Chăm Sóc Và Điều Trị Bỏng Toàn Diện (Total Burn Care – Tập 5)

8  •  Pathophysiology of Burn Shock and Burn Edema
74
Hemodynamic Consequences
The cause of reduced cardiac output (CO) during the resus­
citative phase of burn injury has been the subject of consid­
erable debate. There is an immediate depression of cardiac
output before any detectable reduction in plasma volume.
The rapidity of this response may result from impaired
neurotransmission of cardiac signaling and increased after­
load due to vasoconstriction. Soon after injury a develop­
ing hypovolemia and reduced venous return undeniably
contribute to the reduced cardiac output. The subsequent
persistence of reduced CO after apparently adequate fluid
therapy, as evidenced by restoration of arterial blood pres­
sure and urinary output, has been attributed to circulating
myocardial depressant factor(s), which possibly originates
from the burn wound.10,11 Demling et al.16 showed a 15%
reduction in CO despite aggressive volume replacement
protocol after a 40% scald burn in sheep. However there
are also sustained increases in catecholamine secretion and
elevated systemic vascular resistance for up to 5 days after
burn injury.95,116 Michie et al.121 measured CO and SVR
in anesthetized dogs resuscitated after burn injury. They
found that CO fell shortly after injury and then returned
toward normal; however reduced CO did not parallel the
blood volume deficit. They concluded that the depression
of CO resulted not only from decreased blood volume and
venous return, but also from an increased SVR and from the
presence of a circulating myocardial depressant substance.
After the resuscitation phase of burn shock, patients need
a supranormal CO. This is associated with a hypermeta­
bolic state and systemic inflammatory response syndrome
(SIRS).
MYOCARDIAL DYSFUNCTION
Increases in the afterload of both the left and the right heart
occur due to elevated SVR and PVR. Stroke volume and CO
can be maintained despite contractile depression by aug­
mented adrenergic stimulation, albeit at a cost of increased
myocardial oxygen demands. The right ventricle has a
minimal capacity to compensate for increased afterload.
Myocardial function can be compromised after burn injury
due to direct depression of contractility shown in isolated
heart studies.122,123 In severe cases, desynchronization of
the right and left ventricles is deleteriously superimposed on
a depressed myocardium.124 Howard et al.125 demonstrated
both systolic and diastolic dysfunction in burn-injured chil­
dren during the first few weeks post injury. Burn injury of
greater than 45% TBSA can produce intrinsic contractile
defects. Several investigators reported that aggressive early
and sustained fluid resuscitation failed to correct left ven­
tricular contractile and compliance defects.123,124,126 These
data suggest that hypovolemia is not the sole mechanism
underlying the myocardial defects observed with burn
shock. Serum from patients failing to sustain a normal
CO after thermal injury have exhibited a markedly nega­
tive inotropic effect on in vitro heart preparations, which
may be due to the circulating shock factor described
earlier.69,127 In other patients with large burn injuries and
normal cardiac indices, little or no depressant activity was
detected.
the damaged tissue in a dose-dependent manner. In con­
trast, the SOD content in the group treated with TCV-309
was significantly higher than that of the control group.
These findings suggest that the administration of large
doses of a PAF antagonist immediately after injury may
reduce burn wound edema and the subsequent degree of
burn shock by suppressing PAF and superoxide radical
formation.
ANGIOTENSIN II AND VASOPRESSIN
Angiotensin II and vasopressin or antidiuretic hormone
(ADH) are two hormones that participate in the normal
regulation of extracellular fluid volume by controlling
sodium balance and osmolality through renal function
and thirst.74 During burn shock, sympathetic tone is high
and volume receptors sense hypovolemia, both of which
elevate angiotensin II and ADH to supranormal levels in the
blood. Both are potent vasoconstrictors of terminal arte­
rioles with less effect on the venules. Angiotensin II may
be responsible for the selective gut and mucosal ischemia,
which can cause translocation of endotoxins and bacte­
ria and the development of sepsis and even multiorgan
failure.114,115 In severely burn-injured patients angiotensin
II levels were elevated two to eight times normal in the first
1–5 days after injury, with peak levels occurring on day
3.116 Vasopressin had peak levels of 50 times normal upon
admission and declined toward normal over the first 5 days
after burn injury. Along with catecholamines, vasopressin
may be largely responsible for increased SVR and increased
left heart afterload, which can occur in resuscitated burn
shock. Sun et al.117 used vasopressin-receptor antagonists
to improve hemodynamics and survival time in rats with
burn shock, whereas vasopressin infusion exacerbated
burn shock.
OTHER MEDIATORS
Hydrogen sulfide (H2S) is a small-molecule mediator receiv­
ing increased attention in inflammatory shock. It is capable
of both inducing and inhibiting inflammation. Murine data
support H2S as being an endogenous inflammatory media­
tor increasing both pro-inflammatory cytokine levels and
NF-κB signaling. Studies are similarly being carried out to
define concentrations and clinical utility for its anti-
inflammatory characteristics.57 Hu et al. used a 50% TBSA
burn-injured dog model and reported that use of a nicotinic
agonist with resuscitation increased survival, improved
hemodynamics, increased plasma volume and urine output,
and decreased TN-α, IL-1, and lactic acid.118 Wiggins et al.
elucidated a role of metalloproteinases (MMP) in lung edema
and endothelial damage when a culture of lung endothelial
cells had increased MMP activity and decreased tissue
inhibitor of metalloproteinases (TIMP-2) after burn serum
exposure. These cells had increased monolayer permeabil­
ity, damaged adhesion junction proteins, and incited actin
stress fiber formation. This damage was inhibited effectively
by exogenous TIMP-2.119 Endothelin-1 has been shown to
play a role in alveolar fluid clearance and pulmonary
edema. ET-1 inhibits alveolar fluid clearance by inhibition
of amiloride-sensitive epithelial sodium channels and
increases capillary pressure.120

8  •  Pathophysiology of Burn Shock and Burn Edema
75
There are several organs particularly susceptible to
ischemia, organ dysfunction, and organ failure when burn
resuscitation is delayed or inadequate. These include the
kidney and the gastrointestinal tract. Renal ischemia can
result directly from hypovolemia and increased sympathetic
tone, but elevations in plasma hemoglobin, and particu­
larly myoglobin, correlate with increased renal failure.140,141
Renal failure rates have declined dramatically because of
standardized regimens of adequate fluid therapy, but when
therapy is delayed or associated with hypotension acute
renal failure is not uncommon.140–142
Mesenteric vasoconstriction can occur despite appar­
ently “adequate” resuscitation.115,143 Bacterial and endo­
toxin translocation that can contribute to the development
of sepsis is one consequence of visceral ischemia.
Encephalopathy is not uncommon after large cutaneous
burns, particularly in children, but the exact cause remains
unclear. Studies in anesthetized sheep subjected to a 70%
TBSA scald show that cerebral autoregulation is well main­
tained in the immediate postburn period, but 6 hours after
resuscitation increased cerebral vascular resistance reduced
cerebral blood flow by 50%.144
PULMONARY CIRCULATION AND LUNG EDEMA
In large burns there is a pronounced increase in PVR that
corresponds with the increased SVR.7,54 In contrast to the
systemic circulation, however, pulmonary edema is unusual
and typically does not occur until after the fluid resuscita­
tion phase is complete. Pulmonary wedge pressure is
increased more than left atrial pressure after experimental
burn injury due to postcapillary venular constriction.54,145
By increasing capillary pressure, venular constriction may
contribute to pulmonary edema. It is likely that some degree
of left heart failure also contributes to the increased capil­
lary pressure. However hypoproteinemia may be the great­
est contributing factor to postburn pulmonary edema.146
Analysis of lung lymph sampled in large animal models
after 40% TBSA burn injury showed no evidence of
increased microvascular permeability. Furthermore, lung
lymph flow may increase considerably to counteract inter­
stitial fluid accumulation. As a result, clinical studies of
burn-injured patients suggest that, in the absence of inha­
lation injury, the lungs do not typically develop edema.147,148
Pulmonary dysfunction associated with inhalation injury
is discussed in a separate chapter.
FLUID OVERLOAD AND ABDOMINAL
COMPARTMENT SYNDROME
Prompt and adequate fluid resuscitation has undoubtedly
improved the outcome of burn-injured patients, and
Chapter 9 describes resuscitation strategies in detail. Despite
the advances in burn shock resuscitation, massive edema
of both burned and unburned tissues continues to be a
repercussion of large-volume fluid resuscitation.
It is now clear that there is a trend toward providing fluid
in excess of the published formula, which has been termed
“fluid creep.”149 Over-resuscitation and the resulting edema
are fraught with complications. The problems of the over-
resuscitated burn patient may include optic neuropathy
due to intraocular hypertension,150 pulmonary edema,151,152
Traber and colleagues studied intact, chronically instru­
mented sheep after a 40% TBSA flame burn injury and
smoke inhalation injury, and after smoke inhalation injury
alone. They found that contractile force was reduced after
either burn injury or inhalation injury alone.128,129 Horton
et al.130 demonstrated decreased left ventricular contractil­
ity in isolated, coronary-perfused guinea pig hearts har­
vested 24 hours after burn injury. This dysfunction was
more pronounced in hearts from aged animals and was not
reversed by resuscitation with isotonic fluid. It was largely
reversed by treatment with 4 mL/kg of hypertonic saline
dextran (HSD) but only if administered during the initial
4–6 hours of resuscitation.131,132 These authors also effec­
tively ameliorated the cardiac dysfunction of thermal injury
with infusions of antioxidants, arginine, and calcium
channel blockers.132–134 Cioffi and colleagues,135 using an ex
vivo myocardial preparation, observed persistent myocar­
dial depression after burn when the animals received no
resuscitation after injury. As opposed to most studies, Cioffi
reported that immediate and full resuscitation totally
reversed abnormalities of contraction and relaxation after
burn injury. Murphy et al.136 showed elevations of a serum
marker for cardiac injury, troponin I, for patients with a
TBSA burn of greater than 18%, despite good cardiac
indices. Resuscitation and cardiac function studies empha­
size the importance of early and adequate fluid therapy and
suggest that functional myocardial depression after burn
injury may be minimized in patients receiving prompt and
adequate volume therapy.
The primary mechanisms by which burn shock alters
myocardial cell membrane integrity and impairs mechani­
cal function remain unclear. Oxygen-derived free radicals
may play a key causative role in the cell membrane dysfunc­
tion that is characteristic of several low-flow states. Horton
et al. showed that a combination therapy of free radical
scavengers SOD and catalase significantly improved burn-
mediated defects in left ventricular contractility and relax­
ation when administered along with adequate fluid
resuscitation. Antioxidant therapy did not alter the volume
of fluid resuscitation required after burn injury.137
Increased Systemic Vascular Resistance and
Organ Ischemia
CO may remain below normal after adequate volume
replacement in burn patients and experimental animals.
Increased afterload after burn injury is the result of
release of catecholamines, vasopressin, angiotensin II, and
neuropeptide-Y.116,117 These agents cause contraction of the
arteriolar smooth muscle, which is systemically manifested
by increased afterload and SVR. The increased SVR after
burn injury is also, in part, the result of increased blood
viscosity secondary to the hemoconcentration.
Hilton and others performed experiments in anes­
thetized dogs in which infusion of various peripheral
vasodilators improved CO after burn injury.121,138 They
demonstrated a reduction in the SVR and augmented CO
after verapamil, but the myocardial force of contraction
remained depressed. Pruitt et al. demonstrated the utility
of a vasodilator, hydralazine, to reduce SVR and augment
CO (with the caveat that hypovolemia should first be
corrected).139

8  •  Pathophysiology of Burn Shock and Burn Edema
76
Secondary to the thermal injury there is release of
inflammatory mediators and stress hormones. These circu­
lating mediators deleteriously increase microvascular per­
meability and alter cellular membrane function by which
water and sodium enter cells. Circulating mediators also
favor renal conservation of water and salt, impair cardiac
contractility, and cause vasoconstriction. The end result of
this complex chain of events is decreased cardiac output,
end-organ ischemia, and metabolic acidosis. Without
early and effective resuscitation these derangements can
result in organ dysfunction, cardiovascular collapse,
and death.
Resuscitation is a double-edged sword in that it increases
edema in both burned and unburned tissue. Edema likely
contributes to decreased tissue oxygen diffusion and further
ischemic injury to already damaged cells. Research should
continue to define better treatments that ameliorate burn
shock and burn edema. The success of this research will
require the identification of key circulatory factors that
alter microvascular permeability, cause vasoconstriction,
depolarize cellular membranes, and depress myocardial
function. Cellular or systemic methods to prevent the release
or block the activity of specific mediators are needed.
Complete references available online at

Further Reading
Cancio LC, Chavez S, Alvarado-Ortega M, et al. Predicting increased fluid
requirements during the resuscitation of thermally injured patients. J
Trauma. 2004;56(2):404-413.
Cartotto R, Zhou A. Fluid creep: the pendulum hasn’t swung back yet! J
Burn Care Res. 2010;31(4):551-558.
Lawrence A, Faraklas I, Watkins H, et al. Colloid administration normal­
izes resuscitation ratio and ameliorates “fluid creep”. J Burn Care Res.
2010;31(1):40-47.
Malbrain MLNG, Keulenaer BL, Oda J, et al. Intra-abdominal hypertension
and abdominal compartment syndrome in burns, obesity, pregnancy,
and general medicine. Anaesthesiol Intensive Ther. 2015;47:228-240.
Navickis RJ, Greenhalgh DG, Wilkes MM. Albumin in burn shock resusci­
tation: a meta-analysis of controlled clinical studies. J Burn Care Res.
2016;37(3):e268-e278.
the need for prolonged mechanical ventilation or tracheos­
tomy,153 graft failure, or the need for fasciotomy of unin­
jured extremities154 due to massive edema.
The most life-threatening complication of edema, with a
mortality rate of 75%, is abdominal compartment syn­
drome (ACS).155 Intra-abdominal hypertension (IAH) is
defined as an intra-abdominal pressure of more than 12 cm
H2O and is most often seen during the acute resuscitation
phase up to 48 hours postburn.156 ACS is sustained IAH of
greater than 20 mmHg combined with new organ failure
(e.g., elevated peak inspiratory pressures or oliguria despite
aggressive fluid resuscitation). The syndrome typically leads
to multiple organ dysfunction, characterized by impaired
renal and hepatic blood flow, bowel ischemia, pulmonary
dysfunction, depressed cardiac output, elevated intracranial
pressures, and death.157,158 ACS can occur after major
abdominal trauma or surgery; the condition in the absence
of abdominal injury is known as secondary ACS.159 A
review showed that the prevalence of ACS is between 4%
and 17% in the severely burned.155 The use of albumin
during resuscitation may reduce the risk of ACS.41 Massive
edema of burned and unburned tissues continues to be a
problem in burn-shock resuscitation.
Conclusion
Thermal injury results in massive fluid shifts from the cir­
culating plasma into the interstitial space of both burned
tissue and (in burns >20–30% TBSA) unburned tissue,
causing hypovolemia and edema. Changes in the variables
comprising the Starling equation favor fluid extravasation
from blood to tissue. In burned tissue rapid edema forma­
tion is predominantly due to the development of strongly
negative interstitial fluid pressure and, to a lesser degree, by
an increase in microvascular pressure and permeability. In
uninjured soft tissues, increased microvascular permeabil­
ity is mainly the result of glycocalyx loss and endothelial
activation. The type, volume, and timing of fluid used to
resuscitate affect the magnitude of these fluid shifts.

76.e1
8  •  Pathophysiology of Burn Shock and Burn Edema
30. Kinsky MP, Milner SM, Button B, et al. Resuscitation of severe
thermal injury with hypertonic saline dextran: effects on peripheral
and visceral edema in sheep. J Trauma. 2000;49(5):844-853.
31. Reed RK, Berg A, Gjerde EA, et al. Control of interstitial fluid pres­
sure: role of beta1-integrins. Semin Nephrol. 2001;21(3):222-
230.
32. McGee MP, Morykwas MJ, Argenta LC. The local pathology of
interstitial edema: surface tension increases hydration potential in
heat-damaged skin. Wound Repair Regen. 2011;19(3):358-367.
33. McGee MP, Morykwas M, Campbell D, et al. Interstitial-matrix edema
in burns: mechanistic insights from subatmospheric pressure treat­
ment in vivo. Wound Repair Regen. 2014;22(1):96-102.
34. Arturson G. Microvascular permeability to macromolecules in
thermal injury. Acta Physiol Scand Suppl. 1979;463:111-122.
35. Harms BA, Bodai BI, Kramer GC, et al. Microvascular fluid and
protein flux in pulmonary and systemic circulations after thermal
injury. Microvasc Res. 1982;23(1):77-86.
36. Zetterström H, Arturson G. Plasma oncotic pressure and plasma
protein concentration in patients following thermal injury. Acta
Anaesthesiol Scand. 1980;24(4):288-294.
37. Pitkänen J, Lund T, Aanderud L, et al. Transcapillary colloid osmotic
pressures in injured and non-injured skin of seriously burned
patients. Burns Incl Therm Inj. 1987;13(3):198-203.
38. Demling RH, Kramer G, Harms B. Role of thermal injury-induced
hypoproteinemia on fluid flux and protein permeability in burned
and nonburned tissue. Surgery. 1984;95(2):136-144.
39. Cochran A, Morris SE, Edelman LS, et al. Burn patient character­
istics and outcomes following resuscitation with albumin. Burns.
2007;33(1):25-30. doi:10.1016/j.burns.2006.10.005.
40. Lawrence A, Faraklas I, Watkins H, et al. Colloid administration nor­
malizes resuscitation ratio and ameliorates “fluid creep”. J Burn Care
Res. 2010;31(1):40-47.
41. Navickis RJ, Greenhalgh DG, Wilkes MM. Albumin in burn shock
resuscitation: a meta-analysis of controlled clinical studies. J Burn
Care Res. 2016;37(3):e268-e278.
42. Friedl HP, Till GO, Trentz O, et al. Roles of histamine, comple­
ment and xanthine oxidase in thermal injury of skin. Am J Pathol.
1989;135(1):203-217.
43. Lund T, Onarheim H, Reed RK. Pathogenesis of edema formation in
burn injuries. World J Surg. 1992;16(1):2-9.
44. Harms BA, Kramer GC, Bodai BI, et al. Effect of hypoproteinemia
on pulmonary and soft tissue edema formation. Crit Care Med.
1981;9(7):503-508.
45. Meumann M, Demling RH. Colloid vs crystalloid: a current perspec­
tive. Confed Aust Crit Care Nurses J. 1990;3(3):30-35.
46. Hilton JG. Effects of fluid resuscitation on total fluid loss following
thermal injury. Surg Gynecol Obstet. 1981;152(4):441-447.
47. Kramer GC, Harms BA, Bodai BI, et al. Mechanisms for redistribution
of plasma protein following acute protein depletion. Am J Physiol.
1982;243(5):H803-H809.
48. Turk E, Caliskan M, Karagulle E, et al. A prospective clinical study
of flow-mediated dilatation in burn injury. J Burn Care Res. 2014;
35(2):169-175.
49. Adamson RH, Lenz JF, Zhang X, et al. Oncotic pressures oppos­
ing filtration across non-fenestrated rat microvessels. J Physiol.
2004;557(Pt 3):889-907.
50. Levick JR, Michel CC. Microvascular fluid exchange and the revised
Starling principle. Cardiovasc Res. 2010;87(2):198-210.
51. Curry F-RE, Adamson RH. Vascular permeability modulation at the
cell, microvessel, or whole organ level: towards closing gaps in our
knowledge. Cardiovasc Res. 2010;87(2):218-229.
52. Kozar RA, Peng Z, Zhang R, et al. Plasma restoration of endothelial
glycocalyx in a rodent model of hemorrhagic shock. Anesth Analg.
2011;112(6):1289-1295.
53. Brouhard BH, Carvajal HF, Linares HA. Burn edema and protein
leakage in the rat. I. Relationship to time of injury. Microvasc Res.
1978;15(2):221-228.
54. Kramer GC, Gunther RA, Nerlich ML, et al. Effect of dextran-70 on
increased microvascular fluid and protein flux after thermal injury.
Circ Shock. 1982;9(5):529-541.
55. Kremer T, Abé D, Weihrauch M, et al. Burn plasma transfer induces
burn edema in healthy rats. Shock. 2008;30(4):394-400.
56. Kremer T, Harenberg P, Hernekamp F, et al. High-dose vitamin C
treatment reduces capillary leakage after burn plasma transfer in
rats. J Burn Care Res. 2010;31(3):470-479.
References
1. Cockshott WP. The book shelf; the history of the treatment of burns.
Surg Gynecol Obstet. 1956;102(1):116-124.
2. Haynes BW. The history of burn care. In: Boswick JAJ, ed. The Art and
Science of Burn Care. Rockville, MD: Aspen; 1987:3-9.
3. Underhill FP. Changes in blood concentration with special refer­
ence to the treatment of extensive superficial burns. Ann Surg.
1927;86(6):840-849.
4. Youn YK, LaLonde C, Demling R. The role of mediators in the
response to thermal injury. World J Surg. 1992;16(1):30-36.
5. Aulick LH, Wilmore DW, Mason AD, et al. Influence of the burn
wound on peripheral circulation in thermally injured patients. Am J
Physiol. 1977;233(4):H520-H526.
6. Settle J. Fluid therapy in burns. J R Soc Med. 1982.
7. Demling RH. Fluid replacement in burned patients. Surg Clin North
Am. 1987;67(1):15-30.
8. Demling RH, Will JA, Belzer FO. Effect of major thermal injury on
the pulmonary microcirculation. Surgery. 1978;83(6):746-751.
9. Baxter CR. Fluid volume and electrolyte changes of the early post­
burn period. Clin Plast Surg. 1974;1(4):693-703.
10. Baxter CR, Cook WA, Shires GT. Serum myocardial depressant factor
of burn shock. Surg Forum. 1966;17:1-2.
11. Hilton JG, Marullo DS. Effects of thermal trauma on cardiac force of
contraction. Burns Incl Therm Inj. 1986;12(3):167-171.
12. Clark W. Death due to thermal trauma. In: Dolecek R, Brizio-Moteni
L, Moletni A, et al., eds. Nedocrinology of Thermal Trauma. Philadel­
phia, PA: Lea & Febiger; 1990:6-27.
13. Lund T, Reed RK. Acute hemodynamic effects of thermal skin injury
in the rat. Circ Shock. 1986;20(2):105-114.
14. Arturson G. Pathophysiological aspects of the burn syndrome with
special reference to liver injury and alterations of capillary perme­
ability. Acta Chir Scand Suppl. 1961;Suppl 274:1-135.
15. Leape IL. Kinetics of burn edema formation in primates. Ann Surg.
1972;176(2):223-226.
16. Demling RH, Mazess RB, Witt RM, et al. The study of burn wound
edema using dichromatic absorptiometry. J Trauma. 1978;18(2):
124-128.
17. Onarheim H, Lund T, Reed R. Thermal skin injury: II. Effects on
edema formation and albumin extravasation of fluid resuscita­
tion with lactated Ringer’s, plasma, and hypertonic saline (2,400
mosmol/l) in the rat. Circ Shock. 1989;27(1):25-37.
18. Arturson G, Jakobsson OP. Oedema measurements in a standard
burn model. Burns Incl Therm Inj. 1985;12(1):1-7.
19. Leape LL. Early burn wound changes. J Pediatr Surg. 1968;3(2):
292-299.
20. Leape LL. Initial changes in burns: tissue changes in burned and
unburned skin of rhesus monkeys. J Trauma. 1970;10(6):488-492.
21. Landis EM, Pappenheimer JR. Exchange of substances through the
capillary walls. In: Hamilton WF, Dow P, eds. Handbook of Physi­
ology Circulation. Washington D.C.: American Physiologic Society;
1963:961-1034.
22. Aukland K, Reed RK. Interstitial-lymphatic mechanisms in the
control of extracellular fluid volume. Physiol Rev. 1993;73(1):1-78.
23. Reed RK, Rubin K. Transcapillary exchange: role and importance of
the interstitial fluid pressure and the extracellular matrix. Cardiovasc
Res. 2010;87(2):211-217. doi:10.1093/cvr/cvq143.
24. Chappell D, Jacob M, Hofmann-Kiefer K, et al. A rational
approach to perioperative fluid management. Anesthesiology.
2008;109(4):723-740.
25. Jacob M, Chappell D, Rehm M. The “third space”: fact or fiction? Best
Pract Res Clin Anaesthesiol. 2009;23(2):145-157.
26. Woodcock TE, Woodcock TM. Revised Starling equation and the
glycocalyx model of transvascular fluid exchange: an improved
paradigm for prescribing intravenous fluid therapy. Br J Anaesth.
2012;108(3):384-394.
27. Arturson G, Mellander S. Acute changes in capillary filtration
and diffusion in experimental burn injury. Acta Physiol Scand.
1964;62:457-463.
28. Pitt RM, Parker JC, Jurkovich GJ, et al. Analysis of altered capil­
lary pressure and permeability after thermal injury. J Surg Res.
1987;42(6):693-702.
29. Lund T, Wiig H, Reed RK. Acute postburn edema: role of strongly
negative interstitial fluid pressure. Am J Physiol. 1988;255(5 Pt
2):H1069-H1074.

76.e2
8  •  Pathophysiology of Burn Shock and Burn Edema
86. Heggers JP, Robson MC, Zachary LS. Thromboxane inhibitors for the
prevention of progressive dermal ischemia due to the thermal injury.
J Burn Care Rehabil. 1985;6(6):466-468.
87. LaLonde C, Demling RH. Inhibition of thromboxane synthetase
accentuates hemodynamic instability and burn edema in the anes­
thetized sheep model. Surgery. 1989;105(5):638-644.
88. Jacobsen S, Waaler BA. The effect of scalding on the content of
kininogen and kininase in limb lymph. Br J Pharmacol Chemother.
1966;27(1):222-229.
89. Bauer JA, Hafner M, Fritz H. Balanced antiinflammation: the com­
bined application of a PAF inhibitor and a cyclooxygenase inhibi­
tor blocks the inflammatory take-off after burns. Int J Tissue React.
1990;12(4):203-211.
90. Nwariaku FE, Sikes PJ, Lightfoot E, et al. Effect of a bradykinin antag­
onist on the local inflammatory response following thermal injury.
Burns. 1996;22(4):324-327.
91. Tao K, Wang H-T, Chen B, et al. Effect of nonpeptide NK1 recep­
tor antagonist L-703,606 on the edema formation in rats at early
stage after deep partial-thickness skin scalding. Asian Pac J Trop Med.
2013;6(5):387-394.
92. Carvajal HF, Brouhard BH, Linares HA. Effect of antihistamine-
antiserotonin and ganglionic blocking agents upon increased
capillary permeability following burn trauma. J Trauma. 1975;
15(11):969-975.
93. Ferrara JJ, Westervelt CL, Kukuy EL, et al. Burn edema reduction by
methysergide is not due to control of regional vasodilation. J Surg
Res. 1996;61(1):11-16.
94. Zhang XJ, Irtun O, Zheng Y, et al. Methysergide reduces nonnutritive
blood flow in normal and scalded skin. Am J Physiol Endocrinol Metab.
2000;278(3):E452-E461.
95. Wilmore DW, Long JM, Mason AD, et al. Catecholamines: media­
tor of the hypermetabolic response to thermal injury. Ann Surg.
1974;180(4):653-668.
96. Hilton JG. Effects of sodium nitroprusside on thermal trauma
depressed cardiac output in the anaesthetized dog. Burns Incl Therm
Inj. 1984;10(5):318-322.
97. McCord JM, Fridovich I. The biology and pathology of oxygen radi­
cals. Ann Intern Med. 1978;89(1):122-127.
98. Demling RH, LaLonde C. Early postburn lipid peroxidation: effect of
ibuprofen and allopurinol. Surgery. 1990;107(1):85-93.
99. Slater T, Benedetto C. Free radical reactions in relation to lipid per­
oxidation, inflammayion and prostaglandin metabolism. In: Berti
F, Veto G, eds. The Prostaglandin System. New York: Plenum Press;
1979:109-126.
100. McCord JM. Oxygen-derived free radicals in postischemic tissue
injury. N Engl J Med. 1985;312(3):159-163.
101. Tanaka H, Matsuda H, Shimazaki S, et al. Reduced resuscitation fluid
volume for second-degree burns with delayed initiation of ascorbic
acid therapy. Arch Surg. 1997;132(2):158-161.
102. Tanaka H, Lund T, Wiig H, et al. High dose vitamin C counteracts
the negative interstitial fluid hydrostatic pressure and early edema
generation in thermally injured rats. Burns. 1999;25(7):569-574.
103. Dubick MA, Williams C, Elgjo GI, et al. High-dose vitamin C infu­
sion reduces fluid requirements in the resuscitation of burn-injured
sheep. Shock. 2005;24(2):139-144.
104. Kahn SA, Beers RJ, Lentz CW. Resuscitation after severe burn injury
using high-dose ascorbic acid: a retrospective review. J Burn Care Res.
2011;32(1):110-117.
105. Fischer SR, Bone HG, Powell WC, et al. Pyridoxalated hemoglobin
polyoxyethylene conjugate does not restore hypoxic pulmonary
vasoconstriction in ovine sepsis. Crit Care Med. 1997;25(9):
1551-1559.
106. Farina Junior JA, Celotto AC, da Silva MF, et al. Guanylate cyclase
inhibition by methylene blue as an option in the treatment of vaso­
plegia after a severe burn. A medical hypothesis. Med Sci Monit.
2012;18(5):HY13-HY17.
107. Lange M, Hamahata A, Enkhbaatar P, et al. Beneficial effects of con­
comitant neuronal and inducible nitric oxide synthase inhibition in
ovine burn and inhalation injury. Shock. 2011;35(6):626-631.
108. Rawlingson A, Greenacre SA, Brain SD. Generation of per­
oxynitrite in localised, moderate temperature burns. Burns.
2000;26(3):223-227.
109. Lindblom L, Cassuto J, Yregård L, et al. Importance of nitric oxide in
the regulation of burn oedema, proteinuria and urine output. Burns.
2000;26(1):13-17.
57. Hernekamp JF, Klein H, Schmidt K, et al. 5-HT2a receptor antag­
onism reduces burn-induced macromolecular efflux in rats. Eur J
Trauma Emerg Surg. 2015;41(5):565-573.
58. Hernekamp J-F, Hu S, Schmidt K, et al. Cinanserin reduces
plasma extravasation after burn plasma transfer in rats. Burns.
2013;39(6):1226-1233.
59. Hernekamp JF, Hu S, Schmidt K, et al. Methysergide attenuates sys­
temic burn edema in rats. Microvasc Res. 2013;89:115-121.
60. Kremer T, Hernekamp F, Riedel K, et al. Topical application of cerium
nitrate prevents burn edema after burn plasma transfer. Microvasc
Res. 2009;78(3):425-431.
61. Hernekamp JF, Hu SX, Schmidt VJ, et al. Influence of cdp-
choline administration on early burn edema in rats. Ann Plast Surg.
2015;75(4):388-392.
62. Hernekamp F, Klein H, Schmidt K, et al. Microcirculatory effects
of physostigmine on experimental burn edema. J Burn Care Res.
2015;36(2):279-286.
63. Shires GT, Cunningham JN, Backer CR, et al. Alterations in cellular
membrane function during hemorrhagic shock in primates. Ann
Surg. 1972;176(3):288-295.
64. Nakayama S, Kramer GC, Carlsen RC, et al. Amiloride blocks mem­
brane potential depolarization in rat skeletal muscle during hemor­
rhagic shock. Circ Shock. 1984;13:106-107.
65. Arango A, Illner H, Shires GT. Role of ischemia in the induction of
changes in cell membrane during hemorrhagic shock. J Surg Res.
1976;20(5):473-476.
66. Holliday RL, Illner HP, Shires GT. Liver cell membrane alterations
during hemorrhagic shock in the rat. J Surg Res. 1981;31(6):506-515.
67. Mazzoni MC, Borgström P, Intaglietta M, et al. Lumenal narrowing
and endothelial cell swelling in skeletal muscle capillaries during
hemorrhagic shock. Circ Shock. 1989;29(1):27-39.
68. Garcia NM, Horton JW. L-arginine improves resting cardiac trans­
membrane potential after burn injury. Shock. 1994;1(5):354-358.
69. Button B, Baker RD, Vertrees RA, et al. Quantitative assessment of a
circulating depolarizing factor in shock. Shock. 2001;15(3):239-244.
70. Evans JA, Darlington DN, Gann DS. A circulating factor(s)
mediates cell depolarization in hemorrhagic shock. Ann Surg.
1991;213(6):549-557.
71. Trunkey DD, Illner H, Arango A, et al. Changes in cell mem­
brane function following shock and cross-perfusion. Surg Forum.
1974;25(0):1-3.
72. Brown JM, Grosso MA, Moore EE. Hypertonic saline and dextran:
impact on cardiac function in the isolated rat heart. J Trauma.
1990;30(6):646-651.
73. Evans JA, Massoglia G, Sutherland B. Molecular properties of hemor­
rhagic shock factor. Biophys J. 1993;64:A384.
74. Goodman-Gilman A, Rall T, Nies A, et al. The Pharmacological Basis
of Therapeutics. New York: Pergamon Press; 1990.
75. Räntfors J, Cassuto J. Role of histamine receptors in the regulation
of edema and circulation postburn. Burns. 2003;29(8):769-777.
76. Till GO, Guilds LS, Mahrougui M, et al. Role of xanthine oxidase in
thermal injury of skin. Am J Pathol. 1989;135(1):195-202.
77. Boykin JV, Manson NH. Mechanisms of cimetidine protection follow­
ing thermal injury. Am J Med. 1987;83(6A):76-81.
78. Tanaka H, Wada T, Simazaki S, et al. Effects of cimetidine on fluid
requirement during resuscitation of third-degree burns. J Burn Care
Rehabil. 1991;12(5):425-429.
79. Anggård E, Jonsson CE. Efflux of prostaglandins in lymph from
scalded tissue. Acta Physiol Scand. 1971;81(4):440-447.
80. Harms BA, Bodai BI, Smith M, et al. Prostaglandin release and
altered microvascular integrity after burn injury. J Surg Res.
1981;31(4):274-280.
81. Arturson G. Anti-inflammatory drugs and burn edema formation.
In: Mary R, Dogo G, eds. Care of the Burn Wound. Basel: Karger;
1981:21-24.
82. Arturson G, Hamberg M, Jonsson CE. Prostaglandins in human burn
blister fluid. Acta Physiol Scand. 1973;87(2):270-276.
83. LaLonde C, Knox J, Daryani R, et al. Topical flurbiprofen decreases
burn wound-induced hypermetabolism and systemic lipid peroxida­
tion. Surgery. 1991;109(5):645-651.
84. Huang YS, Li A, Yang ZC. Roles of thromboxane and its inhibitor
anisodamine in burn shock. Burns. 1990;16(4):249-253.
85. Heggers JP, Loy GL, Robson MC, et al. Histological demonstration
of prostaglandins and thromboxanes in burned tissue. J Surg Res.
1980;28(2):110-117.

