
The solution is prepared by mixing 50 mL of 25% human
serum albumin (12.5 g) with 950 mL in an LR solution.
The monitoring of burn shock resuscitation is initiated by
first responders and is generally concluded once the patient’s
fluid needs have decreased to a maintenance rate, based
upon body size and evaporative water loss. Factors influenc­
ing monitoring needs include the extent and depth of burn,
the presence of inhalation injury, associated injuries, preex­
isting medical illnesses, and patient age. The monitoring
process can be classified based upon the intensity and fre­
quency of observations, as well as the methods employed.
While the level of monitoring must be individualized for
each patient, one must weigh the risks and benefits of each
modality. Young, healthy patients with minor burns may
only require the occasional periodic assessment of vital
signs, whereas those with more extensive burns and/or other
risk factors may require more invasive techniques. A recent
survey of 251 burn centers throughout the United States,
Canada, United Kingdom, Australia, and New Zealand
revealed that only 12% frequently used pulmonary artery
catheter (PAC) monitoring during fluid resuscitation in
patients with >30% TBSA burns.60 Moreover, only 60% of
the respondents who addressed treatment goals following
PAC insertion indicated that they utilized predetermined
physiologic parameters to direct fluid therapy.
Clinical monitoring of burn shock resuscitation has tradi­
tionally relied on clinical assessment of cardiovascular, renal,
and biochemical parameters as indicators of vital organ per­
fusion. Heart rate, blood pressure, and electrocardiographic
recordings are the primary modalities for monitoring cardio­
vascular status in any patient. Fluid balance during burn
shock resuscitation is typically monitored by measuring
hourly urine output via an indwelling urethral catheter. It
has been recommended that urine output be maintained
between 30 and 50 mL/h in adults,22 and between 0.5 and
1.0 mL/kg/h in patients weighing less than 30 kg; 26 however,
there have been no clinical studies identifying the optimal
hourly urine output to maintain vital organ perfusion during
burn shock resuscitation.
Because large volumes of fluid and electrolytes are admini­
stered both initially and throughout the course of resus­
citation, it is important to obtain baseline laboratory
measurements of complete blood count, electrolytes, glucose,
albumin, and acid–base balance.61 Laboratory values should
be repeated as clinically indicated throughout the resuscita­
tion period. These parameters are generally sufficient to
assess the physiologic response of most burn patients during
burn shock resuscitation. While clinical interpretation of the
data should rely on the evaluation of trends rather than on
isolated measurements, there have been no studies demon­
strating which tests should be performed, how often they

Total Burn Care
9
122
The phenomenon of ‘fluid creep’
The Parkland formula was broadly accepted but has not gone
unchecked throughout the years. It is important to note that
Baxter’s original formula included an infusion of colloid at
the end of 24 h to complete the restoration of intravascular
volume. This component has been omitted from the consen­
sus formula and other modern iterations of the Parkland
formula. Recent data suggest that the formula does not accu­
rately predict fluid requirements in larger burns and that
patients treated today frequently exceed the volumes pre­
dicted by the formula.87–89 Pruitt first coined the term ‘fluid
creep’ in 2000 to describe this phenomenon of increasing
resuscitation volumes, and stated that clinicians should
‘push the pendulum back.’ Over-resuscitation can produce
significant complications such as abdominal and extremity
compartment syndromes, pulmonary and cerebral edema,
acute respiratory distress syndrome, and multiple organ
dysfunction.90–92 As previously noted, Baxter acknowledged
the fact that certain patient populations will require more
fluid than is predicted, and stressed the importance of careful
observation and monitoring of the patient’s response to
necessary fluid adjustments.
In 2007, Saffle published a comprehensive review of the
incidence, consequences, and possible etiologies of ‘fluid
creep.’93 He recommended a number of potential therapeutic
strategies for the treatment and prevention of overzealous
fluid resuscitation including restricting early fluid resuscita­
tion, considering the use of routine colloid, and utilizing
resuscitation protocols. He also discusses the use of hyper­
tonic saline in special populations and the possible phar­
macological regulation of resuscitation. The labelling of
excessive fluid volumes given during resuscitation as ‘fluid
creep’ has not gone unchallenged. Hartford wrote an edito­
rial in response to Saffle’s article: ‘Fluid creep is a term that
covers up for unfamiliarity with the root causes of admini­
stration of excessive volume of crystalloid and for poor and
organ failure, or ICU days between the control and hyperdy­
namic groups.
In an evidence-based review of these and other citations,
Cooper et al.74 concluded that the existing literature had
inconsistent results regarding the efficacy of goal-oriented
hemodynamic therapy. This conclusion was underscored by
Elliott75 who cited a meta-analysis of seven studies in which
no significant differences in mortality were noted between
control and hyperdynamic resuscitation groups.
The most appropriate endpoints in burn shock resuscita­
tion are also unresolved. As such, the goal of achieving
hyperdynamic resuscitation remains controversial. While
Aikawa76 was able to resuscitate 19/21 patients (90.5%)
using the PAC to reach normal hemodynamic endpoints,
Bernard77 demonstrated that the ability to sustain a supranor­
mal CI was associated with enhanced tissue perfusion and
survival. This was supported by Schiller et al.78 who demon­
strated that an inadequate or unsustained response to hyper­
dynamic resuscitation was associated with non-survival. A
follow-up study by these authors79 also demonstrated signifi­
cantly reduced mortality in those patients where PAC-guided
resuscitation assisted in achieving hyperdynamic endpoints.
The ability to achieve adequate oxygen delivery with hyper­
dynamic burn shock resuscitation has also been recently
evaluated by Barton et al.80 While patients achieved signifi­
cant increases in VO2I and DO2I, they required 63% more
fluid than predicted by the Parkland formula, a mean resus­
citation volume of 9.07 mL/kg/% TBSA burn, and a mean of
50.4 h to complete resuscitation.
More than 20 human studies in critically ill patients have
demonstrated that blood lactate (BL) levels are highly accu­
rate as a guide to the efficacy of resuscitation.75,81 Blood
lactate levels directly reflect anaerobic metabolisms as a con­
sequence of hypoperfusion, and normalizing levels have
long been associated with improved survival from non-burn
shock.82 In other studies, BL has been demonstrated to dis­
tinguish survivors from non-survivors.83,84 In two prospec­
tive, goal-directed studies in critically ill patients, BL proved
superior to not only MAP and urine output but also to DO2,
VO2, and CI.85,86
It is important to emphasize that all of the resuscitation
formulas are only guidelines for burn shock resuscitation.
The Parkland formula, for instance, decreases the volume
administered by 50% at 8 h post-burn. The relationship
between the fluid volume required and time post-burn
depicted by the smooth curve in Figure 9.1 represents the
influence of temporal changes in microvascular permeability
and edema volume on fluid needs. That curve is contrasted
with the abrupt changes in fluid infusion rate as prescribed
by the formula. The formulas are utilized as starting points
for volume replacement and to compare the individual
patient with the ‘average’ burn patient. An interesting ques­
tion is, ‘When has burn shock resuscitation been completed
successfully?’ It is obvious that resuscitation is completed
when there is no further accumulation of edema fluid, which
generally occurs between 18 and 30 h post-burn. The resus­
citation fluids are utilized until the volume of infused fluid
needed to maintain adequate urine volume of 30–50 cc/h in
adults and 1 cc/kg/h in children equals the maintenance
fluid volume. The maintenance fluid requirements following
burn shock resuscitation include the patient’s normal main­
tenance volume plus evaporative water loss.
Figure 9.1  Physiological curve of fluid requirements compared to Parkland
formula, emphasizing that formulas are only guidelines for fluid therapy
during burn shock. (Reproduced from Warden GD. Burn shock resuscitation. World J
Surg. 1992;16:21-23. With kind permission of Springer Science and Business Media.53)
Resuscitation volume (mL/kg/% burn/h)
Time postburn (h)
0.5
0.4
0.3
0.2
0.1
0
4
8
12
16
20
24
Mean calculated
volume requirements
(4 mL/kg/% burn)
Maintenance
28

Fluid resuscitation and early management
123
resuscitation failure remain major causes of early mortality
despite advances in emergency care and transport, resuscita­
tion regimens, and physiologic stabilization.
We have used plasma exchange in patients with major
thermal injuries who failed to respond to conventional fluid
volumes during resuscitation from burn shock.101 The indica­
tions for plasma exchange are ongoing fluid requirements
exceeding twice those predicted by the Parkland formula
despite conversion to hypertonic lactated saline resuscitation
fluid. During a 3-year period, 22 patients underwent plasma
exchange during burn shock resuscitation. A therapeutic
response was documented in 21 of the 22 patients, character­
ized by a sharp decrease in fluid requirements from a mean
of 260% above the predicted hourly volume by the resuscita­
tion formula to within calculated requirements at a mean
time of 2.3 h following plasma exchange. Only one patient,
who had a 100% TBSA burn (88% full-thickness), failed to
respond to plasma exchange and expired at 18 h post-burn.
Schnarrs et al.102 have substantiated the beneficial effect of
plasma exchange in sustaining patients during the immedi­
ate post-burn period when patients fail to respond appropri­
ately to conventional fluid resuscitation. This modality offers
an alternative management technique for the treatment of
refractory burn shock.
Fluid replacement following burn
shock resuscitation
Although the heat-injured microvessels may continue to
manifest increased vascular permeability for several days, the
rate of loss is considerably less than that seen in the first
24 h. Burn edema by this time is near maximal and the
interstitial space may well be saturated with sodium. Addi­
tional fluid requirements will depend on the type of fluid
used during the initial resuscitation. If hypertonic salt resus­
citation has been utilized during the entire burn shock
period, a hyperosmolar state is produced and the addition
of free water will be required to restore the extracellular
space to an isoosmolar state.
If colloid has not been utilized during burn shock and the
serum oncotic pressure is low due to intravascular protein
depletion, protein repletion is frequently needed. The
amount of protein varies with the resuscitation utilized.
Requirements of 0.3–0.5 cc/kg/TBSA burn of 5% albumin
during the second 24 h are utilized with the modified Brooke
formula. The Parkland formula replaces the plasma volume
deficit with colloid. This deficit varies from 20 to 60% of the
circulating plasma volume. We have utilized colloid replace­
ment based on a 20% plasma volume deficit during the
second 24 h (circulating plasma volume × 20%).
In addition to colloid, the patients should receive mainte­
nance fluids. In burn patients the maintenance fluids include
an additional amount for evaporative water loss. The total
daily maintenance fluid requirements in the adult patient
following burn shock can be calculated by the following
formula: basal (1500 cc/m2) +  evaporative water loss [(25 + %
burn)  ×  m2 × 24] = total maintenance fluid (m2 = total body
surface area in square meters). This fluid may be given via
the intravenous route or with enteral feeding. The solution
infused intravenously should be 50% normal saline with
potassium supplements. With the loss of intracellular
inattentive clinical management in acute burn resuscita­
tion.’94 Additionally, in 2008, Blumetti et al. published a
retrospective study of patients resuscitated with the Parkland
formula over a 15-year period to determine accuracy based
on urine output. Their review included data on 483 patients.
They found that 43% received adequate resuscitation and
48% received over-resuscitation. Only 14% of adequately
resuscitated and 12% of over-resuscitated patients met Park­
land formula criteria. They concluded: ‘The actual burn
resuscitation infrequently met the standard set forth by the
Parkland formula’ and ‘patients commonly received fluid
volumes higher than predicted by the Parkland formula.’
They suggest that emphasis be placed on parameters used to
guide resuscitation rather than calculated formula volumes.95
Lawrence and his colleagues in 2010 used the addition of
5% human albumin to patients’ resuscitation fluids when
their fluid requirements are abnormally high.96 They also
considered other factors such as hemodynamic instability,
increasing hematocrit, and persistent lactic acidosis when
making the decision to use a colloid. They termed this prac­
tice ‘colloid rescue’. They used a specific colloid protocol as
a component of their standard LR resuscitation protocol
utilizing I : O ratio introduced by the Army Burn Center.
Increases in the I : O ratio were associated with increased
mortality and morbidity. The total hourly intake of fluid
(mL/kg/% TBSA/h) is divided by the hourly urine output
(UPO; mL/kg/h).97 This is expressed as an intake/output
ratio (I : O ratio). Saffle et al. calculated the actual fluid given
to a group not given colloid with the colloid rescue group;
the results were impressive. In the colloid group, the fluid
requirement for initial treatment was nearly 7 mL/%TBSA/
kg – nearly double the Parkland formula expectations while
the crystalloid group only averaged 4 mL/%TBSA/kg consist­
ent with Parkland calculations. The burn resuscitation used
by the Institute of Surgical Research in Operation Iraqi
Freedom incorporates colloid use and has been associated
with a lower incidence of abdominal compartment syn­
drome which reduced the reported incidence of this compli­
cation to zero.98,99 Of interest, Warden in 1992 suggested that
in patients with massive burns, young pediatric patients and
burns complicated by severe inhalation injury a combina­
tion of fluids may be utilized to achieve the desired goal of
tissue perfusion while minimizing edema. He used the
regimen of modified hypertonic (lactated Ringer’s + 50 mEq
NaHCO3) saline fluid containing 180 mEq Na/L for the first
8 h. After correction of the metabolic acidosis, which gener­
ally requires 8 h, the patients are given lactated Ringers’ only
for the second 8 h. In the last 9 h, a 5% albumin in lactated
Ringers’ was utilized to complete resuscitation.53 Also as
stated above, both the Galveston and Cincinnati utilize
albumin during the first 24 h of resuscitation.
Failure of burn shock resuscitation
In certain patients, failure of burn shock resuscitation still
occurs despite administration of massive volumes of fluid,
hypertonic resuscitation, and colloid. Such patients are
characterized by either extreme age and exceptionally exten­
sive tissue trauma or by major electrical injury, major inha­
lation injury, delay in initiating adequate fluid resuscitation,
or underlying disease that limits metabolic and cardiovas­
cular reserve.100 In these patients, refractory burn shock and

Total Burn Care
9
124
will minimize the amount of edema formation. The rate of
administration of resuscitation fluids should maintain urine
outputs of 30–50 cc in adults and 1–2 cc/kg in children.
When a child weighs 30–50 kg, the urine output should be
maintained at the adult level. Fluid resuscitation based on
our current knowledge of the massive fluid shifts and vascu­
lar changes that occur following burn injury has markedly
decreased mortality related to burn-induced volume loss.
The failure rate for adequate resuscitation is <5% even for
patients with burns >85% TBSA. These improved statistics,
however, are derived from experience in burn centers where
there is substantial knowledge of the pathophysiology of
burn injury. Inadequate volume replacement in major burns
is, unfortunately, common when clinicians lack sufficient
knowledge and experience in this area. The problem of ‘fluid
creep’ is a recent phenomenon and appears to be related to
over-resuscitation with lack of attention to detail during
resuscitation, the use of bolus fluid therapy as suggested by
trauma surgeons and PALS, and the loss of colloid oncotic
pressure in special patients who fail to be resuscitated with
the Parkland formula. The routine use of colloid in the last
8 h of resuscitation or use of a ‘colloid rescue’ in these
patients appears to be beneficial.
Areas of burn shock research that need further attention
include:
•
The definition of the post-burn course of capillary
permeability changes, and identification of humoral or
cellular factors influencing these changes
•
The identification and evaluation of pharmacological
agents that can significantly alter capillary leakage
•
Elucidation of the relationships between resuscitation
fluid composition and pulmonary function changes
•
The effect of resuscitation on late organ dysfunction,
such as post-resuscitation wound, renal, and
pulmonary complications104
•
A prospective multicenter study of colloid-based
resuscitation in comparison with traditional Parkland
therapy.
Further reading
Arturson G. Microvascular permeability to macromolecules in thermal
injury. Acta Physiol Scand. 1979;463(Suppl):111-122.
Baxter CR. Fluid volume and electrolyte changes in the early
post-burn period. Clin Plast Surg. 1974;1:693-703.
Demling RH, Gunther RA, Haines B, et al. Burn edema Part II:
complications, prevention, and treatment. J Burn Care Rehabil.
1982;3:199-206.
Lawrence A, Faraklas I, Watkins H, et al. Colloid administration
normalizes resuscitation ratio and ameliorates ‘fluid creep’. J Burn
Care Res. 2010;31(1):40-47.
Navar PD, Saffle JR, Warden GD. Effect of inhalation injury on fluid
resuscitation requirements after thermal injury. Am J Surg.
1985;150(6):716-720.
Saffle, JI. The phenomenon of ‘fluid creep’ in acute burn resuscitation.
J Burn Care Res. 2007:28(3):382-395.
potassium during burn shock, the potassium requirements
in adults are about 120 mEq/day. In the pediatric patient,
increased fluids are required due to the differences in
BSA to weight ratios compared to adults. In addition,
children also require relatively larger volumes of urine
for excretion of waste products. At the Cincinnati Shriners
Unit, the maintenance fluid requirements are calculated
by the following formula: (35 + % burn) × BSA × 24 (evapora­
tive water loss) + 1500 mL × BSA per day (maintenance
fluids). In Galveston, the recommended fluids needs are
estimated as follows: 3750 mL/m2 BSA per day (burn-related
losses) + 1500 mL/m2 BSA per day (maintenance fluids).
Following the initial 24–48 h post-burn period of resusci­
tation, urinary output is an unreliable guide to adequacy of
hydration.103 Respiratory water losses, osmotic diuresis sec­
ondary to accentuated glucose intolerance, osmotic diuresis
secondary to high protein, high caloric feedings, and derange­
ments in the ADH mechanisms all contribute to increased
fluid losses despite an adequate urine output. In general,
patients with major thermal injuries will require a urine
output of 1500–2000 cc/24 h in adults, and 3–4 mL/kg/h in
children.
The measurement of serum sodium concentration is not
only a means of diagnosing dehydration but also the best
guide for planning and following successful fluid replace­
ment. Other useful laboratory indices of the state of hydra­
tion and guides of therapy include body weight change,
serum and urine nitrogen concentrations, serum and urine
glucose concentrations, the intake and output record, and
clinical examination.
Continuous colloid replacement may be required to main­
tain colloid oncotic pressure in very large burns and in the
pediatric burn patient. Maintaining serum albumin levels
above 2.0 g/dL is desirable.
The electrolytes calcium, magnesium, and phosphate must
also be monitored. Although the replacement of these elec­
trolytes has been studied in detail in burn patients, main­
taining the values within normal limits is desirable and
varies in each patient.
Summary
The volume necessary to resuscitate burn patients is depend­
ent upon injury severity, age, physiological status, and
associated injury. Consequently, the volume predicted by a
resuscitation formula must commonly be modified accord­
ing to the individual’s response to therapy. In optimizing
fluid resuscitation in severely burned patients, the amount
of fluid should be just enough to maintain vital organ func­
tion without producing iatrogenic pathological changes. The
composition of the resuscitation fluid, within limitations, in
the first 24 h post-burn probably makes very little difference;
however, it should be individualized to the particular patient.
The utilization of the beneficial properties of hypertonic,
crystalloid, and colloid solutions at various times post-burn
 