76.e3
8  •  Pathophysiology of Burn Shock and Burn Edema
136. Murphy JT, Horton JW, Purdue GF, et al. Evaluation of troponin-I as
an indicator of cardiac dysfunction after thermal injury. J Trauma.
1998;45(4):700-704.
137. Horton JW, White J, Baxter CR. The role of oxygen-derived free radi­
cals in burn-induced myocardial contractile depression. J Burn Care
Rehabil. 1988;9(6):589-598.
138. Hilton JG. Effects of verapamil on thermal trauma depressed
cardiac output in the anaesthetized dog. Burns Incl Therm Inj. 1984;
10(5):313-317.
139. Pruitt BA, Mason AD, Moncrief JA. Hemodynamic changes in the
early postburn patient: the influence of fluid administration and of
a vasodilator (hydralazine). J Trauma. 1971;11(1):36-46.
140. Holm C, Hörbrand F, von Donnersmarck GH, et al. Acute renal
failure in severely burned patients. Burns. 1999;25(2):171-178.
141. Chrysopoulo MT, Jeschke MG, Dziewulski P, et al. Acute renal dys­
function in severely burned adults. J Trauma. 1999;46(1):141-144.
142. Ibrahim AE, Sarhane KA, Fagan SP, et al. Renal dysfunction in
burns: a review. Ann Burns Fire Disasters. 2013;26(1):16-25.
143. Tokyay R, Zeigler ST, Traber DL, et al. Postburn gastrointestinal vaso­
constriction increases bacterial and endotoxin translocation. J Appl
Physiol. 1993;74(4):1521-1527.
144. Shin C, Kinsky MP, Thomas JA, et al. Effect of cutaneous burn injury
and resuscitation on the cerebral circulation in an ovine model.
Burns. 1998;24(1):39-45.
145. Demling RH, Wong C, Jin LJ, et al. Early lung dysfunction after
major burns: role of edema and vasoactive mediators. J Trauma.
1985;25(10):959-966.
146. Demling RH, Niehaus G, Perea A, et al. Effect of burn-induced
hypoproteinemia on pulmonary transvascular fluid filtration rate.
Surgery. 1979;85(3):339-343.
147. Tranbaugh RF, Lewis FR, Christensen JM, et al. Lung water changes
after thermal injury. The effects of crystalloid resuscitation and
sepsis. Ann Surg. 1980;192(4):479-490.
148. Tranbaugh RF, Elings VB, Christensen JM, et al. Effect of inhalation
injury on lung water accumulation. J Trauma. 1983;23(7):597-604.
149. Pruitt BA. Protection from excessive resuscitation: “pushing the pen­
dulum back”. J Trauma. 2000;49(3):567-568.
150. Sullivan SR, Ahmadi AJ, Singh CN, et al. Elevated orbital pressure:
another untoward effect of massive resuscitation after burn injury.
J Trauma. 2006;60(1):72-76.
151. Blot S, Hoste E, Colardyn F. Acute respiratory failure that complicates
the resuscitation of pediatric patients with scald injuries. J Burn Care
Rehabil. 2000;21(3):289-290.
152. Zak AL, Harrington DT, Barillo DJ, et al. Acute respiratory failure
that complicates the resuscitation of pediatric patients with scald
injuries. J Burn Care Rehabil. 1999;20(5):391-399.
153. Coln CE, Purdue GF, Hunt JL. Tracheostomy in the young pediatric
burn patient. Arch Surg. 1998;133(5):537–539–540.
154. Sheridan RL, Tompkins RG, McManus WF, et al. Intracompartmen­
tal sepsis in burn patients. J Trauma. 1994;36(3):301-305.
155. Strang SG, Van Lieshout EMM, Breederveld RS, et al. A systematic
review on intra-abdominal pressure in severely burned patients.
Burns. 2014;40(1):9-16.
156. Azzopardi EA, McWilliams B, Iyer S, et al. Fluid resuscitation in
adults with severe burns at risk of secondary abdominal com­
partment syndrome–an evidence based systematic review. Burns.
2009;35(7):911-920.
157. Bloomfield GL, Dalton JM, Sugerman HJ, et al. Treatment of increas­
ing intracranial pressure secondary to the acute abdominal com­
partment syndrome in a patient with combined abdominal and head
trauma. J Trauma. 1995;39(6):1168-1170.
158. Ivatury RR, Diebel L, Porter JM, et al. Intra-abdominal hypertension
and the abdominal compartment syndrome. Surg Clin North Am.
1997;77(4):783-800.
159. Maxwell RA, Fabian TC, Croce MA, et al. Secondary abdominal com­
partment syndrome: an underappreciated manifestation of severe
hemorrhagic shock. J Trauma. 1999;47(6):995-999.
160. Paul W, Douglas GJ, Lawrence L, et al. Cutaneous permeability
responses to bradykinin and histamine in the guinea-pig: possible
differences in their mechanism of action. Br J Pharmacol. 1994;
111(1):159-164.
161. Pollard V, Prough DS, DeMelo AE, et al. The influence of carbon
dioxide and body position on near-infrared spectroscopic assess­
ment of cerebral hemoglobin oxygen saturation. Anesth Analg.
1996;82(2):278-287.
110. Lindblom L, Cassuto J, Yregård L, et al. Role of nitric oxide in the
control of burn perfusion. Burns. 2000;26(1):19-23.
111. Lange M, Szabo C, Enkhbaatar P, et al. Beneficial pulmonary effects
of a metalloporphyrinic peroxynitrite decomposition catalyst in burn
and smoke inhalation injury. Am J Physiol Lung Cell Mol Physiol.
2011;300(2):L167-L175.
112. Westphal M, Rehberg S, Maybauer MO, et al. Cardiopulmonary
effects of low-dose arginine vasopressin in ovine acute lung injury.
Crit Care Med. 2011;39(2):357-363.
113. Ono I, Gunji H, Hasegawa T, et al. Effects of a platelet activating
factor antagonist on oedema formation following burns. Burns.
1993;19:202-207.
114. Fink MP. Gastrointestinal mucosal injury in experimental models of
shock, trauma, and sepsis. Crit Care Med. 1991;19(5):627-641.
115. Cui X, Sheng Z, Guo Z. [Mechanisms of early gastro-intestinal
ischemia after burn: hemodynamic and hemorrheologic features].
Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi. 1998;14(4):262-
265.
116. Crum RL, Dominic W, Hansbrough JF, et al. Cardiovascular
and neurohumoral responses following burn injury. Arch Surg.
1990;125(8):1065-1069.
117. Sun K, Gong A, Wang CH, et al. Effect of peripheral injection of
arginine vasopressin and its receptor antagonist on burn shock in
the rat. Neuropeptides. 1990;17(1):17-22.
118. Hu Q, Du M-H, Hu S, et al. PNU-282987 improves the hemody­
namic parameters by alleviating vasopermeability and tissue
edema in dogs subjected to a lethal burns shock. J Burn Care Res.
2014;35(4):e197-e204.
119. Wiggins-Dohlvik K, Oakley RP, Han MS, et al. Tissue inhibitor of
metalloproteinase-2 inhibits burn-induced derangements and
hyperpermeability in microvascular endothelial cells. Am J Surg.
2016;211(1):197-205.
120. Berger MM, Rozendal CS, Schieber C, et al. The effect of endothelin-1
on alveolar fluid clearance and pulmonary edema formation in the
rat. Anesth Analg. 2009;108(1):225-231.
121. Michie DD, Goldsmith RS, Mason AD. Effects of hydralazine and high
molecular weight dextran upon the circulatory responses to severe
thermal burns. Circ Res. 1963;13:468-473.
122. Martyn J, Wilson RS, Burke JF. Right ventricular function and pulmo­
nary hemodynamics during dopamine infusion in burned patients.
Chest. 1986;89(3):357-360.
123. Adams HR, Baxter CR, Izenberg SD. Decreased contractility and
compliance of the left ventricle as complications of thermal trauma.
Am Heart J. 1984;108(6):1477-1487.
124. Merriam TW. Myocardial function following thermal injury. Circ Res.
1962;11:669-673.
125. Howard TS, Hermann DG, McQuitty AL, et al. Burn-induced cardiac
dysfunction increases length of stay in pediatric burn patients.
J Burn Care Res. 2013;34(4):413-419.
126. Horton JW, White J, Baxter CR. Aging alters myocardial response
during resuscitation in burn shock. Surg Forum. 1987;38:249-251.
127. Baxter CR, Shires T. Physiological response to crystalloid resuscita­
tion of severe burns. Ann N Y Acad Sci. 1968;150(3):874-894.
128. Sugi K, Theissen JL, Traber LD, et al. Impact of carbon monoxide
on cardiopulmonary dysfunction after smoke inhalation injury. Circ
Res. 1990;66(1):69-75.
129. Soejima K, Schmalstieg FC, Sakurai H, et al. Pathophysiological
analysis of combined burn and smoke inhalation injuries in sheep.
Am J Physiol Lung Cell Mol Physiol. 2001;280(6):L1233-L1241.
130. Horton JW, Baxter CR, White DJ. Differences in cardiac
responses to resuscitation from burn shock. Surg Gynecol Obstet.
1989;168(3):201-213.
131. Horton JW, White DJ, Baxter CR. Hypertonic saline dextran resusci­
tation of thermal injury. Ann Surg. 1990;211(3):301-311.
132. Horton JW, White DJ, Hunt JL. Delayed hypertonic saline dextran
administration after burn injury. J Trauma. 1995;38(2):281-286.
133. Horton JW, Garcia NM, White DJ, et al. Postburn cardiac contractile
function and biochemical markers of postburn cardiac injury. J Am
Coll Surg. 1995;181(4):289-298.
134. Horton JW, White J, Maass D, et al. Arginine in burn injury improves
cardiac performance and prevents bacterial translocation. J Appl
Physiol. 1998;84(2):695-702.
135. Cioffi WG, DeMeules JE, Gamelli RL. The effects of burn injury
and fluid resuscitation on cardiac function in vitro. J Trauma.
1986;26(7):638-642.

77
Burn Resuscitation
LEOPOLDO C. CANCIO, FREDRICK J. BOHANON, and GEORGE C. KRAMER
9 
helpful to understanding their advantages and limitations.
Intravenous fluid resuscitation for the treatment of burns
owes much to early investigations of the pathophysiology
and treatment of cholera. In 1831, O’Shaughnessy, an Irish
physician, performed studies of the chemical and micro­
scopic features of the blood in cholera patients. Based on
these studies, he proposed “the injection into the veins of
tepid water holding a solution of the normal salts of the
blood.” He did canine experiments of this novel therapy but
did not apply it to humans. One year later, Thomas Latta, a
Scottish physician, read about O’Shaughnessy’s work and
treated patients with cholera using rectal, oral, and then
intravenous saline solutions.8 In 1906, Dr. Haldor Sneve of
St. Paul, Minnesota, described the use of saline solutions,
including enemas, for the treatment of burns.9 His common-
sense recommendations were not followed for years because
the prevailing point of view at the time was that the main
cause of death in patients with extensive burns was not
hypovolemia but the absorption of toxic substances from
the burned skin (“toxemia”).10 This belief led to the wide­
spread adoption of tanning agents such as tannic acid,11
the purpose of which was to “fix” the toxins and prevent
them from entering the bloodstream.
Subsequent mass-casualty disasters and armed conflict
both contributed to resuscitation advances. On November
27, 1921, the Rialto Theatre in New Haven, Connecticut,
caught fire, killing 6 and injuring 80. Dr. Frank Underhill
examined 21 survivors who were admitted following the
fire. Underhill was a veteran of World War I and had previ­
ously reported on the effects of chemical warfare agents on
the lungs. He drew a parallel between the process whereby
the lungs are flooded with fluid following inhalation of toxic
gases and that by which edema forms in wounds follow­
ing thermal injury. He reported that the more severe the
burn, the more severe the hemoconcentration (increased
hemoglobin), and that fluid replacement must be rapid
and is of paramount importance in survival. Additionally
he reported that blister fluid was similar in composition
to plasma and that the fluid lost could be replaced with
an intravenous physiologic salt solution, supplemented
rectally, orally, and subdermally.12 Oral and rectal infu­
sions were de-emphasized until recently, when their
utility in austere and combat-casualty-care scenarios was
revisited.13
In 1931, Alfred Blalock built on Underhill’s reports by
performing experiments in which anesthetized dogs sus­
tained burns of approximately one-third of the TBSA, local­
ized to one-half of the body (right or left). The animals were
not resuscitated. After a period of observation (6–26 hours),
the animals were euthanized, bisected, and the carcasses
weighed. Thus he quantified the amount of fluid lost across
the burn wounds, which averaged 3.34% of the total body
weight. This fluid loss was accompanied by a mean increase
in the hemoglobin level of 48%. Blalock speculated that this
Introduction
Burns in excess of about 20% of the total body surface area
(TBSA) cause shock, manifested by decreased circulating
blood volume, decreased cardiac output (CO), and inade­
quate end-organ perfusion. Fluid resuscitation to address
burn shock is one of the key lifesaving interventions in the
early care of burn patients. Inadequate or delayed fluid
resuscitation causes organ failure and death.1 On the other
hand, provision of excessive amounts of fluid (overresusci­
tation), by augmenting edema formation and engendering
complications such as compartment syndromes, also
increases morbidity and mortality.2 Thus the overarching
goal of fluid resuscitation is to achieve a careful balance
between the two extremes of over- and underresuscitation;
in other words, “to maintain vital organ function at the
least immediate or delayed physiologic cost.”3
The primary cause of burn shock is a reduction in the
circulating blood volume due to loss of fluid similar in com­
position to plasma across the microvasculature. Thus burn
shock is hypovolemic shock. Such fluid loss occurs primarily
in burned tissues but also, for larger burns, in unburned
tissues as well.4 The term “leaky capillaries” is often used
to describe this complex process (for details, see Chapter 8,
Pathophysiology of Burn Shock and Burn Edema). Other
factors that contribute to burn shock include intense vaso­
constriction during the immediate postburn hours, causing
increased afterload,5 and a decrease in intrinsic myocar­
dial contractility.6,7 These three factors—hypovolemia,
vasoconstriction, and decreased myocardial contractility—
contribute to decreased CO. The aims of fluid resuscitation
are simultaneously (1) to counteract the loss of circulating
blood volume with intravenous fluids; (2) to monitor the
physiologic response frequently and diligently; (3) to alter
treatment strategy based on physiologic response (e.g., by
titrating the fluid infusion rate hourly); and (4) to antici­
pate, guard against, and correct the effects of edema for­
mation. This could be summarized as follows: burn shock
mandates simultaneous fluid resuscitation and edema manage­
ment strategies.
Early Approaches to Fluid
Resuscitation
A wide variety of resuscitation formulas dominates much
of the discussion on the treatment of burn shock (Table
9.1). Knowledge of how these formulas came about is
Note: The opinions or assertions contained herein are the private views of
the authors, and are not to be construed as official or as reflecting the
views of the Department of the Army or the Department of Defense.

9  •  Burn Resuscitation
78
process, rather than toxemia, was sufficient to explain the
resultant postburn hypotension.10 Further experiments
involving excision of the burn wound as well as cross-
transfusion (of burned to unburned dogs) supported his
hypothesis.10
With World War II on the horizon, and following battles
such as the Battle of Britain in 1940 and the attack on Pearl
Harbor in 1941, there was great urgency to develop effective
methods to care for wartime burn casualties. Meanwhile
plasma now became available for intravenous administra­
tion. Several formulas were developed for burn-shock resus­
citation using plasma. One recommended enough plasma
to maintain the peripheral circulation, evidenced by the
ease with which blood could be drawn by a needle prick.
Others were based on calculations that incorporated the
hematocrit and/or the protein levels in the blood.14 The
burn-size-based formulas we use today originated from a
conference on January 7, 1942, of the National Research
Council (NRC). This committee stated that a burn patient
should receive 500 mL of plasma initially, followed by
100 mL of plasma per TBSA burned during the first 24 h
post burn. Other fluids (normal saline or dextrose) should
not normally exceed the plasma dose.15 Interestingly,
Harkins (who participated in the NRC meeting) described
a First Aid Formula at the same time that recommended
half this amount, or 50 mL/TBSA of plasma. In addition,
patients should receive about 1000 mL of normal saline
solution and “large amounts” of dextrose, preferably by
mouth.14,16
These preparations were tested when, on November 28,
1942, the Cocoanut Grove nightclub in Boston caught fire,
killing 492 people and injuring hundreds more in the dead­
liest nightclub fire in U.S. history. Patients were resuscitated
with plasma, which, however, was provided by the blood
bank diluted with equal volumes of normal saline.17 Dr.
Cope at the Massachusetts General Hospital provided in
the first 24 hours 50 mL of plasma plus 50 mL saline for
every 1% TBSA burned, followed by adjustments based on
hemoconcentration.18 Dr. Lund at the Boston City Hospital
did not use a formula to guide resuscitation, but rather
clinical parameters such as heart rate, blood pressure, and
hematocrit.19
Later, Cope and Moore reported the first burn formula
based on burn surface area for fluid therapy, recommending
that 75 mL plasma and 75 mL noncolloid isotonic fluid be
administered for every 1% TBSA burned in the first 24
hours, with one-half being given in the first 8 hours and
the remaining being given in the next 16 hours. This prac­
tice of providing half of the fluid needs within the first 8
hours remains a feature of nearly all modern burn resusci­
tation formulas. Additionally, 2000 mL fluid was to be
given on each day to maintain urine flow, preferably by
mouth.16
These formulas were based on a normal-sized adult and
could be unfavorable at the extremes of weight. Thus for­
mulas based on both weight and TBSA were developed.
Dr. Everett Evans developed one such formula. This
formula predicts infusion of 1 mL/kg per TBSA of normal
saline and an equal part colloid, plus 2000 mL of 5% dex­
trose in water (D5W), in the first 24 hours. This is followed
by 0.5 mL/kg per TBSA of saline and an equal part colloid
and of D5W in the second 24 hours.20
Table 9.1  Common Burn Resuscitation Formulas
Formula
First 24 Hours Post Burn
Next 24 Hours Post Burn
Evans Formula
NS: 1 mL/kg/%TBSA burn
NS: 0.5 mL/kg/%TBSA burn
Colloid: 1 mL/kg/%TBSA burn
Colloid: 0.5 mL/kg/%TBSA burn
D5W: 2000 mL
D5W: 2000 mL
Brooke Formula
NS: 1.5 mL/kg/%TBSA burn
NS: 0.5 mL/kg/%TBSA burn
Colloid: 0.5 mL/kg/%TBSA burn
Colloid: 0.25 mL/kg/%TBSA burn
D5W: 2000 mL
D5W: 2000 mL
Modified Brooke
Formula
LR: 2 mL/kg/%TBSA burn
LR: None
Colloid: None
Colloid: 0.3–0.5 mL/kg/%TBSA burn
Parkland Formula
LR: 4 mL/kg/%TBSA burn
LR: None
Colloid: None
Colloid: 5% albumin given at 0.3–1 mL/kg/%TBSA
burn/16 per hour
Shriner’s Cincinnati
(For Children)
LR: 4 mL/kg/%TBSA burn + 1500 mL/m2, 12 given over first 8 h and the
remaining over the next 16 h (older children)
LR: 4 mL/kg/%TBSA burn + 1500 mL/m2 + 50 mEq sodium bicarbonate for
the first 8 h, followed by LR alone in second 8 h, followed by 5%
albumin in LR in third 8 h (younger children)
Galveston Formula
(For Children)
LR: 5000 mL/m2 burn + 2000 mL/m2 total, 12 volume in first 8 h, followed
by remainder in 16 h.
From Hansen SL. From cholera to “fluid creep”: a historical review of fluid resuscitation of the burn trauma patient. Wounds 2008;20(7): 206–213. For earlier
version of the Cincinnati formula, see Merrell SW, Saffle JR, Sullivan JJ, et al. Fluid resuscitation in ther­mally injured children. Am J Surg. 1986;152(6):664–669.
For earlier version of the Galveston formula, see Carvajal HF. Fluid resuscitation of pediatric burn victims: a critical appraisal. Pediatr Nephrol.
1994;8(3):357–366.
D5W, 5% Dextrose in water; LR, lactated Ringer’s solution; NS, normal saline; UO, urinary output; TBSA, total body surface area.

9  •  Burn Resuscitation
79
50–69% TBSA, and 0.5 mL/kg per TBSA for 70–100%
TBSA.27
Today, crystalloid solution, mainly in the form of LR
(see later discussion), is predominately used for burn resus­
citation in the United States. Most burn centers use some
colloid according to physician discretion or other rule.28 The
Parkland and modified Brooke formulas are the two most
commonly used formulas to start fluid infusion rates. The
2012 American Burn Association consensus statement on
quality improvement in fluid resuscitation concluded that
evidence is lacking to recommend a standard of care.29 On
the other hand, the current Advanced Burn Life Support
Guidelines recommend starting with the modified Brooke
formula at 2 mL/kg per TBSA.30 For both formulas, half of
the volume is programmed for delivery during the first 8
hours post burn and half during the second 16 h post burn.
Subsequent adjustment of the fluid infusion rate is made
based on clinical status (see later discussion), and no abrupt
change is normally made at the postburn hour 8.
To simplify fluid calculation in adults, Chung and col­
leagues at the USAISR recently described a “Rule of Tens”:
initial fluid rate (in mL/h) = TBSA × 10. Thus a patient with
a 30% burn would be started at 300 mL/h. In addition,
patients weighing more than 80 kg receive an additional
100 mL/h for each additional 10 kg. This estimate provides
an initial infusion rate that lies between the Parkland and
Brooke estimations for 88% of patients.31 We emphasize
that this formula is appropriate only for adults (weight
≥40 kg).
Children
Formulas have been developed specifically for resuscitation
of children. Graves et al. at the USAISR performed a retro­
spective review of children weighing less than 25 kg who
were resuscitated with the pediatric modified Brooke
formula. This formula estimates 3 mL/kg per TBSA of LR
for the first 24 hours, with half given over the first 8 hours;32
LR is then titrated based on urine output (UO; target UO,
0.5–1.5 mL/kg per hour). Children are also given 5% dex­
trose in one-half normal saline (D5W12NS) at a mainte­
nance rate, which is not titrated. The actual volume of LR
infused was, on average, 3.91 mL/kg per TBSA (3.78 in
those whose UO was within the target range). Maintenance
fluids added an additional 2.39 mL/kg per TBSA to the
total.33 The 2011 Advanced Burn Life Support manual rec­
ommends the use of this 3 mL/kg per TBSA burned formula
for children, with the addition of maintenance fluid of
D5WLR.30
The Shriner’s Cincinnati and Galveston pediatric formu­
las account for the larger body surface area-to-weight ratio
of children. For the first 24 hours post burn, the Cincinnati
formula provides 4 mL/kg per TBSA (with half given in the
first 8 hours), plus maintenance needs (MN), plus evapora­
tive losses (EL). Here, MN = (1500 mL) × (body surface area
in m2), and EL = 35 + (TBSA burned in %) × (body surface
area in m2).34
For the first 24 h post burn, the Galveston formula pro­
vides 5000 mL × (TBSA burned in m2) + 2000 mL × (body
surface area in m2), with half given in the first 8 hours post
burn.35,36
BROOKE AND PARKLAND FORMULAS
The original Brooke formula of 1953 represents the begin­
ning of a transition away from colloid use during the
first 24 hours. In that formula, fluid needs for the first
24 hours are estimated as 2 mL/kg per TBSA: 0.5 mL/kg
per TBSA is given as colloid, and 1.5 mL/kg per TBSA as
crystalloid.21
Moyer eschewed the use of colloids for burn shock resus­
citation, stating that crystalloid solutions alone, such as
lactated Ringer’s (LR), were sufficient to correct what he
termed “sodium deficit shock.”22 G. Tom Shires and col­
leagues reported that hemorrhagic shock involved a loss
not just of blood, but also of functional extracellular fluid
(ECF) volume. This led to the use of large volumes of LR in
the Emergency Department for the treatment of trauma
patients.23 Further studies showed that this depletion of
ECF was accompanied by a decrease in the transmem­
brane potential difference and by intracellular sodium
influx.24
In 1968, Baxter and Shires extended these findings to
thermal injury. They measured the ECF in animals and
humans, demonstrating that restoration of the functional
ECF with LR could be performed, required infusion of a
greater volume (4 mL/kg per TBSA) than recommended by
the extant burn formulas, and led to a more rapid correc­
tion of both CO and metabolic acidosis.6 This occurred
despite a plasma volume deficit that persisted at the end of
the first 24 hours post burn. During the second 24 hours
post burn, plasma became effective as a volume expander
and was indicated to correct this deficit. This was the origin
of the widely used Parkland formula.25
Soon after Baxter’s work, Pruitt and colleagues at the
U.S. Army Institute of Surgical Research (USAISR) reported
that varying the dose of colloid infused during the first
24 hours postburn did not further increase the plasma
volume, meaning that colloid was no more effective than
crystalloid during this period. During the second 24 h post
burn, colloid did become more effective.5 Estimation of
fluid needs as 2 mL/kg per TBSA and elimination of colloid
during the first 24 hours, became known as the modi­
fied Brooke formula. Also at the USAISR, Goodwin et al.
conducted a randomized controlled trial comparing resus­
citation with and without albumin from the time of admis­
sion. The colloid group received 2.5% albumin in LR from
the start of resuscitation, whereas the crystalloid group
received LR alone. They found that patients who received
early albumin (1) had more rapid restoration of CO, (2)
received a lower fluid volume during the first 24 hours, (3)
had increased extravascular lung water on days 3–7 post­
burn, and (4) had increased in-hospital mortality.26 These
data, combined with the earlier study by Pruitt et al., bol­
stered the argument against albumin use during the first
24 hours.
Both the Parkland and modified Brooke formulas rec­
ommend crystalloids during the first 24 h; administration
of colloids (i.e., 5% albumin) is reserved until the second
24 hours. This point should be underscored: these are
not colloid-free, but delayed-colloid formulas. The modi­
fied Brooke formula provides a sliding scale for albumin
dosing during the second 24 hours, as follows: 0.3 mL/
kg per TBSA for 30–49% TBSA, 0.4 mL/kg per TBSA for