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Fluid resuscitation and early management
124.e1
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27. Shires GT. Proceedings of the second NIH workshop on burn
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30. Caldwell FT, Bowser BH. Critical evaluation of hypertonic and
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33. Bowser-Wallace BH, Cone JB, Caldwell FT Jr. A prospective
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34. Bowser-Wallace BH, Cone JB, Caldwell FT Jr. Hypertonic lactated
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35. Bowser-Wallace BH, Caldwell Jr FT. Fluid requirements of
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1986;12:549-555.
36. Bartolani A, Governa M, Barisoni D. Fluid replacement in
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37. Griswold JA, Anglin BL, Love Jr RT, et al. Hypertonic saline
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38. Jelenko III C, Williams JB, Wheeler ML, et al. Studies in shock
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1979;7:157-167.
39. Gunn ML, Hansbrough JF, Davis JW, et al. Prospective
randomized trial of hypertonic sodium lactate vs. lactated
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40. Yoshioka T, Maemura K, Ohhashi Y, et al. Effect of intravenously
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41. Shimazaki S, Yoshioka T, Tanaka N, et al. Body fluid changes
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shock. J Trauma. 1977;17:38-43.
42. Crum R, Bobrow B, Shackford S, et al. The neurohumoral
response to burn injury in patients resuscitated with hypertonic
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43. Huang PP, Stucky FS, Dimick AR, et al. Hypertonic sodium
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44. Du GB, Slater H, Goldfarb IW. Influence of different
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45. Baxter CR. Problems and complications of burn shock
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46. Goodwin CW, Dorethy J, Lam V, et al. Randomized trial of
efficacy of crystalloid and colloid resuscitation on hemodynamic
response and lung water following thermal injury. Ann Surg.
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47. Demling RH. Fluid resuscitation. In: Boswick Jr JA, ed. The art
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48. Demling RH, Kramer GD, Harms B. Role of thermal injury-
induced hypoproteinemia on edema formation in burned and
non-burned tissue. Surgery. 1984;95:136-144.
49. Demling RH, Kramer GC, Gunther R, et al. Effect of non-protein
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50. Alderson P, Bunn F, Lefevre C. Human albumin solution for
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51. Wilkes MM, Navickis RJ. Patient survival after human albumin
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52. Gelin LE, Solvell L, Zederfeldt B. The plasma volume expanding
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53. Warden GD. Burn shock resuscitation. World J Surg. 1992;16:
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54. Carvajal HF. Fluid therapy for the acutely burned child. Compr
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55. Merrell SW, Saffle JR, Sullivan JJ, et al. Fluid resuscitation in
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56. Graves TA, Cioffi WG, McManus WF, et al. Fluid resuscitation of
infants and children with massive thermal injury. J Trauma.
1988;28:1656-1659.
57. Pediatric Advanced Life Support, PALS Provider Manual. New York:
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58. Navar PD, Saffle JR, Warden GD. Effect of inhalation injury on
fluid resuscitation requirements after thermal injury. Am J Surg.
1985;150:716-720.
59. Lalonde C, Picard L, Youn YK, et al. Increased early postburn
fluid requirement and oxygen demands are predictive of the
degree of airways injury by smoke inhalation. J Trauma.
1995;38(2):175-184.
60. Mansfield MD, Kinsell J. Use of invasive cardiovascular
monitoring in patients with burns greater than 30 percent
body surface area: a survey of 251 centres. Burns. 1996;22:549-
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61. Fabri PJ. Monitoring of the burn patient. Clin Plast Surg.
1986;13:21-27.
62. Kirton OC, Civetta JM. Do pulmonary artery catheters alter
outcome in trauma patients? New Horizons. 1997;5:222-227.
63. Pulmonary Artery Catheter Consensus Conference: consensus
statement. Crit Care Med. 1997;25(6):910-925.
64. Aikawa N, Martyn JA, Burke JR. Pulmonary artery catheterization
and thermodilution cardiac output determination in the
management of critically burned patients. Am J Surg.
1978;135:811-817.
65. Agarwal N, Petro J, Salisbury RE. Physiologic profile monitoring
in burned patients. J Trauma. 1982;23:577-583.
66. Dries DJ, Waxman K. Adequate resuscitation of burn patients
may not be measured by urine output and vital signs. Crit Care
Med. 1991;19:327-329.
67. Schiller WR, Bay RC. Hemodynamic and oxygen transport
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475-482.
68. Fleming AW, Bishop M, Shoemaker W, et al. Prospective trial of
supranormal values as goals of resuscitation in severe trauma.
Arch Surg. 1992;127:1175-1181.
69. Bishop MH, Shoemaker WC, Appel PL, et al. Prospective,
randomized trial of survivor values of cardiac index, oxygen
delivery, and oxygen consumption as resuscitation endpoints in
severe trauma. J Trauma. 1995;38:780-787.
70. Pearson KS, Gomez MN, Moyers JR, et al. A cost/benefit analysis
of randomized invasive monitoring of patients undergoing
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71. Ontario Intensive Care Study Group. Evaluation of right heart
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72. Yu M, Levy MM, Smith P, et al. Effect of maximizing oxygen
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patients: a prospective, randomized, controlled study. Crit Care
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73. Gattinoni L, Brazzi L, Pelosi P, et al. A trial of goal-oriented
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74. Cooper AB, Goig GS, Sibbald WJ. Pulmonary artery catheters in
the critically ill. An overview using the methodology of
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75. Elliott DC. An evaluation of the end points of resuscitation.
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76. Aikawa N, Ishbiki K, Naito C, et al. Individualized fluid
resuscitation based on haemodynamic monitoring in the
management of extensive burns. Burns. 1982;8:249-255.
77. Bernard F, Gueugniaud P-Y, Bertin-Maghit M, et al. Prognostic
significance of early cardiac index measurements in severely
burned patients. Burns. 1994;20:529-531.
78. Schiller WR, Bay RC, McLachlan JG, et al. Survival in major burn
injuries is predicted by early response to Swan-Ganz-guided
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79. Schiller WR, Bay RC, Garren RL, et al. Hyperdynamic
resuscitation improves survival in patients with life-threatening
burns. J Burn Care Rehabil. 1997;18:10-16.
80. Barton RG, Saffle JR, Morris SE, et al. Resuscitation of thermally
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therapy. J Burn Care Rehabil. 1997;18:1-9.
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82. Bakker J, Coffemils M, Leon M, et al. Blood lactate levels are
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83. Weil MH, Afifi AA. Experimental and clinical studies on lactate
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93. Saffle J. The phenomenon of ‘fluid creep’ in acute burn
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©2012 Elsevier Ltd, Inc, BV
DOI: 10.1016/B978-1-4377-2786-9.00010-2
Evaluation of the burn wound:
management decisions
Giavonni M. Lewis, David M. Heimbach, Nicole S. Gibran
Introduction
Advances in the resuscitation of burn patients have
greatly improved survival, so that death from burn shock
has become uncommon. In the 21st century, prompt
recovery and good functional outcome for the burn patient
hinges, in large part, on proper management of the burn
wound.
Perhaps the greatest advance in burn care to date has been
the institution of early surgical excision of the burn wound
with immediate or delayed wound closure strategy individu­
alized to each patient.1–4 For many years, burns were treated
by daily washing, removal of loose dead tissue, and applica­
tion of some sort of topical nostrum until wounds healed
by themselves or granulation tissue appeared in the wound
bed. Superficial dermal burns healed within 2 weeks and
deep dermal burns healed over many weeks if infection was
prevented. Full-thickness burns lost their eschar in 2–6
weeks by enzyme production from bacteria and by daily
bedside debridement. Split-thickness skin grafts were applied
usually 3–8 weeks after injury. A 50% graft survival was
considered acceptable and repeated grafting eventually
closed the wound. The prolonged and intense inflammatory
response made hypertrophic scars and contractures part of
normal burn treatment.
Burns that heal within 3 weeks generally do so without
hypertrophic scarring or functional impairment, although
long-term pigment changes may occur. Burns needing longer
than 3 weeks to heal produce unsightly hypertrophic scars,
and may form contractures leading to functional impair­
ment. With few exceptions, state of the art burn care now
involves early excision and grafting of all burns that do not
heal within 3 weeks. The challenge is to determine which
burns will heal within 3 weeks.
Burn wound assessment requires an understanding of skin
biology and the pathophysiological changes caused by
thermal injury. The standard technique for determining burn
depth in the 21st century still remains clinical assessment of
the wound by an experienced burn specialist. Management
decisions should take into account the mechanism of injury,
as this invariably influences the healing potential of the
wound, and therefore guides the timing of surgical
intervention.
Pathophysiology of the burn wound
Skin biology
The skin is the largest organ in the human body and is com­
prised of two layers: the epidermis and the dermis. The
thickness of the epidermis varies among different parts of
the body, from 0.05 mm on the eyelids to over 1 mm on the
soles.5 Most of the skin thickness comes from the dermis,
which varies with age, gender, and body location. The skin
serves as protection against fluid and electrolyte loss, infec­
tion, radiation, and provides thermal regulation. Contact
with the skin provides the individual clues to the surround­
ing environment through touch, perception of temperature
and pain. In addition, skin appearance is a major determi­
nant of identity and affects interpersonal interactions.
The mostly cellular epidermis is derived from ectoderm
and the principal cell is the keratinocyte. These cells begin
their division and differentiation at the basal layer and move
progressively outward over 2–4 weeks6 along the outer four
layers of the epidermis: the stratum spinosum, the stratum
granulosum, the stratum lucidum, and the stratum corneum.
Keratinocytes lose their nuclei in the stratum lucidum and
become flattened dead cells in the stratum corneum. Other
important cells of the epidermis include melanocytes, which
produce the melanin pigment essential for protection against
ultraviolet radiation, and Langerhans cells, which perform
phagocytosis and presentation of foreign antigens. The epi­
dermis, because it is derived from ectoderm, is capable of
regenerative healing. Thus, pure epidermal injuries heal by
regeneration and without scarring. Keratinocytes proliferate
from dermal appendages (hair follicles, sweat glands) and
the edges of the wound to achieve reepithelialization.
Depleted melanocytes after injury, however, regenerate more
slowly and less predictably, which may lead to permanent
pigment changes within the healed wound.7,8
The basement membrane zone connects the epidermis to
the dermis via epidermal projections (rete ridges) that
interdigitate with dermal projections (papillae). The critical
structures that stabilize the epidermal-dermal junction
are keratinocyte-derived collagen VII anchoring fibrils that
extend into the dermis.9,10 These anchoring fibrils may take
several weeks (and sometimes months) to mature during
CHAPTER 10 
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IN THIS CHAPTER
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Total Burn Care
10
126
on the prevention of necrosis in the zone of stasis. Locally,
in the zone of stasis, approximately half of the cells are
undergoing apoptosis versus necrosis as a result of oxidative
stress, ongoing inflammation and decreased blood flow due
to microthrombosis.19 It is relatively unclear if this rate of
apoptosis is associated with conversion to a deeper burn;
however it provides a basis for future study in elucidating
techniques for healing at the zone of stasis.19 Systemically,
protection of this sensitive area is achieved with adequate
fluid resuscitation, avoidance of vasoconstrictors and pre­
vention of infection.20,21 Optimal wound care consists of
non-desiccating dressings, topical antimicrobials, and fre­
quent monitoring of the wound.22–24 Interest in cooling of
the wound to minimize the extent of injury can be traced to
antiquity,25 but to this day, firm evidence of its efficacy is
lacking. To be effective, cooling must be performed immedi­
ately after injury, and should not supersede other priorities
in the evaluation of the injured patient. The optimal tem­
perature and duration of cooling is unknown26–28; in fact,
excessive or prolonged cooling may be harmful in that it
promotes vasoconstriction and systemic hypothermia.29,30
Current guidelines of American Burn Association recom­
mend limiting cooling to 30 min in the management of
minor burns.31 Modalities to improve dermal perfusion and
block injury from released inflammatory mediators have
also garnered much interest. Experimental benefits have
been reported for many pharmacologic agents such as
heparin, steroidal and non-steroidal anti-inflammatory
agents, thromboxane inhibitors, and epidermal growth
factor.32–40,19 Yet, all remain investigational since none has
gained wide acceptance for clinical use.
Assessment of burn depth
Clinical observation
Burn injury may involve one or both layers of the skin, and
may extend into the subcutaneous fat, muscle and even bony
structures.41 Burns involving only the epidermis are ery­
thematous and very painful but do not form blisters. Most
burn wound healing. Minor shearing forces may cause shear­
ing, blistering and sometimes epidermal loss until the inter­
digitations mature.
The dermis with its abundant extracellular matrix compo­
nent is derived from mesoderm and is divided into the more
superficial papillary dermis and the deeper reticular dermis.
Collagen fibers provide the bulk of the dermal structure.
Their organized orientation allows for stretching and tensile
strength of the skin.11 Elastic fibers impart the elastic recoil
properties of skin. Protein turnover (by degradation, produc­
tion and remodeling) increases with mechanical stress and
during healing, accounting for the high plasticity of skin.
Collagen and elastin are both synthesized by fibroblasts, the
principal cell of the dermis. The non-fibrous component of
the dermis is called the ground substance. It is composed of
glycosaminoglycans and proteoglycans such as hyaluronic
acid and chondroitin sulfate, whose function is to entrap
fluid to maintain the semi-fluid matrix and to regulate cel­
lular cross-talk by binding and releasing inflammatory medi­
ators.12 Adnexal structures (sweat glands, sebaceous glands,
and hair follicles) originate in the dermis and extend through
the epidermis. Since they are lined with epidermal keratino­
cytes, adnexal structures provide the epithelial cells necessary
for reepithelialization after a partial dermal injury. The
dermal plexus of capillary vessels delivers the necessary
nutrients to cellular structures in both the dermis and
epidermis. After wounding however, the endothelial cells
also mediate local and systemic inflammatory responses.13
Sensory nerves, which traverse the dermis into the epidermis,
also play a significant role after injury, as they mediate pain
and itching, modulate inflammation, and appear to influ­
ence the remodeling phase of wound healing.14,15 The dermis,
like other structures derived from mesoderm, heals not by
regeneration but by fibrosis and scarring.
Pathophysiological changes of thermal injury
Applied heat at the cellular level causes denaturation of pro­
teins and loss of plasma membrane integrity. Temperature
and duration of contact have a synergistic effect, such that
cell necrosis occurs after 1 s of exposure at 156°F (69°C),
or after 1 h at 113°F (45°C).16 Following a burn, necrosis
occurs at the center of the injury, and becomes progressively
less severe at the periphery. Thus, Jackson’s description in
1953 of the three zones of injury still remains our current
conceptual understanding of the burn wound (Fig. 10.1).17
The zone of coagulation is at the center of the wound where
no viable cells remain. Surrounding it is the zone of stasis,
characterized as a mix of viable and non-viable cells, capil­
lary vasoconstriction, and ischemia. This tenuous area rep­
resents the zone ‘at-risk’ and may convert to necrosis with
hypoperfusion, desiccation, edema, and infection. With
proper wound care management however, these changes
may be reversed.18 Systemic factors such as advanced age,
diabetes, and other chronic illnesses also put the zone of
stasis at higher risk for ‘conversion’. The outer periphery of
the burn wound is the zone of hyperemia, with viable cells
and vasodilation mediated by local inflammatory mediators.
Tissue in this zone usually recovers completely unless com­
plicated by infection or severe hypoperfusion.
Since medical care, for the most part, has little impact on
the outcome of the zone of coagulation, efforts have focused
Figure 10.1  Jackson’s 3 zones of injury on an ankle burn: (a) the zone of
coagulation; (b) the zone of stasis, and (c) the zone of hyperemia.

Evaluation of the burn wound: management decisions
127
The most difficult management decision involves partial-
thickness burns that are intermediate in depth. In this situ­
ation, the determining factor as to whether these burns heal
in 3 weeks may only be a matter of a few tenths of a mil­
limeter. These burns are more aptly called ‘indeterminate’
burns as their healing potential becomes evident with serial
assessments over several days. As evidenced by histologic
studies, burn injury is a dynamic process that peaks at about
3 days.42–44 Initial evaluation by an experienced surgeon as
to whether an indeterminate dermal burn will heal in 3
weeks is only about 50–70% accurate.45–47
Adjuncts to clinical evaluation
An intense search for a more precise diagnosis of burn depth
has been mounted ever since it became recognized that
many patients would benefit from early determination for
operation. The clinical assessment of the burn wound depth
is approximately 64–76% accurate in senior burn surgeons
with serial exams.48 Over the last 80 years, interest in tech­
nologies for improving accurate determination of burn
depth has been robust.48–50 Multiple modalities for deter­
mining burn depth have been entertained, but ultimately
fallen out of favor or reinvented, which include thermogra­
phy, photometry, nuclear imaging, pulse-echo ultrasound
and, more invasive than the aforementioned, serial tissue
biopsy.48–50 These techniques take advantage of the ability to
detect: dead cells or denatured collagen (biopsy, ultrasound,
vital dyes),17,51–54 the color of the wound (light reflectance),55
physical changes, such as edema (magnetic resonance
imaging),56 and altered blood flow (fluorescein, laser
Doppler imaging, and thermography).57–59 Unfortunately,
none of these techniques has been proven superior to serial
clinical assessments by an experienced burn provider. Several
groups, however, have recently reported clinical benefits with
the use of non-contact laser Doppler imaging in indetermi­
nate thickness burns.44,48,60 This technique provides a color
perfusion map of the burn wound to add to the clinician’s
assessment. Since the scanner is held at a distance from the
wound, this test is well tolerated and perhaps more reliable
as no pressure is exerted on the wound. Furthermore, this
test can be repeated over the first several days post-burn
to document dynamic changes in wound bed perfusion.
Although a promising tool, non-contact laser Doppler
imaging has, so far, not been widely adopted into clinical
practice.
Mechanisms of thermal injury
Flash and flame burns
Flash and flame burn injuries represent approximately half
of the admissions to American regional burn centers. Explo­
sions of natural gas, propane, gasoline, and other flammable
liquids cause intense heat for a very brief time. In particular,
gasoline has highly flammable vapors that are 3–4 times
denser than air. At room temperature, gasoline vapors can
diffuse above ground and may accumulate in enclosed
spaces. Victims often describe an inappropriate use of gaso­
line as a fire accelerant (trash burning, outdoor fire). Cloth­
ing, unless it ignites, is protective in flash burns. Hence, flash
sunburns fit this category of superficial, epidermal injury.
Within 3–4 days, the dead epidermis sloughs and is replaced
by regenerating keratinocytes.
Superficial dermal burns extend into the papillary dermis
and characteristically form blisters. Blistering may not occur
immediately following injury and burns thought to be
superficial may subsequently be diagnosed as dermal burns
by day.2 Once the blister is removed from a superficial partial
thickness burn, the wound is pink, wet and hypersensitive
to touch. Wound care is often painful as uncovering the
wound allows currents of air to pass over it. These wounds
blanch with pressure, and the blood flow to the dermis is
increased over that of normal skin due to vasodilation. With
appropriate wound care, superficial dermal burns usually
heal within 2–3 weeks without risk of scarring and therefore
do not require operation.
Deep dermal burns extend into the reticular dermis and
generally will take 3 or more weeks to heal. They also blister,
but the wound surface appears mottled pink and white
immediately following the injury (Fig. 10.2). The patient
complains of discomfort and pressure rather than pain.
When pressure is applied to the burn, capillaries refill slowly
or not at all. The wound is often less sensitive to pinprick
than the surrounding normal skin. By the second day the
wound may be white and is usually fairly dry. As a rule,
partial-thickness burns that are predicted not to heal by 3
weeks should be excised and grafted.
Full-thickness burns involve the entire dermis and extend
into subcutaneous tissue. Their appearance may be charred,
leathery, firm, and depressed when compared to adjoining
normal skin. These wounds are insensitive to light touch and
pinprick. Non-charred full-thickness burns can be deceptive.
Like deep dermal burns, they may be mottled in appearance.
They rarely blanch on pressure, and may have a dry, white
appearance. In some cases the burn may be translucent with
clotted vessels visible in the depths. Some full-thickness
burns, particularly immersion scalds or ‘bake’ injuries
(caused by convective heat), may have a red appearance, and
can be confused by the inexperienced observer as a superfi­
cial dermal burn. These burns, however, do not blanch with
pressure. Full-thickness burns should be excised and grafted
early to expedite the patient’s recovery process and prevent
infection and hypertrophic scarring.
Figure 10.2  Lower extremity burn having components of a superficial
dermal burn (a) with a wet, pink and moist appearance, as well as a deeper
dermal burn; (b) with mottled pink and white areas.
a
b

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128
are examples that should raise suspicion of abuse (Fig. 10.3).
A detailed description on the recognition and management
of intentional burn injuries is available elsewhere in this text.
The evaluating physician therefore, must carefully consider
whether the history provided matches the distribution and
probable cause of the burn; this is best accomplished by an
experienced burn surgeon who is familiar with burn distri­
bution and etiologies.
Grease and hot oils will generally cause deep dermal or
even full-thickness injuries. During cooking, grease and hot
oils are heated to a level below their smoke point to avoid
unpleasant odors from their decompositions. The smoke
point for butter is 350°F (177°C), 400° F (204°C) for lard,
and 450°F (232°C) for corn oil. Cooking oils reach their
flash point at 600°F (316°C). Deep dermal burns com­
monly occur when a victim tries to carry the burning pan
of grease outdoors and douses himself instead of putting
the lid on the pan and extinguishing the fire. The extent of
domestic grease injuries invariably follows a common
pattern.66 A single wrist and forearm is first affected. The
panicked victim lets go of the pan and splashes himself onto
his feet and sometimes thighs and trunk. The now slippery
floor from spilled grease causes the victim to fall and burn
his back and buttocks. Approximately 30–40% of grease
burns require excision and grafting.66,67
Tar and asphalt are a special kind of scald. The ‘mother
pot’ at the back of the roofing truck maintains tar at a tem­
perature of 400–500°F (204–260°C). Burns caused by tar
directly from the ‘mother pot’ are invariably full-thickness.
By the time the tar is spread on the roof, its temperature has
burns generally have a distribution involving all exposed
skin, with the deepest areas facing the source of ignition. For
the most part, flash burns reach progressive layers of the
dermis in proportion to the amount and kind of fuel that
explodes. While such burns will generally heal without
extensive skin grafting, they may cover large areas and may
be associated with thermal damage to the upper airway.
In contrast to flash injuries, flame burns are invariably
deep dermal if not full-thickness because of more prolonged
exposure to intense heat. Although the incidence of injuries
from house fires has decreased with the advent of smoke
detectors, careless smoking, improper use of flammable
liquids, automobile accidents, and clothing ignited from
stoves or space heaters still exact their toll. Patients whose
bedding or clothes have been on fire rarely escape without
some full-thickness burns. Many victims of house fires are
also prone to deeper injuries because of intoxication or con­
fusion caused by carbon monoxide poisoning. In one study
of several burn centers, 28% of flame burns occurred in
patients with high blood ethanol level, and 51% of victims
in fires behaved inappropriately when trying to escape.61 Loss
of consciousness may also expose the victim to convective
heat inside a burning room. This type of ‘bake’ injury may
deceptively appear shallow with intact epithelium to the
inexperienced observer, but is really a full-thickness burn.
Scalds
Hot water scalds are the next most common cause of burns
in the United States. Despite educational programs, the epi­
demiology and incidence of scalds worldwide has changed
very little. The depth of scald injury depends on the water
temperature, the skin thickness and the duration of contact.
Water at 140°F (60°C) creates a deep dermal burn in 3 s but
will cause the same injury in 1 s at 156°F (69°C). Freshly
brewed coffee from an automatic percolator is generally
about 180°F (82°C). Once in the pot, coffee temperature
approximates 160°F (70°C). Boiling water often causes a
deep dermal burn, unless the duration of contact is very
short. Soups and sauces, which are thicker in consistency,
will remain in contact longer with the skin and invariably
cause deep dermal burns. In general, exposed areas tend to
be burned less deeply than clothed areas. Clothing retains
the heat and keeps the liquid in contact with the skin longer.
As a result, scalds are often a mosaic of superficial and inde­
terminate dermal burns. A common example is a toddler
who reaches above head level and spills hot water on himself.
His face bears a superficial burn, his trunk burn is of inde­
terminate thickness, and his skin under his diaper has a deep
dermal burn.
Immersion scalds are often deep because of the prolonged
skin exposure, although the water temperature may not be
as high as in spill scalds.62,63 They occur in individuals who
do not perceive the discomfort of prolonged immersion (i.e.
a diabetic patient soaking his foot in hot water), or who are
not able to escape from the hot water (i.e. young children,
the elderly, or people with physical and cognitive disabili­
ties). This latter group of vulnerable individuals is also sus­
ceptible to non-accidental scald burns.64,65 Child victims of
non-accidental scalds represent about 2% of all children
admitted to our burn center. Circumferential extremity inju­
ries, symmetrical burns to a child’s buttocks and perineum
Figure 10.3  Immersion scald burn on a child. Arrows denote sparing of
bilateral popliteal fossae: the child by reflex bent his knees to avoid contact
with the hot water.