9  •  Burn Resuscitation
80
compartment syndrome (ACS)—e.g., patients with large
burns whose early resuscitation hours feature rapid escala­
tion in the infusion rate—early colloid use is reasonable.
Consistent with this idea, an approach taken at the Univer­
sity of Utah burn center involves use of “albumin rescue”
when the fluid infused-to-UO ratio increases above expected
levels.40,43
Five percent albumin in NS is the most commonly used
colloid for burn resuscitation today. In a previous era in
which albumin was not widely available and donor screen­
ing was rudimentary, infusion of plasma was associated
with a high risk of hepatitis transmission. Today the avail­
ability of safe FFP should cause us to raise the question of
whether FFP offers advantages over albumin or LR. Pati
et al. found that FFP or Kcentra (a factor concentrate) may
be superior to albumin in protecting against increases in
endothelial permeability induced by vascular endothelial
growth factor-A (VEGF-A) or by trauma/hemorrhage.44
Also in hemorrhagic shock models, Peng and colleagues
observed that FFP compared to LR decreases pulmonary
shedding of syndecan-1 from the endothelium, reduces
endothelial permeability, and decreases neutrophil infiltra­
tion.45 These findings in hemorrhagic shock indicate that
more work on the microvascular effects of FFP during burn
resuscitation is needed.
Compared with albumin and FFP, there is currently less
enthusiasm for the use of hetastarch solutions such as 6%
hydroxyethyl starch (HES) for burn shock resuscitation.
Vlachou et al. in the United Kingdom resuscitated 26 adults
with Hartmann’s solution or with a combination of two-
thirds Hartmann’s solution and one-third HES. They found
that the HES group received less fluid (263 mL vs. 307 mL/
kg).46 On the other hand, a Swiss trial in 48 patients com­
pared LR versus 6% HES for the first 72 hours post burn.
They found no difference in volume requirements, renal
function, acute respiratory distress syndrome (ARDS),
length of stay, or mortality.47 A Cochrane review concluded
that HES solutions increase the risk of acute kidney injury
and the need for renal replacement therapy.48 As a conse­
quence of these and other studies, the European Medicines
Agency stated in 2013 that HES should not be used in criti­
cally ill, septic, or burns patients.49
Another approach to reducing the infused volume during
burn resuscitation is the use of hypertonic saline. While
Shires, Baxter, and colleagues were advocating the rapid
correction of the extracellular sodium deficit with large
volumes of LR by means of the Parkland formula, Monafo
argued that hypertonic lactated saline solution, given
intravenously and orally, could just as easily correct the
sodium deficit while avoiding the administration of exces­
sive volumes. His fluid contained 300 mEq/L of sodium,
200 mEq/L of lactate, and 100 mEq/L of chloride.50 Several
burn centers have routinely used hypertonic saline during
resuscitation. For example, Warden at the Cincinnati Shrine
used LR plus 50 mEq of sodium bicarbonate per liter, which
results in a mildly hypertonic solution, for the first 8 hours
postburn.51
During fluid resuscitation using hypertonic solutions, the
extracellular fluid volume deficit is partially corrected by
means of water flux from the intracellular to the extracel­
lular space, in response to the increased extracellular
sodium concentration.32 The serum sodium should be
Choice of Fluid
LR is the most frequently used crystalloid solution for burn
shock resuscitation. Normal saline (NS) was used in the
past, but has been criticized primarily because (1) it may
decrease renal blood flow and glomerular filtration rate,
thus increasing the risk of acute kidney injury; and (2) in
large volumes, it may cause hyperchloremic metabolic aci­
dosis. Clinical trials of NS versus balanced crystalloid solu­
tions such as LR or Plasma-Lyte in nonburn patients are
contradictory,37 and there are no studies in burn patients.
Because LR is slightly hypotonic, it may increase brain
water content and intracranial pressure (ICP).38 This may
explain, in part, the concerning finding of increased ICP in
some burn studies (see later discussion). LR contains a
racemic mixture of D- and L-lactate isomers. Ayuste and
coauthors reported that resuscitation with standard (i.e.,
racemic) LR was associated with lung and liver apoptosis,
which was prevented by removal of the D-lactate isomer
from the LR.39 Plasma-Lyte has an electrolyte composition
and an osmolality that is closer to that of plasma, and it
contains gluconate and acetate instead of lactate.37 However
there are no studies comparing Plasma-Lyte to LR in burn
patients.
Although crystalloid is the mainstay of burn shock
resuscitation, the debate concerning if, when, and how
much colloid is needed has continued. There are several
systematic approaches to colloid use, including (1) immedi­
ate (use colloids during all hours of burn resuscitation), (2)
early/rescue (use colloids when resuscitation is becoming
excessive, typically starting at 8–12 hours post injury), and
(3) late (do not use any colloids for resuscitation during the
first 24 hours).28,40 Increasingly a rational approach to
identifying those patients who may benefit from early
colloid use is followed at many burn centers.
Demling and colleagues developed an ovine model with
chronic lymph fistulas and described the dynamics of edema
formation in burned and unburned tissues. Measurement
of lymph flow rates (QL) and the lymph-to-plasma protein
ratio (CL/CP) revealed that the ability of the microvascula­
ture to retain plasma proteins began to recover between 8
and 12 hours post burn in unburned but not in burned
tissue.41 This provides evidence that a colloid-containing
solution may be more effective than a crystalloid solution
beginning about 8–12 hours post burn.
In a prospective randomized trial, O’Mara and colleagues
compared fresh frozen plasma (FFP) resuscitation and crys­
talloid resuscitation.42 In this trial, the FFP group received
a mixture of 75 mL/kg FFP (titrated to maintain a UO of
0.5–1.0 mL/kg per hour) plus 2000 mL LR (83 mL/h),
while the crystalloid group received LR according to the
Parkland formula (titrated to maintain a UO of 0.5–1.0 mL/
kg per hour). The crystalloid group required significantly
more fluid than the FFP group (260 vs. 140 mL/kg). FFP
resuscitation was associated with a lower peak intra-
abdominal pressure (16 vs. 32 mm Hg). Furthermore the
crystalloid group developed elevated creatinine, blood urea
nitrogen (BUN), and peak airway pressure, whereas the FFP
group developed only elevated peak airway pressure.
This and similar studies suggest that, particularly in
patients who are at risk for complications like abdominal

9  •  Burn Resuscitation
81
electrolytes, and sugars. The sugar component is important
because it increases the uptake of sodium across the intes­
tinal mucosa. If enteral resuscitation is performed via a
nasogastric tube, frequent (e.g., hourly) monitoring of
gastric residual fluid volumes is recommended, especially
during the initial hours post burn.
Patients at Increased Risk During
Resuscitation
Patients with significant comorbidities (e.g., heart failure,
cirrhosis, preexisting renal insufficiency, morbid obesity62)
often do not respond in the usual way to fluid resuscitation
and may benefit from closer monitoring, as described later.63
Patients at the extremes of age—the very young and the
very old—are less tolerant of “swings” in volume status;
that is, their ability to compensate for hypovolemia or
hypervolemia is limited, and they are particularly “volume
sensitive.” Again, closer attention to detailed monitoring is
warranted in these patient populations.
Baxter reported that patients with inhalation injuries
and large burns have the greatest fluid requirements in the
burn population.64 Most studies have reported increased
fluid requirements of 20%–30% when compared to equal-
size burns without inhalation injury.65 However, this
response is unpredictable, such that a modification of the
burn resuscitation formulas because of inhalation injury is
not commonly recommended.
Patients whose resuscitation is delayed may require more
fluids than suggested by the formulas and may have
increased complications because of the deleterious effects
of prolonged ischemia followed by reperfusion.58 Again, no
modification of practice is commonly recommended in this
scenario. Patients with a mechanism of injury suggesting
risk of mechanical trauma and who do not respond to
resuscitation in the usual fashion, may have a missed injury
and ongoing bleeding. Patients with clinically evident myo­
globinuria, as may occur following high-voltage electric
injury, are typically given fluids at an increased rate in order
to decrease pigment deposition in the renal tubules, with a
target urine output of 75–100 mL/h in adults.66
Monitoring Resuscitation
Optimizing resuscitation—that is, ensuring administration
of sufficient volume to achieve organ perfusion at the lowest
physiologic cost—requires hourly monitoring (UO, hemo­
dynamics, and clinical signs of adequate perfusion) and
titration of fluid based on these endpoints. The most com­
monly used assessments are vital signs, laboratory assays,
and UO. The primary index of the adequacy of resuscitation
is most often the UO, with the rationale that it is a surrogate
metric for glomerular filtration rate, renal blood flow, and
CO. Recommended UO is 30–50 mL/h in adults, 0.5 to
1.0 mL/kg per hour in children of less than 30 kg, and 1.0
to 2.0 mL/kg per hour in infants. Recent trends have many
burn caregivers targeting the lower values of these ranges.
UO is usually recorded hourly; however studies validating
this frequency are lacking. UO may fail as an index of resus­
citation adequacy in patients with renal failure and in those
monitored during hypertonic resuscitation, since a level of
greater than 160 mEq/L has been associated with adverse
renal and cerebral effects.52
Huang and colleagues described a study in which a first
cohort of patients was treated with LR, a subsequent cohort
was treated with hypertonic saline (290 mEq/L), and a
third cohort was treated with LR. The hypertonic patients
had a fourfold increase in the risk of renal failure and twice
the mortality.53 This experience dampened enthusiasm for
hypertonic saline. However Oda et al. reported a prospective
study of burn patients resuscitated either with hypertonic
lactated saline (HLS) or with LR. The concentration of
sodium decreased from 300 to 150 mEq/L with each sub­
sequent liter or two administered. Patients who received
HLS had a lower prevalence of intra-abdominal hyperten­
sion and received less fluid (3.1 vs. 5.2 mL/kg per TBSA).54
Thus there may be a role for hypertonic saline resuscitation
in those patients who are particularly volume sensitive or
at risk of overresuscitation.52
A different approach to hypertonic therapy in burn shock
is to use the much more concentrated fluid, hypertonic
saline dextran (HSD), which consists of 7.5% normal saline
and 6% dextran-70 and whose sodium concentration is
1280 mEq/L. Elgjo and colleagues in an ovine model dem­
onstrated that 4 mL/kg of HSD given 1 hour postburn
rapidly restored CO and reduced early, but not late, fluid
requirements.55 In a follow-up study, this group showed
that the fluid-sparing effect of HSD could be sustained to 48
hours by use of a second dose given when net fluid accu­
mulation reached 20 mL/kg.56 We do not have clinical trials
of HSD use in burn shock resuscitation.
Route of Administration
A survey of burn specialists performed by Greenhalgh
revealed that the peripheral intravenous route (70%) is pre­
ferred for burn resuscitation. However, central venous
access is often used (48%).57 In cases of severe injury with
widespread deep burns and edema, use of peripheral veins
may not be possible. As a temporary option, intraosseous
access may be lifesaving, but flow rates are limited due to
the hydraulic resistance of the bone marrow. Later, central
venous access can be established in the intensive care
setting.
Early initiation of fluid resuscitation (within the first
hours of burn injury) is essential for the prevention of
organ failure,1,58 but may be difficult to achieve in austere
environments, combat casualty care, and mass-casualty
events. Here enteral or oral resuscitation should be consid­
ered and may be effective for burns between 10% and 40%
TBSA.59,60 Clinical use of enteral resuscitation of burns was
described by several early authors, including Fox in 1944.61
Its utility might be limited by ileus and reduced gastric func­
tion. The effectiveness and safety of enteral resuscitation
merit further investigation.13
There are no burn-specific oral/enteral fluid resuscitation
solutions. World Health Organization (WHO) oral rehydra­
tion solution is available as a dry powder that is reconsti­
tuted with clean water. It was originally developed for
treatment of dehydration secondary to cholera. These, and
commercially available solutions, contain sodium, other

9  •  Burn Resuscitation
82
this regard. In that study of successful resuscitations, the
plasma volume deficit persisted until after 48 hours post
burn, and CO remained below baseline levels until 36 hours
post burn.
Echocardiography has largely replaced the PAC for the
cardiac evaluation of selected burn patients.75 Transtho­
racic echocardiography (TTE) provides information on
volume status and cardiac function. TTE can be performed
easily without the need for preassessment sedation. Never­
theless, TTE should be performed by well-trained clinicians
to minimize user-dependent errors.76 A further advantage
of echocardiography, in comparison to PAC and TPTD, is
that it can help diagnose heart failure and determine the
response to inotropes. Further prospective randomized con­
trolled trials comparing different echocardiography tech­
niques are warranted.75
An increase in the hematocrit (or hemoglobin) during
burn shock likely indicates a worsening plasma volume
deficit. For this reason, early treatises on burn resuscitation
recommended following this value as an index of volume
status.21 Certainly it can provide supportive information,
bearing in mind that a decrease in hematocrit below normal
levels is frequently seen as resuscitation continues, reflect­
ing red blood cell damage.5
Fluid Creep and Edema
Management
During resuscitation, the desire to maintain adequate per­
fusion of vital organs and the failure to titrate fluid input
appropriately can lead to overresuscitation.40 “Fluid creep”
was first described by Pruitt as a recent trend toward infus­
ing greater volumes of fluid than those predicted by the
burn formulas, leading to organ dysfunction or even life-
threatening complications.2 Overresuscitation may lead to
ACS,77 airway and pulmonary edema,78 extremity compart­
ment syndrome (ECS),79 orbital compartment syndrome,80
and cerebral edema. The risk of cerebral edema is particu­
larly underappreciated. Gueugniaud et al. observed ele­
vated ICP in patients with a TBSA of greater than 60% and
no history of head injury, peaking on day 2 postburn.81
Shin et al. in an ovine 70% TBSA model showed an increase
in ICP and a decrease in cerebral blood flow at the end of 6
hours postburn, with increased brain water content at
autopsy.82 Ding and colleagues conducted studies in a rat
model and demonstrated increased blood–brain barrier per­
meability post burn that could be prevented by tumor
necrosis factor-α (TNF-α) or matrix metalloproteinase-2
blockade.83 Gatson et al. demonstrated increased brain
cytokine levels in burned rats and their blockade with
17-β-estradiol.84
To this list of early complications, we should add the
effect of wound edema on the progression of injury depth
and on the success of wound healing,50 the importance of
which to survival cannot be overstated.85
These complications are highly morbid, and strenuous
efforts to forestall them are a critical aspect of burn shock
resuscitation in the modern era. For example, ACS in burn
patients, when treated by laparotomy, carries a near 100%
mortality in many series. ECS (in burned or unburned
limbs) may be detected late, leading to muscle necrosis,
whose UO is elevated by the use of a diuretic, alcohol intoxi­
cation, or glycosuria. In these patients, alternate methods
of monitoring are recommended.
UO is only one metric of adequate perfusion. Heart rate,
blood pressure, central venous pressure, and echocardiog­
raphy can serve as indices of cardiovascular status, particu­
larly in patients with large burns and complex comorbidities.
These variables must be considered in the context of burn
shock physiology, however. For example, a well-resuscitated
adult with extensive burns should have a heart rate in the
100–130/min range. This is because of the massive release
of catecholamines caused by injury and because of the rela­
tive hypovolemia that characterizes a prudent resuscita­
tion. A mean arterial pressure (MAP) of 60 mm Hg is a
reasonable target for most patients, but some patients will
tolerate a MAP as low as 50–55 mm Hg and still achieve
adequate UO, cerebral perfusion, and decreasing lactic
acidosis.
Laboratory values are an important assessment tool.
Complete blood count, electrolytes, glucose, and acid–base
status should be monitored frequently, although evidence
regarding the optimal frequency of measurement is lacking.
Lactate and base deficit (BD) are often used as indices of the
adequacy of global perfusion. Elevated BD and serum
lactate correlate with larger burn size, inhalation injury,
greater fluid requirements, and mortality.1,67,68 In a prospec­
tive study of BD and outcomes in burn patients, Cartotto
et al. reported that patients with worse BD had greater fluid
requirements as well as higher rates of sepsis, ARDS, and
multiple organ dysfunction syndrome.69 Kamolz et al.
showed that lactate levels and the rate of lactate clearance
are useful markers of shock and resuscitation status.70
Additionally, they demonstrated that if the lactate levels
were normalized within 24 hours the survival rate was
68%, compared to 32% if lactate normalization did not
occur within 24 hours.
The pulmonary artery catheter (PAC) was used for
decades during resuscitation to measure pulmonary capil­
lary wedge pressure, systemic and pulmonary vascular
resistances, CO, and oxygen consumption, a practice now
largely limited to research applications. Transpulmonary
thermodilution (TPTD) is a less invasive option that requires
one access point via a central venous line as well as one
access point via a peripheral artery. Commercial TPTD
monitors also provide beat-to-beat estimates of CO (based
on arterial waveform contour analysis). In addition, one
can measure global end-diastolic volume (GEDV), a marker
of cardiac preload, as well as extravascular lung water, a
marker of pulmonary edema. Sánchez et al. showed that
TPTD, but not MAP or UO, accurately detected hypovolemia
during acute resuscitation (within 24 hours of burn).71 A
recent study in burned children by Kraft et al. confirmed
these findings.72
How best to use TPTD or PAC data during resuscitation is
not obvious. Attempts to “normalize” the CO or the GEDV
during the first 24 hours postburn are often ill-advised
because they may lead to overresuscitation with no net
improvement in outcome.73 Rather, an understanding of
the expected dynamics of the successfully resuscitated
average patient may allow a determination of whether a
given patient is “on course” or “off course” with respect to
his progress.74 Information from Pruitt et al.5 is helpful in

9  •  Burn Resuscitation
83
Pruitt’s, which suggest that most can be resuscitated with
slightly less than 3 mL/kg per TBSA.87
While there are no randomized controlled trials to suggest
the superiority of one burn formula over another, Chung
et al. retrospectively analyzed data from combat casualties
treated in Iraq. Clinical practice guidelines in place during
the war recommended that burn patients be resuscitated
using 2–4 mL/kg per TBSA. In practice, the resuscitation of
most of these patients was initiated at either 2 or 4 mL/kg
per TBSA. This permitted comparison of the modified
Brooke and the Parkland formulas. Patients in both groups
received more than predicted by the formulas: those started
at 2 mL/kg per TBSA received 3.8 mL/kg per TBSA, whereas
those started at 4 mL/kg per TBSA received 5.9 mL/kg per
TBSA. Patients started at 2 mL/kg per TBSA were less likely
to exceed the Ivy Index than were those started at 4 mL/kg
per TBSA (29% vs. 57%).88 This suggests that one answer
to fluid creep is to initiate resuscitation using the more con­
servative modified Brooke formula.
Faraklas et al. and Cancio et al. suggested that clinicians
may be more aggressive at increasing fluid infusion rates
initially than they are at decreasing fluid infusion rates
later.89,90 Furthermore Faraklas et al. concluded that seri­
ously injured patients, pediatric patients, and patients with
combinations of burns and inhalation injuries are more
prone to fluid creep. Greater fluid volumes were associated
with significantly more escharotomies and complications as
well as longer hospital stays.
In 2004, Sullivan et al. suggested that fluid creep might
be associated with increased administration of opioids
during burn shock resuscitation, a phenomenon termed
“opioid creep.”80 They compared fluid requirements in a
cohort of burn patients who received low doses of opioids
(treated in 1975) to those in a group of patients (treated in
2000) who received four times higher doses of opioids. A
significant correlation was noted between opioid dose and
fluid requirements within the first 24 hours of acute hospi­
talization. Nevertheless opioids remain a crucial part of
pain management in severely burned patients.91 The car­
diovascular effects of opioids and benzodiazepines need to
be considered, and the amount given must be strictly
monitored.
Lawrence et al. described a “colloid rescue” in which they
provided 5% albumin to patients who were requiring exces­
sive amounts of crystalloids; this approach permitted a sub­
sequent reduction in crystalloid infusion rates.43 The use of
colloids should be considered in patients heading toward
fluid needs in excess of Parkland volume estimates (see
earlier discussion), particularly after the first 8–12 hours
postburn have passed.41
Pharmacologic and
Extracorporeal Adjuncts
There is a limited role for vasoactive medications during
burn shock resuscitation. Traditionally we have been reluc­
tant to use vasoconstrictors such as norepinephrine or vaso­
pressin during burn shock, recognizing that many of these
patients respond to injury and hypovolemia with intense
catecholamine release and vasoconstriction. However, on
a case-by-case basis, such agents may be useful to support
nerve injury, and possibly limb loss.79 Ivy observed that risk
of ACS increases when the infused volume exceeds 250 mL/
kg during the first 24 hours postburn.77 For this reason,
that volume is often referred to as the “Ivy Index.” Early
identification of patients who are on course for a resuscita­
tion in which the Ivy Index will be exceeded may permit
corrective actions to decrease the infusion rate and preclude
or promptly address these complications. Such corrective
actions include (1) strategies to reduce the fluid infusion
rate and (2) strategies to address edema.
A reduction in fluid infusion rate may be possible by (a)
initiation of colloids, (b) tolerance of a subtarget UO, (c)
initiation of continuous renal replacement therapy to
address acidosis or renal insufficiency, (d) initiation of high-
dose ascorbic acid, and/or (e) a diagnostic work up for non–
volume-related causes of shock, such as echocardiography
to assess cardiac function and the need for inotropes.
Strategies to reduce edema formation or to address its
effects include (a) aggressive elevation of burned extremi­
ties; (b) monitoring of extremity compartment pressures
and/or physical exam, with escharotomies or fasciotomies
as needed;86 (c) monitoring of the bladder pressure to diag­
nose intra-abdominal hypertension (IAH); (d) use of
sedation/paralysis/positioning to reduce IAH; (e) place­
ment of a diagnostic peritoneal lavage (DPL) catheter con­
nected to intravenous tubing to permit evacuation of ascites
and reduction in IAH; and (f) measurement of intraocular
pressures and lateral canthotomy for orbital compartment
syndrome.80
Fig. 9.1 shows a plot of actual 24-h volumes infused for
burn resuscitation when LR was used and hourly rates were
adjusted based on UO. Data are from all studies that were
identified between 1980 and 2015. Clearly most studies
report volumes that exceed Parkland estimations. While
these data suggest a trend toward increased fluid volumes,
more striking are the wide variations reported for mean
values and the large standard deviations reported for most
individual studies. These data stand in sharp contrast to
Baxter’s original publications that suggest most patients
can be resuscitated with 4 mL/kg per %TBSA burned,25 and
1975 1980 1985
Volume infused
(ml/kg per %TBSA)
1990 1995
Year
Meta-analysis of fluid resuscitation
volumes
: Published study
Parkland
Trend line
Brooke
2000 2005 2010 2015
0.0
2.0
4.0
6.0
8.0
10.0
Fig. 9.1  Scatter plot and regression of published studies showing
actual fluid infused over 24 hours compared to fluid requirements esti­
mated using the Parkland and Brooke formulae. Studies were from
1980 to 2014 and the mean fluid infused was 5.3 ± 1.2 (SD) mL/kg per
%TBSA burned. (Unpublished data, Kramer GC et al.)

9  •  Burn Resuscitation
84
acute kidney injury (Acute Kidney Injury Network [AKIN]
level 3, or level 2 with shock). These patients were initiated
on CRRT on mean hospital day 17 ± 24. Compared to his­
torical controls, they had better mortality; fewer of the
patients with shock required vasopressors at 24 hours. The
authors speculated that the mechanism of action for this
improvement could be nonspecific removal of cytokines.98
Application of these findings to patients with refractory
burn shock and who do not meet AKIN criteria for CRRT
would be based on this hypothesis.
Extracorporeal blood purification aims to remove inflam­
matory mediators and/or other molecules from the circula­
tion by means other than CRRT. Linden and colleagues
evaluated a novel extracorporeal cytokine-adsorbing
column, CytoSorb (CytoSorbents Corporation, Monmouth
Junction, NJ), in a porcine model of smoke inhalation injury
and 40% TBSA burns. This column removed interleukin-1b
(IL-1b), IL-6, IL-10, and myoglobin from the extracorporeal
circuit but did not reduce systemic levels. Thus more work
would be needed to optimize factors such as therapy dura­
tion, blood flow rate, and possibly device size.99
Protocol-Driven and
Computerized Resuscitation
Nurse-driven burn resuscitation using hourly flow charts is
an approach to achieving tighter control of fluid therapy.
Nurse-implemented protocols allow nurses to make timely
and effective changes to the resuscitation rates without
having to wait for physicians’ orders, which can delay
needed adjustments in therapy. Additionally these protocols
diminish the effects that experience and/or comfort level
have on titration (a new nurse or intern may be reluctant
to make significant changes). Faraklas and colleagues insti­
tuted a nurse-driven resuscitation protocol (Fig. 9.2) as a
performance-improvement project and showed excellent
protocol adherence. However, large-volume fluid resuscita­
tion still occurred in patients with the largest burns or with
inhalation injury.90
A logical next step to paper protocols is a computerized
decision-support system (CDSS). A CDSS is an open-loop
system that provides recommendations to the clinical team
using data obtained from the patient. Salinas et al. devel­
oped an algorithm that calculates, on an hourly basis, the
infusion rate most likely to achieve a UO within the target
range during the next hour. The inputs used by the algorithm
include the linear trend in the past three urine outputs, the
burn size, the time post burn, and the current fluid infusion
rate. The algorithm was implemented in software and was
shown to decrease the total volume delivered while increas­
ing the percentage of time during which UO rates achieved
the target range. Ventilator days and ICU length of stay
were also decreased.100 Although encouraging, the study
was small and awaits validation in larger trials.
Hourly adjustments in the fluid infusion rate are based
on a convenient but arbitrary time interval, whereas the
kidneys respond to changes in volume status more rapidly.
Thus there may be value in developing a closed-loop system
that continuously measures UO and automatically makes
corrections to the infusion rate on a more frequent basis.
Closed-loop fluid resuscitation systems have been shown to
a minimally acceptable mean arterial blood pressure while
volume resuscitation proceeds.92 Likewise, cardiac ino­
tropes such as dobutamine (or agents which reduce after­
load, such as hydralazine) should be used with caution in
hypovolemic burn patients since afterload reduction in this
population may precipitate overt hypotension.5 However, in
volume-replete patients whose CO remains low, inotropes
may be appropriate. The choice of vasoactive medication
may be facilitated by echocardiography.
High-dose ascorbic acid (vitamin C) has been used as a
pharmacologic adjunct during burn resuscitation. Its pro­
posed mechanism of action is that it is a free-radical scav­
enger capable of reducing post-burn lipid peroxidation and
microvascular leakage. At a dose of 66 mg/kg per hour
(begun as soon as possible after admission), it was evaluated
in a prospective randomized controlled trial by Tanaka and
colleagues. They showed that high-dose ascorbic acid sig­
nificantly reduced 24-hour fluid requirements (from 5.5 to
3.0 mL/kg per TBSA), weight gain, and edema. Addition­
ally, treated patients had fewer ventilator days, less lung
water, lower rates of acute lung injury, and lower levels of
serum malondialdehyde, a marker of oxidative stress. The
ascorbic acid group, although given significantly less fluid
than the control group, had comparable hemodynamics
and hourly UO.93 Dubick and coworkers reported that, in an
ovine model of burns, high-dose isotonic ascorbic acid
reduced total volume infused over the 48-hour study. Fur­
thermore the treatment group had markedly elevated
plasma antioxidant potential and reduced lipid peroxida­
tion.94 A small retrospective study yielded similar findings.95
Specifically ascorbic acid-treated patients had significantly
lower resuscitation volumes and reduced vasopressor use.
These studies suggest that high-dose ascorbic acid holds
promise in resuscitation, but a multicenter trial is yet to be
performed. Ascorbic acid may act as an osmotic diuretic,
which may affect the use of UO as an index of resuscitation
adequacy. Also, institution of this drug upon admission,
rather than at some later time point when a patient appears
to be failing resuscitation, makes sense considering its anti­
oxidant mechanism of action.
Extracorporeal adjuncts to burn resuscitation include
therapeutic plasma exchange (TPE), continuous renal
replacement therapy (CRRT), and extracorporeal blood
purification. TPE has been used at a small number of burn
centers for the treatment of patients who are not respond­
ing to resuscitation appropriately. In TPE, the patient’s
plasma volume is replaced with FFP. The basis for this inter­
vention is the concept that burn shock is mediated, in part,
by circulating cytokines and other factors that can be
removed by TPE. Neff et al. reported on experience with 21
patients who underwent TPE when the volume received
exceeded 1.2 times the goal of 3 mL/kg per TBSA at any
given point during the first 24 hours, along with other evi­
dence of failure such as oliguria or hypotension. TPE was
associated with increases in blood pressure and in UO, and
decreases in the intravenous fluid rate and lactate. There
was no difference in mortality with a control group.96 Klein
et al. applied TPE to 37 patients who typically were receiv­
ing twice the volume predicted by the Parkland formula.
Findings were similar to those of Neff et al.97
There are no data on the utility of CRRT for the treatment
of burn shock. Chung et al. reported on burn patients with

9  •  Burn Resuscitation
85
A closed-loop system may be particularly valuable in non-
burn-center settings or mass-casualty scenarios, where
burn expertise is lacking, diluted, or degraded. However a
closed-loop system should not replace careful patient moni­
toring and should enhance, rather than reduce, a provider’s
situational awareness. Such systems must allow the
be effective (in maintaining resuscitation targets) and effi­
cient (in reducing volume delivered) in large-animal models
of both burn injury and hemorrhage.101 Closed-loop systems
could reduce much of the bedside caregiver’s time in mea­
suring and transcribing UO and making manual adjust­
ments in infusion rates, allowing more time for other tasks.
Protocol for fluid resuscitation of the adult burn patient:
begin LR using burn center fluid resuscitation calculations
STEP ONE
Infuse at calculated rate as ordered by MD.
Measure urine output after one hour
REPEAT STEP ONE EVERY HOUR UNTIL:
CALL PHYSICIAN
Vitals signs stable: HR < 140, BP > 90/60, SaO2 > 90
Vitals unstable:
HR > 140, < 60
BP < 90/60
SaO2 < 90
Urine output
< 15 mL
Urine output < 15 mL/h
for two or more hours
despite increasing fluid
rate
CALL PHYSICIAN:
Check urinary
catheter, assess
breath sounds, vital
signs, bladder
pressure. Consider
albumin protocol
Fluid resuscitation is
complete: switch patient to
maintenance IV of D5/0.45
NaCl + 20 mEq KCI/liter at
calculated maintenance rate
Patient may need colloid
resuscitation: CALL PHYSICIAN
to discuss. Check foley catheter,
vital signs, bladder pressure
If patient again develops
oliguria or hemodynamic
instability, CALL PHYSICIAN.
Restart patient on LR at
current rate and return to
STEP ONE
Albumin protocol: begin a
combination of 5% albumin at 1/3
of currnet IV rate, plus LR at 2/3
current rate. Repeat STEP ONE.
Decrease IV as tolerated,
maintaining the ratio of 1/3
albumin: 2/3 LR until maintenance
rate is maintained for 2 hours
Switch IV fluid to plain LR and
repeat STEP ONE
Calculated maintenance rate
is reached and held for 2
hours AND patient is at least
24 hours post-burn
Patient requires increasing fluids
or more than twice current
calculated rate for 2 or more
hours
Increase IV
rate by 20%
or 200 mL/h
(whichever is
more)
Increase IV
rate by 10%
or 100 mL/h
(whichever is
more)
Decrease IV
rate by 10%
or 100 mL/h
(whichever is
more)
Decrease IV rate every 1/2 hour
by 10% or 100 mL/h, whichever
is more. Measure blood sugar,
lactate, hemoglobin. Call
physician with quesitions
Leave IV as is
Urine output
15–30 mL
Urine output
30–50 mL
Urine output
50–200 mL
Urine output
> 200 mL
Fig. 9.2  Adult Fluid Resuscitation Protocol used at University of Utah. The pediatric protocol differs from the adult protocol in that urine output is
targeted to 1.0–1.9 mL/kg per hour, and patients younger than 2 years receive 25 mL/h of 5% dextrose in lactated Ringer’s (LR) throughout resuscita­
tion. (From Faraklas I, Cochran A, Saffle J. Review of a fluid resuscitation protocol: “fluid creep” is not due to nursing error. J Burn Care Res.
2012;33(1):74–83.)

9  •  Burn Resuscitation
86
multitude of strategies designed to improve resuscitation,
with no single approach having universal acceptance. More
important than any formula or technology is a diligent
burn team of physicians and nurses assessing the overall
adequacy of hemodynamics and end-organ perfusion and
making adjustments as needed.
Complete references available online at

caregiver to override the computer and regain manual
control.102
Conclusion
Fluid resuscitation is the important first step in the critical
care of burn patients. There is still great controversy sur­
rounding optimal resuscitation of patients: there are a

86.e1
9  •  Burn Resuscitation
32. Pruitt BA Jr. Fluid resuscitation of burn patients: does clinical
“success” necessitate “excess”? South Med J. 1976;69(11):1399.
33. Graves TA, Cioffi WG, McManus WF, Mason AD Jr, Pruitt BA Jr. Fluid
resuscitation of infants and children with massive thermal injury.
J Trauma. 1988;28(12):1656-1659.
34. Merrell SW, Saffle JR, Sullivan JJ, et al. Fluid resuscitation in ther­
mally injured children. Am J Surg. 1986;152(6):664-669.
35. Carvajal HF. Fluid therapy for the acutely burned child. Compr Ther.
1977;3(3):17-24.
36. Carvajal HF. Fluid resuscitation of pediatric burn victims: a critical
appraisal. Pediatr Nephrol. 1994;8(3):357-366.
37. Weiss SL. Examining crystalloid resuscitation. Society of Criti­
cal Care Medicine: Clinical Controversies Highlighted at the 45th
Critical Care Congress. August 4, 2016.
Communications/Critical-Connections/Archives/Pages/Examining-
Crystalloid-Resuscitation.aspx.
38. Tommasino C, Moore S, Todd MM. Cerebral effects of isovolemic
hemodilution with crystalloid or colloid solutions. Crit Care Med.
1988;16(9):862-868.
39. Ayuste EC, Chen H, Koustova E, et al. Hepatic and pulmonary
apoptosis after hemorrhagic shock in swine can be reduced
through modifications of conventional Ringer’s solution. J Trauma.
2006;60(1):52-63.
40. Saffle JR. The phenomenon of “fluid creep” in acute burn resuscita­
tion. J Burn Care Res. 2007;28(3):382-395.
41. DemLing RH, Smith M, Bodai B, et al. Comparison of postburn
capillary permeability in soft tissue and lung. J Burn Care Rehabil.
1981;2:86-92.
42. O’Mara MS, Slater H, Goldfarb IW, Caushaj PF. A prospec­
tive, randomized evaluation of intra-abdominal pressures with
crystalloid and colloid resuscitation in burn patients. J Trauma.
2005;58(5):1011-1018.
43. Lawrence A, Faraklas I, Watkins H, et al. Colloid administration nor­
malizes resuscitation ratio and ameliorates “fluid creep”. J Burn Care
Res. 2010;31(1):40-47.
44. Pati S, Potter DR, Baimukanova G, et al. Modulating the endothe­
liopathy of trauma: factor concentrate versus fresh frozen plasma.
J Trauma Acute Care Surg. 2016;80(4):576-584, discussion 584-585.
45. Peng Z, Pati S, Potter D, et al. Fresh frozen plasma lessens pulmo­
nary endothelial inflammation and hyperpermeability after hem­
orrhagic shock and is associated with loss of syndecan 1. Shock.
2013;40(3):195-202.
46. Vlachou E, Gosling P, Moiemen NS. Hydroxyethylstarch supplemen­
tation in burn resuscitation – a prospective randomised controlled
trial. Burns. 2010;36(7):984-991.
47. Bechir M, Puhan MA, Fasshauer M, et al. Early fluid resuscita­
tion with hydroxyethyl starch 130/0.4 (6%) in severe burn injury:
a randomized, controlled, double-blind clinical trial. Crit Care.
2013;17(6):R299.
48. Dart AB, Mutter TC, Ruth CA, Taback SP. Hydroxyethyl starch (HES)
versus other fluid therapies: effects on kidney function. Cochrane
Database Syst Rev. 2010;1(1).
49. Mayor S. EMA confirms that hydroxyethyl starch solutions
should not be used in critically ill, sepsis, or burns patients. BMJ.
2013;347:f6197.
50. Monafo WW. The treatment of burn shock by the intravenous and
oral administration of hypertonic lactated saline solution. J Trauma.
1970;10(7):575-586.
51. Warden GD. Burn shock resuscitation. World J Surg. 1992;16(1):
16-23.
52. Pruitt BA Jr. Does hypertonic burn resuscitation make a difference?
Crit Care Med. 2000;28(1):277-278.
53. Huang PP, Stucky FS, Dimick AR, et al. Hypertonic sodium resus­
citation is associated with renal failure and death. Ann Surg.
1995;221(5):543-557.
54. Oda J, Ueyama M, Yamashita K, et al. Hypertonic lactated saline
resuscitation reduces the risk of abdominal compartment syndrome
in severely burned patients. J Trauma. 2006;60(1):64-71.
55. Elgjo GI, Poli de Figueiredo LF, Schenarts PJ, et al. Hypertonic saline
dextran produces early (8-12 hrs) fluid sparing in burn resuscita­
tion: a 24-hr prospective, double-blind study in sheep. Crit Care Med.
2000;28(1):163-171.
56. Elgjo GI, Traber DL, Hawkins HK, Kramer GC. Burn resuscitation
with two doses of 4 mL/kg hypertonic saline dextran provides sus­
tained fluid sparing: a 48-hour prospective study in conscious sheep.
J Trauma. 2000;49(2):251-263.
References
1. Wolf SE, Rose JK, Desai MH, et al. Mortality determinants in massive
pediatric burns. An analysis of 103 children with ≥80% TBSA burns
(≥70% full-thickness). Ann Surg. 1997;225(5):554-565.
2. Pruitt BA Jr. Protection from excessive resuscitation: “pushing the
pendulum back”. J Trauma. 2000;49(3):567-568.
3. Pruitt BA Jr. The effectiveness of fluid resuscitation. J Trauma. 1979;
19(11 suppl):868-870.
4. Arturson G. Microvascular permeability to macromolecules in
thermal injury. Acta Physiol Scand Suppl. 1979;463:111-122.
5. Pruitt BA Jr, Mason AD Jr, Moncrief JA. Hemodynamic changes in
the early postburn patient: the influence of fluid administration and
of a vasodilator (hydralazine). J Trauma. 1971;11(1):36-46.
6. Baxter CR, Shires T. Physiological response to crystalloid resuscita­
tion of severe burns. Ann N Y Acad Sci. 1968;150(3):874-894.
7. Horton JW. Left ventricular contractile dysfunction as a complication
of thermal injury. Shock. 2004;22(6):495-507.
8. Baskett TF. William O’Shaughnessy, Thomas Latta and the origins of
intravenous saline. Resuscitation. 2002;55(3):231-234.
9. Sneve H. The treatment of burns and skin grafting. J Am Med Assoc.
1905;45(1):1-8.
10. Blalock A. Experimental shock. VII. The importance of the local loss
of fluid in the production of the low blood pressure after burns. Arch
Surg. 1931;22:610-616.
11. Davidson EC. Tannic acid in the treatment of burns. Surg Gynecol
Obstet. 1925;41:202-221.
12. Underhill FP. The significance of anhydremia in extensive superficial
burns. JAMA. 1930;95:852-857.
13. Cancio LC, Kramer GC, Hoskins SL. Gastrointestinal fluid resuscita­
tion of thermally injured patients. J Burn Care Res. 2006;27(5):561-
569.
14. Harkins HN. The treatment of burns in wartime. JAMA.
1942;119(5):385-390.
15. National Research Council, Division of Medical Sciences. Treatment
of burns. War Med (Chic 1941). 1942;2:334-339.
16. Cope O, Moore FD. The redistribution of body water and the fluid
therapy of the burned patient. Ann Surg. 1947;126:1010-1045.
17. Hansen SL. From cholera to “fluid creep”: a historical review of
fluid resuscitation of the burn trauma patient. Wounds. 2008;20(7):
206-213.
18. Cope O, Rhinelander FW. The problem of burn shock complicated by
pulmonary damage. Ann Surg. 1943;117(6):915-928.
19. Stewart CL. The fire at Cocoanut Grove. J Burn Care Res. 2015;36:
232-235.
20. Evans EI, Purnell OJ, Robinett PW, Batchelor A, Martin M.
Fluid and electrolyte requirements in severe burns. Ann Surg.
1952;135:804-817.
21. Reiss E, Stirman JA, Artz CP, Davis JH, Amspacher WH. Fluid and
electrolyte balance in burns. JAMA. 1953;152:1309-1313.
22. Moyer CA, Margraf HW, Monafo WW. Burn shock and extravascular
sodium deficiency – treatment with Ringer’s solution with lactate.
Arch Surg. 1965;90:799-811.
23. Shires GT, Carrico CJ, Coin D. The role of extracellular fluid in shock.
Int Anesthesiol Clin. 1964;2(2):435-454.
24. Shires GT, Cunningham JN, Backer CR, et al. Alterations in cellular
membrane function during hemorrhagic shock in primates. Ann
Surg. 1972;176(3):288-295.
25. Baxter CR. Fluid volume and electrolyte changes of the early post­
burn period. Clin Plast Surg. 1974;1:693-709.
26. Goodwin CW, Dorethy J, Lam V, Pruitt BA Jr. Randomized trial of
efficacy of crystalloid and colloid resuscitation on hemodynamic
response and lung water following thermal injury. Ann Surg.
1983;197(5):520-531.
27. Alvarado R, Chung KK, Cancio LC, Wolf SE. Burn resuscitation.
Burns. 2009;35(1):4-14.
28. Cartotto R. Fluid resuscitation of the thermally injured patient. Clin
Plast Surg. 2009;36(4):569-581.
29. Gibran NS, Wiechman S, Meyer W, et al. American Burn Association
consensus statements. J Burn Care Res. 2013;34:361-385.
30. Anonymous. Advanced Burn Life Support Provider Manual 2011.
Chicago, IL: American Burn Association; 2011.
31. Chung KK, Salinas J, Renz EM, et al. Simple derivation of the initial
fluid rate for the resuscitation of severely burned adult combat casu­
alties: in silico validation of the rule of 10. J Trauma. 2010;69(suppl
1):S49-S54.

86.e2
9  •  Burn Resuscitation
80. Sullivan SR, Friedrich JB, Engrav LH, et al. Opioid creep” is real and
may be the cause of “fluid creep. Burns. 2004;30(6):583-590.
81. Gueugniaud PY, Jauf RM, Bertin-Maghit M, et al. Cerebral oedema
after extensive thermal injury: prognostic significance of early intra­
cranial and cerebral perfusion pressures. Ann Burns Fire Disasters.
1997;10(2):
_2/text/vol10n2p72.htm.
82. Shin C, Kinsky MP, Thomas JA, Traber DL, Kramer GC. Effect of
cutaneous burn injury and resuscitation on the cerebral circulation
in an ovine model. Burns. 1998;24(1):39-45.
83. Reyes R, Guo M, Swann K, et al. Role of tumor necrosis factor-
alpha and matrix metalloproteinase-9 in blood-brain barrier
disruption after peripheral thermal injury in rats. J Neurosurg.
2009;110(6):1218-1226.
84. Gatson JW, Maass DL, Simpkins JW, et al. Estrogen treatment follow­
ing severe burn injury reduces brain inflammation and apoptotic
signaling. J Neuroinflammation. 2009;6:30.
85. Nitzschke SL, Aden JK, Serio-Melvin ML, et al. Wound healing tra­
jectories in burn patients and their impact on mortality. J Burn Care
Res. 2014;35(6):474-479.
86. Orgill DP, Piccolo N. Escharotomy and decompressive therapies in
burns. J Burn Care Res. 2009;30(5):759-768.
87. Pruitt BA. Advances in fluid therapy and the early care of the burn
patient. World J Surg. 1978;2:139-150.
88. Chung KK, Wolf SE, Cancio LC, et al. Resuscitation of severely burned
military casualties: fluid begets more fluid. J Trauma. 2009;67(2):
231-237.
89. Cancio LC, Chavez S, Alvarado-Ortega M, et al. Predicting increased
fluid requirements during the resuscitation of thermally injured
patients. J Trauma. 2004;56(2):404-413.
90. Faraklas I, Cochran A, Saffle J. Review of a fluid resuscitation pro­
tocol: “fluid creep” is not due to nursing error. J Burn Care Res.
2012;33(1):74-83.
91. MacLennan N, Heimbach DM, Cullen BF. Anesthesia for major
thermal injury. J Am Soc Anesthesiol. 1998;89(3):749-770.
92. Ennis JL, Chung KK, Renz EM, et al. Joint Theater Trauma System
implementation of burn resuscitation guidelines improves outcomes
in severely burned military casualties. J Trauma. 2008;64(2 suppl):
S146-S151.
93. Tanaka H, Matsuda T, Miyagantani Y, et al. Reduction of resusci­
tation fluid volumes in severely burned patients using ascorbic
acid administration: a randomized, prospective study. Arch Surg.
2000;135(3):326-331.
94. Dubick MA, Williams C, Elgjo GI, Kramer GC. High-dose vitamin
C infusion reduces fluid requirements in the resuscitation of burn-
injured sheep. Shock. 2005;24(2):139-144.
95. Kahn SA, Beers RJ, Lentz CW. Resuscitation after severe burn injury
using high-dose ascorbic acid: a retrospective review. J Burn Care Res.
2011;32(1):110-117.
96. Neff LP, Allman JM, Holmes JH. The use of therapeutic plasma
exchange (TPE) in the setting of refractory burn shock. Burns.
2010;36(3):372-378.
97. Klein MB, Edwards JA, Kramer CB, et al. The beneficial effects
of plasma exchange after severe burn injury. J Burn Care Res.
2009;30(2):243-248.
98. Chung KK, Lundy JB, Matson JR, et al. Continuous venovenous
hemofiltration in severely burned patients with acute kidney injury:
a cohort study. Crit Care. 2009;13(3):R62.
99. Linden K, Scaravilli V, Kreyer SF, et al. Evaluation of the CytosorbTM
hemoadsorptive column in a pig model of severe smoke and burn
injury. Shock. 2015;44(5):487-495.
100. Salinas J, Chung KK, Mann EA, et al. Computerized decision support
system improves fluid resuscitation following severe burns: an origi­
nal study. Crit Care Med. 2011;39(9):2031-2038.
101. Kramer GC, Kinsky MP, Prough DS, et al. Closed-loop control of fluid
therapy for treatment of hypovolemia. J Trauma Acute Care Surg.
2008;64(4):S333-S341.
102. Salinas J, Drew G, Gallagher J, et al. Closed-loop and decision-
assist resuscitation of burn patients. J Trauma. 2008;64(4 suppl):
S321-S332.
57. Greenhalgh DG. Burn resuscitation: the results of the ISBI/ABA
survey. Burns. 2010;36(2):176-182.
58. Barrow RE, Jeschke MG, Herndon DN. Early fluid resuscitation
improves outcomes in severely burned children. Resuscitation.
2000;45(2):91-96.
59. Kramer GC, Michell MW, Oliveira H, et al. Oral and enteral resuscita­
tion of burn shock the historical record and implications for mass
casualty care. Eplasty. 2010;10.
60. Michell MW, Oliveira HM, Kinsky MP, et al. Enteral resuscitation of
burn shock using World Health Organization oral rehydration solu­
tion: a potential solution for mass casualty care. J Burn Care Res.
2006;27(6):819-825.
61. Fox CL. Oral sodium lactate in treatment of burns and shock. JAMA.
1944;124:207-212.
62. Rae L, Pham TN, Carrougher G, et al. Differences in resuscitation
in morbidly obese burn patients may contribute to high mortality.
J Burn Care Res. 2013;34(5):507.
63. Pham TN, Cancio LC, Gibran NS. American Burn Association
practice guidelines: burn shock resuscitation. J Burn Care Res.
2008;29(1):257-266.
64. Baxter CR. Guidelines for fluid resuscitation. J Trauma. 1981;21(suppl):
687-689.
65. Navar PD, Saffle JR, Warden GD. Effect of inhalation injury on
fluid resuscitation requirements after thermal injury. Am J Surg.
1985;150:716-720.
66. Cancio LC, Jimenez-Reyna JF, Barillo DJ, et al. One hundred ninety-
five cases of high-voltage electric injury. J Burn Care Rehabil.
2005;26(4):331-340.
67. Kaups KL, Davis JW, Dominic WJ. Base deficit as an indicator or
resuscitation needs in patients with burn injuries. J Burn Care
Rehabil. 1998;19(4):346-348.
68. Cancio LC, Galvez E Jr, Turner CE, et al. Base deficit and alveolar-
arterial gradient during resuscitation contribute independently but
modestly to the prediction of mortality after burn injury. J Burn Care
Res. 2006;27(3):289-296.
69. Cartotto R, Choi J, Gomez M, Cooper A. A prospective study on the
implications of a base deficit during fluid resuscitation. J Burn Care
Rehabil. 2003;24(2):75-84.
70. Kamolz LP, Andel H, Schramm W, et al. Lactate: early predictor
of morbidity and mortality in patients with severe burns. Burns.
2005;31(8):986-990.
71. Sánchez M, García-de-Lorenzo A, Herrero E, et al. A protocol for
resuscitation of severe burn patients guided by transpulmonary
thermodilution and lactate levels: a 3-year prospective cohort study.
Crit Care. 2013;17(4):1.
72. Kraft R, Herndon DN, Branski LK, et al. Optimized fluid manage­
ment improves outcomes of pediatric burn patients. J Surg Res.
2013;181(1):121-128.
73. Aboelatta Y, Abdelsalam A. Volume overload of fluid resuscitation
in acutely burned patients using transpulmonary thermodilution
technique. J Burn Care Res. 2013;34(3):349-354.
74. Serio-Melvin ML, Salinas J, Chung KK, et al. Burn shock and resus­
citation: proceedings of a symposium conducted at the meeting of
the American Burn Association, Chicago, IL, 21 April 2015. J Burn
Care Res. 2017;38(1):e423-e431.
75. Maybauer MO, Asmussen S, Platts DG, et al. Transesophageal
echocardiography in the management of burn patients. Burns.
2014;40(4):630-635.
76. Howard TS, Hermann DG, McQuitty AL, et al. Burn induced cardiac
dysfunction increases length of stay in pediatric burn patients.
J Burn Care Res. 2013;34(4):413.
77. Ivy ME, Atweh NA, Palmer J, et al. Intra-abdominal hypertension
and abdominal compartment syndrome in burn patients. J Trauma.
2000;49(3):387-391.
78. Zak AL, Harrington DT, Barillo DJ, et al. Acute respiratory failure
that complicates the resuscitation of pediatric patients with scald
injuries. J Burn Care Rehabil. 1999;20(5):391-399.
79. Sheridan RL, Tompkins RG, McManus WF, Pruitt BA Jr. Intracom­
partmental sepsis in burn patients. J Trauma. 1994;36(3):301-
305.

87
Evaluation of the Burn Wound:
Management Decisions
ELISHA G. BROWNSON and NICOLE S. GIBRAN
10 
body image and affects interpersonal interactions. The
largest organ in the human body, skin is comprised of two
layers: the epidermis and the dermis. Epidermal thickness
varies among different body parts: from 0.05 mm on the
eyelids to over 1 mm on the soles.5 Most skin thickness
comes from the dermis, which varies with age, gender, and
body location.
Epidermis derives from ectoderm; the principal cell is the
keratinocyte, but epidermis also contains melanocytes,
Langerhans cells, Merkel cells, and inflammatory cells.
Keratinocytes begin their division and differentiation at the
stratum basale and migrate progressively outward over 2–4
weeks6 through the stratum spinosum, the stratum granu­
losum, the stratum lucidum, and the stratum corneum, at
which point they are flattened anuclear cornified struc­
tures. In a wound with a sloughed epidermal basal layer,
keratinocytes proliferate and migrate from the wound edges
and epidermal appendages (hair follicles, sweat glands, and
sebaceous glands) to achieve epithelialization. Melanocytes
produce melanin pigment essential for protection against
ultraviolet radiation, and Langerhans cells and other
inflammatory cells perform phagocytosis and antigen pre­
sentation. After injury, melanocytes regenerate more slowly
and less predictably, leading to potential permanent pigment
changes.7,8
Epidermal projections (rete ridges) interdigitate with
dermal projections (papillae) at the basement membrane
zone, which connects the epidermis and dermis via
keratinocyte-derived collagen VII anchoring fibrils, critical
structures that stabilize the epidermal–dermal junction.9,10
Since anchoring fibrils take several months to mature
during wound healing, minor shearing forces cause shear­
ing, blistering, and epidermal loss.
The dermis is comprised of the superficial papillary and
deeper reticular dermis, separated by a capillary plexus that
delivers necessary nutrients to dermal cellular structures.
The abundant extracellular matrix, comprised primarily of
collagen and elastin fibers, provides the dermal structure;
organized collagen fiber orientation provides tensile
strength11 and elastin fibers impart cutaneous elastic recoil
properties. Glycosaminoglycans and proteoglycans, such as
hyaluronic acid and chondroitin sulfate, attract water to
maintain matrix hydration, provide absorption, and regu­
late cellular cross-talk by binding and releasing inflamma­
tory mediators.12,13 Protein turnover, accounting for the
high plasticity of skin, increases with mechanical stress and
responses to injury.14 After wounding, microvascular endo­
thelial cells mediate local and systemic inflammatory
responses and eventually proliferate and migrate to form
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 func­
tional recovery for the burn patient hinges on proper early
management of the burn wound. The greatest advance in
burn care to date has been the institution of early surgical
burn wound excision with an immediate or delayed wound
closure strategy individualized to each patient.1-4 For years,
burns were treated by daily washing, removal of loose dead
tissue, and application of some sort of topical nostrum until
wounds healed or granulated. Superficial dermal burns
healed within 2 weeks, and deep dermal burns healed over
many weeks if infection could be prevented. Full-thickness
burns lost their eschar in 2–6 weeks by bacterial enzyme
production and daily bedside debridement; split-thickness
skin grafts were applied usually 3–8 weeks after injury.
A 50% graft survival rate was acceptable, and repeated
grafting eventually closed the wound. The prolonged and
intense inflammatory response led to hypertrophic scars,
contractures, and considerable physical and psychological
disability.
Burns that heal within 3 weeks generally do so without
significant hypertrophic scarring or functional impairment,
although long-term pigmentation is unpredictable. Burns
needing longer than 3 weeks to heal often result in unsightly
hypertrophic scars and functional impairment. State-of-
the-art burn care now involves early excision and grafting.
The challenge is to define “early.” Knowing which burn
wounds benefit from early excision and grafting requires
understanding of skin biology and pathophysiological
changes caused by thermal injury. In spite of ongoing
efforts to objectively assess wound depth, the standard tech­
nique for determining burn depth in the 21st century
remains clinical assessment of the wound by a burn
specialist.
Pathophysiology of the
Burn Wound
SKIN BIOLOGY
Skin protects against fluid and electrolyte loss, infection,
and radiation and provides thermal regulation. Skin contact
provides clues to the surrounding environment through
touch, perception of temperature, and pain. In addition,
skin appearance is a major determinant of identity and

10  •  Evaluation of the Burn Wound: Management Decisions
88
new vessels during angiogenesis.15 Sensory nerves, which
traverse into the epidermis, also play a significant role after
injury, as they mediate pain and itching, modulate inflam­
mation, and influence the remodeling phase of wound
healing.16,17 The dermis, like other mesoderm-derived struc­
tures, heals not by regeneration but by fibrosis and
scarring.
Pathophysiological Changes of
Thermal Injury
Applied heat at the cellular level causes denaturation of
proteins and loss of plasma membrane integrity. Tempera­
ture and duration of contact have a synergistic effect; cell
necrosis occurs after 1s of exposure at 156°F (69°C), or
after 1h at 113°F (45°C).18 Following a burn, necrosis
occurs at the center of the injury and becomes progressively
less severe at the periphery. Jackson’s description in 1953
of the three zones of injury remains our conceptual under­
standing of the burn wound (Fig. 10.1).19 The zone of
coagulation at the center of the wound has no remaining
viable cells. A mix of viable and nonviable cells, capillary
vasoconstriction, and ischemia characterizes the surround­
ing zone of stasis; this “at-risk” zone may convert to necro­
sis in the presence of hypoperfusion, desiccation, edema, or
infection. Approximately half of the cells in the zone of
stasis undergo apoptosis or necrosis as a result of oxidative
stress, ongoing inflammation, and decreased blood flow due
to microthrombosis.20 Systemic factors such as advanced
age, diabetes, and other chronic illnesses increase risk for
“conversion.” Efforts to enhance wound healing have
focused on prevention of necrosis in the zone of stasis since
medical care has little impact on the outcome of the zone
of coagulation. Protection of this sensitive area is achieved
with adequate fluid resuscitation, avoidance of vasocon­
striction and edema, and prevention of infection.21,22
Optimal wound care consists of nondesiccating dressings,
topical antimicrobials, and regular monitoring of the
wound.23–25 At the periphery of the burn wound, the zone
of hyperemia contains viable cells with vasodilation medi­
ated by local inflammatory mediators. Tissue in this zone
usually recovers unless complicated by infection or
hypoperfusion.
Interest in cooling of the wound to minimize the extent
of injury can be traced to antiquity26 but, firm evidence of
its efficacy is lacking. Cooling immediately after injury
should not supersede other priorities in the evaluation of
the injured patient. The optimal temperature and duration
of cooling is unknown27–29 but excessive or prolonged
cooling may be harmful in that it promotes vasoconstric­
tion and systemic hypothermia.30,31 Current guidelines of
the American Burn Association recommend limiting
cooling to 30 min in the management of minor burns.32
Modalities to improve dermal perfusion and block injury
from released inflammatory mediators have also garnered
much interest. Whereas beneficial effects of many pharma­
cologic agents such as heparin, steroidal and nonsteroidal
anti-inflammatory agents, thromboxane inhibitors, and
epidermal growth factor have been reported,20,33 all remain
investigational since none has demonstrated clinical
validity.
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.34 Burns involving only the outer layers of
the epidermis (first-degree burns) are erythematous and
very painful, but do not form blisters. Most sunburns fit this
category of superficial, epidermal injury. Within 3–4 days,
the dead epidermis sloughs and is replaced by regenerating
keratinocytes. These burns are not included in burn size
calculations for estimates of injury severity and resuscita­
tion fluid estimations.
Superficial dermal burns (superficial second-degree
burns) extend into the papillary dermis and characteristi­
cally form blisters. Blistering may not occur immediately
after injury, and burns initially perceived to be superficial
might subsequently be diagnosed as dermal burns. The
wound bed underlying a blister on a superficial partial
thickness burn is pink, wet, and hypersensitive to touch.
Debriding the blister may be painful due to the currents of
air passing over the wound. These wounds blanch with
pressure because of vasodilation and increased blood flow
in the dermis compared to normal skin. With appropriate
wound care, superficial dermal burns usually heal within 2
weeks without risk of scarring and therefore do not require
operation.
Deep dermal burns (deep second-degree burns) extend
into the reticular dermis and generally take 3 or more
weeks to heal. They blister, but the underlying wound
surface appears mottled pink and white immediately fol­
lowing the injury (Fig. 10.2A). 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 postburn day 2, the wound may be white
and dry (Fig. 10.2B). As a rule, most partial-thickness
Fig. 10.1  Jackson’s three zones of injury on an ankle burn: (A) the zone
of coagulation; (B) the zone of stasis, and (C) the zone of hyperemia.