Evaluation of the burn wound: management decisions
129
intermediate-depth palm burns heal in about 2–3 weeks. On
the other hand, unoperated deep palm burns heal from the
edges with contracture of the palm leading to permanent
disability. The decision to perform excision and grafting
using thick split-thickness grafts or full-thickness grafts to
deep palm burns71,72 should be tempered by the knowledge
that sensory nerve endings unique to glabrous skin (Pacinian
and Meissner’s corpuscles) cannot be replaced by a skin
graft. Therefore, an observation period of 2–3 weeks with
splinting and aggressive exercise appears prudent.
Chemical burns
Chemical burns, usually caused by strong acids or alkali, are
most often the result of industrial accidents, drain cleaners,
assaults, and the improper use of harsh solvents. Chemical
burns cause progressive damage until the chemicals are inac­
tivated by reaction with the tissue or dilution by flushing
with water. Although individual circumstances vary, acid
burns are usually more self-limiting than alkali burns. Acid
tends to ‘tan’ the skin, creating an impermeable barrier
that limits further penetration of the acid. Alkali, on the
other hand, combines with cutaneous lipids to create soap
and thereby continues ‘dissolving’ the skin until it is
neutralized.
Initial management consists of diluting the agent with
copious water, preferably at the site of the accident. To this
end, many industrial workplaces are now equipped with
such showers and eye wash stations. The victim should have
the contact site irrigated for 15–20 min at minimum. A
paper pH test applied to the patient’s burn can verify that
the agent has been neutralized. Attempts to neutralize alkalis
with acids (and vice-versa) are contraindicated because these
maneuvers are dangerous and may induce an exothermic
reaction leading to a thermal injury superimposed on the
chemical burn. An exception to the irrigation rule is expo­
sure to a chemical powder. In this instance, it is safer to brush
the agent off. Examples of common dry chemicals include
dry concrete, cement and sodium hydroxide. A full-thickness
chemical burn may appear deceptively superficial, clinically
causing only a mild brownish discoloration of the skin. The
skin may appear intact during the first few days post-burn,
and only then begin to slough spontaneously. Unless the
observer can be absolutely sure, chemical burns should
be considered deep dermal or full-thickness until proven
otherwise.
Burns caused by wet cement can be vexing. Workers often
kneel in wet cement or spill cement inside boots or gloves
and do not become symptomatic for hours.73–75 By the time
they seek medical help, the wounds are often deep and most
often need grafting.
Hydrofluoric acid (HF) burns are potentially very destruc­
tive. HF is widely used in the circuit board etching, cleaning
solvents, and paint removers. HF coagulates the skin at site
of exposure. Fluoride ions penetrate the skin and cause deep
tissue destruction by combining with cellular calcium and
magnesium.76,77 Fluoride is also a metabolic poison that
inhibits key enzymes of cellular metabolism. A 10% TBSA
HF burn may be life threatening due to systemic hypocal­
cemia78; this may be one instance where urgent surgical
wound excision is indicated. As with cement, the worker may
not become symptomatic for several hours after exposure,
diminished to the point where most of the burns are deep
dermal in nature. Initially evaluation consists of tar removal
before injury depth can be assessed. Tar can be removed by
application of petroleum-based ointment under a dressing.
The dressing is changed and ointment reapplied every 2–4 h
until the tar has dissolved. Medi-Sol adhesive remover spray
(Orange-Sol, Gilbert, AZ, USA) can be successfully used to
remove the tar without injury to the burn wound.
Partial thickness scald burns can be usually managed non-
operatively for 10–14 days, unless they are obviously deep.
Burns should be excised and autografted as soon as it is clear
that they will not heal by 3 weeks. Desai et al. confirmed the
validity of this strategy in a randomized trial.68 Children with
large scald burns (approximately 25% TBSA) were either
excised early (within 72 h) or after 2 weeks post-injury. Chil­
dren in the late group required excision of significantly
smaller areas, while half achieved reepithelialization without
surgery.
Contact burns
Contact burns result from hot metals, plastic, glass, or hot
coals. Although generally small in size, contact burns are
challenging in that the injury is often very deep (Fig. 10.4).
Burn depth can be predicted based on the temperature of
the material and the duration of contact. Thus, molten
ma­terials in industrial accidents instantaneously cause a
burn extending below the dermis. Likewise, an unconscious
victim lying on top of a heating blanket all night will have
a burn extending into fat and sometimes muscle. Industrial
accidents involving presses or other hot, heavy objects may
cause both contact burns and crush injuries. In these circum­
stances, the clinician must anticipate the possibility of exten­
sive myonecrosis and myoglobinuria despite the relative
small size of the wound. Contact burns with a hot muffler
are usually full-thickness and require excision and grafting.
Traffic accidents where the victim is trapped against a muffler
or engine block may generate significant defects requiring
flap coverage.69
Domestic contact burns often involve palm and finger
burns in toddlers. The unsuspecting child typically puts his
hands on a wood-stove, fireplace insert, iron press or oven
door.70 With aggressive wound care and hand therapy, most
Figure 10.4  Deep contact burn in an elderly patient who was unconscious
next to a space heater. Arrows denote the imprints of the space heater grill
on his lateral thigh.

Total Burn Care
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130
intense heat with less dissipation. Therefore, fingers, hands,
forearms, feet, and lower legs are often totally destroyed,
whereas the trunk usually dissipates enough current to
prevent extensive damage to viscera (unless the entrance or
exit wound is on the abdomen or chest).91–93 Arc electrical
burns are also common as the current takes the most direct
path, rather than a longer path of seeming less resistance.
These injuries occur at joints in close apposition at the time
of injury. Most common are burns of the volar aspect of the
wrist, the antecubital fossa when the elbow is flexed, and the
axilla if the shoulder is adducted.
There are two reasons for early operation in the patient
with electrical burns. Massive deep tissue necrosis may lead
to acidosis or myoglobinuria that will not clear with stand­
ard resuscitation techniques. In this unusual circumstance,
fasciotomies, major debridement, and amputation may be
needed urgently. More commonly, tissue swelling raises the
risk of compartment syndrome. Careful monitoring of the
injured extremity is mandatory. Compartmental release is
indicated with any sign of progressive peripheral neuropa­
thy. Thus, worsening median or (less commonly) ulnar nerve
deficit in the injured hand is an indication for immediate
median and ulnar nerve release at the wrist. The use of a
technetium scan to help identify damaged and necrotic
muscle has been advocated,94 but has not achieved wide­
spread use. This test is overly sensitive in detecting damage
to deep, unexposed muscle groups that, left alone, will
fibrose and not require excision.95
If immediate decompression or debridement is not
required, definitive operations can be performed between
days 3 and 5, before bacterial contamination occurs and after
the tissue necrosis is delineated.95,96 Extraordinary measures,
such as vascular grafts to replace clotted arteries, and urgent
free flaps may sometimes be indicated,97,98 but the surgeon
is cautioned that they may actually increase morbidity and
prolong the patient’s recovery. A well-fitting prosthesis might
give better function than a hand or foot that is weak and has
diminished sensation.
Further reading
Burke JF, Bondoc CC, Quinby WC. Primary burn excision and
immediate grafting: a method shortening illness. J Trauma.
1974;14(5):389-395.
Gray DT, Pine RW, Harnar TJ, et al. Early surgical excision versus
conventional therapy in patients with 20 to 40 percent burns.
A comparative study. Am J Surg. 1982;144(1):76-80.
Jackson DM. The diagnosis of the depth of burning. Br J Surg.
1953;40(164):588-596.
Riordan CL, McDonough M, Davidson JM, et al. Noncontact laser
Doppler imaging in burn depth analysis of the extremities. J Burn
Care Rehabil. 2003;24(4):177-186.
Shupp JW, Nasabzadeh TJ, Rosenthal DS, et al. A review of the local
pathophysiologic bases of burn wound progression. J Burn Care
Res. 2010;31(6):1-25.
Yannas IV, Burke JF. Design of an artificial skin. I. Basic design
principles. J Biomed Mater Res. 1980;14(1):65-81.
when severe pain develops in the involved fingers. Delayed
or inadequate treatment can lead to amputation. Older rec­
ommendations of calcium-containing topical gels79,80 and
direct injection of calcium gluconate into the involved tissue
have now largely been replaced by intra-arterial infusion of
calcium ions into vessels perfusing the injured area.81–84 Such
treatment is almost magical, with immediate cessation of
pain and minimal tissue destruction. However, once acute
symptoms resolve, it has no further role in preventing tissue
damage.
Electrical burns
Electrical burns are in reality thermal burns from very high
intensity heat generated as the victim’s body becomes an
accidental resistor. Low voltage injuries (<440 volts) rarely
cause significant damage beyond a small deep thermal burn
at contact points. An exception to this rule is the child who
chews on an active electrical connection.85 The child’s saliva
completes the circuit between the positive and neutral leads.
The short circuit may cause a severe burn inside the mouth
and lip. Burns involving the oral commissure are at high-risk
for late contracture and warrant an aggressive splinting and
exercise regimen.86,87 In addition, eschar separation at the
corner of the mouth by day 7–10 after injury may be associ­
ated with brisk labial artery bleeding that requires surgical
control.88 High voltage injuries (over 1000 volts) are more
apt to cause deep tissue destruction. In fact, most electrical
burns are work-related (i.e. construction workers, linemen,
utility and electrical workers). In this setting, extensive deep
tissue destruction may take place underneath a relatively
small, innocuous-appearing wound (Fig. 10.5).
High resistance at skin contact points is partially protective
as a dry calloused hand may provide twice the resistance of
normal skin, and five times the resistance of wet skin. High
resistance within the victim’s body, on the other hand, causes
more harm. As electricity travels through the body, electrical
energy is converted to heat in direct proportion to current
and electrical resistance. Deep muscle necrosis may occur
adjacent to bone, which has high resistance.89,90 A smaller
body part conducting the electricity will generate more
Figure 10.5  High-voltage contact point on an electrician’s knee: (a) prior
to, and (b) after débridement.
A
B
Access the complete reference list online at

Evaluation of the burn wound: management decisions
130.e1
© Copyright 2012 Elsevier, Inc. All rights reserved.
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Burns Incl Therm Inj. 1984;10(5):344-348.
65. Bird PE, Harrington DT, Barillo DJ, et al. Elder abuse: a call to
action. J Burn Care Rehabil. 1998;19(6):522-527.
66. Klein MB, Gibran NS, Emerson D, et al. Patterns of grease burn
injury: development of a classification system. Burns. 2005;31(6):
765-767.
67. Murphy JT, Purdue GF, Hunt JL. Pediatric grease burn injury.
Arch Surg. 1995;130(5):478-482.
68. Desai MH, Rutan RL, Herndon DN. Conservative treatment of
scald burns is superior to early excision. J Burn Care Rehabil.
1991;12(5):482-484.
69. Gibran NS, Engrav LH, Heimbach DM, et al. Engine block burns:
Dupuytren’s fourth-, fifth-, and sixth-degree burns. J Trauma.
1994;37(2):176-181.
70. Yanofsky NN, Morain WD. Upper extremity burns from
woodstoves. Pediatrics. 1984;73(5):722-726.
71. Pensler JM, Steward R, Lewis SR, et al. Reconstruction of the
burned palm: full-thickness versus split-thickness skin grafts –
long-term follow-up. Plast Reconstr Surg. 1988;81(1):46-49.
72. Merrell SW, Saffle JR, Schnebly A, et al. Full-thickness skin
grafting for contact burns of the palm in children. J Burn Care
Rehabil. 1986;7(6):501-507.
73. Lewis PM, Ennis O, Kashif A, et al. Wet cement remains a poorly
recognised cause of full-thickness skin burns. Injury. 2004;35(10):
982-985.
74. Fisher AA. Cement burns resulting in necrotic ulcers due to
kneeling on wet cement. Cutis. 1979;23(3):272-274, 370.
75. Early SH, Simpson RL. Caustic burns from contact with wet
cement. JAMA. 1985;254(4):528-529.
76. Bertolini JC. Hydrofluoric acid: a review of toxicity. J Emerg Med.
1992;10(2):163-168.
77. Anderson WJ, Anderson JR. Hydrofluoric acid burns of the hand:
mechanism of injury and treatment. J Hand Surg [Am]. 1988;
13(1):52-57.
78. Mayer TG, Gross PL. Fatal systemic fluorosis due to hydrofluoric
acid burns. Ann Emerg Med. 1985;14(2):149-153.
79. Bracken WM, Cuppage F, McLaury RL, et al. Comparative
effectiveness of topical treatments for hydrofluoric acid burns.
J Occup Med. 1985;27(10):733-739.
80. Chick LR, Borah G. Calcium carbonate gel therapy for
hydrofluoric acid burns of the hand. Plast Reconstr Surg.
1990;86(5):935-940.
81. Siegel DC, Heard JM. Intra-arterial calcium infusion for
hydrofluoric acid burns. Aviat Space Environ Med. 1992;63(3):
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82. Vance MV, Curry SC, Kunkel DB, et al. Digital hydrofluoric acid
burns: treatment with intraarterial calcium infusion. Ann Emerg
Med. 1986;15(8):890-896.
83. Velvart J. Arterial perfusion for hydrofluoric acid burns. Hum
Toxicol. 1983;2(2):233-238.
84. Pegg SP, Siu S, Gillett G. Intra-arterial infusions in the treatment
of hydrofluoric acid burns. Burns Incl Therm Inj. 1985;11(6):
440-443.
85. Rai J, Jeschke MG, Barrow RE, et al. Electrical injuries: a 30-year
review. J Trauma. 1999;46(5):933-936.
86. Holt GR, Parel S, Richardson DS, et al. The prosthetic
management of oral commissure burns. Laryngoscope.
1982;92(4):407-411.
87. al-Qattan MM, Gillett D, Thomson HG. Electrical burns
to the oral commissure: does splinting obviate the need for
commissuroplasty? Burns. 1996;22(7):555-556.
88. Orgel MG, Brown HC, Woolhouse FM. Electrical burns of the
mouth in children; a method for assessing results. J Trauma.
1975;15(4):285-289.
89. Chilbert M, Maiman D, Sances A, et al. Measure of tissue
resistivity in experimental electrical burns. J Trauma. 1985;25(3):
209-215.
90. Lee RC, Kolodney MS. Electrical injury mechanisms: dynamics of
the thermal response. Plast Reconstr Surg. 1987;80(5):663-671.
91. Yang JY, Tsai YC, Noordhoff MS. Electrical burn with visceral
injury. Burns Incl Therm Inj. 1985;11(3):207-212.
92. Branday JM, DuQuesnay DR, Yeesing MT, et al. Visceral
complications of electrical burn injury. A report of two cases and
review of the literature. West Indian Med J. 1989;38(2):110-113.
93. Honda T, Yamamoto Y, Mizuno M, et al. Successful treatment of a
case of electrical burn with visceral injury and full-thickness loss
of the abdominal wall. Burns. 2000;26(6):587-592.
94. Hunt J, Lewis S, Parkey R, et al. The use of Technetium-99m
stannous pyrophosphate scintigraphy to identify muscle damage
in acute electric burns. J Trauma. 1979;19(6):409-413.
95. Mann R, Gibran N, Engrav L, et al. Is immediate decompression
of high voltage electrical injuries to the upper extremity always
necessary? J Trauma. 1996;40(4):584-587; discussion 587-589.
96. Yowler CJ, Mozingo DW, Ryan JB, et al. Factors contributing to
delayed extremity amputation in burn patients. J Trauma.
1998;45(3):522-526.
97. Bartle EJ, Wang XW, Miller GJ. Early vascular grafting to prevent
upper extremity necrosis after electrical burns: anastomotic
false aneurysm, a severe complication. Burns Incl Therm Inj.
1987;13(4):313-317.
98. Wang XW, Bartle EJ, Roberts BB, et al. Free skin flap transfer in
repairing deep electrical burns. J Burn Care Rehabil. 1987;8(2):
111-114.

©2012 Elsevier Ltd, Inc, BV
DOI: 10.1016/B978-1-4377-2786-9.00011-4
Enzymatic debridement
of burn wounds
Lior Rosenberg
Introduction
Burn eschar may have different appearances and thicknesses,
and may behave in different ways as a function of etiology
and time since injury, as well as topical and other treatment
modalities. It can cause severe complications that may be
life-threatening. Effective burn eschar removal (debride­
ment) is the first and obligatory step for preventing eschar-
related complications and initiating the wound healing
process. Ideally, debridement should also be effective in pre­
venting and resolving burn-induced compartment syndrome
(BICS).
At present, the method and timing of eschar removal rely
heavily on accurate diagnosis of burn depth. However, this
diagnosis is least easy when most important, i.e. in mixed-
depth burns, which make up the majority of injuries.
Immediate or very early wound eschar removal is life-
saving in massive, mostly full-thickness burns of more than
50% of the total body surface area (>50% TBSA), and is
beneficial in all burns. For less severe burns, especially those
with uncertain depth (‘indeterminate’ – the substantial
majority of injuries), eschar removal is attempted usually
after 2–4 days post injury, though it may be postponed for
up to 2 weeks until diagnosis of burn depth becomes
clearer.1 At this point in time secondary eschar-related
damage has already begun in the zones of stasis and hyper­
emia. Recent reports indicate that immediate debridement
(within 24 hours post injury) may prevent or attenuate the
inflammatory response and eschar-related problems. Current
‘early’ eschar removal in the 3–4 days after injury can only
be surgical, as no other method or means is fast enough. The
choice of surgery, considering its dangers and drawbacks,
should be weighed carefully, especially in ‘indeterminate’
burns.2–6
The indication and decision for surgical eschar removal
depends on pre-debridement diagnosis. The procedure
is traumatic, non-selective, and demanding of resources,
general anesthesia, and facilities, but is quick and effective.
It sacrifices some of the non-injured surrounding tissues (up
to 50%).7 Following surgical debridement, usually not
enough dermal and epidermal elements are salvageable for
potentially spontaneous epithelialization, so the exposed
raw bed should be protected and covered by an autograft
(additional sacrifice of donor site) or other permanent cover.
Surgical debridement may involve complications such as
severe blood and temperature loss, inflammation and
infection due to bacterial dissemination, pain, and all the
anesthesia-related complications.8–18 More selective debride­
ment has been recently advocated by some to preserve more
dermis for grafting or spontaneous epithelialization, with
the development of more selective means of surgical debrid­
ing (i.e. dermabrasion or Versajet).19,20
Non-surgical ‘conservative’ treatment is based mainly on
autolytic (maceration) processes, involving the combined
activity of topical medicaments (antimicrobial or chemical
agents), contamination and lysis by microorganisms, and
the inflammation process combined with daily bathing
(showers) with superficial scraping and removal of loose
debris and dressing changes. These infectious–inflammatory
processes are slow (lasting between 10 and 14 days), and
may involve significant systemic and local complications.
Using topical antibacterial or anti-inflammatory medica­
ments may reduce the infectious–inflammatory processes,
but will delay eschar separation (sloughing). Locally, all
these processes may lead to additional tissue damage,
particularly death of the zones of stasis and hyperemia,
deepening and transforming partial-thickness damage into
full-thickness burns. In addition to its local and systemic
significance, the long debridement time with sustained
inflammatory–infectious processes can lead to the forma­
tion of granulation tissue that will develop into heavy
scars.21–25 The benefits of the technique include its relative
selectivity and the fact that it is not based on diagnosis,
does not involve surgery, and is simple to practice. When
the epithelial remnants in the cutaneous dermis are pre­
served and provided with the proper conditions for prolif­
eration and propagation, the newly debrided dermal bed
provides adequate conditions for spontaneous and rapid
re-epithelialization, generally in less than 3 weeks. Rapid
epithelialization prevents the formation of granulation
tissue that may eventually to develop into heavy scar tissue.
Non-surgical debridement may involve complications such
as fever and infection owing to bacterial dissemination and
slow decomposition of the contaminated eschar, enabled by
numerous painful dressing changes.24–26
Hand burns, which are involved in 30–60% of all burn
patients, have a special place in the field of burn care and
demand special attention and treatment. The initial assess­
ment should include not only the depth and extent of the
cutaneous injury, but also diagnosis of increased interstitial/
compartment pressure (burn induced compartment syn­
drome – BICS), which may harm local blood perfusion.
Circumferential burns to extremities may cause BICS and
CHAPTER 11 
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IN THIS CHAPTER
PowerPoint Presentation Online