10  •  Evaluation of the Burn Wound: Management Decisions
89
ADJUNCTS TO CLINICAL EVALUATION
The search for technologies to obtain a more precise method
to diagnose burn depth surged when the benefits of early
operation were recognized. Multiple modalities have been
trialed, including thermography, photometry, nuclear
imaging, pulse-echo ultrasound, and, more invasive than
the aforementioned, serial tissue biopsy.43–45 These tech­
niques take advantage of the ability to detect dead cells or
denatured collagen (biopsy, ultrasound, vital dyes)19,46–49;
wound color (light reflectance)50; physical changes, such as
edema (magnetic resonance imaging)51; and altered blood
flow (fluorescein, laser Doppler imaging, and thermogra­
phy).52–54 Unfortunately, none of these techniques has
proved superior to serial clinical assessment by an experi­
enced burn provider. Several groups have recently reported
clinical benefit with the use of noncontact laser Doppler
imaging in indeterminate thickness burns.37,43,55 This tech­
nique provides a color perfusion map of the burn that can
be assessed without direct contact with the skin surface,
making this test well tolerated; furthermore, serial exams
can track dynamic changes in wound bed perfusion.
Although identified as an accurate measurement tool, non­
contact laser Doppler imaging remains an adjunct, rather
than a substitute, for clinical assessment.56
Mechanisms of Thermal Injury
FLASH AND FLAME BURNS
Flash and flame burn injuries represent approximately 40%
of the admissions to American regional burn centers.57
Explosions of natural gas, propane, gasoline, and other
flammable liquids cause intense heat for a very brief time,
causing flash burns. Flash burns often result from an inap­
propriate use of a flammable liquid as a fire accelerant on
camp, trash, and brush fires. For the most part, flash burns
reach progressive layers of the dermis in proportion to the
amount and kind of fuel involved. Gasoline, especially, has
highly flammable vapors that are 3–4 times denser than air.
At room temperature, gasoline vapors diffuse above ground
and accumulate in enclosed spaces. Clothing, unless it
ignites, is protective in flash burns. Thus, a flash burn injury
distribution typically involves exposed skin, with the deepest
areas facing the source of ignition. If a flash burn causes
clothing or hair to catch on fire, the injury will be more
typical of a flame burn. Whereas such flash burns generally
heal without extensive skin grafting, they may cover large
areas and may be associated with thermal injury to the
upper airway.
Flame burns invariably involve deep dermal or full-
thickness injury because of 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 usually sustain some full-thickness burns.
Victims of house fires with prolonged exposure to flames or
heat due to immobility, intoxication, or confusion caused by
hypoxemia or carbon monoxide toxicity are also prone to
burns that have not healed by 3 weeks should be excised
and grafted.
The most difficult management decision involves inter­
mediate partial-thickness burns. The determining factor as
to whether these burns heal in 3 weeks may be less than a
millimeter. These burns are aptly called “indeterminate”
burns because their healing potential becomes evident with
serial assessments over several days after injury. Histologic
studies suggest that burn injury is a dynamic process that
peaks around 3 days after injury.35–37 Initial evaluation by
an experienced surgeon as to whether an indeterminate
dermal burn will heal in 3 weeks is only 50%–70%
accurate.38–40
Partial thickness scald burns usually should be
managed nonoperatively for 10–14 days, unless they are
obviously full thickness. However, these burns should
be excised and grafted once it is clear that they will not
heal by 3 weeks.41 Serial clinical exams for partial thick­
ness burns for 2 weeks after injury have been associated
with excision of significantly smaller areas or avoidance of
surgery entirely.
Full-thickness burns (third-degree burns) involve the
entire cutaneous layer and may extend into the superficial
subcutaneous tissue. Their appearance may be charred,
leathery, dry, firm, and depressed when compared to adjoin­
ing normal skin. Noncharred 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
appear translucent with clotted vessels visible. These
wounds are insensate to light touch and pinprick. Some
full-thickness burns, particularly immersion scalds or
“bake” injuries (caused by convective heat), may have a red
appearance and can be confused with a superficial dermal
burn by an inexperienced observer; these burns do not
blanch with pressure. Most full-thickness burns should
undergo early excision and grafting to minimize infection
and hypertrophic scarring and to expedite patient recovery.
Deeper burns that involve adipose tissue (fourth-degree
burns), muscle (fifth-degree burns), and bone (sixth-degree
burns) also require surgical management.42
a
b
Fig. 10.2  Lower extremity deep dermal burn: (A) on day of presenta­
tion wound has a wet, pink and moist appearance; (B) on day 3 post-
injury wound has a mottled appearance with both moist pink and dry
white areas.

10  •  Evaluation of the Burn Wound: Management Decisions
90
indeterminate dermal burns. A common example is a
toddler who reaches above head level and spills hot water;
his face bears a superficial burn, the trunk burn is of inde­
terminate thickness, and skin under his diaper has a deep
dermal burn.
Immersion scalds are often deep because of prolonged
skin exposure, although the water temperature may not be
as high as with spill scalds.59,60 They occur in individuals
who do not perceive the discomfort of prolonged immersion
(i.e., diabetic patients or spinal cord injury patients with
peripheral neuropathy), or who are not able to escape from
the hot water (i.e., young children, elderly, or people with
physical and cognitive disabilities). This latter group of vul­
nerable individuals is susceptible to nonaccidental scald
burns,61,62 which account for about 2% of all children
admitted to our burn center. Circumferential extremity
injuries, symmetrical burns to a child’s buttocks and
perineum represent a few injury characteristics that should
raise suspicion of nonaccidental trauma (Fig. 10.3). Allega­
tions of abuse should include expert burn wound assess­
ment by an experienced burn surgeon who is familiar with
burn distribution and etiologies.
Grease and hot oils cause deep dermal or full-thickness
injuries. During cooking, grease and hot oils are usually
heated to a level below their smoke point to avoid unpleas­
ant odors from their decomposition. The smoke point is
350°F (177°C) for butter, 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). Domestic grease burns occur in a
have deeper burns. 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 inappro­
priately when trying to escape.58 Loss of consciousness
exposes victims 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, representing approximately one third
of cases.57 Despite educational programs, the epidemiology
and incidence of scalds worldwide has changed very little.
The depth of scald injury depends on the water tempera­
ture, skin thickness, and duration of contact. Water at
140°F (60°C) creates a deep dermal burn in 3 s but causes
the same injury in 1 s at 156°F (69°C).(18) Freshly brewed
coffee from an automatic percolator is generally about
180°F (82°C). Once in the pot, coffee temperature approxi­
mates 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 due to proteins and oil,
remain in contact longer with the skin and invariably cause
deep dermal burns. Exposed areas tend to incur shallower
burns because clothing (such as diapers and socks) retains
heat and keeps the liquid in contact with the skin longer.
Consequently, scalds are often a mosaic of superficial and
B
A
Fig. 10.3  Immersion scald burns: (A) on a child; arrows denote sparing of bilateral popliteal fossae: the child by reflex bent his knees to avoid contact
with the hot water; (B) pattern of nonaccidental trauma: line denotes water level, note soles of feet and buttocks are spared as they were pressed
against the bottom of the tub.

10  •  Evaluation of the Burn Wound: Management Decisions
91
burn must be considered. Deep palm burns may epithelial­
ize from the wound edges, allowing granulation tissue
development to lead to palmar contracture and permanent
disability. However, burn excision and grafting with either
thick split-thickness or full-thickness grafts67,68 results in
loss of sensory nerve endings unique to glabrous skin
(Pacinian and Meissner’s corpuscles). Therefore, an obser­
vation period of 3–4 weeks with meticulous wound care
and aggressive exercise provides a prudent compromise.
CHEMICAL BURNS
Chemical burns caused by strong acids or alkalis often
result from industrial accidents, drain cleaners, assaults,
and the improper use of harsh solvents. Chemical burns
cause progressive tissue damage until the chemicals are
inactivated by reaction with the tissue or by dilution by
copious water. Although 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. Conversely, alkali
combines with cutaneous lipids to create soap and thereby
continues “dissolving” tissue until it the reagent is neutral­
ized. A full-thickness chemical burn may appear deceptively
superficial, clinically appearing as a mild brownish discol­
oration of the skin (Fig. 10.5). The skin may appear intact
for the first few days postburn and later will slough
spontaneously.
Initial management consists of diluting the agent with
copious water for at least 15–20 min, preferably at the site
of the accident; to this end, many industrial workplaces are
now equipped with showers and eye wash stations. An
important exception to immediate irrigation is exposure to
a chemical powder, such as dry concrete, cement, and
sodium hydroxide; in this instance, it is critical to brush the
predictable pattern, attributed to patients trying to carry
the burning pan of grease outdoors instead of putting the
lid on the pan and extinguishing the fire. The majority of
patients sustain an isolated upper extremity burn, but inju­
ries may involve the face, lower extremities, or trunk.
Approximately 30%–40% of grease burns require excision
and grafting.63,64
Tar and asphalt represent a special kind of scald. The
“mother pot” at the back of the roofing truck maintains tar
at a temperature of 400–500°F (204–260°C). Burns
caused by tar directly from the “mother pot” are invariably
full-thickness. By the time tar is spread on the roof, its tem­
perature has diminished to the point where most of the
burns are deep dermal in nature. Initial evaluation and
injury depth assessment requires tar removal with applica­
tion of a petroleum-based ointment that is reapplied every
2–4 hours until the tar has dissolved. Medi-Sol adhesive
remover spray (Orange-Sol, Gilbert, AZ, USA) successfully
removes tar without injury to the burn wound.
CONTACT BURNS
Contact burns resulting from hot metals, plastic, glass, or
hot coals are generally small but are challenging in that the
injury is often very deep (Fig. 10.4). The temperature of the
material and the duration of contact determine burn depth.
Molten materials in industrial accidents instantaneously
cause a burn extending below the dermis. An unconscious
victim with prolonged contact to a hot surface will often
sustain 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 circumstances, the clinician must anticipate the
possibility of extensive myonecrosis and myoglobinuria
despite the relative small size of the wound. Contact burns
with a hot muffler or engine block are usually full-thickness
and often require serial surgeries to achieve wound closure.65
In toddlers, contact burns often involve palms and fingers
when the child puts his hands on a wood-stove, fireplace
insert, clothing iron, or oven door.66 With aggressive wound
care and hand stretching, most intermediate-depth palm
burns heal in about 3–4 weeks. Beyond this time, careful
consideration of management of the unhealed deep palm
Fig. 10.4  Deep contact burn in an elderly patient who was uncon­
scious next to a space heater. Arrows denote the imprints of the space
heater grill on his lateral thigh.
Fig. 10.5  Chemical burn on lower extremity from cement. The discol­
oration of the skin is characteristic of a full-thickness chemical burn.

10  •  Evaluation of the Burn Wound: Management Decisions
92
parts including fingers, hands, forearms, and feet also gen­
erate more intense heat with less dissipation and subse­
quently sustain more injury than the trunk, which may
dissipate enough current to prevent extensive damage to
internal viscera (unless the contact wound is on the
abdomen or chest).84–86 Arc electrical burns that result
because current takes the most direct path occur at joints
in close apposition at the time of injury, such as the popli­
teal fossa with a bent knee, the antecubital fossa with a
flexed elbow, and the axilla with the shoulder adducted.
There are two indications for early operation in a patient
with electrical burns: acidosis or myoglobinuria that will
not clear with standard resuscitation techniques or the
development of compartment syndrome. In these circum­
stances, urgent fasciotomy, major debridement, and ampu­
tation may be needed. If immediate decompression or
debridement is not required, definitive operations can be
performed 3–5 days after injury, before bacterial contami­
nation occurs and after the tissue necrosis is delineated.87,88
Extraordinary measures, such as vascular grafting for
clotted arteries or free tissue transfer may sometimes be
indicated,89,90 but the zone of injury should be defined
before assuming that vascular anastomoses will remain
patent. Extensive operative salvage in lieu of a well-fitting
prosthesis may increase morbidity and prolong the patient’s
recovery.
Complete references available online at

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 conven­
tional 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 patho­
physiologic 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.
agent off before irrigation since moisture activates the
chemical. A paper pH test applied to the burn surface can
verify that the agent has been neutralized. Attempts to neu­
tralize alkalis with acids (and vice-versa) are contraindi­
cated because the ensuing exothermic reaction leads to a
thermal injury superimposed on the chemical burn.
Hydrofluoric acid represents a unique and very destruc­
tive chemical, one that is widely used in the circuit board
etching process, cleaning solvents, and paint removers.
Fluoride ions penetrate the skin, binding with cellular
calcium and magnesium and causing progressive deep
tissue destruction as sequential cells undergo necrosis.69,70
Fluoride is also a metabolic poison that inhibits key enzymes
of cellular metabolism. A 10% TBSA hydrofluoric acid burn
may be life-threatening due to systemic hypocalcemia71
and may indicate urgent surgical wound excision. A patient
may not become symptomatic for several hours after expo­
sure, when severe pain develops in the involved fingers;
unfortunately, delayed or inadequate treatment may lead to
amputation. Older recommendations of calcium-containing
topical gels and direct injection of calcium gluconate into
the involved tissue72,73 have largely been replaced by intra-
arterial infusion of calcium gluconate74–77 which results in
immediate cessation of pain and minimal tissue destruction
and may be discontinued when acute symptoms resolve.
ELECTRICAL BURNS
Electrical burns are thermal burns from very high-intensity
heat generated as the patient’s body becomes an accidental
resistor. Many electrical burns are work-related (i.e., con­
struction workers, field workers, linemen, utility and elec­
trical workers). Evaluation of the injured patient in these
settings must account for associated trauma because these
injuries may have occurred in association with associated
myoclonic contractions or a fall.
Low-voltage injuries (<440 volts) rarely cause significant
damage beyond deep thermal burns at contact points. An
exception is the child who chews on an active electrical
connection78; the child’s saliva completes the circuit
between the positive and neutral leads, causing a severe
burn inside the mouth and lip. Eschar separation at the
oral commissure 7–10 days after injury may be associated
with brisk labial artery bleeding that requires hemostasis
by digital pressure to the corner of the mouth.79 Burns
involving the oral commissure are at high risk for late con­
tracture and warrant an aggressive splinting and exercise
regimen.80,81
High-voltage injuries (>1000 volts) are more apt to cause
deep tissue destruction. In this setting, extensive deep tissue
destruction may take place underneath a relatively small,
innocuous-appearing wound (Fig. 10.6). High resistance at
skin contact points is partially protective because a dry cal­
loused hand may provide twice the resistance of normal
skin and five times the resistance of wet skin. High resis­
tance within the body causes more harm due to conversion
of electrical energy to heat in proportion to current and
electrical resistance. Hence even when superficial muscle
appears uninjured, deep muscle necrosis may occur adja­
cent to bone, which has high resistance.82,83 Smaller body
A
B
Fig. 10.6  High-voltage contact point on a hand: (A) prior to, and (B)
after débridement. Once wound is debrided, much deeper injury to
tendon and bone is revealed.

92.e1
10  •  Evaluation of the Burn Wound: Management Decisions
29. King TC, Price PB. Surface cooling following extensive burns. JAMA.
1963;183:677-678.
30. Purdue GF, Layton TR, Copeland CE. Cold injury complicating burn
therapy. J Trauma. 1985;25(2):167-168.
31. Sawada Y, Urushidate S, Yotsuyanagi T. Ishita K. Is prolonged and exces­
sive cooling of a scalded wound effective? Burns. 1997;23(1):55-58.
32. American Burn Association. Practice guidelines for burn care. J Burn
Care Rehabil. 2001;(suppl):10s-13s.
33. Robson MC, Kucan JO, Paik KI, Eriksson E. Prevention of dermal
ischemia after thermal injury. Arch Surg (Chicago, IL: 1960).
1978;113(5):621-625.
34. Forage AV. The history of the classification of burns (diagnosis of
depth). Br J Plast Surg. 1963;16:239-242.
35. Boykin JV, Eriksson E, Pittman RN. In vivo microcirculation of a scald
burn and the progression of postburn dermal ischemia. Plast Reconstr
Surg. 1980;66(2):191-198.
36. Nanney LB, Wenczak BA, Lynch JB. Progressive burn injury doc­
umented with vimentin immunostaining. J Burn Care Rehabil.
1996;17(3):191-198.
37. 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.
38. Hlava P, Moserova J, Konigova R. Validity of clinical assessment of the
depth of a thermal injury. Acta Chir Plast. 1983;25(4):202-208.
39. Niazi ZB, Essex TJ, Papini R, et al. New laser Doppler scanner, a valu­
able adjunct in burn depth assessment. Burns. 1993;19(6):485-489.
40. Yeong EK, Mann R, Goldberg M, Engrav L, Heimbach D. Improved
accuracy of burn wound assessment using laser Doppler. J Trauma.
1996;40(6):956-961, discussion 961-962.
41. 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.
42. Dupuytren G. Clinical Lectures on Surgery: Delivered at Hotel Dieu,
in 1832 [Doane SA, Trans.]. Boston: Carter, Hendee, & Company;
1833:326.
43. Jaskille AD, Ramella-Roman JC, Shupp JW, Jordan MH, Jeng JC. Criti­
cal review of burn depth assessment techniques: part II. Review of
laser doppler technology. J Burn Care Res. 2010;31(1):151-157.
44. Jaskille AD, Shupp JW, Jordan MH, Jeng JC. Critical review of burn
depth assessment techniques: part I. Historical review. J Burn Care
Res. 2009;30(6):937-947.
45. Hoeksema H, Van de Sijpe K, Tondu T, et al. Accuracy of early burn
depth assessment by laser Doppler imaging on different days post
burn. Burns. 2009;35(1):36-45.
46. Ho-Asjoe M, Chronnell CM, Frame JD, Leigh IM, Carver N. Immu­
nohistochemical analysis of burn depth. J Burn Care Rehabil.
1999;20(3):207-211.
47. Moserova J, Hlava P, Malinsky J. Scope for ultrasound diagnosis of
the depth of thermal damage. Preliminary report. Acta Chir Plast.
1982;24(4):235-242.
48. Cantrell JH Jr. Can ultrasound assist an experienced surgeon in esti­
mating burn depth? J Trauma. 1984;24(9 suppl):S64-S70.
49. Kaufman T, Hurwitz DJ, Heggers JP. The india ink injection tech­
nique to assess the depth of experimental burn wounds. Burns.
1984;10(6):405-408.
50. Heimbach DM, Afromowitz MA, Engrav LH, Marvin JA, Perry B. Burn
depth estimation: man or machine. J Trauma. 1984;24(5):373-378.
51. Koruda MJ, Zimbler A, Settle RG, et al. Assessing burn wound
depth using in vitro nuclear magnetic resonance (NMR). J Surg Res.
1986;40(5):475-481.
52. Black KS, Hewitt CW, Miller DM, et al. Burn depth evaluation with fluo­
rometry: is it really definitive? J Burn Care Rehabil. 1986;7(4):313-317.
53. Pape SA, Skouras CA, Byrne PO. An audit of the use of laser Doppler
imaging (LDI) in the assessment of burns of intermediate depth.
Burns. 2001;27(3):233-239.
54. Hackett ME. The use of thermography in the assessment of depth of
burn and blood supply of flaps, with preliminary reports on its use in
Dupuytren’s contracture and treatment of varicose ulcers. Br J Plast
Surg. 1974;27(4):311-317.
55. Jeng JC, Bridgeman A, Shivnan L, et al. Laser Doppler imaging deter­
mines need for excision and grafting in advance of clinical judgment:
a prospective blinded trial. Burns. 2003;29(7):665-670.
56. Shin JY, Yi HS. Diagnostic accuracy of laser Doppler imaging in
burn depth assessment: systematic review and meta-analysis. Burns.
2016;42(7):1369-1376.
References
1. Burke JF, Bondoc CC, Quinby WC. Primary burn excision and immediate
grafting: a method shortening illness. J Trauma. 1974;14(5):389-395.
2. Engrav LH, Heimbach DM, Reus JL, Harnar TJ, Marvin JA. Early exci­
sion and grafting vs. nonoperative treatment of burns of indetermi­
nant depth: a randomized prospective study. J Trauma. 1983;23(11):
1001-1004.
3. Thompson P, Herndon DN, Abston S, Rutan T. Effect of early excision
on patients with major thermal injury. J Trauma. 1987;27(2):205-207.
4. Gray DT, Pine RW, Harnar TJ, et al. Early surgical excision versus
conventional therapy in patients with 20 to 40 percent burns. A com­
parative study. Am J Surg. 1982;144(1):76-80.
5. Southwood WF. The thickness of the skin. Plast Reconstr Surg (1946).
1955;15(5):423-429.
6. Rudolph R, Ballantyne DL Jr. McCarthy J, eds. Skin Grafts. Philadel­
phia: WB Saunders; 1990:221-274.
7. Tyack ZF, Pegg S, Ziviani J. Postburn dyspigmentation: its assessment,
management, and relationship to scarring: a review of the literature.
J Burn Care Rehabil. 1997;18(5):435-440.
8. de Chalain TM, Tang C, Thomson HG. Burn area color changes after
superficial burns in childhood: can they be predicted? J Burn Care
Rehabil. 1998;19(1 Pt 1):39-49.
9. Compton CC, Press W, Gill JM, et al. The generation of anchoring
fibrils by epidermal keratinocytes: a quantitative long-term study. Epi­
thelial Cell Biol. 1995;4(3):93-103.
10. Regauer S, Seiler GR, Barrandon Y, Easley KW, Compton CC. Epithelial
origin of cutaneous anchoring fibrils. J Cell Biol. 1990;111(5 Pt 1):
2109-2115.
11. Yannas IV, Burke JF. Design of an artificial skin. I. Basic design prin­
ciples. J Biomed Mater Res. 1980;14(1):65-81.
12. Yannas IV, Burke JF, Gordon PL, Huang C, Rubenstein RH. Design of
an artificial skin. II. Control of chemical composition. J Biomed Mater
Res. 1980;14(2):107-132.
13. Tredget EE, Levi B, Donelan MB. Biology and principles of scar man­
agement and burn reconstruction. Surg Clin North Am. 2014;94(4):
793-815.
14. Wong VW, Gurtner GC, Longaker MT. Wound healing: a paradigm for
regeneration. Mayo Clin Proc. 2013;88(9):1022-1031.
15. Gibran NS, Heimbach DM. Current status of burn wound pathophysi­
ology. Clin Plast Surg. 2000;27(1):11-22.
16. Crowe R, Parkhouse N, McGrouther D, Burnstock G. Neuropeptide-
containing nerves in painful hypertrophic human scar tissue. Br J
Dermatol. 1994;130(4):444-452.
17. Dunnick CA, Gibran NS, Heimbach DM. Substance P has a role in
neurogenic mediation of human burn wound healing. J Burn Care
Rehabil. 1996;17(5):390-396.
18. Moritz AR, Henriques FC. Studies of thermal injury: II. The relative
importance of time and surface temperature in the causation of cuta­
neous burns. Am J Pathol. 1947;23(5):695-720.
19. Jackson DM. The diagnosis of the depth of burning. Br J Surg.
1953;40(164):588-596.
20. 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):849-873.
21. Rico RM, Ripamonti R, Burns AL, Gamelli RL, DiPietro LA. The effect
of sepsis on wound healing. J Surg Res. 2002;102(2):193-197.
22. Knabl JS, Bauer W, Andel H, et al. Progression of burn wound depth
by systemical application of a vasoconstrictor: an experimental study
with a new rabbit model. Burns. 1999;25(8):715-721.
23. Winter GD. Formation of the scab and the rate of epithelisation
of superficial wounds in the skin of the young domestic pig. 1962.
J Wound Care. 1995;4(8):366-367, discussion 368-371.
24. Hinman CD, Maibach H. Effect of air exposure and occlusion on exper­
imental human skin wounds. Nature. 1963;200:377-378.
25. Palmieri TL, Greenhalgh DG. Topical treatment of pediatric patients
with burns: a practical guide. Am J Clin Dermatol. 2002;3(8):529-534.
26. Davies JW. Prompt cooling of burned areas: a review of benefits and
the effector mechanisms. Burns. 1982;9(1):1-6.
27. Boykin JV Jr, Eriksson E, Sholley MM, Pittman RN. Cold-water treat­
ment of scald injury and inhibition of histamine-mediated burn
edema. J Surg Res. 1981;31(2):111-123.
28. Demling RH, Mazess RB, Wolberg W. The effect of immediate and
delayed cold immersion on burn edema formation and resorption.
J Trauma. 1979;19(1):56-60.

92.e2
10  •  Evaluation of the Burn Wound: Management Decisions
75. Vance MV, Curry SC, Kunkel DB, Ryan PJ, Ruggeri SB. Digital hydro­
fluoric acid burns: treatment with intraarterial calcium infusion. Ann
Emerg Med. 1986;15(8):890-896.
76. Velvart J. Arterial perfusion for hydrofluoric acid burns. Hum Toxicol.
1983;2(2):233-238.
77. Pegg SP, Siu S, Gillett G. Intra-arterial infusions in the treatment of
hydrofluoric acid burns. Burns. 1985;11(6):440-443.
78. Rai J, Jeschke MG, Barrow RE, Herndon DN. Electrical injuries: a
30-year review. J Trauma. 1999;46(5):933-936.
79. 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.
80. Holt GR, Parel S, Richardson DS, Kittle PE. The prosthetic manage­
ment of oral commissure burns. Laryngoscope. 1982;92(4):407-411.
81. 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.
82. Chilbert M, Maiman D, Sances A Jr, et al. Measure of tissue resistivity
in experimental electrical burns. J Trauma. 1985;25(3):209-215.
83. Lee RC, Kolodney MS. Electrical injury mechanisms: dynamics of the
thermal response. Plast Reconstr Surg. 1987;80(5):663-671.
84. Yang JY, Tsai YC, Noordhoff MS. Electrical burn with visceral injury.
Burns. 1985;11(3):207-212.
85. Branday JM, DuQuesnay DR, Yeesing MT, Duncan ND. Visceral com­
plications of electrical burn injury. A report of two cases and review
of the literature. West Indian Med J. 1989;38(2):110-113.
86. 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.
87. Mann R, Gibran N, Engrav L, Heimbach D. Is immediate decompres­
sion of high voltage electrical injuries to the upper extremity always
necessary? J Trauma. 1996;40(4):584-587, discussion 587-589.
88. Yowler CJ, Mozingo DW, Ryan JB, Pruitt BA Jr. Factors contribut­
ing to delayed extremity amputation in burn patients. J Trauma.
1998;45(3):522-526.
89. Bartle EJ, Wang XW, Miller GJ. Early vascular grafting to prevent upper
extremity necrosis after electrical burns: anastomotic false aneurysm,
a severe complication. Burns. 1987;13(4):313-317.
90. Wang XW, Bartle EJ, Roberts BB, et al. Free skin flap transfer in repair­
ing deep electrical burns. J Burn Care Rehabil. 1987;8(2):111-114.
57. American Burn Association. 2016 National Burn Repository: Report
of Data from 2006–2015. Chicago: 2016.
58. Byrom RR, Word EL, Tewksbury CG, Edlich RF. Epidemiology of flame
burn injuries. Burns. 1984;11(1):1-10.
59. Ding YL, Pu SS, Pan ZL, et al. Extensive scalds following accidental
immersion in hot water pools. Burns. 1987;13(4):305-308.
60. Walker AR. Fatal tapwater scald burns in the USA, 1979–86. Burns.
1990;16(1):49-52.
61. Kumar P. Child abuse by thermal injury – a retrospective survey.
Burns. 1984;10(5):344-348.
62. Bird PE, Harrington DT, Barillo DJ, et al. Elder abuse: a call to action.
J Burn Care Rehabil. 1998;19(6):522-527.
63. Klein MB, Gibran NS, Emerson D, et al. Patterns of grease burn injury:
development of a classification system. Burns. 2005;31(6):765-767.
64. Murphy JT, Purdue GF, Hunt JL. Pediatric grease burn injury. Arch
Surg (Chicago, IL: 1960). 1995;130(5):478-482.
65. Gibran NS, Engrav LH, Heimbach DM, Swiontkowski MF, Foy HM.
Engine block burns: Dupuytren’s fourth-, fifth-, and sixth-degree
burns. J Trauma. 1994;37(2):176-181.
66. Yanofsky NN, Morain WD. Upper extremity burns from woodstoves.
Pediatrics. 1984;73(5):722-726.
67. Pensler JM, Steward R, Lewis SR, Herndon DN. Reconstruction of the
burned palm: full-thickness versus split-thickness skin grafts–long-
term follow-up. Plast Reconstr Surg. 1988;81(1):46-49.
68. Merrell SW, Saffle JR, Schnebly A, Kravitz M, Warden GD. Full-thick­
ness skin grafting for contact burns of the palm in children. J Burn
Care Rehabil. 1986;7(6):501-507.
69. Bertolini JC. Hydrofluoric acid: a review of toxicity. J Emerg Med.
1992;10(2):163-168.
70. Anderson WJ, Anderson JR. Hydrofluoric acid burns of the hand: mech­
anism of injury and treatment. J Hand Surg Am. 1988;13(1):52-57.
71. Mayer TG, Gross PL. Fatal systemic fluorosis due to hydrofluoric acid
burns. Ann Emerg Med. 1985;14(2):149-153.
72. Bracken WM, Cuppage F, McLaury RL, Kirwin C, Klaassen CD. Com­
parative effectiveness of topical treatments for hydrofluoric acid
burns. J Occup Med. 1985;27(10):733-739.
73. Chick LR, Borah G. Calcium carbonate gel therapy for hydrofluoric
acid burns of the hand. Plast Reconstr Surg. 1990;86(5):935-940.
74. Siegel DC, Heard JM. Intra-arterial calcium infusion for hydrofluoric
acid burns. Aviat Space Environ Med. 1992;63(3):206-211.

93
Treatment of Infection in
Burn Patients
JANOS CAMBIASO-DANIEL, JAMES J. GALLAGHER, WILLIAM B. NORBURY, CELESTE C.
FINNERTY, DAVID N. HERNDON, and DEREK M. CULNAN
11 
reduction in colony counts, breaks down and removes bio­
films, and purges the devitalized tissue that pathogens thrive
upon.8 Systemic antimicrobials kill and suppress the invad­
ing pathogens accessing perfused areas of tissue. Quantita­
tive wound culturing enables effective diagnosis and directed
application of the most efficacious antimicrobial with the
lowest toxicity. Coordinated critical care, therapy, and nutri­
tion ensure that the wounds have a sufficient supply of
nutrients and immune-cell–laden blood to clear pathogens,
expand skin grafts, and reepithelialize wounds.
Prevention of Infection
Prevention is the optimal way to minimize infection.9 Patho­
gens can be carried into or transmitted around the unit by
staff, by visitors, or on equipment. Patients should have
single rooms separated from other rooms by a door. Positive
pressure in the rooms further aids in minimizing bacterial
contamination. Patient rooms should undergo a daily
cleaning in addition to deep cleaning upon patient dis­
charge. This terminal cleaning should include washing the
walls and ceiling and should be done 72 hours prior to
admitting another patient to avoid the transfer of more
virulent strains.10 Another important prevention measure
is the use of contact precautions with all patients, including
gowns and gloves. These items should be donned before
entering and doffed prior to exiting the room, regardless of
the bacteriological status of the particular patient. Routine
hand hygiene before and after patient interaction is also
mandatory to prevent infection. Dressing materials, sup­
plies, devices, and equipment must not be shared between
patients. Bathing, showering, tubbing, mobile diagnostic
equipment, and operating facilities should be decontami­
nated between each patient use. Furthermore, fomites, such
as ties, rings, watches, and cell phones, should be prohibited
since these are possible pathogen vectors.11,12 Water and air
filters ought to screen particles down to 0.2 and 0.3 µm,
respectively, be changed monthly, and be cultured routinely
as part of infection control monitoring. By maintaining
these strict measures, transmission of infectious organisms
between patients can be limited.13
Diagnosis of Burn
Wound Infection
Diagnosis of burn infection in burn wounds can be compli­
cated. The typical cytokine and immune cascades that
Introduction
Skin is the first immune defense mechanism and functions
as a barrier against microorganisms. Infections are a signifi­
cant problem once open wounds compromise this barrier.
According to the U.S. National Burn Repository, the four
leading causes of burn morbidity are (1) pneumonia, (2)
cellulitis, (3) urinary tract infections, and (4) burn wound
infections. Infections are a primary factor contributing to
mortality, accounting for 51% of deaths in burn patients,
as discussed in both Chapters 30 and 32, on multisystem
organ failure and critical care, respectively.1–3
A cutaneous burn is initially sterile as commensal skin
flora are killed with the skin in the thermal event. Unfortu­
nately the burn wound provides optimal bacterial growth
conditions due to a reduced blood supply and a nutrient-
rich environment, leading to rapid wound colonization.
The 2007 American Burn Association Consensus Confer­
ence defined wound colonization as follows: (1) low con­
centrations of bacteria on the wound surface, (2) absence
of invasive infection, and (3) less than 105 organisms per
gram tissue.3 In a superficial burn, skin flora can survive in
hair follicles and sebaceous glands in the same manner as
keratinocytes to repopulate a physiological microbiome.4-6
However, burns are customarily colonized by pathogens
from the environment, the patient’s gut, or the naso-
oropharyngeal tract.
A race thus exists between the patient and the pathogen
to dominate the wound surface. In the log phase growth,
bacteria double 2–3 times per hour; consequently a single
bacterium can become 10 million in 1 day, far faster than
any human cell can multiply.7 Therefore colonization can
quickly become an infection capable of converting partial-
thickness into full-thickness burns by causing vessel throm­
bosis and necrosis in viable tissues in the wound penumbra.
Gram-positive bacteria tend to colonize an affected area first,
with subsequent colonization by gram-negative bacteria.
Delayed treatment risks colonization by extended-spectrum
pathogens, bloodstream invasion, and the development of
sepsis, all of which increase the likelihood of death.2
The model of burn care advocated throughout this text is
to rig this race for wound dominance in favor of the patient.
Early wound excision eliminates the devitalized tissue that is
the main reservoir for pathogen nourishment and habitat.
Prompt autografting reestablishes skin barrier function and
denies pathogens access to the host. Topical antimicrobials
suppress bacterial growth and colony counts while allowing
host fibroblasts and keratinocytes to proliferate and cover
the wound. Assiduous washing technique allows 2-log

11  •  Treatment of Infection in Burn Patients
94
of invasion is present, systemic antibiotics should be admin­
istered and the wound excised.6,19,20
Studies by Robson demonstrated that if burn wound
colony counts from biopsies or after cleaning of the surface
of the wound are greater than 105/g tissue, the graft sur­
vival rate is only 19%, whereas colony counts of less than
105/g tissue are associated with a 94% chance of graft sur­
vival.21 Sensitivities to available antibiotics, both systemic
and topical, should instruct therapy. In the setting of resis­
tant organisms, antibiotic synergy testing is advised. Thus
the ultimate diagnosis of burn wound infection and the
guidance of antimicrobials are directed by culture data.
Physical examination of the patient also provides valu­
able insight into the infectious nature of the burn wound.
Burn wound erythema is a physiologic phenomenon pro­
duced sterilely by the liberation of inflammatory mediators
from tissues surrounding the burn area and must not be
confused with cellulitis. Normally this erythema presents
within 2–3 days of the burn injury and resolves by 1 week
post burn (Fig. 11.2). The best differential diagnosis comes
from clinical palpation: erythema lacks significant indura­
tion or tenderness compared to an infectious process like
cellulitis.8
Cellulitis is a noninvasive infection of the tissues sur­
rounding the burn wound.3 Cellulitis can be caused by a
variety of pathogens.6 This infection is characterized by
edema, hyperesthesia, erythema, induration, and tender­
ness detectable upon examination (Fig. 11.3). The color of
the wound contour and the odor from the wound may also
raise suspicion of cellulitis. Furthermore it can have a lym­
phangitic component. Particular attention should be given
to elderly patients and diabetic patients due to the ease and
speed with which infections progress in these populations.
Cellulitic burn wounds benefit from systemic antimicrobials
to cover likely causative agents in addition to standard burn
treatments, such as topical antimicrobials or surgical exci­
sion and grafting. Progression of cellulitis despite antibiot­
ics must always trigger suspicions of resistant organisms,
such as methicillin-resistant Staphylococcus aureus (MRSA),
and these organisms should be covered empirically.6
Graft ghosting (impetigo) is a wound infection that can
cause late graft loss (Fig. 11.4). This phenomenon can
occur after spontaneous closure of a partial-thickness
wound, following loss of previously adherent graft sites,
and in skin donor sites. Characterized by multiple small
abscesses, graft ghosting can lead to the complete destruc­
tion of the healed wound.6 The culprit typically responsible
for this condition is S. aureus, particularly MRSA. The diag­
nosis is essentially clinical and can be confirmed by cultur­
ing. Treatment requires regular dressing changes,
débridement of abscesses, local disinfection, and applica­
tion of topical antimicrobials, such as mupirocin.
Toxic shock syndrome (TSS) is a complication of severe soft
tissue infections (SSTI), which occurs predominately in
small burns. This syndrome results from colonization with
TSS toxin-1–producing S. aureus. This disease is primarily
seen in young children with burns covering less than 10%
of the total body surface area (TBSA) and that would oth­
erwise be expected to heal without problems. The incidence
is approximately 2.6% with a mean age of 2 years. TSS is
clinically characterized by a prodromal period lasting 1–2
days with pyrexia, diarrhea, vomiting, and malaise. While
create the typical presentations of infection known to all
doctors are often initiated in the burn patient via the elabo­
ration of damage-associated molecular patterns (DAMPS)
and pathogen-associated molecular patterns (PAMPS) from
burn wounds. This complicates diagnoses of infection and
sepsis in the burn patient where clinical signs, such as ele­
vated temperature or tachycardia, are normal components
of burn pathophysiology, as discussed in Chapter 29 on
hypermetabolism.
Wound culturing is a critical tool to guide the treatment of
burn wounds and to determine what bacteria are coloniz­
ing the burn wound. In patients with major burns, the
wound usually becomes colonized 5–7 days after injury.6
Since most initial infections in burn patients derive from
endogenous bacteria flora, it is good clinical practice to
perform initial wound cultures upon patient admission.
This screening should include swabs of both sides of the
groin and axilla, as well as of the nose and throat.14 In addi­
tion, at each burn excision, and whenever suspicion of
invasive infection warrants, quantitative tissue cultures
may be helpful.
Wound appearance and odor changes can help to diag­
nose wound colonization versus wound infection (Fig.
11.1). Kwei et al. described three main methods that exist
for culturing a wound: qualitative (presence or absence of
growth), semi-quantitative (grading of the bacterial pres­
ence as scanty, few, moderate, or numerous), and quantita­
tive (an absolute quantity is determined).15,16 Swabs are
useful but limited since they cannot distinguish between
infection and colonization and are only accurate for the
region sampled. These problems are mitigated by perform­
ing multiple tissue biopsies, which can reveal significant
quantitative differences in different areas.17 Although
quantitative cultures are more expensive, bacterial counts
have been shown to correlate with histological evidence of
wound infection in approximately 80% of cases after biop­
sies are taken or after sterilization of the surface with anti­
microbials.6,18 Histological examinations can be used to
confirm invasive bacterial infection when counts exceed
105 organisms per gram of tissue. If histological evidence
Fig. 11.1  Burn wound colonization. Flame burn to the left medial arm
depicted post-burn day 7. The eschar has degraded but is still present.
However, the surrounding tissue is not cellulitic.

11  •  Treatment of Infection in Burn Patients
95
partial-thickness burns progress to full-thickness necro­
sis and begin expanding into unburned tissues. The 2007
American Burn Association Consensus Conference defined
invasive infections as follows: “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, inva­
sion of adjacent unburned tissue or cause the systemic
response of sepsis syndrome.”3 Goal-standard diagnosis is
made with histologic examination; however, clinical exam
and quantitative cultures usually suffice (Fig. 11.6). It
should be noted that sepsis does not always develop during
invasive infections (Fig. 11.7). Treatment must be immedi­
ate and include aggressive surgical intervention augmented
by the administration of systemic and topical antimicro­
bials. If no culture results are initially available, a broad-
spectrum empirical therapy against fungi, drug-resistant
gram-positive and -negative organisms should be initiated
until culture data become available. Surgical extirpation
must be aggressive and encompass excision of all necrotic
and infected tissue, including fascia and muscle when war­
ranted. Definitive wound coverage is not always indicated
in this extirpative operation as dressing changes and hydro­
therapy may be needed to further decrease heavy bacte­
rial loads. In cases where tissue has already been excised
or there is a life-threatening infection, limb amputation
may be indicated. Topical antimicrobials and assiduous
washing technique are indicated after extirpation to sup­
press microbial growth. However, the optimal methodology
is to prevent infection, with swift action being taken should
an infection arise.23
Sepsis and septic shock are complicated diagnoses in burn
patients because large burns create a systemic inflamma­
tory response syndrome (SIRS) and hypermetabolism of
their own, as discussed in Chapter 8 on the etiology of
shock. This hypermetabolism is a natural part of the body’s
a rash is often present, at this stage, the burn appears clean
(Fig. 11.5). Shock subsequently develops in untreated cases,
but determining the cause of shock to be TSS can be com­
plicated in this early phase of the patient’s presentation
when a litany of potential and more common etiologies of
shock exist. Once shock has developed, mortality can be as
high as 50%. Awareness and aggressive action are the prin­
cipal safeguards against the development and progression
of TSS. A possible diagnosis of TSS should be considered in
small burns where the patient is unexpectedly in shock.
Because MRSA has emerged as the most commonly identi­
fied cause of SSTI, initiation of empiric anti-MRSA antimi­
crobials is warranted in all cases of suspected TSS.19,22
Invasive wound infections manifest clinically with wound
color changes, exudate, and odor. Within a short time,
B
A
Fig. 11.2  Burn wound erythema. A hot oil scald burn on the lateral thigh is depicted with (A) surrounding erythema noted on post-burn day 2. (B)
Resolution of redness and healing on post-burn day 12.
Fig. 11.3  Burn wound cellulitis. Cultures demonstrated Staphylococcus
aureus. Clinical findings include increased pain, local inflammatory
signs, and fever. Treatment includes systemic and topical antibiotics,
excision, and autografting.

11  •  Treatment of Infection in Burn Patients
96
burden in the wound and periwound areas while allowing
skin grafts to proliferate and cover the wound. Systemic
antimicrobials are administered to treat invasive pathogens
and prevent or reduce the systemic spread of infection.
TOPICAL ANTIMICROBIAL COMPOUNDS
Topical antimicrobial compounds have significantly reduced
burn mortality.7,27 However, no single agent is entirely effec­
tive. Each possesses its own spectrum, advantages, and dis­
advantages. Some retard wound healing while others have
systemic metabolic effects on the patient. Recent studies have
demonstrated that some agents used in the past are now
ineffective in inhibiting bacterial growth.28,29 Wounds may
be dressed with any topical agent when quantitative culture
counts persist at less than 102/g tissue. However, higher
colony counts warrant culture-directed topical antimicro­
bial selection. Topical antimicrobial agents fall into five major
classes, each possessing different antimicrobial spectra, dura­
tion of action, penetration, and toxicities (Box 11.2).
Soaps are the first form of topical antimicrobial and are
employed during washing. They are effective in disrupting
biofilms and washing pathogens from the patient. Biofilms
are coherent clusters of bacterial cells embedded in a bio­
polymer matrix that, compared with planktonic cells, resist
host defenses and show increased tolerance to topically
(antiseptics) and systemically (antibiotics) administered
antimicrobials, thus creating the perfect environment for
bacterial growth.30 Biofilm bacteria are extremely difficult
to remove, requiring surgical or sharp instruments and/
or mechanical wound débridement and washing with soap
and water. According to recent recommendations, burn
compensatory mechanism to burn injury and can last for
up to a year following the insult, making it difficult to fit
shock in burn patients into the definitions of sepsis and
septic shock established by the Society of Critical Care
Medicine.24–26 Patients with high concentrations of bacteria
in the burn wounds in conjunction with delayed admission
to a burn center or delayed removal of burned tissues are
at the greatest risk of developing sepsis.8 Rapid and com­
plete closure of deep burns is the best defense against this
condition. An additional factor influencing the develop­
ment of sepsis and increasing mortality during hospitaliza­
tion in patients with equal burn sizes is decreased lean body
mass. The identification of parameters associated with
sepsis in burn patients is extremely important and ongoing.
The American Burn Association Consensus Conference in
2007 provided criteria (Box 11.1).3 These criteria are useful
markers and indicators for sepsis but are by no means
gospel. A skilled physician must take these factors into
account along with changes in the patient’s clinical condi­
tion over time to make a presumptive diagnosis of sepsis.
Aggressive treatment should be initiated and de-escalated
based upon definitive diagnosis and patient response.
Treatment of Burn
Wound Infections
Treatment of burn wound infections is multimodal. Surgi­
cal débridement and assiduous washing technique decrease
the bacterial and nutritive burden. Aggressive grafting
denies the pathogens wound surface area to colonize and
infect. Topical antimicrobial compounds reduce pathogen
B
A
Fig. 11.4  Burn wound impetigo. Right hand in a 13-year-old boy with 85% TBSA burn, third-degree to the hands shown (A) 4 months post-burn at
hospital discharge. (B) Three weeks later the patient presented with reopening of the previously taken skin grafts to the hand and clinical impetigo.
Cultures were positive for MRSA, and the patient was treated with vancomycin, mupirocin, and tub therapy.

11  •  Treatment of Infection in Burn Patients
97
AD
AC
AB
AA
Fig. 11.5  Toxic shock syndrome (TSS) rash. Cutaneous rash commonly seen in patients with TSS. This rash does not universally appear in cases of TSS.
Patients with small burns developing shock should be evaluated and treated for TSS with excision, grafting, and vancomycin. (A) A 13-year-old girl
presenting TSS rash following a 10% TBSA burn. (B) The typical macular erythroderma lesions. (C) A hematoxylin and eosin 4× magnification micrograph
of a TSS rash lesion showing an epidermal blister. (D) Further hematoxylin and eosin 40× magnification micrograph with low inflammation. (Courtesy
of Omar P. Sangüeza, MD; Professor and Director of Dermatopathology, Wake Forest University School of Medicine, North Carolina.)
Fig. 11.6  Gram-negative bacilli invading deep viable tissue. Histopath­
ologic confirmation is the gold standard test to diagnose burn wound
infection by bacteria in viable tissue. Shown is a typical hematoxylin
and eosin stained section at 1000× magnification.
Fig. 11.7  Invasive burn wound infection. Seventy-five percent TBSA
full-thickness burns with wound sepsis due to Enterococcus faecalis and
Enterobacter cloacae. Prompt excision, homografting, hemodynamic
support, and systemic antibiotics controlled the infection. This patient
was subsequently autografted and survived.

11  •  Treatment of Infection in Burn Patients
98
and is described as full-strength Dakin’s Solution. Studies
have demonstrated full-strength to be tissue toxic, as are
the pharmacy-available half- and quarter-strength Dakin’s
solutions, though they are effective antimicrobials. Investi­
gations by Heggers and coworkers established the efficacy
of NaOCl at a concentration of 0.025%, or one-twentieth
Dakin’s.23,37,38 Buffered one-twentieth Dakin’s was formu­
lated to mimic normal human physiologic parameters,
with the added benefits that it is a broad-spectrum anti­
septic, yet nontoxic to fibroblasts nor inhibiting of wound
healing. It is bactericidal against P. aeruginosa, S. aureus,
methicillin-resistant staphylococci, enterococci, and other
gram-negative and gram-positive organisms, and it may
be used separately or in combination with other agents.23
Subsequently Carrel and Dakins developed oxychlorosene
(Clorpactin) to allow longer tissue half-life, neutral pH, and
lower tissue toxicity. It is used intravesicularly and intrare­
nally to control hemorrhage in genitourinary cancer cases
and has been recently resurging as a topical antimicro­
bial.39 It has been demonstrated to be nontoxic to skin grafts
when tested as a wound irrigant.40 Currently products are
coming to market using hypochlorous acid as an active oxi­
dizing agent in pH-neutral, isotonic formulations.41,42 While
of interest as topical antimicrobials for burn wounds, they
lack the century-long experience of sodium hypochlorite
solutions and so require further research.
Povidone-iodine (Betadine) is another halide used as a
topical antimicrobial; it is available as a liquid or an oint­
ment in varying concentrations. It has a broad-spectrum of
activity, covering gram-positive and gram-negative bacteria,
yeast, and fungi. Quantitative bacteriological assessments
imply that iodine is most efficacious when administered
every 6 hours. Topical application of this agent can be
painful. The iodine component of this topical agent may
be absorbed more extensively in burn wounds, resulting
in iodine toxicity, renal failure, acidosis, and dermatitis (in
intact skin). Furthermore povidone-iodine is cytotoxic to
fibroblasts and keratinocytes. However, it remains a highly
effective disinfectant when used on intact skin.43,44
Acetic acid, also called ethanoic acid or vinegar, is a col­
orless topical agent used as a disinfectant for skin and soft
tissue infections. It is effective against gram-negative bacte­
ria, especially P. aeruginosa. Its clinical antibacterial efficacy
requires a minimum concentration of 0.5%.45 Philips et al.
reported the use of acetic acid as a topical agent for the treat­
ment of superficial wounds infected by Pseudomonas46; later
Sloss et al. investigated topical use of acetic acid at concen­
trations between 0.5% and 5%.47 Sloss showed all strains of
Pseudomonas exhibited a minimum inhibitory concentra­
tion (MIC) of 2% in vitro, yet other studies determined a
concentration of 3% acetic acid to have bacteriostatic activ­
ity, including against multiple antibiotic-resistant strains of
Pseudomonas.45,48 The results of in vitro studies indicate that
acetic acid is toxic to fibroblasts and substantially decreases
cell viability, effects that increase with the concentration.
Although these results are not considered decisive for the
treatment of burn wounds, a surgeon should always con­
sider the eventual cytotoxic interaction, especially on fresh
skin grafts, while using acetic acid.49
Silver ions are a common topical heavy metal antimicro­
bial. Silver is delivered as solutions, creams, or bound to
dressing materials. The silver ions bind to proteins and
wounds not associated with clinical signs or symptoms of
infection yet suspected of having biofilm should be treated
with débridement, antimicrobial dressings, antiseptic
soaks, and thorough cleansing with antiseptic products to
prevent bacterial growth.31 Findings from Kennedy and col­
leagues support the significant role played by biofilms in
burn wound sepsis and the importance of early excision
and closure of the wound.32 Herndon et al. demonstrated
that washing burn wounds with soap and water using
assiduous washing techniques can cause a 2-log reduction
in bacterial counts over 48 hours, improving autograft take
by infected wounds.8
Many oxidative halides are used as topical antimicrobials.
Classically sodium hypochlorite (Dakin’s solution) has been
employed due to its broad bactericidal range and effective
dissolution of biofilms.33–36 Commercially available Clorox
bleach is 5.25% NaOCl; the original Carrel-Dakin’s Solu­
tion used in World War I was diluted with water to 0.5%
Box 11.1  The 2007 American Burn Association
Consensus Conference Definition of Sepsis.3
“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 of sepsis:
I. Temperature >39mpera<36.5er
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)
VI. Inability to continue enteral feedings >24 hours
A. Abdominal distension
B. Enteral feeding intolerance (residual >150 mL/h in children
or 2ce (residual er 24 hours
C. Uncontrollable diarrhea (>2,500 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.

11  •  Treatment of Infection in Burn Patients
99
some yeasts, such as C. albicans. However, recent reports
of P. aeruginosa resistance and inadequacy against some
strains of Klebsiella have emerged. More frequent dress­
ing changes are required if a creamy exudate develops.
Although this topical agent is facile in use and reduces
pain, it retards wound healing.53 Unlike mafenide acetate,
tissue-penetration of silver sulfadiazine is limited to the
surface epidermal layer, and it is not associated with acid–
base disturbances or pulmonary fluid overload. It can be
used separately or in combination with other antibacterials.
An adverse drug reaction may be a reversible granulocyte
reduction due to silver toxicity, although this is controver­
sial and transient.7,27 Over multiple applications a pseudoe­
schar of silver sulfadiazine cream builds up on the wound,
making assessment of the wound depth difficult because it
then bears a strong resemblance to burn eschar. This limits
the utility of this topical agent in our center.
Over the past decades there has been a proliferation of
silver-containing dressings formulated to remain in place
over a prolonged period. On superficial burns, these dress­
ings are utilized as functional skin substitutes to permit
re-epithelialization in a bacterially suppressed, moist envi­
ronment. Many centers employ silver-containing dressings
rather than applying solutions of topical antimicrobials like
silver nitrate because they are easier to manage, have more
consistent antimicrobial levels, and are generally less messy.
enzymes, damaging those systems, and to DNA, resulting
in an antimicrobial effect via a heavy metal oxidative
pathway.50 In debrided wounds, a 0.5% silver nitrate
(AgNO3) solution is a potent disinfectant. It does not injure
regenerating epithelium in the wound and is bacteriostatic
against S. aureus, E. coli, and P. aeruginosa. AgNO3 has
limited wound penetration because the silver binds rapidly
to the surface proteins.27 Its hypotonic nature can cause
osmolar dilution, resulting in hyponatremia and hypochlo­
remia, so serum electrolytes must be monitored. AgNO3
turns black when exposed to light or on contact with tissues
or chlorine-containing compounds, but this is nontoxic. It
can be combined with miconazole powder to yield an
aqueous solution of 0.5% silver nitrate and 2% miconazole
for greater efficacy in preventing bacterial and fungal over­
growth in burn wounds.51 Klebsiella spp., Providencia spp.,
and other Enterobacteriaceae are less susceptible to 0.5%
AgNO3 than other bacteria. Rarely the combination of
0.5% AgNO3 solution with Enterobacter cloacae or other
nitrate-positive organisms can cause methemoglobinemia
by converting nitrate to nitrite in the body.52
Silver sulfadiazine (Silvadene, Thermazine, Flamazine,
SSD), a 1% water-soluble cream, is a combination of sul­
fadiazine and silver with antimicrobial efficacy lasting up
to 24 hours. While most effective against P. aeruginosa and
the enterics, silver sulfadiazine has great utility against
Box 11.2  Topical Antimicrobial Agents.
CLASS
AGENTS
ANTIMICROBIAL SPECTRUM
GRAFT TOXICITY
SYSTEMIC TOXICITY
Soaps
Johnson’s Baby Shampoo
Broad-spectrum + Biofilm
Low
None
Oxidative Halides
Full-Strength Dakin’s Solution
(0.5% NaOCl)
Broad-spectrum + Biofilm
High
Hyponatremia
1/20th Buffered Dakin’s
Solution (0.025% NaOCl)
Broad-spectrum + Biofilm
Low
None
Oxychlorosene (Clorpactin)
Broad-spectrum + Biofilm
Low
None
Hypochlorous acid
Broad-spectrum + Biofilm
Unk.
Unk.
Povidone-iodine (Betadine)
Broad-spectrum
High
High
Acids
Acetic Acid 0.5%
Bacteriostatic
Low
None
Acetic Acid 2%
Bacteriostatic
Moderate
Moderate
Acetic Acid 3%
Bacteriostatic
High
High
Heavy Metals
Silver Nitrate 0.5%
Broad-spectrum
None
Electrolyte imbalance
Silver Sulfadiazine (Silvadene)
Broad-spectrum
None
Low
Silver Releasing Dressings
Broad-spectrum
None
Low
Xeroform - Bismuth
tribromophenate
Limited Bacteriostatic
Low
None
BIPPS - Bismuth subnitrate and
iodoform
Bacteriostatic
High
High if >1% TBSA
Antibiotics
Mafenide acetate (Sulfamylon)
Broad-spectrum
Low
Metabolic acidosis
Gentamicin sulfate (Gentamicin)
Broad-spectrum
Low
Low
Bacitracin/polymyxin
(Polysporin)
Broad-spectrum
Non-toxic
Low
Nitrofurazone (Furacin)
Broad-spectrum, no Pseudomonas
Low
Low
Mupirocin (Bactroban)
Broad-spectrum, no Pseudomonas
Moderate
Moderate
Nystatin 100,000 U/g
(Mycostatin)
Weak Antifungal
Low
Low
Nystatin 6,000,000 U/g
Strong Antifungal
Low
Low

11  •  Treatment of Infection in Burn Patients
100
Bacitracin/polymyxin (Polysporin) ointment is commonly
used to prevent mechanical shear and suppress bacterial
growth on newly grafted tissue. Both drugs are cell wall
lytic agents, and polymyxin is a topical analogue of colis­
tin, discussed in the systemic antimicrobial section. Drug
concentrations available in the ointment do not treat infec­
tion. However, many surgeons rely on this topical agent for
skin graft coverage as it is nontoxic and maintains the moist
wound environment needed for epithelial growth. Effective­
ness in contaminated or infected burns post excision can be
enhanced by use in combination with other agents, such as
silver nitrate or mafenide. Prolonged use is associated with
hypersensitivity development.
Nitrofurazone (Furacin), available as an ointment, solu­
tion, or cream, has been proved effective in the treatment
of methicillin-resistant staphylococci. Furthermore, nitrofu­
rantoin was demonstrated to be 75% effective against gram-
negative bacterial isolates other than P. aeruginosa, whereas
bacitracin/polymyxin was only 21% effective.3
Mupirocin (Bactroban, pseudomonic acid A) is an anti­
biotic derived from the Pseudomonas fluorescens capsule and
inhibits isoleucyl t-RNA synthetase and thus bacterial protein
synthesis.61 It is the topical treatment of choice for MRSA
infections, gram-positive microbes, and intranasal carriage.62
Mupirocin inhibits wound healing by a half-life of 2 days com­
pared to controls, but the breaking strength of the wound is
significantly enhanced.63 Due to rapid development of resis­
tance, mupirocin should not be used for longer than 10 days.
Nystatin (Mycostatin, Nilstat) is an antifungal antibiotic
produced by Streptomyces noursei. Nystatin is the highly
potent topical equivalent of Amphotericin-B; both exert anti­
fungal activity by binding to ergosterol and lysing fungal cell
membranes. Low-dose applications of 100,000u/g as creams,
lotions, or ointments are used as prophylaxis against fungal
growth. Treatment with pure nystatin powder at a concentra­
tion of 6,000,000 U/g on burn wounds has proved effective
in eradicating invasive fungal infections. This novel applica­
tion is not only effective superficially but also eradicates inva­
sive clusters of fungi in deep wound tissues, as documented by
pathological examination.64 The application of the powder is
easy and does not produce pain, discomfort, or impair wound
healing. All previously autografted areas heal uneventfully.64
Liquid nystatin ‘swish and swallow’ is used prophylactically
to prevent the oral or perineal overgrowth of yeast and fungi
in patients receiving multiple systemic antibiotics.64
SYSTEMIC ANTIMICROBIALS IN BURN PATIENTS
Long maligned, routine prophylactic use of antibiotics is
well indicated for select burn patients. Whereas prophylac­
tic antibiotics may be warranted for patients arriving from
endemic areas, with penetrating traumas, open fractures,
or from highly contaminated scenes, no prophylactic anti­
biotic treatments are typically initiated at admission or for
routine perioperative prophylaxis. This is principally to
avoid creation of antibiotic resistances with more difficult
subsequent treatment. Additionally thermal wounds are
normally aseptic in the first hours following injury as the
burn sterilizes the wound surfaces.65,66
Empiric antibiotics are indicated in the setting of clini­
cally suspected invasive wound infections, suspected sepsis,
or septic shock. These antibiotics should broadly cover
The antimicrobial actions of the dressings derive from the
silver ions, so their spectrum is thus defined. Each product’s
dressing substrate and particular silver formulation provide
different dressing characteristics; however, the release and
efficacy of silver against bacteria in wounds have not been
largely studied or reported. Furthermore there are to date
no large-scale studies defining the supremacy of any par­
ticular product, so preference of the practitioner and cost
typically define use. It is important to remember that no
dressing, no matter how well marketed, replaces the tenets
of burn surgery: aggressive débridement of devitalized
tissue, coverage of wounds with skin, assiduous wound
cleansing to remove pathogens and contaminants, and
physical examination.
Bismuth is another heavy metal commonly employed as
a topical antimicrobial. It is bacteriostatic against enterics,
but not cytotoxic to dermal fibroblasts and does not inhibit
wound healing.54 It is usually used on the commercially
available dressing Xeroform, a gauze impregnated with
bismuth tribromophenate and petroleum jelly. Bismuth is
also delivered in conjunction with iodine in the compounded
paste, BIPP (1 part bismuth subnitrate, 1 part liquid paraf­
fin, and 2 parts iodoform). We have used BIPP effectively
on thousands of patients treated in our hospital for more
than 50 years. Coated liberally on cotton gauze, this paste
is used to dress small, débrided areas of exposed bone and
tendons.55,56 BIPP should not be applied to areas greater
than 1% TBSA, and the course of treatment should be as
brief as possible to limit the risk of bismuth toxicity.57,58 In
our experience, this compound prevents the development of
infection and promotes the prodigious formation of granu­
lation tissue, thereby permitting split-thickness skin grafting
over surfaces conventionally described to be ungraftable.
Antibiotic-based topical antimicrobials define the fourth
major class, and their mechanism of action is determined
by the specific biochemistry characteristic of each particu­
lar agent. Mafenide acetate (Sulfamylon), available both as
an 8.5% water-soluble cream and a 5% aqueous solution,
is among the most commonly employed topical agents.
While broad-spectrum, mafenide is particularly effective
against all strains of Pseudomonas and Clostridium.59 The
cream is applied twice a day and has the advantage that it
does not require a dressing to adhere to wounds. Studies
have reported that the use of 5% mafenide acetate solution
in patients with major burns results in a 33% reduction
in death.6 When used as a solution, an eight-ply dressing
should be resaturated with fresh solution every 8 hours to
remain above MIC. Mafenide has excellent tissue penetra­
tion, including eschar. This penetration makes it the topical
agent of choice for deep ear burns because it effectively pre­
vents invasive chondritis. It can cause pain on application
and, like other sulfa drugs, can lead to allergic reactions.
Since mafenide can inhibit carbonic anhydrase, metabolic
acidosis can develop. Furthermore protracted use may lead
to the growth of C. albicans. While it can be used with other
antimicrobials, mafenide acetate retards wound healing
and reduces the breaking strength of healed wounds.27
Gentamicin sulfate (Gentamicin) is an aminoglycoside
available as a 0.1% water-soluble cream or solution. It has
broad-spectrum bactericidal activity against aerobes and
is often deployed against P. aeruginosa. However, resistance
can develop and sensitivities should be monitored.60