Total Burn Care
11
132
represent an emergency necessitating pressure release by
deep surgical incisions, i.e. escharotomy. Owing to the
anatomy of the hand (important and delicate structures
crowded in a small limited space without subdermal soft
tissue), surgical debridement and/or escharotomy is techni­
cally intricate, and because of the difficult diagnosis is often
executed late or unnecessarily.8–10,21,22,27,28
Thus there is an unmet need for an immediate, effective,
selective, fast, and safe non-invasive debriding agent that will
combine the efficacy and speed of surgery with the non-
invasiveness of non-surgical methods, allowing very early or
even immediate, complete, non-traumatic, selective wound
debridement and accurate diagnosis of burn depth.
Debridement factors and assessment
The factors that define the clinical value of any debriding
means or methods are as follows:
1. Safety: no systemic side effects, trauma, or bleeding
2. Selectivity: no damage to surrounding local viable
tissues (not diagnosis dependent)
3. Efficacy: complete debridement in a single use, with
release of BICS
4. Speed: debridement completed as fast and as soon as
possible, within hours of admission
5. Cost-efficiency and simplicity of use: minimal
specialized facilities and personnel required.
All these factors are as important, and probably even more
so, in children, the elderly, and patients with burns of the
hands, feet, face, and neck, where important vital structures
lie cramped under thinner skin. Assessing the merit of any
debriding means or technique should include all of these
factors (Table 11.1).
End of debridement
The debridement process may be deemed complete when
the wound bed is free of eschar based on visual assessment
by an experienced physician. The end of the debridement
phase is characterized by discontinuation of debriding treat­
ments (surgical and/or non-surgical) and the initiation of
treatment modalities aimed at and leading to wound closure
(autografting, modulation of epithelialization etc.).
Debriding enzymes
The notion of using debriding enzymes or chemical agents
to ‘dissolve’ the burn eschar in place of traumatic surgical
debridement is not new. Ideally, one desires an ointment,
cream, or other topical preparation that could be easily and
rapidly applied immediately after initial cleansing as a first-
line intervention. This preparation should be safe to viable
tissues, and not extend the original trauma or harm undam­
aged tissues. This ideal debriding agent should quickly and
selectively digest only the damaged tissues, leaving an intact
raw dermal surface that can heal spontaneously or support
a skin graft if required, or exposed subdermal tissue that can
be autografted.
In his comprehensive review, Klasen24 covered the history
of all the past and present topical debriding preparations,
concluding that they did not fulfill the expectations of
replacing surgery. Enzymes of plant origin (papain) were first
evaluated in 1940, and with the addition of urea and chlo­
rophyll (e.g. Panafil) are still in use in many parts of the
world, but require daily application for up to 3 weeks. Acids
(pyruvic, phosphoric) were tried for a short period in 1946
and later in the 1960s, with relatively good results, but were
superseded by the efficacious tangential excision. Proteolytic
enzymes of bacterial origin (Clostridium histolyticum, strep­
tokinase, and Pseudomonas (Varidase) derived from hemo­
lytic streptococci were tried and abandoned. In the 1970s
and 1980s, sutilains derived from Bacillus subtilis (Travase)
were applied clinically, mainly in the US. In dermal burns,
additional tangential excision was required to remove the
bed’s surface for successful grafting and debridement of full-
thickness burns, which could take more than a week to be
completed. Additional Travase experience and reports con­
cluded that the great advantage of debridement with suti­
lains lay in the possibility this treatment offers of debriding
large wound areas soon after the accident, thus permitting
early skin grafting.29 In practice, it was used on the fifth to
seventh days for a better effect and to avoid epithelial
damage. On the basis of seven publications on sutilains, it
was concluded that in fact this potential has not been real­
ized in practice. Silverstein et al.30 warned that lengthy and
repeated enzymatic debridement may result in excessive
fluid loss and potential bacterial invasion that should be
prevented by additional antimicrobial agents and frequent
(every 4–6 hours) dressing changes.
Collagenase from Clostridium histolyticum (Collagenase
Ointment, Santyl) has been in use since the 1950s, and is
still occasionally used today. Complete debridement may
take from several days to up to 2 weeks. Collagenase is effec­
tive only in dermal burns and not in burned subcutaneous
fat or muscle, and uninjured dermis should be protected
from digestion. Hand burns treated by sutilains and colla­
genase could be debrided and grafted within a week, with
blood loss of only 20–50 mL per hand.31–33
Agents such as, trypsin (Trypsin, Tryptar), chemotrypsin
(Alpha Chymar), fibrolysin–deoxyribonuclease (Elase),
blowfly larvae extracts, vibriolysin, and fig tree sap (ficin)
were tested but were slow-acting and most effective on few-
day-old eschar; they did not gain acceptance as a standard
of burn care.
The currently available slow chemical/enzymatic or bio­
logical debridement agents are still less efficient than surgery,
requiring many applications and days to take effect, and in
some cases protection of surrounding tissues is needed. The
slow digestion process exposes the patient to complications
similar to those observed with autolysis. In addition, the use
of such chemicals/enzymes requires up to four painful daily
dressing changes for several days. The longer it takes to
remove the entire eschar, the greater the possibility that rich
granulation tissue will develop, resulting in scarring and
contracture formation. Repeated handling and debridement
of the same contaminated eschar area can also result in
trauma, and dispersion of bacterial and catabolic products
that may contribute to secondary bacteremia, septicemia,
and sepsis. To date, none of the available debriding products
has found acceptance as a standard of care (SOC) in burn
treatment. Klasen24 concluded that in spite of the disap­
pointing performance of all the agents tested, debriding

Enzymatic debridement of burn wounds
133
Table 11.1  Debridement index assessment chart
This assessment chart is intended to enable an objective comparison between debridement means and methods. Each of these five principal criteria that
are pertinent to debridement is composed of several factors that need to be assessed independently. Each factor has its own ‘positive’ and ‘negative’
score, with score values commensurate with the importance of the specific factor in the grand scheme of the debridement process. After tallying the
positive ‘credit’ and the negative ‘debit’ points, the higher total score corresponds to a better debridement agent and method.
Obviously each factor may have a different score depending on the type of the specific eschar (i.e. thermal burn vs pressure sore), but for a given type of
eschar, all the debridement means can be judged using the same criteria and scores. The scores of large eschars are calculated according to a standard
given area (for burns, calculated for a fresh burn of 15% TBSA). In a shorter, less comprehensive debridement index, a maximum score of 10 is given to
each of the five main factors, while still considering the subcriteria that reflect clinical importance. Previous versions of the Debridement Index have been
presented in national, ABA, EBA, ISBI and MBC meetings and modified following peers’ comments to reach the present one.
Factor Maximum score Credit Debit
A.  Safety (systemic safety)
1.
No systemic trauma,
toxicity, not pyretic
5
Excessive trauma
10
2.
Wide safety margin in
wrong/excessive use
5
3.
Does not cause bleeding
10
4.
Debridement may strat
immediately
5
For each additional day
3
5.
Not allergenic
5
B.  Selectivity (local safety)
6.
Desstroys only the eschar
(highly selective)
15
7.
Does not harm epithelium
3
8.
Does not harm dermal
components
3
9.
The debrided bed could
be diagnosed accurately
5
C.  Efficacy % of eschar debrided
10.
Can produce completely
clean bed in a single use
15
For any additional
procedure needed to
reach clean bed
3
11.
Can be used for early, fast
(<2 hours) escharotomy
15
D.  Speed
12.
Time needed post
admission to complete
debridement, for each
hour
1
13.
Time needed to recover
between teo
procedures (measured
in hours)
1
E.  Cost & simplicity of use for 15% TBSA
14.
Number of nurses
needed, each x
2
15.
Number of doctors
needed, each x
3
16.
Number of specialized
MDs (surgeons or
other) each
4
17.
Cost of all material &
manpower needed, for
every $US: 100
1
18.
Could be used in
outpatient setup
3
19.
No need for pain
medication
9
20.
Need only oral pain
medication
6
21.
Need only IV analgesia
3
22.
Need IV sedation
4
23.
Need general
anesthesia
6
24.
Need O.R. facilities
3
25.
Need blood bank
facilties
3
Grand Total
(Courtesy Lior Rosenberg)
enzymes remain an intriguing possibility owing to their
selectivity toward damaged but salvageable tissue, and with
further development ‘these remarkable components will find
a useful role to play in the challenge of wound debridement,
preparation and repair.’21,22,24,34,35
Recent development with bromelain extracts
During the last decade there have been several reports
of animal and human studies with a good manufactur­
ing practice (GMP)-produced bromelain-derived topical
debriding medicinal preparation (Debridase, Debrase,
NexoBrid).24,36–39
Studies in pigs confirmed the efficacy and speed of eschar
removal, selectivity, preservation of zone of stasis, beneficial
effect on re-epithelialization of partial-thickness burns, and
efficacy in resolving increased compartment pressure within
less than 1 hour of application.36–38 In six human multi­
center, multinational studies with more than 530 burn
patients, this agent proved effective in completely and selec­
tively debriding deep or full-thickness burns in a single
4-hour application. The debridement, performed at the

Total Burn Care
11
134
IIa
IIm
III
S
IIb
A
C
B
Figure 11.1  (a) Graphical representation of the skin structure and the debrided bed of changing depths with the punctate bleeding typical of each depth:
intact skin (S), second superficial degree (IIa), mid-dermal depth (IIm) deep second degree (IIb) and full-thickness third degree (III). (b) Deep hand burn with
areas that appear to be (S) intact skin, (IIa) second superficial degree, (IIb) deep second degree and (III) full-thickness third degree. Some keratin (K) remnants
(charred blister) still adhere to the eschar. Direct interstitial/anterior compartment measurement reached 70 cmH2O (70 mmHg). (c) Following 4 hours of
topical application of bromelain extract (NexoBrid) the burn is debrided, revealing a clean bed with changing depths (from superficial dermal to full
thickness) and typical bleeding patterns to the different cutaneous anatomical levels (see Figure 1a). Some of the eschar that has been covered by keratin
was not debrided (K). Pressure (direct interstitial/anterior compartment measurement) was reduced to 15 cmH2O (15 mmHg). (Courtesy Lior Rosenberg.)
patient’s bedside under analgesia (as done during dressing
changes), started and ended on the admission day, com­
pared to more than 6–12 days needed to complete debride­
ment in the control (surgical and non-surgical SOC) group,
with 15% of the enzymatically treated wounds needing addi­
tional surgery compared to 62% treated by SOC. The early
debridement and exposure of the viable bed allowed early
accurate visual diagnosis of the true burn depth and plan­
ning of the ensuing wound closure phase (Figs 11.1, 11.2).
The exposed raw surface after this debridement is the inter­
face layer (IL), which comprises the burn bed’s superficial
layers of healthy tissues, i.e. dermal remnants or subdermal
structures. In partial-thickness (’dermal’) burns, even deep
ones, this layer preserves all viable components, such as deep
epithelial elements inside the adnexae and deep dermal
remnants (collagen fibres and blood vessels). In all but
the deepest wounds, the presence of the IL permits spontan­
eous healing (epithelialization over dermal remnants). If
autografting is required to cover full-thickness burns, or after
the spontaneous healing potential has been exhausted, to
speed dermal wound closure, a simple brushing of the bed
before graft application is sufficient to achieve >95% graft
take. By exploiting the healing potential of the enzymatically
debrided bed’s dermal remnants, epithelialization of the
exposed bed reduced skin grafting compared to all surgically
and non-surgically SOC treated burn wounds from 21.5% to
8.4%. Blood loss was halved by Nexobrid use. This approach,
based on effective, selective and fast enzymatic, non-surgical
debridement followed by maximal epithelialization and cal­
culated use of skin grafts, was termed ‘minimally invasive
modality’ in burn care.39 This approach may extend wound
closure by 3–4 days compared to early grafting of exposed
dermis, but reduces excisional and grafting surgery. Care of
hand burns presented similar findings, with early (<1 day)
eschar removal, reducing grafting (4.2% vs 65% in SOC) and
preventing escharotomy; no escharotomy was required in
117 enzymatically treated deeply burned hands, versus four
escharotomies in 44 SOC-treated hands (9.8%).
Conclusion
The search for an effective, selective, safe and fast means of
debriding is 70 years old. Surgery has been the standard of
care because of its efficacy and potential speed, but it is
diagnosis dependent, non-selective, highly traumatic and
demanding. Until recently, non-surgical means did not fulfill
all the above unmet needs, but because they are not diagno­
sis dependent they provide more selective and less traumatic

Enzymatic debridement of burn wounds
135
Further reading
Klasen HJ. Review on the nonoperative removal of necrotic tissue
from burn wounds. Burns. 2000;26(3):207-222.
Krieger Y, Rosenberg L, Lapid O, et al. Escharotomy using an
enzymatic debridement agent for treating experimental burn-
induced compartment syndrome in an animal model. J Trauma.
2005;58(6):1259-1264.
Orgill DP, Piccolo N. Escharotomy and decompressive therapies in
burns. J Burn Care Res. 2009 Sep-Oct;30(5):759-768.
Ozcan C, Ergun O, Celik A, et al. Enzymatic debridement of burn
wound with collagenase in children with partial-thickness burns.
Burns. 2002 Dec;28(8):791-794.
Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and
efficacy of a proteolytic enzyme for enzymatic burn debridement:
a preliminary report. Burns. 2004;30(8):843-850.
Figure 11.2  (a) Deep flame burn to the hand with unclear definition between the different depths. Direct interstitial/anterior compartment measurement
reached 75 cmH2O (75 mmHg). (b) Following 4 hours of topical application of bromelain extract (NexoBrid) the burn is debrided, revealing a clean bed with
typical features of mixed dermal burn depths, appearance and punctate bleeding typical of the skin anatomy and blood supply. The skin area protected by
the watch was not harmed by the enzyme. Pressure (direct interstitial/anterior compartment measurement) was reduced to 25 cmH2O (25 mmHg). (From
Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns 2004; 30(8): 843–50.)
S
A
S
IIa
IIa
IIb
IIb
IIm
IIm
B
debridement, inefficient though they may be. Recent progress
with a bromelain-based enzymatic topical debriding agent
appears to promise the sought-after solution.
Conflict of interest statement
Debridase, Debrase and NexoBrid22,36–39 are produced by
MediWound Ltd, Israel, which financed the last five multi­
center, multinational clinical studies. Lior Rosenberg was
involved in most of the clinical studies, including the non-
supported ones, and has a financial interest in MediWound.
None of the other investigators (36 burn centers and over
100 investigators) had any financial interests in Mediwound,
the products or the studies. All data have been reviewed by
the European (EMA) and US (FDA) authorities.
Access the complete reference list online at

Enzymatic debridement of burn wounds
135.e1
© Copyright 2012 Elsevier, Inc. All rights reserved.
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12. Kisslaogglu E, Yuksel F, Uccar C, et al. Rationale for early
tangential excision and grafting in burn patients. Acta Chir Plast.
1997;39(1):9-12.
13. Monafo WW, Aulenbacher CE, Pappalardo C. Early tangential
excision of the eschars of major burns. Arch Surg. 1972;104:
503-508.
14. Prasanna M, Singh K, Kumar P. Early tangential excision and
skin grafting as a routine method of burn wound management:
an experience from a developing country. Burns. 1994;20(5):
446-450.
15. Salisbury RE. Thermal burns. In: McCarthy JG, ed. Plastic Surgery.
Philadelphia, PA: W.B. Saunders Company; 1990:787-830.
16. Sorensen B, Fisker NP, Steensen JP, Kalaja E. Acute excision or
exposure treatment. Final results of a three-year-old randomized
controlled clinical trial. Scand J Plast Reconstr Surg. 1984;18:87-93.
17. Xiao-Wu W, Herndon DN, Spies M, et al. Effects of delayed
wound excision and grafting in severely burned children. Arch
Surg. 2002;137(9):1049-1054.
18. Young D. Burn and Electrical Injury. In: Mathes SJ, ed. Total Burn
Care. 2nd ed. Elsevier; 2006.
19. Rennekampff HO, Schaller HE, Wisser D, et al. Debridement of
burn wounds with a water jet surgical tool. Burns. 2006
Feb;32(1):64-69.
20. Wang XQ, Kempf M, Liu PY, et al. Conservative surgical
debridement as a burn treatment: supporting evidence from a
porcine burn model. Wound Repair Regen. 2008 Nov-Dec;16(6):
774-783.
21. Bessey PQ. Wound care. In: Herndon DN, ed. Total Burn Care. 3rd
ed. Elsevier; 2007.
22. Cubison TCS, Pape SA, Arkhouse N. Evidence for the link
between healing time and the development of hypertrophic scars
(HTS) in paediatric burns due to scalds. Burns. 2006;32:992-999.
23. Hummel RP, Kautz PD, MacMillan BG, et al. The continuing
problem of sepsis following enzymatic debridement of burns.
J Trauma. 1974 Jul;14(7):572-579.
24. Klasen HJ. A review of the nonoperative removal of necrotic
tissue from burn wounds. Burns. 2000;26(3):207-222.
25. Press B. Thermal and electrical injuries. In: Smith JW, Aston SJ,
eds. Plastic Surgery. 4th ed. Boston/Toronto/London: Little, Brown
and Company; 1991:675-730.
26. Pham TN, Gibran NS, Heimbach D. Evaluation of the burn
wound: management decisions. In: Herndon DN, ed. Total Burn
Care. 3rd ed. Elsevier; 2007.
27. Barret JP. Cost-containment and outcome measures. In: Herndon
DN, ed. Total Burn Care. 3rd ed. Elsevier; 2007.
28. Orgill DP, Piccolo N. Escharotomy and decompressive therapies
in burns. J Burn Care Res. 2009 Sep-Oct;30(5):759-768.
29. Makepeace AR. Enzymatic debridement of burns: a review. Burns
Incl Therm Inj. 1983 Jan;9(3):153-157.
30. Silverstein P, Maxwell P, Duckett L. Enzymatic debridement.
In: Boswick JA, ed. The art and Science of burn Care. Rockville:
Aspen publishers; 1987:75-81.
31. Gant TD. The early enzymatic debridement and grafting of
deep dermal burns to the hand. Plast Reconstr Surg. 1980;66(2):
185-190.
32. Wachtel TL, Parks SN, Dimick AR. Early enzymatic debridement
and grafting of burned hands: evaluating the travase fast-graft
method in deep dermal burns. JBCR. 1983;4(5):325-330.
33. Ozcan C, Ergun O, Celik A, et al. Enzymatic debridement of burn
wound with collagenase in children with partial-thickness burns.
Burns. 2002 Dec;28(8):791-794.
34. Eldad A, Weinberg A, Breiterman S, et al. Early nonsurgical
removal of chemically injured tissue enhances wound healing in
partial thickness burns. Burns. 1998;24(2):166-172.
35. Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and
efficacy of a proteolytic enzyme for enzymatic burn debridement:
a preliminary report. Burns. 2004;30(8):843-850.
36. Krieger Y, Rosenberg L, Lapid O, et al. Escharotomy using an
enzymatic debridement agent for treating experimental burn-
induced compartment syndrome in an animal model. J Trauma.
2005;58(6):1259-1264.
37. Singer AJ, McClain SA, Taira BR, et al. Rapid and selective
enzymatic debridement of porcine comb burns with bromelain-
derived Debrase: acute-phase preservation of noninjured tissue
and zone of stasis. J Burn Care Res. 2010 Mar-Apr;31(2):304-309.
38. Singer AJ, Taira BR, Anderson R, et al. The effects of rapid
enzymatic debridement of deep partial-thickness burns with
Debrase on wound reepithelialization in swine. J Burn Care Res.
2010 Sep-Oct;31(5):795-802.
39. Rosenberg, L., The minimal invasive modality (MIM or the
PNN-Primum Non Nocere Protocol) for burn treatment: A
preliminary report. Plenary, the 10th Quadrennial ISBI Meeting,
1998, Jerusalem.

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©2012 Elsevier Ltd, Inc, BV
DOI: 10.1016/B978-1-4377-2786-9.00012-6
Treatment of infection in burns
James J. Gallagher, Ludwik K. Branski, Natalie Williams-Bouyer,
Cynthia Villarreal, David N. Herndon
Introduction
Infection is a most undesirable partner in any surgical pro­
cedure and is especially troublesome in burn injury. Burn
patients have lost their primary barrier to infection, the skin.
Additionally, the larger burn causes immunosuppression,
thereby lessening cellular and humoral defenses against
infection. Finally, the damaged tissue is fertile ground for
growth of pathogens. An understanding of pathophysiology,
definitions of infection, the potential pathogens and treat­
ment options are discussed.
Infection control best practice
The microorganisms initially populating the burn wound
represent a mixture of endogenous resident flora and
airborne contaminants seeded by contact with the
environment and attending personnel. Burn patients are
immunosuppressed and should be protected from exposure
to environmental contaminants. The most elaborate methods
of isolation have failed to eliminate infection, although they
have significantly reduced the incidence of cross contamina­
tion.1,2,3 The most effective means of reducing exposure of
burned patients to exogenous bacteria is strict observation
of appropriate hand washing by carers. Universal contact
isolation is often routine in burn centers. Face masks, water­
proof gowns and gloves should be worn whenever direct
contact with body fluids and wound exudates is possible,
thereby protecting both the patient and the carer from
inadvertent contamination. All dressing materials should
be maintained as patient specific. Intravenous pumps
and poles, blood pressure devices, monitoring equipment,
bedside tables and beds should be cleaned on at least a
daily basis with antibacterial solutions. Terminal cleaning,
following the discharge of the patient, should include
the walls, ceiling, baseboards and floors. Mattresses should
be covered with vinyl or other impermeable surface that
allows culturing and cleaning without soiling, and be fre­
quently inspected for cracks in their surfaces. At our institu­
tion we use Hepa air filters with 99.99% efficiency on 0.3 µm
sized particles. They are changed regularly and cultured,
if clinically indicated, by infection control monitoring.
Most units now house major burn patients in individual,
self-contained positive-pressure isolation rooms. However,
common areas exist even within these units, mainly the
bathing or showering facilities. These areas should be
conscientiously cleaned between patients with an effective
bactericidal agent specifically directed at the bacteria
common to an individual unit. Disposable liners for clean­
ing surfaces are encouraged, and sterilizable instruments
should be used for debridements.
Pathophysiology of the burn wound
Bacteria of normal endogenous skin flora are resistant to
heat injury in practically the same degrees as are the skin
cells. The bacteria on the surface are heat killed, as are the
tissue cells of the surface, and initial cultures are usually
sterile. The bacteria in the hair follicles and sebaceous glands
may survive (depending on the extent of the burn injury),
and the quantitative counts of biopsied specimens may show
the same numbers of bacteria per gram (103) as found in the
tissue prior to burning.4,5,6 The mean cell generation time in
optimum conditions is approximately 20 minutes. There­
fore, a single bacterial cell can increase in numbers to over
10 billion within a 24-hour period.7 As these bacteria increase
in number following the thermal injury and reach levels of
>105 bacteria per gram of tissue, they will erupt from the hair
follicles and sebaceous glands and begin transmigrating over
the injury, colonizing the dermal–subcutaneous boundary.
If the burn is left untreated, perivascular growth is accompa­
nied by thrombosis of vessels and necrosis of any remaining
dermal elements, potentially transforming partial-thickness
burns to full-thickness ones. As the levels of bacterial growth
increase, so does the incidence of invasion of viable tissue
and septicemia.8,9 Histologically, invasive infection is seen
with bacteria in unburned tissue. Other signs of invasion can
be the presence of hemorrhage in unburned tissue, small-
vessel thrombosis with ischemic necrosis of unburned tissue,
and dense bacterial growth in the subeschar space. The usual
progression of bacterial colonization as the days pass is from
Gram-positive to Gram-negative. By the 21st day post burn
57% of burn wounds still open will be colonized with
extended-spectrum β-lactamase Pseudomonas. The natural
progression with multiplication of bacteria and deepening
of the burn wound is routinely avoided with modern
burn care. With a combination of cleansing, antimicrobial
topicals, antibiotic dressings, adherent dressings, and early
surgery, burn wound progression and infection are avoided
in most burn patients. However, even in the presence of
modern care, early exposure to a virulent pathogen following
injury can quickly progress to invasive burn wound infection
and necrotizing soft tissue infection. Awareness of the
CHAPTER 12 
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IN THIS CHAPTER
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Total Burn Care
12
138
Burn wound erythema
The most common burns are smaller than 10% of the total
body surface area (TBSA). When presented early for treat­
ment these smaller burns are typically clean. The presence
of fever alone does not indicate infection, as burn is associ­
ated with an elevation in the body temperature set point.
Similarly, fever frequency or severity is not proportional to
burn size or depth. Fever can accompany burns of any size.
To evaluate a burn for possible infection and determine a
need for antibiotics, the examiner must be aware of the
phenomenon of burn wound erythema. Burn wound ery­
thema is defined as a redness surrounding the burn injury
that is not a first-degree burn, and is not infectious. It nor­
mally appears 2–3 days following injury and dissipates by
post burn day 5 or 6. It is likely related to the liberation of
cytokines and other mediators of inflammation. In contrast
to true infectious cellulitis, burn wound erythema is nor­
mally non-tender to palpation. Figure 12.1 demonstrates
burn wound erythema.
Burn wound impetigo/graft ‘melting or ghosting’/
folliculitis / persistently open donor sites
Burn wound impetigo, graft melting or ghosting, which
is loss of a previously present skin graft (Fig. 12.2), and
folliculitis (Fig. 12.3) are conditions that are well known to
the burn care clinician. However, these clinical problems
were not addressed specifically in the definitions put forth
in the burn care consensus conference on infection and
sepsis. These conditions are all most likely the result of bac­
terial colonization of the wound. Burn wound impetigo has
been described as small multifocal superficial abscesses,
which can cause extensive destruction of previously healed
split-thickness skin grafts and donor sites (Fig. 12.4).6 This
characteristic has led some to call the phenomenon graft
melting or ghosting. On the scalp, a very similar problem
Figure 12.1  Burn wound erythema in a hot oil
scald burn on the lateral thigh. (a) demonstrates
surrounding erythema noted on post burn day 2.
(b) demonstrates resolution of the redness and
healing on post burn day 12.
A
B
circumstances of the burn and the natural evolution of a
healing or surgically treated burn is critical to keeping
patients safe.
Infection and the burn wound
Definitions for the burn patient
The Society of Critical Care Medicine (SCCM) and the Amer­
ican College of Chest Physicians (ACCP) have developed
and reported on definitions for the systemic inflammatory
response syndrome (SIRS), sepsis, severe sepsis and septic
shock in the United States.10–12 Similar definitions were
adopted at an international forum. This important effort has
been made to help to standardize the diagnosis and manage­
ment of patients, which is fundamental to clinical study and
the advancement of care. Unfortunately, owing to the nature
of burn injury, the established definitions have been found
to be inadequate to describe the burn patient. Severe burn
injury is associated with the most profound response to
injury seen in any disease state. The hypermetabolism seen
with burn injury can, in many ways, mimic the SIRS response.
This hypermetabolism is a natural part of the body’s com­
pensatory mechanism in response to burn injury and can
last for up to a year following injury. Therefore, in 2007, a
consensus conference was formed within the American Burn
Association (ABA) tasked with authoring definitions of
sepsis and infections in burn injury.13 The methodology of
the conference was not unique to this committee, but rather
has been broadly used in many disciplines in medicine,
including the SCCM and ACCP in the development of the
general definitions of SIRS and sepsis. In this section the
discussion offered on SIRS, sepsis, burn wound infection,
pneumonia, bloodstream infection, catheter-related blood­
stream infection and urosepsis are in keeping with the con­
sensus definitions put forth in that publication.

Treatment of infection in burns
139
occurs that is termed folliculitis. It is not certain whether
these different clinical entities represent one or multiple
disease processes pathophysiologically. They are grouped
here for their similarities in clinical presentation and treat­
ment. Cultures commonly reveal Staphylococcus aureus, par­
ticularly methicillin-resistant S. aureus (MRSA). Treatment
consists of twice daily cleansing with surgical detergent dis­
infectant, unroofing any abscesses, and twice daily applica­
tion of a topical antimicrobial such as silver nitrate, Dakin’s
solution, or most commonly mupirocin (N3). With follicu­
litis, trimming or shaving of the hair is also helpful.
Figure 12.2  Burn wound impetigo. Right hand
in a 13-year-old boy with 85% TBSA burn,
fourth-degree to the hands. (a) four months post
burn at hospital discharge. (b) Three weeks later
in the clinic with reopening of the hand. Culture
was positive for MRSA.
A
B
Figure 12.3  Chronic folliculitis to the scalp. Hairs from hair-bearing areas
are embedded in the granulation tissue of converted second-degree burns
and donor sites, and microorganisms are entrapped, prolonging the
process. Shaving of the affected area, topical treatment and eventually skin
autografting resolve the problem.
Figure 12.4  Staphylococcus aureus infection in donor sites. Note the
secretions and the geographic appearance of the wound, which is typical
of this pathogen.
Burn wound colonization
Burn wound colonization (Fig. 12.5) as recently defined, is
‘bacteria present on the wound surface at low concentra­
tions. No invasive infection. Pathologic diagnosis: <105
bacteria per gram of tissue’.13 Clinically, the eschar or pseu­
doeschar may have a deteriorated or ‘infected’ appearance.
No surrounding cellulitis is noted. Treatment consists of
continued burn care with cleaning, topical antimicrobials,
and surgery. If serial colony counts have been performed and
an increase in colony counts has been noted, a change in
topical agent may be advised.

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is a form of severe soft tissue infection (SSTI). In the burn
wound this syndrome results from colonization with TSS
toxin-1-producing Staphylococcus aureus. This disease is pri­
marily of the young child, with a burn of <10% TBSA that
would normally be thought to heal without problems. The
incidence has been reported at approximately 2.6% with a
mean age of 2 years. Clinically it is characterized by a pro­
dromal period lasting 1–2 days with pyrexia, diarrhea, vom­
iting and malaise. A rash is often present, but at this stage
the burn appears clean. Shock then develops in untreated
cases. This is the time of maximal illness and is usually 2–4
days after the burn injury. Once shock has developed, mor­
tality can be as high as 50%. The main defense against the
development of this condition is knowledge and aggressive
treatment. Since MRSA has emerged as the most common
identifiable cause of severe SSTI, initiation of empiric
anti-MRSA antimicrobials is warranted in all cases of sus­
pected TSS.14,15
Invasive burn wound infection
Invasive burn wound infection is ‘the presence of pathogens
in a burn wound at concentrations sufficient in conjunction
with depth, surface area involved and age of patient to cause
suppurative separation of eschar or graft loss, invasion of
adjacent unburned tissue or cause the systemic response of
sepsis syndrome’.13 Invasive burn wound infection can occur
without sepsis. However, many invasive burn wound infec­
tions are rapidly progressive, life-threatening, and require
urgent surgical treatment as part of a spectrum of care to gain
control of the wound (Fig. 12.7). The clinical diagnosis can
be manifested by a change in appearance of the wound from
pink and white to yellow, brown, black and green, with
distinct odors. Time and some topical agents also can
produce color changes that can be misleading. Therefore, it
must be recognized that the most reliable sign of invasive
burn wound infection is conversion of an area of partial-
thickness burn to full-thickness necrosis, or the necrosis of
previously viable tissue in an excised wound bed (Fig. 12.8).
Figure 12.6  Burn wound cellulitis caused by Staphylococcus aureus. Clinical
findings include increased pain, local inflammatory signs, and fever.
Treatment includes systemic intravenous antibiotics, excision, and
autografting.
Figure 12.5  Burn wound colonization. Flame burn to the left medial arm
at post burn day 7. Eschar has degraded, but the surrounding tissue is not
cellulitic.
Burn wound infection
Burn wound infection is defined as ‘bacteria present in
the wound and wound eschar at high concentrations. No
invasive infection. Pathologic diagnosis: >105 bacteria per
gram of tissue’. Clinically, the presence of cellulitis is the
foundation of the diagnosis. Cellulitis involves advancing
erythema, warmth, and tenderness (Fig. 12.6). The early
burn with surrounding blanching erythema likely has an
area of surrounding first-degree burn or burn wound ery­
thema, and therefore no antibiotics are indicated. However,
the burn wound with surrounding clinical cellulitis may
have an atypical history or a late presentation. Often patho­
logic colors and odors alert the clinician to the strong likeli­
hood of infection. Usual treatment of the infected burn
wound consists of thorough cleansing, application of topical
antimicrobials, and systemic antimicrobials. The offending
organism is usually a drug-sensitive staphylococcus, and
antimicrobials are started appropriately. Further choice of
antibiotics and duration of treatment can be made by culture
and sensitivity results, or merely by clinical progress of the
wound. If the circumstances, appearance, or comorbidity
history make consideration of Gram-negative pathogens rea­
sonable, expansion of coverage is indicated. Occasionally,
the severely neglected wound can progress to full thickness
and even have a contained area of pus beneath a true eschar.
Clinical suspicion for this situation arises when a desiccated
eschar is encountered with the impression of fluctuance on
examination. Such an area needs to be opened like any other
abscess. This can be accomplished through a cruciate inci­
sion or partial sharp removal of the eschar. Special care
should be taken with the evaluation of burn wounds in the
elderly and diabetics, as the inflammatory response can be
blunted and the wound severely underestimated.
The burn wound and toxic shock syndrome
One area of special consideration when caring for the small
burn is the complication of toxic shock syndrome (TSS). TSS

Treatment of infection in burns
141
dressings, with a plan to return to the operating room in the
near future. The empiric antimicrobial choice should be
broad coverage for fungi, drug-resistant Gram-positive and
-negative organisms. Once pathogens are identified and
sensitivities reported, antimicrobial management follows
this information with persistent efforts to cover the offend­
ing organisms with adequate well-timed doses of effective
antibiotics chosen for their specific activity against the path­
ogen. This requires a coordinated effort from clinician,
microbiologist and pharmacist. The treatment of the surface
is aggressive also. Following the complete removal of dead
tissue, topical antimicrobial soaks are commonly used,
including silver nitrate, sulfamylon, and Dakin’s solution.16
Each can be used with topical nystatin to improve kill of
fungus if this is a concern. In association with this, increasing
the change frequency of the soaking dressing to four times
a day may be warranted.
The best treatment for invasive burn wound infection is
prevention. In particular, with large burns this translates to
excellent surgical management with aggressive removal of
dead tissue before it becomes infected. This eliminates the
main reservoir for bacterial growth.
Extremely virulent pathogens
Following modern principles in the clinical care of burn
patients has led to rewarding outcomes. However certain
pathogens have appeared that defy the usual measures that
control other organisms. The appearance of these organisms
has often returned death rates to a time before the current
era of early excision and grafting. The following discussion
is born out of the clinical management of these difficult
pathogens.
Ecthyma gangrenosum is a purple bluish-black spot in
previously healthy tissues. Classically this is caused by inva­
sive Pseudomonas. Histologically it is characterized by throm­
bosis of vessels with perivascular hemorrhage. Unfortunately,
multidrug-resistant (MDR) Pseudomonas has become a
common enemy. Invasive Pseudomonas in combination with
vancomycin-resistant Enterococcus have clinically demon­
strated a severe coagulopathy leading to death. The use of
Figure 12.7  Seventy-five percent TBSA full-thickness burns with wound
sepsis due to Enterococcus faecalis and Enterobacter cloacae. Prompt excision
and homografting, hemodynamic support, and systemic antibiotics
controlled the infection.
Figure 12.8  Bacilli invading deep viable tissue. Histopathologic
confirmation is currently the only way to diagnose burn wound infection
(hematoxylin and eosin, ×1000).
Figure 12.9  Ecthyma gangrenosa. Satellite lesions in invasive burn wound
infection with Gram-negative organisms, usually Pseudomonas.
There are other reasons for burn wound deepening and con­
version, and these must be considered. Once an invasive
infection is established, progression can be very rapid. Hem­
orrhagic bullae, satellite lesions and previously normal skin
go from erythematous to necrotic and are characteristic of
an aggressive Gram-negative pathogen, usually Pseudomonas
species (spp). Such lesions are termed ecthyma gangrenosa
(Fig. 12.9).
Treatment of invasive burn wound infection is the elimi­
nation of all dead tissue, including aggressive removal of
dead muscle if present. Here the surgeon must be as aggres­
sive as in necrotizing fasciitis, if the wound is to come under
control and eventually support grafting. Surgical control can
mean conversion of a tangential excision to fascial level, or
amputation where previous attempts were being made to
spare a limb. Dead muscle in particular can be problematic
as compromised areas can be hidden from view. In the larger
burn, any burden of dead tissue with loss of the skin barrier,
combined with immunosuppression, makes a very aggres­
sive surgical approach mandatory. Often the initial opera­
tion to gain control of an invasive burn wound infection
may conclude with no wound coverage other than soaking

Total Burn Care
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142
Candidal infections occur most commonly in patients with
large burn injuries who are hospitalized for long periods and
have received multiple courses of antibiotics. Prophylactic
treatment with oropharyngeal and topical nystatin has there­
fore become recommended,17 although fluconazole may be
more effective in some cases. Mortality associated with
Candida is usually from amphotericin-associated renal
failure.
Culturing of the burn wound
Daily inspection of the burn wound by a burn surgeon is
mandatory for decision making. Major burn wounds usually
become colonized or infected within 3–5 days after admis­
sion. Often, infection arises from the patient’s own bacterial
flora and not from an exogenous source. Burn wound biop­
sies should be taken from any area of the wound that has
changed in appearance. If a simultaneous sample is exam­
ined by a pathologist, a diagnosis of burn wound invasion
in need of emergency surgical treatment can be made. Quan­
titative cultures showing high bacterial counts correlate with
histologic evidence of burn wound infection in approxi­
mately 80% of cases.6,23,24 If quantitative biopsies reveal >103
organisms/g of tissue, a change in topical therapy is indi­
cated. If bacterial counts exceed 105/g of tissue, localized
burn wound infection should be considered and a histologi­
cal examination performed. If histological evidence of inva­
sion is present, systemic antibiotics should be given and the
wound should be excised.6,15,25 Bacterial sepsis is often her­
alded by changes in the color, odor or amount of exudate
from the wound, whereas fungal invasion is clinically sug­
gested by a rapidly emerging and spreading dark discolora­
tion. Consequently, the burn wound must be closely assessed
for these manifestations.
There is considerable practice variation in the more routine
use of wound cultures. The literature from Robson et al. in
1973 demonstrated that burn wound colony counts >105/g
tissue led to only a 19% graft survival rate, whereas colony
counts <105/g tissue had a 94% chance of graft survival.26
This led to widespread use of burn wound biopsies and
cultures. In 1996 Steer et al. demonstrated a wide variation
in bacterial densities within a wound at the same moment.27
This information brought into question the value of clinical
management change based on routine burn wound cultur­
ing. In 2003 Barret and Herndon looked at the effect of burn
wound excision on bacterial colonization and invasion.28
They noted that even preoperative colony counts of >105
were reduced to <104 when wounds were treated aggressively
through surgery. As a result of this type of treatment, skin
graft take was excellent. This is in contrast to Robson’s find­
ings of 40 years earlier. The change is likely related to the
change in surgical paradigm and technique. Interestingly, in
the Herndon and Barret study, a subgroup was identified
with preoperative colony counts >106/g tissue. This group
had post-excision pregrafting cultures that averaged 104/g
tissue, but they suffered a 75% infection rate and graft loss.
It is clear that burn wound colony counts have significant
value in guiding the care of the patient. However, these
counts may also possibly be unreliable and inaccurate
because of sample site variation. Box 12.1 gives a list of
reasons and uses for burn wound cultures.
colistimethate has recently enabled control of MDR Pseu­
domonas. MDR Acinetobacter, another problematic pathogen
associated with burn wound infection, has also been found
to be sensitive to colistimethate.
Amphotericin-resistant Fusarium has the ability to invade
living tissue and create a wavefront of necrosis. This pattern
is histologically recognizable by the presence of fungal
hyphae extending like fingers to the border between necrotic
and intact tissue, and represents dangerous invasion of
viable tissue. Very aggressive removal of all dead tissue, and
voriconazole administered systemically along with the use
of topical antifungals, can be successful against this virulent
organism. A similar virulent profile is possessed by Aspergil­
lus and Mucor spp. Candida colonization will be present in
30% of burn patients with burns >40% during their hospital
stay. It is for this reason that nystatin was added to topical
silver sulfadiazine. This change has resulted in a marked
decrease in three-organ involvement with Candida, which is
usually required for the diagnosis of candidal sepsis (Fig.
12.10).17 Serum antibody titers to Candida have recently
been advocated to assist in the early diagnosis.18 Pre-mortem
diagnosis, confirmed with sufficient time to implement
appropriate treatment, occurs in <40% of infected patients.19
Because of their relatively large size, Candida are usually fil­
tered out of blood at the capillary level; therefore, arterial
blood cultures are recommended. Organisms are usually
seen in the urine when sepsis from a distant site occurs.
Candidal sepsis is considered when C. albicans can be iso­
lated from any three of the following tissue sites: blood,
wound, urine, bronchial washings, or by a positive retinal
examination. Candidal spores are omnipresent in the burned
patient, appearing in stools, nasopharynx swabs, urine
samples and cultures of intact integument. However, fewer
than 20% of patients with candidal wound colonization
develop widespread candidiasis.20 Only when the control­
ling bacterial populations are eradicated by systemic antibi­
otics or the host becomes immunosuppressed does candidal
infection occur, frequently following a bacterial sepsis. There
is a 3–5% incidence of candidemia in the burned popula­
tion17,20–22 and a comparable rate of burn wound invasion.21
Figure 12.10  Candida infection in a healing second-degree burn wound.
Pain and itch is usually present in this kind of infection. Treatment with silver
sulfadiazine mixed with mycostatin has proved effective in controlling
Candida.