11  •  Treatment of Infection in Burn Patients
101
polymerase and blocking RNA transcription.69 Due to its
high resistance pattern when employed alone, rifampin
must be used in conjunction with other antiinfectives, such
as sulfamethoxazole-trimethoprim (Bactrim) or levofloxa­
cin, in the treatment of MRSA. Linezolid is a bacteriostatic
synthetic antibacterial agent of a newer class of antibiotics,
the oxazolidinones, developed for MRSA, methicillin-
resistant S. epidermidis, enterococci, and staphylococci.
Linezolid inhibits bacterial protein synthesis by binding to
the 50S ribosomal subunit to prevent translation.69 Adverse
effects of linezolid include myelosuppression (e.g., anemia,
leukopenia, pancytopenia, and thrombocytopenia), which
is generally reversible on discontinuation of the drug, and
Clostridium difficile colitis. A weak, nonselective, and revers­
ible inhibitor of monoamine oxidase, linezolid may cause
increased serotonin serum levels and serotonin syndrome
in patients on various serotonin reuptake inhibitors, such
as fluoxetine and sertraline. Prolonged use also carries a
risk of polyneuropathy.
Invasive wound infections, graft loss, sepsis, and septic
shock from suspected gram-positive bacteria should be
treated empirically with intravenous vancomycin until
culture-directed de-escalation can occur. Vancomycin is
bactericidal, preventing gram-positive bacterial cell wall
glycopeptide polymerization thereby producing immediate
inhibition of cell wall synthesis and lysing the cytoplasmic
membrane.69 As a time-dependent antimicrobial, serum
levels of this drug must unceasingly exceed the MIC to
provide sufficient bactericidal activity. Due to the wide vari­
ability in vancomycin elimination among burn patients, the
dosage must be individualized to optimize serum concentra­
tions by serially following trough levels, with a typical goal of
10–15 µg/mL for most burn wound infections. Due to poor
penetration, certain compartments, such as the lungs and
central nervous system, require higher trough concentra­
tions to achieve therapeutic levels of vancomycin; in cases
of pneumonia or meningitis, concentrations of 15–20 µg/
mL are recommended.70
Alarmingly, gram-positive strains resistant to vancomy­
cin, such as vancomycin-resistant Enterococcus (VRE) and
vancomycin-intermediate S. aureus (VISA), have emerged.
These bacteria are often susceptible to linezolid, as discussed
earlier, as well as to tigecycline, daptomycin, quinupristin-
dalfopristin, and dalbavancin, which have been developed
specifically to tackle this problem. Working closely with a
clinical pharmacist who can help establish an antibiotic and
dosing regimen best fitting the specific resistance pattern in
a given patient is critical.
Gram-negative infections more frequently require admis­
sion and intravenous antibiotics. While empiric therapy
should be directed by local antibiogram, consideration
must also be given to additive toxicity when combined with
empiric gram-positive agents. In our hospital, we empirically
use imipenem/cilastatin due to their low nephrotoxicity
when used in conjunction with vancomycin.71 De-escalation
and discontinuation of antibiotics should occur as soon as
cultures, wounds, and physiology warrant. Because gram-
negative bacteria frequently become multidrug-resistant,
testing for synergy between different classes of antibiotics
is advisable.
Third-
and
fourth-generation
cephalosporins
and
extended-spectrum penicillins are the antibiotics of choice
all likely infecting organisms and be instituted as a com­
ponent of multimodal critical and surgical care of the
burned patient. Clinical response should be followed to
ensure adequate treatment and antibiotics de-escalated as
soon as possible based on culture findings. After time and
culture data allow definitive diagnosis of infection, culture-
directed treatment antibiotics should be continued for a
finite treatment course, until cultures return negative or the
wounds close.67
Greatly altered in burn patients, pharmacokinetics and
pharmacodynamics require regular evaluation by a skilled
clinical pharmacologist to ensure safe and effective drug
dosing.68 During the resuscitative phase of burn injury,
which occurs within the first 48 hours post-trauma, burn
shock can decrease blood flow to organs and tissues.68 Drug
treatments during this phase result in a slower distribution
rate, slower renal and hepatic elimination, and delayed
absorption of enteral, subcutaneous, and intramuscular
drugs. After 24–48 hours, the patient enters the hypermeta­
bolic phase, discussed extensively in Chapters 29 and 32
covering the hypermetabolic response, endocrine function,
and critical care. During this period, burn patients exhibit
increased blood flow to organs and tissues, an increased
internal core temperature, and hypoproteinemia and edema
formation.68 Intravenous drugs have a shorter half-life due
to the enhanced glome rular filtration rate and elimination
of renally excreted drugs. Antibiotic treatments in these
patients must be administered at higher doses and/or fre­
quency. Time-dependent, renally excreted antibiotics, such
as vancomycin, must be carefully monitored to ensure they
exceed the MIC of the bacteria. Oral drugs will also exhibit
greater absorption from the gastrointestinal tract and a
faster onset of action.68 The hypermetabolic phase causes
hypoalbuminemia and raises the levels of acute-phase pro­
teins.68 Albumin binds to acidic and neutral drugs, such as
aminoglycosides, vancomycin, aztreonam, and cefotetan;
consequently in hypoalbuminemia more free drugs are cir­
culating so a lower dose will be required for therapeutic
effect. Conversely acute-phase proteins bind tightly to basic
drugs, such as penicillins and cephalosporins, resulting in
less free drug and necessitating higher drug dosages to
produce a therapeutic effect. The hepatic response occur­
ring during the hypermetabolic phase will present as a
decrease in phase 1 metabolism, such as oxidation, reduc­
tion, or hydroxylation of a drug by the cytochrome P450
system, affecting many antibiotics, such as the quinolones
and the macrolides. The decreased activity of these hepatic
drug–metabolizing enzymes, as well as their decreased
hepatic clearance and prolonged half-life, may produce sys­
temic toxicity. However, phase 2 metabolism in the liver,
such as conjugation reactions between the drug and the
endogenous substrate, will not be impaired.68 In light of the
myriad of changes, care in the modern burn unit is greatly
enhanced by the active participation of a pharmacist famil­
iar with systematic drug level monitoring in burn patients.
Selection of systemic antibiotics is based on the likely
etiologic organism, local antibiogram, and systemic toxicity.
In the setting of an outpatient with cellulitis around a burn
wound, empiric gram-positive coverage to include MRSA is
indicated. We routinely cover these outpatients with
rifampin, a bactericidal antibiotic inhibiting RNA synthesis
by binding to the β-subunit of the DNA-dependent RNA

11  •  Treatment of Infection in Burn Patients
102
Antifungal treatment is complicated by the limited
number of agents and their relative toxicities. The most
commonly used antifungal agent, fluconazole, has excel­
lent activity against C. albicans and low toxicity. However,
non-albicans Candida spp. are increasingly frequent causes
of invasive candidiasis, and these are resistant to flucon­
azole.78 The Infectious Disease Society of America advocates
echinocandins as the best empiric treatment for yeast infec­
tions, as most yeast are susceptible to them.79 However, these
are recommended only until cultures become available. Cul­
tures should be performed frequently in these patients since
resistance can develop quickly.80,81 There is an increased
prevalence of Candida spp. with greater antimicrobial resis­
tance and higher mortality rates than C. albicans, such as C.
tropicalis and C. krusei.82,83 Ponziconazole and voriconazole,
both azoles, are the treatment of choice for invasive Asper­
gillus and Fusarium. They are also effective against infec­
tions caused by Candida spp., including fluconazole-resistant
ones. However, azoles have unpredictable, nonlinear phar­
macokinetics with extensive interpatient and intrapa­
tient variation in serum levels. Due to this and numerous
drug–drug interactions, therapeutic drug monitoring is
crucial.84,85
For decades Amphotericin B dexolate (AmBd), an intrave­
nous polyene analogue of nystatin, has been the standard
choice for intravenous treatment of life-threatening inva­
sive molds. This drug is associated with significant toxicity,
including infusion-related events and dose-limiting renal
dysfunction.86 Three new lipid formulations of amphoteri­
cin B (AmB lipid complex [ABLC], AmB colloidal dispersion,
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 reticuloen­
dothelial organs, a decrease in infusion-related events (espe­
cially with ABLC and AmB-L), and a marked decrease in
nephrotoxicity.86 These lipid drugs are more expensive, but
their enhanced safety profiles make them the new standard
for treating invasive molds, particularly Mucor. The most
successful treatment for fungal infection is prevention via
swift removal of all burned tissue and closure of wounds
with autografts. In the presence of active mold infections,
voriconazole is the first-line treatment, followed by ABLC.
An echinocandin, such as caspofungin, can be considered
for combination treatment of Aspergillus and Fusarium.71
Fusarium spp. have demonstrated innate resistance to
Amphotericin.87
Pathogens will continue to evolve novel resistance mecha­
nisms more rapidly than researchers can develop antibiotics.
In the dire case where no antibiotic susceptibility exists for
an infecting pathogen, it is important to remember excision
of infected tissue, graft coverage of wounds, and topical care
remain effective treatment plans. Barret and Herndon noted
that aggressive, early surgical treatment reduced wound
culture counts from greater than 105/g to less than 104/g
and yielded excellent skin graft take. In contrast, poorer
skin graft take occurred in patients with initial counts of
greater than 106/g, but were reduced to 104/g only after
delayed surgical excision, thus underscoring the correlation
between early and aggressive wound excisions and better
patient outcomes in the treatment of severe burns.8,15 While
infections can become overwhelming, there is no bacterial
resistance mechanism to the surgeon’s knife.
for many burn centers for empiric coverage of gram-
negative infections due to their broad coverage and low
toxicity. Fourth-generation cephalosporins (e.g., cefepime),
extended-spectrum β-lactamase inhibitor penicillins (e.g.,
piperacillin-tazobactam and ticarcillin-clavulanate), and
most importantly the carbapenems (e.g., imipenem/
cilastatin, meropenem, and ertapenem) are important
tools in eradicating gram-negative infections. Newer fifth-
generation cephalosporins were developed to treat resistant
Pseudomonas; unfortunately novel resistance patterns are
already emerging.72 These antibiotics are time-dependent
and most efficacious when serum concentrations between
dosing intervals are maintained at 1–2 times the MIC; thus
extended infusions over 3–4 hours or continuous infusion
may be necessary to keep concentrations above MIC, par­
ticularly when a pathogen is near the resistance threshold.72
In perforating the cell wall, penicillins are often synergistic
with intracellular antibiotics, such as aminoglycosides, and
testing is warranted in the setting of highly or pan-resistant
organisms.73,74
Aminoglycosides remain effective for significant sus­
ceptible gram-negative infections. Much of critical care
has moved to once-daily dosing of these concentration-
dependent antibiotics since it is as effective and less toxic
than conventional dosage intervals. Pooled data from ran­
domized controlled studies in adults showed that once-daily
administration of aminoglycosides is associated with similar
or greater efficacy (e.g., bacteriologic and/or clinical cure),
less nephrotoxicity, and no greater risk of ototoxicity than
administration of multiple daily doses.69 Some clinicians
remain concerned that traditional dosing intervals may be
preferable in severe infections or in patients with unpre­
dictable pharmacokinetics, as described in burn patients.75
Therefore monitoring aminoglycoside serum concentrations
and/or the peak serum concentration to MIC ratio in burn
patients with life-threatening infections, suspected toxicity
or nonresponse to treatment, decreased or varying renal
function, and increased aminoglycoside clearance is well
indicated.
Multidrug-resistant (MDRO) and pan-drug-resistant
(PDRO) gram-negative organisms are increasingly preva­
lent. Many of these islets have sensitivities to polymyxins,
a class of cell-wall intercalating antibiotics that includes
the topical agent polymyxin-B and its intravenous analogue
colistimethate sodium (colistin, polymyxin-E).71 These anti­
biotics were largely abandoned in the 1970s due to con­
cerns of toxicity when Kunin and Bugg showed polymyxin
accumulation highest in the kidney and brain tissues, fol­
lowed by liver, muscle, and lung. It was also reported that
colistimethate appeared to increase the incidence of C.
difficile colitis, renal dysfunction, and neuropathies pro­
portionately to the duration of its use.76,77 However, colis­
timethate use against MDRO has surged due to a lack of
other systemic options. Branski et al. reported that, in
118 patients with life-threatening MDRO gram-negative
infections, colistimethate provided an important salvage
option for burn patients with otherwise incompletely
treated infections. They further found that hepato-, neuro-,
and nephrotoxicity were no different in matched patients
treated with or without colistimethate, indicating con­
cerns from 40 years ago might be unfounded with modern
critical care.71

11  •  Treatment of Infection in Burn Patients
103
be responsible for sepsis leading to burn-related death.2,18
Both local environments and gastrointestinal tracts (via
translocation of endogenous gastrointestinal flora) are
believed to be the primary sources of this bacterium. This
species has a predilection for moist environments, and
human burn wound exudates have been shown to stimu­
late the expression of virulence factors of P. aeruginosa, the
pathogen chiefly responsible for nosocomial respiratory
tract infections.96 Additionally it breeds invasive and trou­
blesome wound infections in burn patients. A superficial
wound infection caused by P. aeruginosa typically will have
a yellow-green color and noxious fruity smell.97 This may
become an invasive infection, ecthyma gangrenosum,
causing purplish-blue ‘ ‘punched-out’ ’ lesions in the skin,
and, if local thrombosis of vessels is present, the wound
requires immediate dif local t to remove newly necrotic
tissues (Fig. 11.8). Empiric treatment for P. aeruginosa infec­
tion has evolved from aminoglycosides to antipseudomonal
β-lactams, such as piperacillin/tazobactam, cefepime, and
carbapenems.98 The increasing prevalence of MDRO P. aeru­
ginosa requires the expanding use of antibiotics based on
culture data, employment of fifth-generation cephalospo­
rins, use of synergistic antibiotic coverage, and use of colis­
timethate, as discussed in the systemic antimicrobial
section. This rapidly evolving and virulent pathogen is best
eradicated by rapidly closing wounds to deny the bacterium
access to any susceptible wound surface.
Acinetobacter spp. are gram-negative rods used commer­
cially to convert wine to vinegar and are native flora of the
respiratory tract, skin, gastrointestinal tract, and genitouri­
nary tract. This organism may lead to numerous opportu­
nistic infections, including pneumonia and infections of the
surgical site and urinary tract.99 Second only to P. aerugi­
nosa in prevalence, this pathogen has an enhanced capacity
for transfer between patients due to its ability to survive in
both dry and wet conditions and equally on animate and
inanimate objects, whether metal or plastic, making noso­
comial transmission a major concern.100,101 Acinetobacter
spp. have been isolated from diverse clinical sources, includ­
ing the upper and lower respiratory tracts, the urinary
tract, and surgical and burn wounds, as well as in bactere­
mias secondary to intravenous catheterization. An agent of
low virulence, it has a predilection for infecting patients
with dysfunctional host defense mechanisms. Although
traditionally susceptible to ceftazidime and ciprofloxacin,
Acinetobacter has developed resistance to such an extent
that only carbapenems (e.g., imipenem and meropenem)
can now be relied on to treat these infections. In cases of
MDRO Acinetobacter, colistin has become the rescue treat­
ment, as with Pseudomonas infections.71,102
Stenotrophomonas maltophilia (also known as P. malto­
philia or Xanthomonas maltophilia) is an aerobic gram-
negative bacillus responsible for nosocomial infections in
immunocompromised patients.103 Increasingly reported in
burn patients, this pathogen causes life-threatening infec­
tions which are very difficult to clear due to the particularly
obturant biofilm Stenotrophomonas produces.104 Addition­
ally S. maltophilia is inherently resistant to a variety of
antimicrobial agents, such as aminoglycosides, β-lactam
agents, and carbapenems. The most common types of infec­
tions caused by S. maltophilia are wound and bacteremia;
pneumonia and generalized infections associated with this
Specific Pathogens in
Burn Wounds
Staphylococcus aureus, gram-positive cocci in clusters,
remains the chief cause of burn wound infection and is a
well-documented opportunistic pathogen in humans.18,88
Colonization with these bacteria in an uninjured individual
is usually asymptomatic, but they are a source of opportu­
nistic infection that can lead to severe illness and death,
especially in burn patients.89 Staphylococcus produces viru­
lence factors, such as proteinases, coagulases, and hyal­
uronidases, that enable it to invade local tissues and
disseminate hematogenously, causing generalized systemic
infection and sepsis.90 The most common infections of
Staphylococcus spp. are septicemia, cellulitis, impetigo,
scalded skin syndrome, and postoperative wound infec­
tions. However, puerperal sepsis, pneumonia, osteomyelitis,
endocarditis, and burn wound infection are the most grave.
Exotoxins, which are produced by pathogenic strains of
staphylococci, include a pyrogenic toxin, a dermonecrotiz­
ing toxin, and leukocidin. In addition to the exotoxin
TSST-1, these organisms can produce enterotoxins A, B,
and C, risk factors for TSS in susceptible patients.91 Staphy­
lococcus spp. generally produce penicillinases that make
natural penicillins ineffective and thus require treatment
with penicillinase-resistant penicillins, such as oxacillin.
MRSA is now the predominant isolate, with rates of infec­
tion greater than 50% in burn units.92,93 Empiric coverage
should be vancomycin for intravenous therapy or Bactrim
and rifampin orally, as detailed earlier, based on the local
antibiogram and patient cultures.
Streptococci were once the leading cause of burn wound
infection but are now less prevalent. Arranged in chains,
these gram-positive cocci are particularly virulent when
infecting a burn wound and quantitatively do not require
less than 105 CFU/g tissue to prevent wound closure. A
mere few β-hemolytic streptococci can cause wound infec­
tion, failure of a primary closure, and loss of a skin graft.9
The major infecting species are Streptococcus pyogenes (also
referred to as group A streptococci and the most problem­
atic) and S. agalactiae (group B streptococci).94 Natural
penicillins, such as penicillin G and penicillin V, and first-
generation cephalosporins are bactericidal to these species.
While resistance to these penicillins or cephalosporins has
not yet emerged, culture and antibiotic sensitivity data
should be followed.
Enterococci are important inciters of gram-positive burn
wound infection. Encouragingly a recent review comparing
sepsis mortality between consecutive decades (1989–1999
and 1999–2009) found a steep decline in the rate of infec­
tion with enterococci (25% to 2%, respectively), perhaps
stemming from the more liberal use of vancomycin of recent
years.2 However, with the increasing prevalence of
vancomycin-resistant enterococci, VRE mortality rates are
now greater than those of MRSA (58% and 33%, respec­
tively).95 While most Enterococcus spp. respond to vancomy­
cin, VRE is treated with linezolid, a combination of ampicillin
and aminoglycosides, or quinupristin/dalfopristin (Synercid).
De-escalation is advised as soon as indicated by culture data.
Pseudomonas is not just the most ubiquitous gram-
negative burn wound pathogen, but also the most likely to

11  •  Treatment of Infection in Burn Patients
104
to a larger array of MDRO and PDRO.108 Carbapenem-
resistant Enterobacteriaceae (CRE) are increasing in inci­
dence and in many cases require treatment with colistin.
Anaerobic bacteria, such as Bacteroides spp. and Fusobac­
terium spp., are rarely a cause of invasive burn infection.
These bacteria are normal flora from the oropharyngeal
cavity to the gastrointestinal tracts. Anaerobic flora are
responsible for 2%–5% of surgical wound infections in the
oropharyngeal area109,110 and 10%–15% of wound infec­
tions in the gastrointestinal and urogenital tracts.111 In
burn patients, anaerobic infections are usually associated
with avascular myonecrosis secondary to electrical injuries,
pathogen are less common.105,106 Infections are sensitive to
trimethoprim-sulfamethoxazole alone or used with levoflox­
acin, and sensitivities should be monitored. Aggressive sur­
gical dulfamethox and assiduous washing technique with
soap and water are vital to combat the resultant biofilm.
Enterobacteriaceae, such as Escherichia coli, Klebsiella spp.,
Enterobacter spp., Serratia marcescens, and Proteus spp., are
often revealed as the cause of burn wound infections and
other nosocomial infections in burn patients.107 Although
these pathogens have greater sensitivity to antibiotics than
other gram-negative bacteria, emerging resistance patterns
to carbapenems and fourth-generation cephalosporins led
AC
AB
AA
Fig. 11.8  Ecthyma gangrenosa. A tissue-invasive burn wound infection here seen in a 7-year-old girl transferred to our hospital after a 6-week treat­
ment at another hospital. Note the (A) extensive greenish and slime-coated wound consistent with an invasive wound infection. The patient died
subsequently from an overwhelming hematogenously spread pneumonia. (B) The vessel wall at 40× magnification micrograph shows a clear bacterial
infiltration. (C) A typical purplish ecthyma gangrenosa lesion in a 35-year-old man. (C courtesy of Omar P. Sangüeza, MD; Professor and Director of Der­
matopathology, Wake Forest University School of Medicine, North Carolina.)

11  •  Treatment of Infection in Burn Patients
105
blood cultures from ICU patients; however, invasive infec­
tion with molds such as Aspergillus is correlated more closely
with death.121 Candidemia warrants retinal examination
for retinal plaques, as further discussed in Chapter 43 on
burn injuries of the eye (Fig. 11.11)
Most patients infected with molds are exposed to spores
in the environment at the time of injury, from either rolling
on the ground or extinguishing flames in contaminated
surface water. Other environmental foci have been cited as
the source of nosocomial mold infection, including bandag­
ing supplies left open to the air, heating and air-conditioning
ducts, and floor drains.110,115 Once colonized, hyphae extend
into subcutaneous tissue, stimulating an inflammatory
response. This phenomenon is diagnostic of mold wound
infection. Vascular invasion and systemic dissemination are
common and often accompanied by thrombosis and avas­
cular necrosis, clinically observed as rapidly advancing dark
discolorations of the wound margins or well-described
lesions120 (Fig. 11.10). Treatments for yeasts and molds
vary greatly due to the vastly different pathogenicities of
these organisms. Yeasts found in burn wounds are more
often associated with colonization and do not represent
infection. Treatment is usually considered when the same
yeast is identified at multiple sites, and topical treatment is
applied liberally; if invasive infection is considered systemic,
antifungals are administered. In contrast, the identification
of mold in a burn wound is a very serious condition. Often
invasive, infection with mold requires radical débridement
including amputation and high-dose topical and systemic
antifungals, such as 6,000,000 U/g nystatin powder.64
Hyphae invading live tissues and blood vessels should be
considered a surgical emergency and treated aggressively. It
is essential to work closely with a pathologist to make rapid
diagnosis of invasive mold and ensure complete surgical
resection at the margin, as one would resect a malignant
cancer.
Viral infections, particularly Herpesviridae, have become
more significant causes of morbidity. Prospective and retro­
spective assays of sera have documented a large incidence
of subclinical viral infections. In one of the first large retro­
spective studies from the 1980s, Linnemann et al. found a
fourfold increase in anti-cytomegalovirus (CMV) antibodies
in 22% of patients, increased herpes simplex virus (HSV) in
8%, and a rise in varicella-zoster (VZV) titers in 5%.122 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.122
The most common cause of viral infection is reactivation of
latent infection due to the debilitated, immunosuppressed
state of the patient after a substantial injury. Herpes viruses,
especially HSV and VZV, have by far the greatest occur­
rence, but CMV is not unusual.
CMV infection frequently occurs concurrently with bac­
terial and fungal infections but rarely alters the patient’s
clinical course. Kealey and coworkers showed that, in addi­
tion to blood transfusions, cadaver skin is a principal source
of CMV infections in burn patients.123 Overall seropreva­
lence in burn patients ranges between 37% and 73%.124,125
Gong and coworkers studied the reactivation rate and
found 108 of 180 patients to be positive at admission.126
Linnemann and colleagues determined that primary infec­
tion or reactivation of CMV was reported with an overall
frostbite, or cutaneous flame burns with concomitant
crush-type injuries.112 With the advent of early excision and
grafting, the incidence of anaerobic infections in thermal
injury has been reduced significantly. If anaerobic infection
is suspected, it is vital that collected specimens be placed in
appropriate transport tubes void of oxygen. In these cases,
broad-spectrum antibiotics covering anaerobes should be
given until sensitivities are available to ensure the adminis­
tration of the appropriate drug.113,114
Fungal wound infection and colonization have become
increasingly prevalent following the introduction of topical
antibacterials and liberal use of broad-spectrum antibiot­
ics.115 This has resulted in a surge in invasive fungal infec­
tion linked to higher death rates, regardless of the extent of
the burn, coincident inhalation injury, or patient age.116 In
a recent review of 15 burn units, fungi were isolated at least
once from 6.3% (435/6,918) of patients,117 with positive
cultures being most commonly obtained from the wound
itself followed by (in order of decreasing frequency) respira­
tory, urine, and blood specimens.118 Yeasts are identified
primarily on the basis of specific biochemical tests, but both
macroscopic and microscopic morphologies are also used to
make final identification (Fig. 11.9). Mold identification is
based on growth rate, colony structure, microscopic/
microscopic appearance, dimorphism at different incuba­
tion temperatures, and inhibition of growth by cyclohexi­
mide, as well as various biochemical tests (Fig. 11.10).119
Early diagnosis of fungal infection can be difficult because
clinical symptoms frequently mimic low-grade bacterial
infections. Routine culture techniques may require 7–14
days to identify fungal contaminants, delaying initiation of
treatment.118 In contrast to bacterial sepsis, venous blood
cultures might not reflect the causative fungal organism.120
For this reason, arterial blood cultures and retinal examina­
tion for characteristic candidal lesions can be useful. Candida
spp. are the most common fungal colonizers of the burn
wound, although fungi like Aspergillus spp., Penicillium spp.,
Rhizopus spp., Mucor spp., Rhizomucor spp., Fusarium spp.,
and Curvularia spp. can also be present, and they have a
vastly greater invasive potential than yeasts.110,115 Candida
albicans is the fourth most frequently identified pathogen in
Fig. 11.9  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 was effective in controlling
Candida in this patient.

11  •  Treatment of Infection in Burn Patients
106
AD
AC
AB
AA
Fig. 11.10  Diagnosis of invasive mold infection. Invasive mold infection carries a significant increase in morbidity and mortality. Physical examination
reveals (A) a left forearm and hand wound with macroscopical fungal growth (a white, fluffy appearance) and necrotic borders before repeated surgical
débridement. Diagnosis on histological examination is critical to guide both surgical treatment as well as selection of antifungal therapy. Below are
40× magnification micrographs of (B) Aspergillus, (C) Mucor, and (D) Fusarium findings. (B, C, D courtesy of Omar P. Sangüeza, MD; Professor and Director
of Dermatopathology, Wake Forest University School of Medicine, North Carolina.)

11  •  Treatment of Infection in Burn Patients
107
CMV infection incidence was reported at 1 : 280 and 1 : 870
in German and U.S. burn centers, respectively. When testing,
70% of German and 19% of U.S. burn centers used serol­
ogy, 52% German and 25% U.S. centers used body fluid
viral isolation, and 43% German and 6% U.S. centers used
leukocyte CMV-DNA analysis. Two-thirds of the German
and half of the U.S. centers distinguished infection from
disease. A total of 43% German and 19% U.S. centers would
subsequently treat the established disease; however, no dif­
ferences were observed in mortality.136 CMV infection is an
undesirable outcome and should always be considered in
cases of unexpected fever and hepatitis, especially in burned
children.122
Treatment of CMV infection is commonly initiated with
intravenous acyclovir or its longer-acting oral prodrug
valacyclovir, despite both demonstrating only moderate
anti-CMV activity. This is because they are inexpensive and
readily available in most hospitals. Less obtainable intra­
venous ganciclovir, a medication designed for CMV, is the
agent of choice for treatment of patients with symptoms
of significant CMV infection.137 Valganciclovir, the longer
acting oral prodrug of ganciclovir, has similar efficacy to
intravenous ganciclovir but does not require a chemother­
apy hood for preparation by the pharmacy. Thus valgan­
ciclovir has emerged as the drug of choice whenever oral
therapy is possible.138–140 Prophylactic therapy against CMV
is not recommended in burned patients.
Viral infections arising in healing burn wounds are
often attributed to HSV, particularly on the face and geni­
tals. These infections most commonly manifest as vesicles
in healing partial-thickness burns or split-thickness donor
sites (Fig. 11.12). Partial-thickness burns and donor sites
infected with herpes may convert to full-thickness inju­
ries requiring skin grafting for ultimate closure. Skin graft
donor sites can convert to full-thickness injury, also requir­
ing grafting to close.8 In the immunocompromised burn
patient, the infection usually starts with the formation of
vesicles at the edge of the wound, with these vesicles then
coalescing into a confluent raw area. A near-total loss of
epidermal coverage can occur (Fig. 11.13). Other epithe­
lial surfaces, such as oral or intestinal mucosa, can also
be involved, potentially causing erosion and perforation.
frequency of 33%.122 In this study, prospective analyses
“directly correlated CMV infection with more severe burns,
more skin grafts, and subsequent higher numbers of blood
transfusions.” In contrast Rennekapff and coworkers found
in 2007 a seroconversion rate between 18% and 22% for
burn patients seronegative for CMV prior to burn injury.127
CMV inclusions may be identified in the cells of multiple
organs but have not been reported in the burn wound.128
Immunocompromised patients have a higher frequency of
CMV infection, resulting in a broad range of adverse condi­
tions from febrile illness to systemic infections with organ
involvement.129 CMV infection has also been associated
with unexplained fever and lymphocytosis, as seen by a
concomitant rise in specific antibodies.122,128 Systemic CMV
disease is an unusual occurrence; the majority of patients
who demonstrate increased CMV-specific antibody sustain
more limited CMV infections. The absence of reports of
severely burned patients with increased CMV antibodies
suggests that most of these infections are subtle and have
been overlooked by past studies. Nevertheless a higher
number of CMV copies per milliliter of blood is associated
with a higher rate of major infections, more ventilator days,
and longer hospitalizations.130,131
Generalized, nonhealing burn wounds have been associ­
ated with CMV-related pathological changes in endothe­
lial and periendothelial cells.124 Inclusion bodies consistent
with CMV infection, as well as CMV antigens, have been
detected by immunohistochemical staining of a skin biopsy
from a transplanted cadaver allograft (from a CMV-positive
donor) on a severely burned adult male; however, the
relationship of the CMV infection to necrosis, inflamma­
tion, and increased vascularity evident in infected skin is
unknown.132 Severe burn injury has been shown to predis­
pose experimental animals to murine CMV infection, which
is associated with greater susceptibility to sepsis.133,134
Tennenhaus and colleagues surveyed and evaluated U.S.
and German burn centers for awareness, perception, diag­
nosis, and treatment of CMV in patients with burn injury.135
Fig. 11.11  Candidal retinopathy. Yeasts are an increasingly common
infectious agent in burn patients. Funduscopic examination is critical
to diagnose candidal retinal implants and determine the length and
success of antifungal treatment. The picture reveals the typical multi­
ple creamy white intra retinal lesions with hemorrhage.
Fig. 11.12  Herpetic wound infection. Herpes simplex virus type I infec­
tion in a patient with 35% partial-thickness and full-thickness burns.
Extreme pain and itching are typical of this infection.