Treatment of infection in burns
143
of seropositive patients reactivate CMV based on a fourfold
or greater rise in antibody titer.33,34 The fact that only two
reports of systemic CMV infection in severely burned patients
were published suggests33,35 that systemic disease is an
unusual occurrence and that the majority of patients who
demonstrate increased CMV-specific antibody sustain more
limited CMV infections. The absence of reports that account
for the frequency of severely burned patients with increased
CMV antibodies suggests that most of these infections are
subtle and have been overlooked by past studies. General­
ized, non-healing burn wounds have been associated with
CMV pathology in endothelial and periendothelial cells.33
Inclusion bodies consistent with CMV infection, as well as
CMV antigens, were detected by immunohistochemical
staining of a skin biopsy from a transplanted cadaver allo­
graft (from a CMV-positive donor) on a severely burned
adult male, but the relationship of the CMV infection to
necrosis, inflammation and increased vascularity evident in
the infected skin is not known.36 Results from animal experi­
ments demonstrated that severe burn injury predisposes to
murine CMV infection, and murine CMV infection was asso­
ciated with increased susceptibility to sepsis.37,38
The burned patients who most commonly contract the
infection are known to have received multiple blood transfu­
sions, which represent a major source of contamination. In
addition, it has been shown in an animal model that cadaver
skin has the ability to transmit CMV infection. In a recent
study by Tennenhaus et al.39 US and German burn centers
were surveyed and evaluated for awareness, perceptions,
diagnosis, and treatment of CMV in patients with burn
injury. CMV infection incidence was reported at 1 : 280 in
German and 1 : 870 in US burn centers. When testing, 70%
of German and 19% of US burn centers used serology; 52%
German and 25% US centers used body fluid viral isolation;
and 43% German and 6% US centers used leukocyte
CMV-DNA analysis. Two-thirds of the German and half of
the US centers distinguished infection from disease. A total
of 43% German and 19% of the US centers would treat the
established disease.
Herpes simplex infections most commonly manifest
themselves
as
vesicles
in
healing
partial-thickness
burns or split-thickness donor sites (Fig. 12.11). In the
Box 12.1  Burn wound cultures in burn care
1. Early cultures should be negative or have low counts, with
sensitive gram positive organisms. Therefore, positive cultures or
high counts suggests early contamination of the burn wound.
2. If an invasive burn wound infection is suspected, wound culture
and histologic analysis can aid in confirmation of the clinical
diagnosis.
3. Routine culturing and identification of colonization may aid in
empiric antimicrobial coverage if the patient subsequently
becomes ill.
4. Increasing colony counts may indicate a need to change topical
antimicrobial agents.
5. Not all organisms are created equal. Wound colonization with
particularly virulent or resistant organisms may be a predictor
of impending invasive burn wound infection.
6. Operative wound colony counts of >106 suggest a high risk of
infectious complication and graft failure.
7. Burn wound culture results may aid in the evaluation of
nosocomial spread of organisms and guide infection control
practice.
Figure 12.11  Herpes simplex virus type I infection in a patient with 35%
partial-thickness and full-thickness burns. Extreme pain and itching are
typical of this infection.
Viral infection of the burn wound
In recent years more attention has been turned to the diag­
nosis and treatment of viral infections in burned patients.
Prospective and retrospective assays of sera have documented
a large incidence of subclinical viral infection. In one of the
first large retrospective studies from the 1980s, Linnemann
et al. assayed stored sera of burned children.29 A fourfold
increase in antibodies to cytomegalovirus (CMV) was found
in 22% of patients, 8% had increased herpes simplex titers,
and 5% demonstrated a rise in varicella zoster titers. The
study continued in a prospective manner, with 33% of the
children developing CMV infection, 25% developing her­
petic infection, and 17% developing adenovirus infection.29
Cytomegalovirus infection frequently occurs concurrently
with bacterial and fungal infections, but rarely alters the
patient’s clinical course. Primary CMV infection or reactiva­
tion of CMV was reported with an overall frequency of
33%.29 Importantly, in that study, prospective analyses
‘directly correlated CMV infection with more severe burns,
more skin grafts, and subsequent higher numbers of blood
transfusions.’ The clinical manifestation rarely occurs in
patients with <50% TBSA burn infected, and typically
presents approximately 1 month post burn as a fever of
unknown origin and lymphocytosis.29 Rennekapff et al., in
a 2006 review, identified a seroconversion rate of between
18 and 22% for burn patients who were seronegative for
HCMV prior to their burn injury.30
Pathophysiologically, CMV inclusions may be identified in
the cells of multiple organs but have not been reported in
the burn wound.31 Immunocompromised patients have a
higher frequency of CMV infection, which results in a broad
range of adverse conditions ranging from febrile illness to
systemic infections with organ (e.g., lungs, brain, liver, colon,
pancreas) involvement.32 CMV infection has also been asso­
ciated with unexplained fever and lymphocytosis based on
a concomitant rise in specific antibodies.29,31 More recent
studies have suggested that up to 23% of seronegative
patients with severe burns seroconvert, while more than 50%

Total Burn Care
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144
immunocompromised burn patient, however, the infection
usually starts with barely noticeable red macules, which then
progress rapidly and spread over entire donor sites and previ­
ously healed areas. A near-total loss of epidermal coverage
can occur (Fig. 12.12a,b and Fig. 12.13a,b). Other epithelial
surfaces such as the oral or intestinal mucosa can also be
involved, potentially causing erosion and perforation. The
clinical manifestations of lesions may be preceded by unex­
plained fever unresponsive to routine antibiotic coverage.40
In recent years, an increased mortality, extensive visceral
involvement, and necrotizing tracheobronchitis have been
associated with herpetic infections after burns. A retrospec­
tive study characterizing the incidence, presentation, and
outcome of 14 patients with facial herpes rashes out of 95
severely burned intubated adults was performed by Fidler
A
Figure 12.12  A 13-month-old girl with 80%
TBSA scald burn who developed a fulminant
herpes simplex II infection 2 weeks after
admission. (a) 10 days post burn, prior to clinical
manifestation of infection. (b) Post-burn day 18.
Full manifestation of herpetic lesions that affect
the entire body surface area and convert
previously healed areas into open wounds.
B
Figure 12.13  Same patient as in Figure 12.12.
(a) The left arm, which was used twice as a donor
site for split-thickness skin graft (days 4 and 11).
The image is from day 17, with initial
manifestation of herpetic infection with red
macules. (b) Day 18 post burn; 30 hours later,
conversion to confluent defects with near total
loss of epidermis.
A
B
et al., showing that rashes attributed to herpetic infections
were found in at least 15% of patients, but no difference in
mortality or length of stay could be observed between
patients with or without the infection.41 The authors also
noted that the course of this infection was relatively benign
in this group of acyclovir-treated patients. Partial-thickness
burns and donor sites infected with herpes may convert to
full-thickness injuries, requiring skin grafting for ultimate
closure. Necrotizing hepatic and adrenal lesions may lead to
multisystem organ failure. Mortality in patients with dis­
seminated infection is about twice that expected for patients
of similar age and burn size. Split-thickness grafts provide
adequate coverage of previously infected herpetic wounds,42
but the coverage is frequently associated with secondary graft
loss and the need for reoperation and patch grafting.

Treatment of infection in burns
145
VI. Inability to continue enteral feedings >24 hours
A. Abdominal distension
B. Enteral feeding intolerance (residual >150 mL/h
in children or 2× feeding rate in adults)
C. Uncontrollable diarrhea (>2500 mL/d for adults
or >400 mL/d in children)
In addition, it is required that a documented infection
(defined below) is identified
A. Culture positive infection, or
B. Pathologic tissue source identified, or
C. Clinical response to antimicrobials.
Pneumonia
The use of mechanical ventilation should be avoided when­
ever possible. This life-saving support for the lungs and pro­
tection for the airway comes with inherent complications.
Modern care dictates the use of a care regime to reduce the
incidences of ventilator-associated pneumonia. However
this complication is common, especially in those burn
patients with inhalational injury. Ventilator-associated pneu­
monia (VAP) has two basic etiologies: direct contamination
of the tracheobronchial tree via airborne or aspirated bacte­
ria, and pneumonia spread hematogenously. The hematog­
enous etiology seen later in the hospital course is often
bilateral and carries a worse prognosis than the former.
Organisms cultured from pneumonia of burn patients often
reflect the flora of the burn wound. The diagnosis of pneu­
monia is a clinical one, with two of the following being
required: chest X-ray revealing a new and persistent infiltrate
(Fig. 12.14), consolidation or capitation.13 Sepsis, as defined
in the burn patient, is a clinical deterioration in status and
a change or purulence in sputum. Once a clinical diagnosis
is made, prior to the start of antimicrobials for treatment,
specimens are sent for microbial analysis. Either tracheal
Chickenpox (varicella zoster) infection is a frequent occur­
rence in school-aged children and is rapidly spread through
inhalation of the virus. Varicella infections can be life-
threatening in an immunocompromised host and small
epidemics have occurred within pediatric burn units.42 The
characteristic fluid-filled lesions appear in healed or healing
partial-thickness burns, as well as uninjured epithelium and
mucous membranes. Owing to the fragility of the newly
healed or healing skin, the vesicles are much more destruc­
tive in the injured than in the uninjured skin, and may
present as hemorrhagic, oozing pockmarks, which are prone
to secondary infection and subsequent scarring. Neovascu­
larized skin grafts may be lost, and further grafting pro­
cedures should be delayed until the lesions are quiescent.
Burn-associated infections
Sepsis
Rapid and complete closure of deep burns is the best defense
against the development of sepsis in the burn patient. If a
comparison is made between burn patients of equal size,
those who have an occurrence of sepsis during their hospi­
talization will have decreased lean body mass and increased
mortality. A major focus of rounds in the burn intensive care
unit is on the identification of sepsis. Sepsis was addressed
at the American Burn Association Consensus Conference to
Define Sepsis and Infection in Burns.13 Below is the defini­
tion as outlined in the publication:
Sepsis is a change in the burn patient that triggers
the concern for infection. It is a presumptive diagnosis
where antibiotics are usually started and a search for
a cause of infection should be initiated. While there is
need for clinical interpretation, the diagnosis needs to
be tied to the discovery of an infection (defined below).
The definition is age-dependent with adjustments
necessary for children.
The trigger includes at least three of the following:
I. Temperature >39° or <36.5°C
II. Progressive tachycardia
A. Adults >110 bpm
B. Children >2 SD above age-specific norms (85%
age-adjusted max heart rate)
III. Progressive tachypnea
A. Adults >25 bpm not ventilated
i. Minute ventilation >12 L/min ventilated
B. Children >2 SD above age-specific norms (85%
age-adjusted max respiratory rate)
IV. Thrombocytopenia (will not apply until 3 days after
initial resuscitation)
A. Adults <100 000/mcl
B. Children <2 SD below age-specific norms
V. Hyperglycemia (in the absence of pre-existing
diabetes mellitus)
A. Untreated plasma glucose >200 mg/dL or
equivalent mM/L
B. Insulin resistance – examples include
i. >7 units of insulin/h intravenous drip
(adults)
ii. Resistance to insulin (>25% increase in insulin
requirements over 24 hours)
Figure 12.14  Left lower pneumonia. Burn patient with typical radiographic
picture of lobar pneumonia. The diagnosis of pneumonia in patients with
inhalation injury and respiratory distress syndrome is still very difficult.

Total Burn Care
12
146
detailed discussion). It is interesting to note that the bacteria
cultured from infected catheters can be traced to the skin in
96% of cases. These data tend to support the hypothesis that
catheter-related infections arise primarily from burn wound
contaminants migrating down the catheter to the tip. Strict
aseptic technique for insertion of intravascular catheters, the
use of Teflon catheters, and rotation of catheter sites are
useful measures to prevent infection. There is currently still
debate regarding the effectiveness of antibiotic-coated cath­
eters to reduce the number of line infections and to allow
longer safe retention of a venous access point in the burn
ICU. Further study is needed to elucidate the effect this tech­
nology may have on the management of intravenous access
in the burn patient. It is recommended that each burn center
adopt a line change protocol to standardize the management
of access, and track the outcome.
Suppurative thrombophlebitis should be suspected in
those patients who have persistent positive blood cultures
without signs of local infection. Often suppuration can occur
after the time of catheter removal, so cultures at the time of
removal may be an unreliable predictor of infection. Gross
clinical signs of suppurative thrombophlebitis are frequently
not present.45 Upon confirmation of the diagnosis, immedi­
ate operative excision is essential to prevent progressive
sepsis. Entire excision of a vein to the port of entry into the
central circulation may be required because of the tendency
of phlebitis to migrate to vein valves, leaving an apparently
normal vein in between the infected foci. The subcutaneous
tissue and skin should be packed open where a grossly puru­
lent vein is removed and allowed to granulate and close by
secondary intention (Fig. 12.15).
Abdominal sepsis
The abdomen as an infectious source in the burn patient can
be a clinical challenge. The abdomen is often involved in
larger burns, which can lead to a perceived limitation in the
clinical examination compared to other similarly complex
ICU patients. The defects in the overlying skin should not
be allowed to interfere with a proper physical examination.
aspirate, bronchoalveolar lavage (BAL) or protected bron­
chial brush (PBB) are performed to obtain a specimen. BAL
and PBB are recommended over tracheal aspirate. Positive
microbiological results are: tracheal aspirate ≥105 colony-
forming units, BAL ≥104 organisms and PBB ≥103 organisms.
The data modify the clinical diagnosis in one of three ways
in a post hoc manner: (1) if a pathogen is isolated in sufficient
quantities, then the clinical diagnosis is confirmed; (2) if the
clinical diagnosis was strong but the microbiologic data fail
to confirm, then the diagnosis is probable; (3) with low or
moderate clinical suspicion but with a the presence of a
positive specimen, the pneumonia diagnosis is possible.
This definition suggests that, once made, the clinical diagno­
sis cannot be removed by a lack of confirmation by the
microbiology report. Controversy about this position per­
sists.13 In a 2005 study by Wahl et al., it was reported that
negative BAL results (<104 cfu) reduced the clinical VAP diag­
nosis rate by 21%. The negative BAL prompted the discon­
tinuation of antibiotics started for the clinical suspicion of
VAP. In none of the patients in the study in whom antibiotics
were discontinued were antibiotics restarted based on clini­
cal grounds.43
Unique to burn patients is the possibility of using surface
quantitative wound cultures (QWC) to predict the pathogens
found in a VAP in the same patient. In a study by Ramzy
et al., an attempt was made to establish the relationship of
the burn wound flora to microbial pathogens in the tracheo­
bronchial tree.44 In 30 (48%) of the 62 bronchial lavage fluid
(BLF) cultures there was a match between the organism iden­
tified in the BLF and the QWC. When strict quantitative
criteria were applied, however, the match rate was only 9 of
62 (14%). Burn size and inhalation injury had no significant
effect on match rate. Whereas the microbial pathogens were
similar in the QWC and BLF, linear regression showed no
value of QWC in predicting BLF culture results. The differ­
ence between qualitative and quantitative match rates
suggests cross-colonization between the burn wound and
tracheobronchial tree, but little to no cross-infection. The
QWC and BLF cultures must be performed when determin­
ing antimicrobial specificity in the burned patient. This
study supports routine surveillance of the burn wound to
help guide early thoughtful institution of antibiotics in a
suspected pneumonia.
Bloodstream infection (BSI)/catheter-related
BSI (CR-BSI)/suppurative thrombophlebitis
One of the following two criteria must be met to diagnose
a bloodstream infection (BSI): (1) the patient has two or
more positive blood cultures for a known pathogen or one
positive in the presence of sepsis, or (2) the patient has a
common skin contaminate cultured from two or more blood
cultures on separate occasions and sepsis.13 The BSI is con­
sidered primary if the same organism has not been cultured
at another site. If the same organism is cultured at another
site it is considered secondary. A catheter-related blood­
stream infection (CR-BSI) is present if a patient has sepsis
and no other source of infection, and the signs of sepsis
resolve within 24 hours of catheter removal. Additionally,
any bacteremia or fungemia in a patient with an intravascu­
lar catheter, clinical signs of sepsis and no other source of
infection is a CR-BSI (reference N2 for a complete and
Figure 12.15  Suppurative thrombophlebitis. Infection was noted along the
length of vein. Proper treatment is total excision of the vein from the site of
infection to the point of entry into central circulation.

Treatment of infection in burns
147
suppurative chondritis has significantly decreased with its
use (Fig. 12.16). Characteristically, the patient will complain
of dull pain. The ear will become warm, red, tender and
edematous. Appropriate antibiotics should be initiated
immediately, and if there is an identifiable site, immediate
incision and drainage of the abscess should be undertaken,
with culture and sensitivity obtained. Should induration and
tenderness continue, a more extensive debridement is imper­
ative. Generally the helix is bivalved at the posterior helical
margin and all necrotic cartilage debrided. Difficulty may
arise in distinguishing between viable and necrotic tissue,
and frequently normal cartilage is sacrificed in order to
ensure debridement. However, infected cartilage is usually
soft, whereas normal cartilage will feel granular on curettage.
If appropriate and adequate excision of the necrotic tissue is
not performed, suppurative chondritis can proceed to invade
the mastoid bone, creating a potential for intracranial abscess
formation.
Urosepsis
Urinary tract infections are usually associated with a history
of catheterization. When infection occurs patients should be
treated with appropriate systemic antibiotics. The source of
urine identified with sepsis is defined previously in the burn
patient. Candiduria is often insignificant but may reflect
active infection or septicemia, especially when mycelia can
be demonstrated. When present, an active infection with
Candida species usually responds to low doses of amphoter­
icin B, fluconazole or itraconazole.
Burn patients, like all patients, can develop appendicitis,
intussusception, bowel obstruction, etc. Additionally, in
severe burns peritoneal dialysis may be chosen to aid com­
promised renal function and potentially introduce another
possible source for infection. Larger burns have episodes of
hypoperfusion at times leading to sloughing of intestinal
mucosa. Heme-positive mucoid or watery stools, abdominal
distension, and diminished bowel sounds often characterize
this condition. Stool for reducing substances is usually posi­
tive, thus indicating malabsorption. A patient with a very
severe burn, often combined with sepsis, can have critical
ischemia to the gut as a result of global hypoperfusion and
progress to necrosis. Clostridium difficile (C. diff.) is a well
known entity in critically ill patients, especially those with a
history of antibiotic use. With the ubiquitous emergence of
methicillin-resistant staphylococcus the intravenous use of
vancomycin has increased to such a degree as to reduce our
observed clinical incidence of C. diff. diarrhea. However, this
supposition is unproven. Necrotizing enterocolitis can occur
in patients who are severely granulocytopenic from any
cause. Left upper quadrant abdominal pain is usual. Irrita­
tion of the adjacent diaphragm may result in pain referred
to the left shoulder. Splenic enlargement and tenderness are
often present, with high, spiking temperatures. Radiographic
examination may reveal an elevated left hemidiaphragm,
basilar pulmonary infiltrates, atelectasis, or a left pleural
effusion. Shift of the colon and stomach down and to the
right and extraintestinal gas, either diffusely mottled or pro­
ducing an air–fluid level in the left upper quadrant, may also
be seen. Ultrasonography, CT, and MRI are the preferred
diagnostic techniques for the evaluation of suspected splenic
abscess. Initial antibiotic therapy should have a broad spec­
trum of activity. A combination of antibiotics that has activ­
ity against streptococci and both aerobic and anaerobic
Gram-negative bacilli would be appropriate initial anti­
microbial therapy.
Ophthalmic infections
The eyes in the burn unit are at great risk. They may have
suffered an insult from the original trauma or from the time
in the burn ICU. The retraction of the lids from scar and the
sedation that is at times necessary can interfere with the eye’s
natural protective mechanism. The avascular corneal stroma
is protected by one layer of epithelium. Once damaged, a
perforation can mean loss of the eye. The cornerstone of
treatment is prevention through treatment of abrasions with
antimicrobial drops, early eyelid release and vigilance to the
risk of exposure trauma.46
Chondritis
Burns to the ear represent a clinical management challenge.
Full-thickness injuries can injure the cartilage of the ear,
resulting in autoamputation of part of or the entire external
auricle. Because of the auricles’ comparatively low blood
supply, chondritis frequently follows the progression of
tissue ischemia. Chondritis is usually seen 3–5 weeks follow­
ing the injury, but may be seen earlier and may occur fol­
lowing partial- and full-thickness injuries. The introduction
of mafenide acetate has become the topical agent of choice
for burned cartilaginous surfaces, and the incidence of
Figure 12.16  Left ear with suppurative chondritis. Chondritis seen 3 weeks
after flame burn to the left ear. Note the erythema and drainage from the
helical rim.

Total Burn Care
12
148
Prior to analysis, the specimen collection site must be
selected and must represent a location of active disease. The
area of the wound that looks clinically the worst is a good
place to find the pathogens. Even careful collection methods
will produce a specimen of little clinical value if they are not
obtained from a site where the infection is active. Also, col­
lectors must be aware of the appropriate device for sample
collection.
With burn wounds, it is particularly important to obtain
a culture which is free from contamination of the normal
flora that may be present on the surface of the injured skin.
In addition, the size or amount of the specimen plays an
essential role in the appropriate identification of the etio­
logic agent. The use of prophylactic antimicrobials (both
topical and systemic) should also be noted so that appropri­
ate inhibitors and sufficient dilutions can be prepared, or
reagents added to void any effects of drug interactions. The
specimen should be collected and placed in a sterile con­
tainer with appropriate media for transport to the laboratory.
All specimens must be transported promptly, so as to obtain
optimal results. In addition, direct communication with the
microbiologist can often be very helpful.
Pharmacodynamics and kinetics
in the burn patient
Pharmacotherapy in the control of infection in a burn
patient can be a challenge for the clinician. The normal
course of burn trauma effects pathophysiologic changes in
the cardiovascular, renal, metabolic, hepatic, gastrointesti­
nal, epidermal and immunological responses that change
the patient’s pharmacodynamic and pharmacokinetic state.51
Two distinct phases characterize the changes seen with burn
injury: the acute or resuscitative, and the hypermetabolic.
The acute or resuscitative phase
In the acute or resuscitative phase of burn trauma, which
occurs within the first 48–72 hours post burn, cardiovascular
factors produce hypovolemia, often with decreased blood
flow to organs and tissues.51 Intravenous drug treatments
during this phase will result in a slower rate of distribution
and elimination through the kidneys. The burn patient will
also exhibit delayed absorption of enteral, subcutaneous and
intramuscular drugs. Pharmacotherapy regimens during this
acute phase will result in delayed onset of action and peak
concentrations.
The hypermetabolic phase
The hypermetabolic response phase, mediated by greatly
increased levels of catecholamines, prostaglandins, gluca­
gons, and cortisol, occurs after the acute phase and also
produces pathophysiologic changes. The burn patient will
exhibit increased blood flow to organs and tissues, an
increased internal core temperature, and hypoproteinemia
and edema formation.51 Intravenous drugs will have an
increased onset of action owing to the increased rate of dis­
tribution. These drugs will also have a shorter half-life owing
to the enhanced glomerular filtration rate and elimination
of renally excreted drugs. The antibiotic treatment of these
patients requires higher doses for these drugs and perhaps a
shorter dosing interval. Renally excreted antibiotics such as
Suppurative sinusitis
An infection of this type has become more obvious recently
because of transnasal intubation and the use of nasogastric
or nasoduodenal tubes for enteral feeding. The diagnosis is
usually delayed due to clinically subtle symptoms, and only
after more frequent causes of fever are ruled out does it
become evident. Diagnosis is confirmed based on X-rays or
CT scans. Therapy with broad-spectrum antibiotics and pro­
motion of drainage is initiated. Surgical drainage of the
involved sinuses may be necessary if the infection is unre­
sponsive to the antibiotics. Oral intubation and nasogastric
feeding may be used as a temporary measure, but if sinusitis
becomes complicated and prolonged treatment is necessary,
then a tracheostomy and/or orogastric feeding is indicated.
Tetanus
As part of the admission protocol to the burn center, routine
prophylaxis for tetanus (Clostridium tetani) is 0.5 mL tetanus
toxoid, if it has not been administered in the previous 3
years.47,48 In addition, if the patient’s last booster was more
than 10 years ago, 250 units of tetanus antitoxin is also
administered.
HIV and the burn patient
The incidence of HIV infection is very common in many
parts of the world. In sub-Saharan Africa some countries
have rates of 35–39% in the total adult population. In the
US, although the incidence is much less, a burn care practice
in a large city will likely have patients who are infected with
HIV. HIV seems to have an additive effect on the immuno­
suppression of the burn, as reflected in the CD4/CD8 cell
counts. In a 2003 prospective study from Zimbabwe,
Mzezewa et al. found graft survival after split skin grafting
of burn wounds in HIV-infected patients impaired and hos­
pital stay prolonged, with significant alterations in the levels
of pro- and anti-inflammatory cytokines.49 The authors con­
cluded that HIV infection results in immune dysregulation,
which might be related to impaired skin graft survival.
Microbiologic and pharmacologic
considerations in the care of the burn patient
Selection, collection and transport
of specimens
There are several major benchmarks that must be adhered to
in order to achieve reliable clinical microbiology results in
its association with the thermal injury. Most important to
effective microbiologic diagnosis is the appropriate selec­
tion, collection and transport of specimens sent to the labo­
ratory. Appropriate specimen management affects patient
care in several significant ways:
•
it is the key to accurate laboratory diagnosis that
directly affects patient care and patient outcome;
•
it influences therapeutic decisions;
•
it affects hospital infection control, patient length of
stay, and overall hospital costs;
•
it plays a major role in laboratory costs, and influences
laboratory efficiency.50

Treatment of infection in burns
149
opportunistic pathogen.24,50,52 As a nosocomial pathogen,
S. aureus has been a major cause of morbidity and
mortality.50
Most common infections where Staphylococcus spp. are
encountered and are considered pathognomonic are septi­
cemia, cellulitis, impetigo, scalded skin syndrome, and post­
operative wound infections. However, the most serious
staphylococcal infections are puerperal sepsis, pneumonia,
osteomyelitis, endocarditis, and burn wound infection. Sta­
phylococcal pseudomembranous enterocolitis occurs most
frequently as a complication of antibiotic therapy. Strains of
S. aureus as well as other Staphylococcus species produce a
wide variety of metabolites. Some are pathognomonic and
also toxigenic, but those with minimal toxicity or no toxic
effects at all are of some diagnostic significance. An array of
byproducts such as proteinases, collegenases and hyaluroni­
dase digest the extracellular matrix, which serves as the struc­
tural integrity essential in wound healing.52 Exotoxins, which
are produced by the pathogenic strains of staphylococci,
include a pyrogenic toxin, a dermonecrotizing toxin, and
leukocidin. These organisms can also produce an exotoxin,
TSST-1 and enterotoxins A, B and C, which are risk factors
for toxic shock syndrome in susceptible patients (as dis­
cussed earlier).52 Toxic shock syndrome (TSS) was first
described as such in 1978.53 The disease is characterized by
sudden onset of fever, vomiting, diarrhea, shock, and a
diffuse macular erythematous rash, followed by desquama­
tion of the skin on the hands and feet as well as hyperemia
of various mucous membranes. However, the role of TSS has
not been completely elucidated in the burn patient. It has
been our experience that although burn patients may be
infected with a TSS-producing S. aureus, no other serious or
untoward complications have been observed. In fact, treat­
ment of their burn wounds was no different from that in
patients infected with a non-toxic S. aureus strain.
S. aureus and Staphylococcus spp. generally produce peni­
cillinases, which hydrolyze the penicillin β-lactam ring
and make natural pencillins ineffective against these
bacteria. Therefore, these types of infections are treated with
penicillinase-resistant penicillins. These antibiotics include
the parenteral antibiotics nafcillin, methicillin, and oxacillin
and the oral antibiotics cloxacillin, dicloxacillin, nafcilllin
and oxacillin. The staphylococcal infections that are
resistant to penicillinase-resistant penicillins are termed
‘methicillin-resistant’.
Vancomycin alone or in conjunction with other anti-
infectives has generally been considered the treatment
of choice for infections caused by methicillin-resistant
staphylococci. Vancomycin is bactericidal and appears to
bind to the bacterial cell wall, causing blockage of glyco­
peptide polymerization. This effect, which occurs at a site
different from that affected by the penicillins, produces
immediate inhibition of cell wall synthesis and secondary
damage to the cytoplasmic membrane.54 However, vanco­
mycin is a time-dependent antimicrobial, which requires
that the serum level of this drug must remain at all times
above the minimum inhibitory concentration (MIC) in
order to provide adequate bactericidal activity. The hyper­
metabolic burn patient exhibits an increased glomerular fil­
tration rate and increased excretion of the renally cleared
vancomycin. Because of the wide interpatient variability of
vancomycin elimination in burn patients, the dosage must
vancomycin that are time dependent in their ability to kill
Gram-positive bacteria must be carefully monitored to
ensure that they are meeting the minimum inhibitory con­
centration of the bacteria in the serum. Oral drugs will also
exhibit an increased absorption from the GI tract and
increased onset of action.51 The hypermetabolic phase will
produce decreased levels of albumin and increased levels of
acute-phase proteins.51 Albumin binds to acidic and neutral
drugs such as aminoglycosides, vancomycin, aztreonam and
cefotetan. These drugs will exist as free drug in hypoalbu­
minemia, which results in an increased volume of distribu­
tion. Lower doses of these drugs may be needed for
therapeutic effect. Acute-phase proteins bind to basic drugs
such as penicillins and cephalosporins. These drugs will be
tightly bound and there will be less free drug in the blood
and a decreased volume of distribution. Higher drug dosages
may be necessary to produce a therapeutic effect. The hepatic
response in the hypermetabolic phase will present as a
decrease in phase I metabolism, such as oxidation, reduc­
tion, or hydroxylation of a drug by the cytochrome P-450
system. This will affect the metabolism of many antibiotics,
such as the quinolones and the macrolides. The decreased
activity of these hepatic drug-metabolizing enzymes as well
as the decreased hepatic clearance and prolonged half-life
may produce systemic toxicity. Phase II metabolism in the
liver, such as conjugation reactions between the drug and the
endogenous substrate, will not be impaired. The gastrointes­
tinal response during the hypermetabolic phase results in
increased proton secretion. It is reported that erosion of the
stomach lining and duodenum occurs in 86% of adult
patients within 72 hours post-injury and 40% had GI bleed­
ing.51 In children, the incidence of stress ulceration is twice
that of adults. Erosion of the stomach lining and duodenum
allows the transmigration of GI bacteria from the gut into
the body’s bloodstream. The use of antacids, H2 antagonists
and proton-pump inhibitors may actually permit the prolif­
eration of bacteria that are not normally present in the gut.
Transmigration means these bacteria may be found in other
parts of the body, such as the lungs, heart and intestinal tract.
Finally, the immunological response will exhibit major
changes in the hypermetabolic phase. The burn patient
suffers damage to the epidermis of the skin. The depression
in this first line of defense allows systemic microbial inva­
sion. However, there is also depression in the second line of
defense, with a burn size related depression of both cellular
and humoral aspects of the immune response and phago­
cytic activity of fixed and bloodborne macrophages and neu­
trophils. The patient suffers a release of chemical mediators
including prostaglandins, serotonin, thromboxanes and
leukotrienes, which mount an inflammatory response.
The modern burn unit’s care is often greatly enhanced by
the active participation of a pharmacist familiar with burn
patients.
Bacteria and their treatment
Gram-positive organisms
Staphylococcus aureus
Staphylococcus aureus is the most important cause of bacterial
burn wound infections and is well documented as a human

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12
150
high as 20% has been noted. Therefore, enterococci appear
to be not only common but also virulent burn wound
pathogens.56
Oral treatment of Gram-positives
The oral treatment of methicillin-resistant staphylococci may
present a greater challenge to a burn clinician. Rifampin is
a bactericidal antibiotic that has efficacy in the treatment of
these organisms. Rifampin produces its action by inhibiting
RNA synthesis in the bacteria, binding to the β subunit of
the DNA-dependent RNA polymerase and blocking RNA
transcription.54 However, it must be used in combination
with other anti-infectives in the treatment of methicillin-
resistant staphylococci because of its high resistance pattern
when used alone. Other anti-infectives with a different mech­
anism of action reduce the resistance of rifampin. Oral anti­
biotics such as Bactrim (sulfamethoxazole and trimethoprim)
or levofloxacin are often used in conjunction with rifampin.
Linezolid is a synthetic antibacterial agent of a new class of
antibiotics, the oxazolidinones, which has joined the arma­
mentarium against MRSA and MRSE. Linezolid inhibits bac­
terial protein synthesis by binding to a site on the bacterial
23S ribosomal RNA of the 50S subunit and prevents the
formation of a functional 70S initiation complex, which is
an essential component of the bacterial translation process.54
The results of time–kill studies have shown linezolid to be
bacteriostatic against enterococci and staphylococci. For
streptococci, linezolid was found to be bactericidal for the
majority of the strains. In vitro studies, however, show that
point mutations in the 23S ribosomal RNA are associated
with linezolid resistance and have been reported with some
strains of Enterococcus faecium and S. aureus.54 Adverse drug
effects of linezolid include myelosuppression (e.g. anemia,
leukopenia, pancytopenia and thrombocytopenia) which is
generally reversible upon discontinuation of the drug, and
Clostridium difficile-associated colitis. Linezolid is also a weak,
non-selective, reversible inhibitor of monoamine oxidase
(MAO) and may cause increased serotonin serum levels and
serotonin syndrome in patients on various serotonin reuptake
inhibitors such as fluoxetine and sertraline. Staphylococcal
infections may also be treated with quinupristin/dalfopristin
(Synercid). Quinupristin/dalfopristin is bactericidal and
inhibits bacterial protein synthesis by binding to different
sites on the 50S ribosomal subunit, thereby inhibiting
protein synthesis in the bacterial cell.
Enterococcal bacterial infections
Most enterococcal bacteria are susceptible to vancomycin.
Vancomycin-resistant enterococci usually will require treat­
ment with a combination of agents such as ampicillin and
aminoglycosides. If this combination is not effective, the
VRE may be treated with the quinupristin/dalfopristin
(Synercid) combination or linezolid. The literature also
reports that the use of quinupristin/dalfopristin resulted in
resistance in one study and a superinfection in another study
during the treatment of VRE infection.54
Gram-negative organisms
This family of Gram-negative rods contains a distinctive
group of etiologic agents for burn wound infections.
be individualized in order to provide an optimal time-
dependent serum concentration. The peak and trough levels
are derived from the MIC for a particular bacterial organism.
Because vancomycin is a concentration-independent, or
time-dependent, antibiotic and because there are practical
issues associated with determining a precise peak serum con­
centration with this multicompartment antibiotic, most cli­
nicians have abandoned the routine practice of determining
peak serum concentrations. The trough level for vancomycin
monitoring is normally 10–15 µg/mL, and it is critically
important to maintain that serum level between dosing
intervals to achieve therapeutic as well as clinical success.
Prolonged exposure to serum levels close to the MIC pro­
motes the emergence of resistance; therefore, it is important
to maintain adequate serum concentrations in patients with
fast or rapidly changing creatinine clearance, such as burn
patients. There are also certain body compartments in which
penetration is poor, such as the lung and the CNS. It would
also seem prudent to keep concentrations from being
suboptimal in patients with pneumonia or meningitis,
as well as in patients receiving dialysis for renal failure.
The American Thoracic Society published guidelines for
hospital-acquired ventilator-associated and healthcare-
associated pneumonia. These guidelines recommend vanco­
mycin trough concentrations of 15–20 µg/ mL for the
treatment of methicillin-resistant S. aureus pneumonia.55
These higher concentrations may be needed for sequestered
infections or in situations where vancomycin penetration
has been documented to be poor. Recent testing has shown
‘vancomycin MIC creep’ that may necessitate higher vanco­
mycin trough serum concentrations to eradicate these micro­
organisms in burn wound infections.55
Streptococci
The streptococci produce a variety of hemolytic activity in
the presence of blood. This hemolysis is considered a viru­
lence factor, and quantitatively this group of organisms do
not lend themselves to the standard rule of <105 for any
tissue closure. In burn injury, the presence of even a few
β-hemolytic streptococci can cause a wound infection, failure
of a primary closure, and loss of a skin graft. The major
species that can be diagnosed with this particular type of
hemolysis are Streptococcus pyogenes (also referred to as group
A streptococci) and S. agalactiae (also referred to as group B
streptococci). The natural penicillins, which consist of peni­
cillin G and penicillin V, and the first-generation cepha­
losporins are bactericidal to these bacteria. Should resistance
or intolerance to the natural penicillins or first-generation
cephalosporins develop, then culture and antibiotic sensitiv­
ity data should be used to treat the streptococcal infection
appropriately.
Enterococci
The enterococci have become one of the most important
causes of burn wound infection. This is likely due to wide­
spread use of third-generation cephalosporins over the last
decade, to which enterococci are resistant. Additionally, a
major cause for concern is the emergence of vancomycin-
resistant enterococci (VRE) in burn units. Although the exact
rate of morbidity associated with VRE itself is unclear, when
it occurs as a polymicrobial bacteremia a mortality rate as

Treatment of infection in burns
151
The overall survival rate was 84%.60 Colistimethate sodium
provided an important salvage option for burn patients with
otherwise incompletely treated and life-threatening Gram-
negative infections. Monitoring the dose-dependent nephro­
toxicity and CNS toxicity associated with its systemic use,
however, is necessary to achieve a therapeutic outcome.
When polymixin B is given to animals or humans, it binds,
via its free amino acid groups, to negatively charged phos­
pholipids in tissues. Kunin and Bugg showed that binding is
greatest to kidney and brain tissues, followed by liver, muscle
and lung tissues.61,62 After repeated doses, the drug accumu­
lates in tissues to concentrations four to five times higher
than peak serum concentrations and persists for at least 5–7
days. Removal of the drug by dialysis can be difficult owing
to extensive tissue binding. Colistimethate sodium appears
to proportionately increase the incidence of C. difficile-
associated colitis, renal dysfunction and neuropathies in
relation to the duration of its use. In the study from Galve­
ston, however, no increased hepato-, neuro-, or nephrotoxic­
ity was reported as compared to a control group without
colistimethate treatment.60
Aminoglycoside antimicrobials continue to be a frequent
choice when sensitive organisms are encountered. Current
evidence suggests that once-daily dosing of aminoglycosides
is as effective as, and may be less toxic than, conventional
dosage regimens employing multiple daily doses of the drug.
Results of several analyses of pooled data from randomized
controlled studies in adults found that once-daily adminis­
tration of aminoglycosides was associated with similar or
greater efficacy (e.g. bacteriologic and/or clinical cure), less
nephrotoxicity, and no greater risk of ototoxicity than admin­
istration of multiple daily dosing of these drugs.54 Less fre­
quent (e.g. once-daily) dosing may minimize or prevent the
occurrence of aminoglycoside-induced adaptive resistance
(i.e. reversible refractoriness to the antimicrobial effects of
subsequent aminoglycoside doses because of decreased
uptake of the drug following the initial dose) and selection
of aminoglycoside-resistant subpopulations in Gram-
negative bacteria by allowing a recovery period during the
dosing interval in which serum aminoglycoside concentra­
tions are negligible.54 In burns, however, some clinicians
have suggested that once-daily dosing of aminoglycosides
may not be advisable in patients with serious infections and
impaired host defenses (e.g. P. aeruginosa infections in
patients with neutropenia) and/or clinical conditions associ­
ated with rapid clearance or unpredictable pharmacokinetics
of aminoglycosides (e.g. extensive burns, cystic fibrosis,
massive ascites), as these regimens could allow prolonged
intervals of undetectable aminoglycoside concentrations.
Therefore, monitoring of aminoglycoside serum concentra­
tions and/or peak serum concentration/MIC ratio in burn
patients with life-threatening infections, suspected toxicity
or non-response to treatment, decreased or varying renal
function, and increased aminoglycoside clearance is
mandatory.
The usage of extended-spectrum penicillin in the treat­
ment of Gram-negative bacterial infections provides a burn
population with a much less toxic antibiotic than the
aminoglycosides, as the most frequent adverse reactions
include hypersensitivity reactions, gastrointestinal effects,
and local reactions. Fourth-generation cephalosporins such
as cefepime, extended-spectrum β-lactamase inhibitor
The presence of this group of organisms is partially due to
translocation of the bacteria from the gastrointestinal tract
of patients. Of this group, the Pseudomonas species are the
most repeatedly encountered burn wound pathogens.
Pseudomonas spp. have a worldwide distribution with a
predilection for moist environments. Because of their ability
to survive in aqueous environments, these organisms have
become problematic in the hospital environment.50 The
spectrum of disease caused by this agent ranges from super­
ficial skin infections to fulminant sepsis. P. aeruginosa is the
leading cause of nosocomial respiratory tract infection.
Wound infections due to P. aeruginosa are also particularly
troublesome in burn patients.57 Other significant Gram-
negative pathogens commonly associated with burn infec­
tion include Acinetobacter spp., which can be found as part
of the indigenous flora of the respiratory, skin, gastrointesti­
nal and genitourinary tracts of humans and animals. They
have been isolated from a diversity of clinical sources, includ­
ing upper and lower respiratory tracts, urinary tract, surgical
and burn wounds, and in bacteremias secondary to intra­
venous catheterization. Many of the patients who develop
infections with this microorganism have had various manip­
ulations, including the use of respiratory therapy equipment,
tracheal intubation, or bladder or central venous line cath­
eterization. It is an agent of low virulence and has a predilec­
tion for infecting patients with dysfunctional host defense
mechanisms. Acinetobacter spp. tend to have a high degree of
antimicrobial resistance, which is most likely associated with
previous antimicrobial therapy.58
The Enterobacteriaceae, such as Escherichia coli, Klebsiella
spp., Enterobacter spp., Serratia marcescens, and Proteus spp.,
are additional Gram-negative organisms associated with
burn patients. These organisms are often encountered as a
cause of nosocomial pneumonia in patients with inhalation
injury, as well as those with urinary tract infections associ­
ated with indwelling urinary catheters.59
Treatment of Gram-negative organisms
Treatment of Gram-negative infection is usually guided
empirically by an antibiogram specific for the unit or hospi­
tal, until culture and sensitivity reports become available.
Testing for synergy between different classes of antibiotics is
an option used to determine efficacy for multiply drug-
resistant organisms (MDROs), although such testing is not
yet widely available outside clinical reference laboratories.
The aminoglycosides, particularly gentamicin, were histori­
cally the antibiotics of choice in the treatment of Gram-
negative infections; however, some Gram-negative bacteria
encountered in the burn unit are now resistant to all the
aforementioned antibiotic classes and often the treatment
option is relegated older drug classes, namely the
polymyxins.
Polymyxins are recommended for serious systemic infec­
tions caused by Gram-negative bacteria that are resistant to
other agents, and have a definite role in therapy of multidrug-
resistant Gram-negative bacterial infections. Branski et al.
reported the use of colistimethate sodium in a series of 118
patients between 2000 and 2006 (median and mean age of
9 years) with a mean TBSA of 64 ± 19% at the Galveston
Shriners Hospital for Children. The median treatment dura­
tion was 12 days and the mean dosage 4.4 ± 0.9 mg/kg/d.

Total Burn Care
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152
infections. Routine culture techniques may require from 7 to
14 days to identify fungal contaminants, delaying the initia­
tion of treatment.68 In contrast to bacterial sepsis, venous
blood cultures may not reflect the causative fungal organ­
ism.22 Arterial blood cultures and retinal examination for
characteristic candidal lesions can be useful. Unlike candidal
infections, true fungal infections occur early in the hospital
course of patients with specific predisposing characteristics.
Most frequently, burned patients infected with fungi are
exposed to spores in the environment, from either rolling
on the ground or jumping into contaminated surface water
at the time of injury. Other environmental foci have been
cited as the source of nosocomial fungal infection, including
bandaging supplies left open to the air, heating, and aircon­
ditioning ducts and floor drains.65,67 Once colonized, broad
non-branching hyphae extend into subcutaneous tissue,
stimulating an inflammatory response. This phenomenon is
diagnostic of fungal wound infection. Vascular invasion is
common and often accompanied by thrombosis and avas­
cular necrosis, clinically observed as rapidly advancing dark
discolorations of the wound margins or well-described
lesions.22 Systemic dissemination of the infection occurs
with invasion of the vasculature. Treatments for yeasts and
molds are vastly different, owing to their vastly different
pathogenicities. Yeasts found in a burn wound are more
often associated with colonization and do not represent an
infection. Treatment usually is considered when the same
yeast is identified at multiple sites, in which case topical
treatment is used more liberally. In contrast, the identifica­
tion of a mold in a burn wound is taken very seriously.
Infection with mold is often invasive and requires very
aggressive treatment, topically, surgically, and with IV medi­
cation. It is common to work with the pathologist to ensure
that clean margins free of hyphae are obtained at the con­
clusion of a debridement. Amphotericin B has been the
standard choice for intravenous treatment of invasive
infection with mold. Currently, there are five classes of
systemic antifungal medication, including the polyenes, the
azoles, nucleoside analogs, echinocandins, and allylamines.
These new drugs offer improved side-effect profiles over
amphotericin B.
Although amphotericin B dexolate (AmBd), a polyene, has
been the standard choice for IV treatment of life-threatening
invasive mold, this drug is associated with significant toxic­
ity, including infusion-related events and dose-limiting renal
dysfunction.69 Three new lipid formulations of AmB (AmB
lipid complex (ABLC), AmB colloidal dispersion (ABCD),
and liposomal AmB (AmB-L)) offer several advantages over
AmBd, including increased daily doses of the parent drug
(up to 10–15-fold), high tissue concentrations in reticulo­
endothelial organs, a decrease in infusion-related events
(especially ABLC and AmB-L), and a marked decrease in
nephrotoxicity.69 These lipid drugs are more expensive than
AmBd, but cost is best assessed pharmacoeconomically (cost
of drug acquisition as well as cost of hospital stay, monitor­
ing, complications, etc.). Authorities agree that these agents
are indicated for patients who are intolerant of or refractory
to AmBd, but controversy exists about the lipid drugs as
initial therapy both in neutropenic patients with persistent
fever and in patients with invasive mold disease.
For the majority of patients with systemic candidiasis,
cryptococcosis
and
the
endemic
mycoses,
e.g.,
penicillins (piperacillin/tazobactam, ticarcillin/clavulanate)
and most importantly the carbapenems (imipenem/
cilastatin, meropenem, ertapenem) provide important tools
in killing Gram-negative infections. Because these antibiotics
work most efficaciously by maintaining a serum concentra­
tion of 1–2 times the MIC between dosing intervals, many
clinicians suggest that more frequent dosing or longer infu­
sions of 3–4 hours may be necessary to maintain this MIC
for an effective kill rate. Because of their different mecha­
nisms of action these different penicillin antibiotic drug
classes may also be used in combination with other antibi­
otic drug classes to produce a synergistic therapeutic response.
Anaerobes
The most repeatedly confronted organisms in this group
which may play a role in surgical and burn wound infections
are Bacteroides spp. and Fusobacterium spp. These anaerobes
are considered normal flora of the human body, beginning
at the oropharyngeal cavity and ending at the gastrointesti­
nal (GI) and urogenital tracts. Numerically they account for
the major population in the oropharyngeal region in a 5 : 1
ratio over the aerobes and facultative anaerobes, whereas in
the urogenital and GI tracts the ratio is more dynamic, at
1000 : 1.50,63 Yet when one scrutinizes the current statistics of
anaerobic infections related to locality, all but 2–5% of surgi­
cal wound infections in the oropharyngeal area are caused
by the anaerobic flora.64,65 Those occurring in the GI and
urogenital tracts are only responsible for about 10–15% of
the wound infections,53,66 Anaerobic infections in burned
patients are usually associated with avascular muscle found
in electrical injuries, frostbite, or cutaneous flame burns with
concomitant crush-type injuries.18 With the advent of early
excision and grafting, the incidence of anaerobic infections
in thermal injury has been significantly reduced. If anaerobic
infection is suspected, it is important that the collected speci­
mens be placed in appropriate transport tubes void of
atmospheric oxygen to provide ideal recovery conditions.
Fungi – yeast and mold
Until the advent of topical antimicrobial agents, fungal
infections were not common in burned patients. However,
the incidence of mycotic invasion has doubled since the
implementation of topical antimicrobial agents to control
bacterial colonization.67 The burn wound is the most com­
monly infected site, although local or disseminated fungal
infections of the respiratory, urinary and GI tracts and the
vagina are becoming increasingly common.67,68 Yeasts are
identified primarily on the basis of specific biochemical tests,
but both macroscopic and microscopic morphology are also
used in making a final identification. Mold identification
is based on growth rate, colony structure, microscopic/
microscopic appearance, dimorphism at different incuba­
tion temperatures, inhibition of growth by cyclohexamide,
as well as some biochemical tests.64 Candida spp. are the
most common fungal colonizers of the burn wound,
although true fungi such as Aspergillus spp., Penicillium spp.,
Rhizopus spp., Mucor spp., Rhizomucor spp., Fusarium spp.
and Curvularia spp. can also be present, and have a vastly
greater invasive potential than yeasts.65,67
Early diagnosis of fungal infection can be difficult, as
clinical symptoms frequently mimic low-grade bacterial

Treatment of infection in burns
153
formulated to mimic normal human physiologic parame­
ters. It is an excellent cleansing agent which was found to be
bactericidal, non-toxic to fibroblasts, and did not inhibit
wound healing. However, the NaOCl 0.025% solution is
only effective over a 24-hour time frame after the buffer (0.3
N NaH2 HPO4) is added to the NaOCl.
Buffered NaOCl 0.025% solution soaks are most benefi­
cial in reducing bacterial numbers in a wound. NaOCl
0.025% solution is a broad-spectrum antiseptic and is
bactericidal against P. aeruginosa, S. aureus, and other Gram-
negative and Gram-positive organisms. It is effective against
methicillin-resistant staphylococci and enterococci. A
0.025% NaOCl solution may be used separately or in com­
bination with other antibacterial agents to control coloniza­
tion or infection. This solution also enhances wound healing
and increases wound breaking strength compared to maf­
enide acetate.16,74
Silver nitrate (AgNO3)
Silver nitrate was formerly used as a 10% solution but was
found to be toxic at this concentration. It has now been
reinstated as a 0.5% solution, which is non-toxic, does not
injure regenerating epithelium in the wound and is bacterio­
static against S. aureus, E. coli, and P. aeruginosa. AgNO3 is
most effective when the wound is carefully cleansed of all
emollients and other debris, and debrided of all dead tissue.
Multilayered coarse-mesh dressings should be placed over
the wound and saturated with the AgNO3 solution. Like
silver sulfadiazine, AgNO3 has limited penetration because
silver is rapidly bound to the body’s natural chemical sub­
stances.7,71 Because it is hypotonic in nature it can cause
osmolar dilution, resulting in hyponatremia and hypochlo­
remia. Serum electrolytes must be monitored very carefully.
A 0.5% solution of AgNO3 is light sensitive, and when it is
allowed to dry out it turns black on contact with tissues and
other Cl-containing compounds. Hyperpyrexia may also
occur if AgNO3 becomes dry and is covered with an impervi­
ous dressing. Some institutions are combining silver nitrate
with miconazole powder to produce an aqueous solution of
silver nitrate 0.5% and miconazole 2% that is effective in
preventing fungal overgrowth in burn wounds treated with
silver nitrate 0.5% solution alone. Klebsiella spp., Providencia
spp., and other Enterobacteriaceae are not as susceptible to
AgNO3 0.5% solution as other bacteria. The combination of
AgNO3 0.5% solution with Enterobacter cloacae and other
nitrate-positive organisms may cause methemoglobinemia
by converting nitrate to nitrite in the body.71,74
Silver sulfadiazine
Silver sulfadiazine (Silvadene, Thermazine, Flamazine, SSD),
a 1% water-soluble cream, is a combination of sulfadiazine
and silver. The silver ion binds with the DNA of the organ­
ism, releasing the sulfonamide which interferes with the
intermediary metabolic pathway of the microbe.74–76 It is
most effective against P. aeruginosa and the enterics, and
equally effective as any antifungal drug against C. albicans
and S. aureus. However, some strains of Klebsiella have been
less effectively controlled. Recently there have been reports
of P. aeruginosa resistance to silver sulfadiazine. Silver sulfadi­
azine can be applied with equal effectiveness using either
blastomycosis, histoplasmosis, and coccidioidomycosis),
AmBd or the azole drugs (voriconazole, fluconazole or itra­
conazole, posaconazole) should be used as initial therapy.
Initial treatment with a lipid drug for these patients cannot
be justified, unless the patient requires AmB therapy and has
pre-existing renal dysfunction. However, the IDSA recom­
mends that invasive aspergillosis be treated with the azole
antibiotic voriconazole, because of its efficacy and lower
toxicity profile.70 AmBd may still be used as an alternative.
Posaconazole has also been cited as an effective treatment
agent against aspergillosis. The azoles (fluconazole, itracona­
zole, voriconazole, and posaconazole) demonstrate similar
activity against most Candida species, but each has less activ­
ity against C. glabrata and C. krusei. The echinocandins
(caspofungin, anidulafungin, micafungin) have very good
efficacy against these two Candida species and exhibit few
adverse side effects. The echinocandins, however, may have
less activity against C. parapsilosis. Flucytosine, a pyrimidine,
has limited clinical indications, primarily in combination
with AmBd, as therapy for cryptococcal meningitis and
selected life-threatening Candida syndromes.
Topical antimicrobial compounds and agents
One of the most effective means to achieve a microbial
balance in a colonized or infected wound is the proper use
of prophylactic topical agents. Maintaining wounds at low
colonization levels diminishes the frequency and duration
of septic episodes caused by wound flora. The introduction
of topical antimicrobial agents has resulted in a significant
reduction in burn mortality to date.7,71 However, no single
agent is completely effective against all organisms, and each
possesses its own advantages and disadvantages. Whereas
topical agents retard wound healing, the application of some
antimicrobial agents may increase the patient’s metabolic
rate. Their effectiveness is measured by their ability to inhibit
bacterial growth in vitro and reduce wound colony counts
in vivo. Recent studies have demonstrated that some agents
used in the past are no longer effective in inhibiting bacterial
growth.72,73
Wounds in which the quantitative culture counts remain
<102/g tissue may remain dressed in the topical agent of
choice. However, should the colony count increase beyond
that point, a change in the topical agent is strongly
recommended.
Sodium hypochlorite (NaOCl)
Currently the most effective topical antibacterial for cleans­
ing a wound is sodium hypochlorite (NaOCl).16 It tran­
scends the topical antimicrobial effects and tissue toxicity of
such products as povidone-iodine, acetic acid, and hydrogen
peroxide.16 Whereas povidone-iodine is bactericidal at con­
centrations of 1% and 0.5%, it is toxic to fibroblasts; acetic
acid at a 0.25% concentration is not bactericidal and is toxic
to fibroblasts; and hydrogen peroxide at 3% and 0.3% con­
centrations is toxic to fibroblasts, but only the 3% concentra­
tion is bactericidal.16 Studies by Heggers and co-workers16
reported on the efficacy of NaOCl at a concentration of
0.025%. This is one-tenth the concentration of ‘Half-Strength
Dakins’, the formulation used by many hospitals as a
topical antimicrobial agent. Buffered NaOCl 0.025% was

Total Burn Care
12
154
it is quite effective in burn wound areas that are not well
perfused, such as the ear. The 5% aqueous solution of maf­
enide acetate can be used in a wet dressing covered by the
splint.
Studies have reported that the use of mafenide acetate 5%
solution in patients with major burns resulted in a 33%
reduction of fatality. As with silver sulfadiazine, mafenide
acetate can be used individually or in conjunction with other
antimicrobials. However, mafenide acetate retards wound
healing and reduces the breaking strength of healed wounds.7
Povidone-iodine (Betadine)
A 10% ointment of povidone-iodine was developed after the
active agent demonstrated a broad spectrum of antimicro­
bial attributes in liquid form. Although its active antimicro­
bial component is iodine, there has been no documentation
associated with intact skin hypersensitivity or toxic effects. It
has a broad spectrum of antibacterial and antifungal activi­
ties.7,74,77 Povidone-iodine ointment can be employed effec­
tively in both closed and open techniques. Quantitative
bacteriological assessments imply that iodine is most effica­
cious when administered every 6 hours. When it is used in
this manner, it is effective in controlling and/or preventing
bacterial colonization. However, there are some adverse
effects associated with the use of this topical antimicrobial
at burn wound sites. The topical application of this agent is
painful. Recent studies imply that the iodine component of
this topical agent may be absorbed more extensively in burn
wound sites, resulting in iodine toxicity, renal failure, and
acidosis. It has also been shown to be cytotoxic to fibro­
blasts, as previously described.7,71,77,78 However, it remains a
highly effective disinfectant when used on intact skin.
Gentamicin sulfate (Garamycin)
Gentamicin sulfate is available as a 0.1% water-soluble
cream and is chemically similar to other aminoglycosides,
such as kanamycin and neomycin. It has a broad spectrum
of antimicrobial activity. Its popular use in wounds was
based on its antimicrobiocidal efficacy against P. aeruginosa.
However, gentamicin resistance has rapidly developed due
to its widespread use as a topical antimicrobial agent.7,71
Bacitracin/polymyxin (Polysporin)
The topical antibiotics bacitracin and polymyxin are used in
an ointment to ‘butter’ bolsters to prevent mechanical shear­
ing of newly grafted tissue. However, this topical ointment
barrier used after a grafting procedure has not shown to be
effective in controlling infection. Many surgeons rely on this
topical agent for skin graft coverage because it is non-toxic
and is similar to petrolatum gauze dressings, which were
previously considered as a dressing for grafts. These two
antibiotics combined have little or no effect on localized
burn wound infections, and prolonged use is associated with
hypersensitivity development.
Nitrofurantoin (Furacin)
The topical antimicrobial nitrofurantoin was used in the past
but had questionable value therapeutically. Recent research,
however, has shown that nitrofurantoin is effective in the
closed or open methods. Antimicrobial effectiveness has
been observed to last for up to 24 hours. More frequent
changes are required if a creamy exudates forms on the
wound. Some of the benefits of this topical agent are its ease
of use and its ability to reduce pain. It has some tissue-
penetrating ability, but this is limited to the surface epider­
mal layer. However, it is not associated with acid–base
disturbances or pulmonary fluid overload, as is mafenide
acetate.71 Silver sulfadiazine can be used separately or in
combination with other antibacterials and with enzymatic
escharotomy compounds. It can be combined with nystatin,
which enhances the antifungal capability of this agent. By
itself, silver sulfadiazine has been shown to retard wound
healing. An adverse drug reaction may be a reversible granu­
locyte reduction, although this is controversial.7,71
Mafenide acetate (Sulfamylon)
Mafenide acetate is available both as an 8.5% water-soluble
cream and a 5% aqueous solution. This agent has more
substantial bacteriological data to support its efficacy than
any other topical antimicrobial. Mafenide acetate has been
shown to be effective against a broad range of microorgan­
isms, especially against all strains of P. aeruginosa and
Clostridium. After the wound has been cleansed of debris,
mafenide acetate 8.5% cream is applied to the wound like
butter (Lindberg’s Butter). The treated burn surface is left
exposed for maximal antimicrobial potency. The cream is
applied a minimum of twice daily and is reapplied between
applications if rubbed off the wound. Advantages of the
cream are its ability to control P. aeruginosa wound infec­
tions, ease of application, and the lack of a need for dress­
ings. Additionally, it has the ability to penetrate burn eschar
and circumvent the colonization of the burn.
The 5% solution is used to saturate an eight-ply gauze
dressing which is then applied to the burn wound. The dress­
ing should be kept saturated with the mafenide acetate 5%
solution in order to achieve maximal antimicrobial effects.
The dressings may be changed every 8 hours. Mafenide
acetate 5% solution is proclaimed to have effective tissue-
penetrating ability and appears to be especially effective after
the dead tissue is removed from the granulating bed.7
However, there are several detrimental aspects to the use of
mafenide acetate. Protracted use, combined with its low
environmental pH, favors the growth of C. albicans. Maf­en­
ide acetate 5% solution is converted by monoamine oxidase
to p-sulfamylvanzoic acid, a carbonic anhydrase inhibitor.
Carbonic anhydrase inhibitors prevent the conversion of
hydrogen ions in the body to carbonic acid, leading to meta­
bolic acidosis in the patient. If the patient has sustained an
inhalation injury and developed a respiratory acidosis, the
use of mafenide acetate over large areas of the body may
produce a metabolic acidosis, which can be fatal. This com­
plication can also be seen when treatment with mafenide
acetate occurs during septic episodes with metabolic acidosis
or when applied over large areas of the body surface. Another
detrimental problem encountered with mafenide acetate is
that it is painful when applied to superficial partial-thickness
burns with intact free nerve endings. The open application
of mafenide acetate 8.5% cream to a burn wound site
for increased antimicrobial activity may be considered a dis­
advantage if a burn wound dressing is necessary. However,

Treatment of infection in burns
155
albicans and C. guilliertnondi. Concentrations of 6.25 µg/mL
are required to inhibit C. krusei and Geotrichum lactis. In
general, there is little difference between minimum inhibi­
tory and fungicidal concentrations for a particular organism.
Nystatin is not active against bacteria, protozoa, or viruses.
Nystatin is not absorbed systemically and is used orally for
the treatment of intestinal candidiasis. In our burn popula­
tion, nystatin ‘swish and swallow’ is used prophylactically
to prevent the oral or perineal overgrowth of yeast and fungi
in patients receiving two or three systemic antibiotics. In
patients with coexisting intestinal candidiasis and vulvovagi­
nal candidiasis, nystatin may be administered orally in con­
junction with the intravaginal application of an antifungal
agent. Most evidence suggests that combined therapy does
not substantially reduce the risk of recurrence of vulvovagi­
nal candidiasis, compared to intravaginal therapy alone.
However, limited evidence suggests that the reduction of
intestinal candidal colonization in combination with intra­
vaginal antifungal therapy may provide some improvement
in mycologic response and a reduction in recurrence rate of
vulvovaginal candidiasis. For the treatment of cutaneous or
mucocutaneous candidal infections, nystatin 100 000 units/g
may be applied topically as a cream, lotion, or ointment to
affected areas 2–4 times daily. The cream or lotion formula­
tions are preferred to the ointment for use in moist, inter­
triginous areas. The use of occlusive dressings and ointment
formulations should be avoided in the treatment of candi­
diasis because they favor the growth of yeast and the release
of its irritating endotoxin. Concomitant therapy should
include attention to proper hygiene and skin care to prevent
the spread of infection and reinfection. In addition, the
affected areas should be kept dry and exposed to air when­
ever possible. Burn patients are affected by an immunocom­
promised system and thus more susceptible to opportunistic
infections. Depletion of the number of neutrophils, defects
in neutrophil function, and T-cell defects all predispose the
host to fungal infections. Aspergillosis and hyalohyphomy­
cosis (specifically Fusarium) are the most common angio­
invasive fungal infections in burn patients. Barret et al.
examined the curative effects of direct application of nystatin
powder on severely burned children affected by angioinva­
sive fungal infection.90
The topical treatment of burn wounds with nystatin
powder at a concentration of 6 000 000 U/g proved to be
effective in eradicating the invasive fungal infections. This
new regimen of topical treatment not only is effective super­
ficially but also eradicates invasive clusters of fungi in deep
wound tissues, as documented by pathological examination.
The application of the powder is easy and does not produce
pain or discomfort. It did not impair wound healing and all
previously autografted areas healed uneventfully.90 Nystatin
powder may be combined with silver sulfadiazine 1% cream
and mafenide acetate 5% aqueous solution to prevent the
overgrowth of yeast and fungi at the wound site due to con­
tinuous application of these potent topical antimicrobial
agents.91
Further reading
Branski LK, Al-Mousawi A, Rivero H, et al. Emerging Infections in
Burns. 2009;10(5):389-397.
treatment of MRSA and other methicillin-resistant staphylo­
cocci. Nitrofurantoin has also proved to be 75% effective
against Gram-negative bacterial isolates other than P. aerugi­
nosa, whereas bacitracin/polymyxin was only 21% effective.
Mupirocin (Bactroban)
Mupirocin is one of several antibiotics derived from the
fermentation of P. fluorescens and is also known as pseudo­
monic acid A. Although the antimicrobial activity derived
from cultures of P. fluorescens was first reported over a century
and a half ago, this agent could not be used as an antimi­
crobial until Fuller et al. had executed a more complete
isolation and purification of pseudomonic acid A.79 Further
research described the antimicrobial activity of mupirocin as
an inhibition of microbial isoleucyl t-RNA synthetase that
causes inhibition of protein synthesis in the bacterial cell.80
In vitro studies have subsequently established that mupi­
rocin has omnipotent inhibitory activity against the Gram-
positive microbes, specifically S. aureus and S. epidermidis.
Mupirocin’s efficiency in the treatment of infection or colo­
nization due to S. aureus, whether methicillin sensitive or
not, has been shown in various clinical settings. Rode and
coworkers have provided additional data regarding the effi­
cacy of mupirocin in the treatment of established wound
infections with S. aureus that were resistant to systemic
methicillin, topical mafenide acetate, and povidone-iodine.81
Recent in vitro and in vivo endeavors have shown mupirocin
to be as efficacious in methicillin-resistant burn wound
infections.82–84 Mupirocin, albeit not sanctioned for Gram-
negative organisms, has been shown to be 75% effective
against most enteric organisms and is significantly more
effective against these microorganisms than bacitracin/
polymyxin81 Mupirocin inhibits wound healing by a half-life
of 2 days compared to controls, but the breaking strength of
the wound is significantly enhanced.
Acticoat AB
Acticoat AB Dressing consists of two sheets of high-density
polyethylene mesh coated with ionic silver with a rayon/
polyester core. Acticoat AB Dressing provides broad-spectrum
antimicrobial, bactericidal coverage against VRE, MRSA, P.
aeruginosa, Candida sp. and approximately 150 other organ­
isms. It can remain intact for several days on the wound, if
there is minimal exudation. Acticoat must remain moist to
be active. Rewetting with water is recommended to avoid
creating the silver salt. However, it has been reported that
Acticoat remains active when covering a moist wound.85–89
Nystatin (Mycostatin, Nilstat)
Nystatin is an antifungal antibiotic produced by Streptomyces
noursei. Nystatin exerts its antifungal activity by binding to
sterols in the fungal cell membrane. The drug is not active
against bacterial and mammalian cells because they do not
contain sterols in their cell membrane. As a result of this
binding, the membrane is no longer able to function as a
selective barrier to prevent the loss of potassium and other
cellular constituents from the fungal cell. Nystatin has fungi­
static or fungicidal activity against a variety of pathogenic
and non-pathogenic strains of yeasts and fungi. In vitro,
nystatin concentrations of approximately 3 µg/mL inhibit C.

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Polavarapu N, Olgilvie MP, Panthaki ZJ. Microbiology of Burn Wound
Infections. J Craniofacial Surgery. 2008;19(4):899-902.
Williams FN, Herndon DN, Hawkins HK, et al. The leading causes of
death after burn injury in a single pediatric burn center. Crit Care.
2009;13(6):R183.
Church D, Elsayed S, Reid O, et al. Burn Wound Infections. Clin
Microbiol Rev. 2006;19(2):403-434.
Greenhalgh DG, Saffle JR, Holmes JH, et al. American Burn
Association consensus conference to define sepsis and infection in
burns. J Burn Care Res. 2007;28:776-790.
Patel JA, Williams-Bouyer NM. Infections in Burn Patients. In: Feigen
RD, ed. Textbook of Pediatric Infectious Diseases. 6th ed.
Philadelphia: WB Saunders; 2009:1139-1151.
Access the complete reference list online at