11  •  Treatment of Infection in Burn Patients
108
cultures, PCR has thus become the standard in our burn
center.
Increased mortality, extensive visceral involvement, and
necrotizing tracheobronchitis have become associated with
herpetic infections post-burn in recent years. Fidler and
colleagues performed a retrospective study characterizing
the incidence, presentation, and outcome of 14 patients
with facial herpes rashes out of 95 severely burned intu­
bated adults. Rashes attributed to herpetic infections were
found to be present in at least 15% of patients, but no dif­
ference in mortality or length of stay between patients
with or without the infection was detected.143 Necrotizing
hepatic and adrenal lesions may lead to multisystem organ
failure. Mortality in patients with disseminated infection is
The clinical manifestations of lesions may be preceded
by unexplained fever unresponsive to routine antibiotic
coverage.141
Tzanck smears, viral cultures, and polymerase chain
reaction (PCR) are the methods of choice to diagnose her­
petic infections. Tzanck smears are a rapid, inexpensive, and
minimally invasive tool used to detect infections by cytology
over the course of the past last century (Fig. 11.14). While
they lack the diagnostic precision necessary to discriminate
between different types of Herpesviridae or even primary
versus recurrent infections, they can reveal active infec­
tions that warrant treatment.142 Viral cultures are effec­
tive means of diagnosis, but they take several days and are
expensive. More sensitive than smears and quicker than
D
C
B
A
Fig. 11.13  Fulminant herpetic infection. A 13-month-old girl with 80% TBSA scald burn who developed a fulminant herpes simplex II infection 2 weeks
after admission. (A) Ten 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. (C) The left arm, which was used twice as a donor site for
split-thickness skin graft (days 4 and 11) prior to herpetic infection. The image is from day 17, with initial manifestation of herpetic infection with red
macules. (D) Day 18 post burn; 30 hours later, conversion to confluent defects with near total loss of epidermis.

11  •  Treatment of Infection in Burn Patients
109
Fig. 11.14  Tzanck smear. This cytology can be performed rapidly as a
touch prep or as a scraping smear of a suspicious lesion. The Tzanck
smear should be performed on a fresh blister. Once identified: 1. Gently
deroof the lesion with a scalpel. 2. Scrape the base of the lesion. 3.
Smear the tissue onto a clean microscope slide. 4. Allow it to dry in the
air. 5. Fix the specimen with preservatives. 6. Stain the slide and analyze
it under microscope. Pathognomonic multinucleated giant cells are
diagnostic of a herpetic infection. While not determinant of the type
of herpes simplex virus, a test can be performed in minutes inexpen­
sively, and a positive result indicates treatment.
approximately twice that expected for patients of similar
age and burn size.
Split-thickness grafts provide adequate coverage of previ­
ously infected herpetic wounds,144 but the coverage is fre­
quently associated with secondary graft loss and the need
for reoperation and patch grafting. Furthermore skin graft
donor sites can convert to full-thickness injuries due to
active herpetic infection. As such, skin donor sites should
not be harvested for grafting for 10–14 days following
infection resolution.145 In burn patients with active her­
petic infection, intravenous acyclovir or valacyclovir should
be administered systemically for no less than 10 days and
often longer.146 Recent studies indicate that valacyclovir has
greater bioavailability and steadier plasma concentration
than acyclovir. While the best treatment remains controver­
sial, both are acceptable for herpetic infection.147
VZV infection (chickenpox) is prevalent among school-
aged children and rapidly spreads through inhalation of the
virus. While rare in burned patients, VZV infections can be
life-threatening in immunocompromised hosts, and small
epidemics have occurred within pediatric burn units.144 In
the nonimmunized pediatric population, acute VZV infec­
tion directly correlates with morbidity and mortality.148
Characteristic fluid-filled lesions appear in healed or healing
partial-thickness burns, as well as in uninjured epithelium
and mucous membranes. Owing to the fragility of newly
healed or healing skin, the vesicles are much more destruc­
tive in injured than uninjured skin and may present as hem­
orrhagic, oozing pockmarks prone to secondary infection
and subsequent scarring. Neovascularized skin grafts may
be lost, and further grafting procedures should be delayed
until the lesions are quiescent. Antiviral treatment with
acyclovir is indicated in case of infection and, as suggested
by Sheridan and colleagues, should be given prophylacti­
cally to nonimmunized pediatric patients.148 The thera­
peutic effect of antiviral agents administered post-burn
remains to be fully elucidated, as recently elaborated by
Wurzer and Lee.149
Infections From Sources Other
Than Wounds in the Burn Patient
Pneumonia is a leading cause of morbidity and mortality
in burn patients.1 Inciting infectious organisms can enter
the lung either through direct contamination of the airway
or hematogenously. Mechanical ventilation increases the
risk of pneumonia; patients should be extubated as soon
as clinically possible to prevent ventilator-assisted pneu­
monia (VAP), as discussed in Chapter 32 on critical care.
Inhalation injury further increases the risk of VAP. Carry­
ing a worse prognosis than pneumonias originating in the
airways, the hematogenous etiology of pneumonia presents
later in the hospital course and is often bilateral. Etiological
organisms typically match those colonizing or infecting the
burn wounds. Centers for Disease Control clinical diagnos­
tic criteria of pneumonia are as follows: (1) chest X-ray
revealing a new and persistent infiltrate, consolidation, or
capitation3,95 (Fig. 11.15); (2) sepsis (as defined for burn
patients); and (3) a change or purulence in expectorated
or aspirated sputum. If two of these criteria are found, a
clinical diagnosis of pneumonia is then made, and, prior to
the start of antimicrobial treatments, specimens should be
collected for microbial analysis.
Tracheal aspirate, bronchoalveolar lavage (BAL), or pro­
tected bronchial brush (PBB) is performed to obtain a speci­
men. In burn patients, the possibility exists to use surface
quantitative wound cultures (QWC) to predict pathogens
found in VAP. Ramzy et al. investigated the relationship
between burn wound flora and microbial pathogens in the
tracheobronchial tree and found a 48% match. However,
when strict quantitative criteria were applied, the match
Fig. 11.15  Left lower pneumonia. Burn patient with typical radio­
graphic picture of lobar pneumonia. The diagnosis of pneumonia in
patients with inhalation injury and respiratory distress syndrome is still
arduous.

11  •  Treatment of Infection in Burn Patients
110
Cultures should be performed of both the blood and cathe­
ters for evaluation as potential causes of sepsis. When there
is concern of sepsis, dogmatic culturing of removed vascu­
lar access devices and blood is crucial to proper burn criti­
cal care. Rates of catheter-associated infection and septic
thrombophlebitis in burn patients are as high as 57%.153–155
One of the following two criteria must be met to diagnose
a bloodstream infection: (1) the patient has two or more
positive blood cultures for a known pathogen or one positive
blood culture in the presence of sepsis, or (2) the patient has
a common skin contaminant cultured from two or more
blood cultures on separate occasions, as well as sepsis.3 The
bloodstream infection is considered primary if the same
organism has not been cultured at another site. If the same
organism is cultured at an alternate location, the blood­
stream infection is considered secondary. A catheter-related
bloodstream infection is present if a patient has sepsis and
no other source of infection and if the signs of sepsis resolve
within 24 hours of catheter removal. Unfortunately these
administrative definitions do not often comport with the
patient’s clinical course and, generally, CLABSI is overdi­
agnosed. However, it is imperative to place the concerns of
proper patient care and diagnosis exemplified by potential
source control, early empiric antibiotics, and liberal use of
cultures above inaccurate administrative definitions that
fail to improve patient health.
Franchesi and coworkers156 reported a 50% correspon­
dence between the organisms cultured from the tip and
connectors of the catheter within 2 days of placement.
Furthermore, they found that a negative correlation existed
between the frequency of catheter infection and the dis­
tance separating the point of catheter insertion from the
burn wound. These data support the hypothesis that cath­
eter infections arise primarily from burn wound contami­
nation migrating to the catheter tip. Serious complications
can often be avoided by following strict aseptic techniques.
General guidelines for protecting against catheter-related
infections are157: training health care staff on the correct
procedures for inserting and maintaining catheters, includ­
ing indications and suitable infection control practices; use
of a mask, hat, gown, sterile gloves, and drapes during place­
ment of CVCs; use of 2% chlorhexidine to prevent infection;
and avoiding routine CVC changes. In the event that infec­
tion continues despite adhering to the guidelines, use short-
term CVCs coated with an antibiotic, antiseptic, or both.
Suppurative thrombophlebitis should be suspected
in patients with persistent positive blood cultures in the
absence of signs of local infection. Often suppuration can
occur subsequent to catheter removal, so cultures at the
time of removal may be unreliable predictors of infection.
Gross clinical signs of suppurative thrombophlebitis are fre­
quently not present.158 Upon confirmation of the diagnosis,
immediate operative excision is essential to prevent progres­
sive sepsis. Entire excision of a vein to the port of entry into
the central circulation may be necessary because phlebi­
tis tends to migrate to vein valves, leaving an apparently
normal vein between infected foci. The subcutaneous tissue
and skin should be packed open where a grossly purulent
vein is removed and allowed to granulate and close by sec­
ondary intention (Fig. 11.16).
Gastrointestinal infections can limit clinical examina­
tion, thereby complicating burn care. Like all patients,
rate fell to 14%. Burn size and inhalation injury had no
significant effect on match rate.150 The difference between
qualitative and quantitative match rates suggests cross-
colonization between the burn wound and tracheobron­
chial tree but little to no cross-infection. Thus both QWC
and BLF cultures must be performed when determining
antimicrobial specificity in the burned patient. However,
wound cultures can be helpful in guiding empiric treatment
for VAP and should be covered until BAL or PBB samples
allow for culture-directed therapy.
BAL and PBB are recommended over tracheal aspirate for
definitive diagnosis and treatment of VAP.151 Positive micro­
biological results are tracheal aspirate showing 105 or more
colony-forming units (CFU); BAL, 104 or more organisms;
and PBB, 103 or more organisms. The data subsequently
modify the clinical diagnosis in one of three ways:
■ If a pathogen is isolated in sufficient quantities, then
the clinical diagnosis is confirmed.
■ If the clinical diagnosis was strong but the microbio­
logic data fail to confirm, then the diagnosis is probable.
■ With low or moderate clinical suspicion, but with the
presence of a positive specimen, the pneumonia diag­
nosis is possible.
In many quality assurance programs, a clinical diagnosis
cannot be vacated by a lack of confirmation by the micro­
biology report, often resulting in inappropriately diagnosed
and treated VAP.3 In a 2005 study, Wahl and colleagues
reported that negative BAL results (<104 CFU) reduced the
clinical VAP diagnosis rate by 21%. Negative BAL results
prompted the discontinuation of antibiotics administered
based on clinical suspicion of VAP. In this study, none of the
patients whose antibiotics were discontinued had antibiot­
ics restarted based on clinical grounds.152
Regardless the tenets of pneumonia treatment remain
consistent with standard critical care. Broad-spectrum anti­
biotics are instituted empirically to cover all likely etiologic
agents. Utilization of ventilator support allows the patient
to oxygenate and ventilate. Clinical diagnosis is made and
confirmed with tracheal or bronchial cultures. Antibiotics
are changed to treat the identified etiologic pathogen and
discontinued after a finite course or when cultures are nega­
tive and the clinical condition resolved.67
Bloodstream infections in burn patients develop from
a myriad of sources: burn wounds, urinary tract infec­
tions, pneumonias, translocation from the gut, or from the
intravenous and intra-arterial lines essential to their care.
Treatment of bloodstream infections is the same as for all
infections: source control by removal of possible etiological
causes, early institution of broad-spectrum antibiotics cov­
ering likely organisms, cultures of the blood and potential
sources to make a definitive diagnosis, tailoring antimicro­
bials to the cultures, and discontinuation of the antibiotics
following the course of treatment.67 In most major burn
patients, vascular access devices are requisite for treat­
ment. Many central venous catheters (CVCs) must be placed
through burned tissue or cannot have standard dressings
applied due to poor skin quality or wound therapy. These
limitations are known to increase central line–associated
bloodstream infection (CLABSI) risk but are required for
care. If burn patients demonstrate symptoms of SIRS or
sepsis, their catheters should be removed or changed.

11  •  Treatment of Infection in Burn Patients
111
Fungi can lead to urinary tract infections in burn patients.
These organisms are often introduced via the prolonged or
unnecessary use of urinary catheters. This underlines, once
again, the importance of infection prevention following the
guidelines repeated earlier (e.g., aseptic techniques, cath­
eter care, routine urine monitoring, and early removal). In
some burn patients, especially those with genital burns or
protracted shock, a prolonged catheterization may be well
indicated, balancing the elevated risk of infection against
the care benefit. If infection develops, patients should have
their catheters removed or changed, urine cultured, appro­
priate empiric antibiotics administered, and then culture-
directed antimicrobials utilized. In cases of highly resistant
pathogens, urinary catheters may need to be discontinued,
with the patient only intermittently catheterized.163
Chondritis typically occurs in full-thickness injuries to
the ear resulting in infection of the auricular cartilage.
The auricles have a comparatively low blood supply, and
chondritis frequently follows tissue ischemia. Chondritis
usually presents 3–5 weeks after thermal injury but may
be seen earlier and may develop following partial-thickness
injuries. Mafenide acetate cream has become the topical
agent of choice for burned cartilaginous surfaces like the
ear because it coats and adheres to the irregular surfaces
well while deeply penetrating the wound and saturating
the cartilage to prophylactically guard it against infection.
With its use, the incidence of suppurative chondritis has
significantly decreased164 (Fig. 11.17). Chondritis presents
with dull pain and a warm, red, tender, and edematous
ear. Appropriate antibiotics should be immediately admin­
istered, and, if there is an identifiable site, the abscess
immediately excised and drained, with culture and sensi­
tivity obtained. Should induration and tenderness persist,
a more extensive débridement is imperative. Generally the
helix is bivalved at the posterior helical margin and all
necrotic cartilage débrided. Difficulty may arise in distin­
guishing between viable and necrotic tissue, and normal
cartilage is frequently sacrificed to ensure débridement.
However, infected cartilage is usually soft, whereas normal
cartilage will feel granular on curettage. If appropriate and
sufficient excision of the necrotic tissue is not performed,
the auricle can auto-amputate and suppurative chondritis
can invade the mastoid bone, potentiating the formation of
intracranial abscesses.165
Ophthalmic infections occur from injuries suffered in the
initial trauma, from corneal exposure due to poor lid func­
tion due to edema or facial burns, herpetic reactivation,
or hematogenous spread of infection. Corneal injury can
lead to bacterial infection with subsequent corneal perfo­
ration and loss of the eye. The cornerstone of treatment
is prevention through treatment of abrasions with topical
antimicrobial agents, early eyelid release, and vigilance in
protecting against risk of exposure trauma.166 In incapaci­
tated patients, the entire burn team must be vigilant and
monitor the eye for injuries and infection. This topic is dis­
cussed in depth in Chapter 43 on burn injuries of the eye.
Suppurative sinusitis is an uncommon infection but can
cause ICU sepsis. In patients with no identifiable source of
sepsis, diagnosis can be made based on X-rays or CT scans.
Therapy with broad-spectrum antibiotics and promotion of
drainage should be initiated immediately. Surgical drainage
of the involved sinuses may be necessary if the infection is
those burned can develop conditions such as appendici­
tis, intussusception, ileus, and bowel obstruction. Ascetic
fluid or peritoneal dialysis fluid can also become infected.
Larger burns are associated with episodes of hypoperfusion,
leading to sloughing of intestinal mucosa. Heme-positive
mucoid, watery stools, abdominal distension, and dimin­
ished bowel sounds often characterize this condition. Diar­
rhea is a common issue, and osmotic causes from feeds
should be excluded by testing for reducing substances. C.
difficile is a well-known entity in critically ill patients, espe­
cially those with a history of antibiotic use and in immuno­
compromised patients. Current guidelines for the treatment
of the first episode of C. difficile include oral or intravenous
metronidazole, oral or rectal vancomycin, and fidaxomi­
cin.159 Possible complications due to C. difficile infections
can be pseudomembranous colitis with the potential to
progress to fulminant toxic colitis and bowel perforation.
Should any of these develop, subtotal or total abdominal
colectomy with an ileostomy may be required.160 A loop ile­
ostomy with colonic lavage using postoperative vancomycin
colonic flushes via the ileostomy is an alternative surgical
approach with perhaps lower morbidity and mortality.161
Necrotizing enterocolitis can occur in patients severely
granulocytopenic from any cause, including burn. Splenic
enlargement and tenderness are often present, along with
high fever. Chest X-ray may reveal an elevated left hemi­
diaphragm, basilar pulmonary infiltrates, atelectasis, or a
left pleural effusion, while abdominal X-rays can demon­
strate a shift of the colon and stomach down and to the
right, extraintestinal or bowel wall gas, or air–fluid levels
in the upper left quadrant. Ultrasonography and computed
tomography (CT) are the preferred diagnostic techniques
for the determination of suspected splenic abscess and nec­
rotizing enterocolitis. As with all infections, initial antibiotic
therapy should have a broad spectrum of activity. A combi­
nation of antibiotics with activity against both aerobic and
anaerobic gram-negative bacilli would be most appropriate.
Free air or suspected necrotic bowel due to an unresolving
lactic acidosis are indications for a laparotomy.162
Genitourinary infections occur from indwelling urinary
catheters or hematogenous dissemination of bacteria.
Fig. 11.16  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.

11  •  Treatment of Infection in Burn Patients
112
adult population. In the United States, the incidence is much
lower, but since people with HIV do get burned, care of this
disease in the burn unit is worth consideration. HIV seems
to have an additive effect on the immunosuppression of the
burn, as reflected in the CD4/CD8 cell counts. In a 2003
prospective study from Zimbabwe, Mzezewa and colleagues
found that graft survival after split-thickness skin grafting
of burn wounds in HIV-infected patients was impaired and
hospital stay was prolonged, with significant alterations in
the levels of pro- and antiinflammatory cytokines.169 The
authors concluded that HIV infection results in immune
dysregulation, which might be related to impaired skin graft
survival. Recent data have emerged describing a substantial
burden of sepsis in the infected population receiving highly
active antiretroviral therapy, in addition to a much poorer
prognosis in this group compared with the uninfected pop­
ulation. Although there is a lack of literature regarding
the implications of antiretroviral medications on burned
patients and the effect on wound healing and graft take,
using antiretroviral therapy to reduce septic incidences
should be considered.170
Conclusion
Treatment of infection in the burn patient follows the same
algorithm dominating treatment of all infections in every
critically ill patient: (1) early source control, (2) culture
identification of infecting microbes, (3) early institution of
empiric antimicrobials with subsequent transition to
culture-directed antibiotics when sensitivities are ascer­
tained, and (4) discontinuation of antimicrobials following
the administration of a sufficient course or when the
wounds are closed. The considerations specific to burn care
are (1) source control is determined by excising the burn
wound and covering it with skin graft, (2) aggressive use of
quantitative wound cultures guides antimicrobial selection,
and (3) careful and frequent evaluation to diagnose sepsis
and treatment with empiric antibiotics when indicated.
unresponsive to the antibiotics. In the ICU, transnasal intu­
bation and the use of nasogastric or nasoduodenal tubes for
enteral feeding are considered risk factors. However, in 25
years of routine nasotracheal intubations and routine pro­
longed nasojejunal and nasogastric tube placements, we
have not encountered a single case of suppurative sinusitis
in Galveston. Oral intubation and nasogastric feeding may
be employed as temporary measures, but if sinusitis becomes
complicated and prolonged treatment is necessary, then a
tracheostomy and/or orogastric feeding is indicated.
Folliculitis is an infection commonly occurring on the
scalp, male face, and scalp skin graft donor sites. As in the
case of impetigo, cultures commonly reveal S. aureus, partic­
ularly MRSA (Fig. 11.18). Treatment consists of twice-daily
cleansing with soap and water, unroofing any abscesses,
and twice-daily application of mupirocin. Shaving the hair
is helpful both prophylactically and for treatment. Keratin­
ocytes in the viable hair shafts allow rapid reepithelial­
ization once bacterial counts are brought under control.
Excision and grafting is rarely required.
Tetanus is a rare complication of burn wounds in the
developed world. Routine prophylaxis at admission with
0.5 mL tetanus toxoid is given, if it has not been admin­
istered in the previous 3 years.167,168 In addition, if the
patient’s last booster was more than 10 years prior, 250 U
of tetanus antitoxin is also administered. Should Clostrid­
ium tetani, an anaerobic gut flora of ruminants, colonize
or infect a burn wound in an unvaccinated individual,
the resulting intoxication can lead to a horrific and easily
avoided mortality.
HIV infection is endemic in areas such as sub-Saharan
Africa; some countries have rates of 35%–39% in the total
Fig. 11.17  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.
Fig. 11.18  Chronic folliculitis of 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 healing process. Shaving of the affected area, topical treatment
with mupirocin, and cleansing with soap and water typically resolve
this problem in several days to a week.

11  •  Treatment of Infection in Burn Patients
113
tailoring of antimicrobials to the patient’s infecting micro­
biota, thereby reducing toxicity from superfluous antibiot­
ics. All vascular access devices removed from a burn patient
should be cultured to ensure that any colonizing or infect­
ing bacteria are identified, correct diagnoses are made, and
antimicrobial sensitivities are monitored.
Due to their hypermetabolic states, determining when a
burn patient is septic is complicated. When a presumptive
diagnosis of sepsis is made, broad-spectrum coverage should
be instituted to cover all likely pathogens. The choice of
initial agent is based on the local antibiogram; in many
burn centers, carbapenems and vancomycin are appropri­
ate choices. Once sensitivities return, empiric antibiotics
should be de-escalated.
The ultimate infection control method in burn care is
closing the burn wound with skin. In the setting of pan-
resistant organisms, this is the only treatment. Every time
the patient has skin available for grafting, this opportunity
must be exploited to reduce the wound surface area avail­
able to pathogens and provide definitive prophylaxis and
treatment of burn wound infections.
Complete references available online at

All eschar must be excised as quickly as possible, ideally
within the first 48 hours post-burn, because eschar pro­
vides an ideal microbial culture medium. Burn wounds
should be closed as rapidly as feasible with autograft. The
tenet, “every donor, every time” should be employed in all
large burns: every area of donor skin should be harvested
and autograft applied at every operation. When insufficient
autograft is available to cover the wounds, homograft
should be used to temporize wounds. Homograft overlay of
widely expanded autograft, in the methodology of Alexan­
der, is an effective way to limit the wound surface area avail­
able to pathogens and maximize utilization of finite donor
areas, as detailed in Chapter 12 on operative wound man­
agement. Every moment a burn wound lacks a complete
epithelial surface, there is a cumulative risk for wound
infection and resistant organisms to take hold. Source
control is also obtainable by assiduous washing and débrid­
ing in hydrotherapy, which has been demonstrated to be an
indispensible component of modern burn care. High con­
centrations of antimicrobials can and should be delivered
topically to burn wounds for colonization and infection
treatment and for prophylaxis.
Aggressive use of quantitative wound cultures is the
standard of care in modern burn wound management, and
sensitivities determined from these studies direct effective

113.e1
11  •  Treatment of Infection in Burn Patients
27. Greenhalgh DG. Topical antimicrobial agents for burn wounds. Clin
Plast Surg. 2009;36(4):597-606.
28. Glasser JS, Guymon CH, Mende K, et al. Activity of topical antimicro­
bial agents against multidrug-resistant bacteria recovered from burn
patients. Burns. 2010;36(8):1172-1184.
29. Dai T, Huang YY, Sharma SK, et al. Topical antimicrobials
for burn wound infections. Recent Pat Antiinfect Drug Discov.
2010;5(2):124-151.
30. Burmolle M, Thomsen TR, Fazli M, et al. Biofilms in chronic infec­
tions – a matter of opportunity – monospecies biofilms in multispe­
cies infections. FEMS Immunol Med Microbiol. 2010;59(3):324-336.
31. Bianchi T, Wolcott RD, Peghetti A, et al. Recommendations for
the management of biofilm: a consensus document. J Wound Care.
2016;25(6):305-317.
32. Kennedy P, Brammah S, Wills E. Burns, biofilm and a new appraisal
of burn wound sepsis. Burns. 2010;36(1):49-56.
33. Wilkins RG, Unverdorben M. Wound cleaning and wound healing: a
concise review. Adv Skin Wound Care. 2013;26(4):160-163.
34. Dusane DH, Rajput JK, Kumar AR, et al. Disruption of fungal
and bacterial biofilms by lauroyl glucose. Lett Appl Microbiol.
2008;47(5):374-379.
35. Seo Y, Bishop PL. Influence of nonionic surfactant on attached
biofilm formation and phenanthrene bioavailability during simu­
lated surfactant enhanced bioremediation. Environ Sci Technol.
2007;41(20):7107-7113.
36. Eginton PJ, Holah J, Allison DG, Handley PS, Gilbert P. Changes in
the strength of attachment of micro-organisms to surfaces following
treatment with disinfectants and cleansing agents. Lett Appl Micro­
biol. 1998;27(2):101-105.
37. Fader RC, Maurer A, Stein MD, Abston S, Herndon DN. Sodium hypo­
chlorite decontamination of split-thickness cadaveric skin infected
with bacteria and yeast with subsequent isolation and growth of
basal cells to confluency in tissue culture. Antimicrob Agents Che­
mother. 1983;24(2):181-185.
38. Cotter JL, Fader RC, Lilley C, Herndon DN. Chemical parame­
ters, antimicrobial activities, and tissue toxicity of 0.1 and 0.5%
sodium hypochlorite solutions. Antimicrob Agents Chemother.
1985;28(1):118-122.
39. Smith RA. Clorpactin XCB: its use in urology in the surgical treat­
ment of malignant neoplasms. J Urol. 1959;81(4):554-557.
40. Castigliano SG, Shigeoka EH. Incidence of skin graft “takes” after clo­
rpactin XCB wound irrigation in cancer surgery. A preliminary study
on acceptance of human skin grafts. Arch Surg. 1960;81:992-996.
41. Wang L, Bassiri M, Najafi R, et al. Hypochlorous acid as a potential
wound care agent: Part I. Stabilized hypochlorous acid: a compo­
nent of the inorganic armamentarium of innate immunity. J Burns
Wounds. 2007;6:e5.
42. Robson MC, Payne WG, Ko F, et al. Hypochlorous acid as a potential
wound care agent: Part II. Stabilized hypochlorous acid: its role in
decreasing tissue bacterial bioburden and overcoming the inhibition
of infection on wound healing. J Burns Wounds. 2007;6:e6.
43. Gelmetti C. Local antibiotics in dermatology. Dermatol Ther.
2008;21(3):187-195.
44. Georgiade NG, Harris WA. Open and closed treatment of burns with
povidone-iodine. Plast Reconstruct Surg. 1973;52(6):640-644.
45. Nagoba BS, Selkar SP, Wadher BJ, Gandhi RC. Acetic acid treatment
of pseudomonal wound infections—a review. J Infect Public Health.
2013;6(6):410-415.
46. Phillips I, Lobo AZ, Fernandes R, Gundara NS. Acetic acid in the
treatment of superficial wounds infected by Pseudomonas aeruginosa.
Lancet. 1968;1(7532):11-14.
47. Sloss JM, Cumberland N, Milner SM. Acetic acid used for the elimina­
tion of Pseudomonas aeruginosa from burn and soft tissue wounds. J
R Army Med Corps. 1993;139(2):49-51.
48. Nagoba BS, Deshmukh SR, Wadher BJ, Patil SB. Acetic acid treat­
ment of pseudomonal postoperative wound infection. J Hosp Infect.
1997;36(3):243-244.
49. Duc Q, Breetveld M, Middelkoop E, et al. A cytotoxic analysis of anti­
septic medication on skin substitutes and autograft. Br J Dermatol.
2007;157(1):33-40.
50. Duran N, Duran M, de Jesus MB, et al. Silver nanoparticles: a new
view on mechanistic aspects on antimicrobial activity. Nanomedicine
(Lond). 2016;12(3):789-799.
51. Politano AD, Campbell KT, Rosenberger LH, Sawyer RG. Use of silver
in the prevention and treatment of infections: silver review. Surg
Infect (Larchmt). 2013;14(1):8-20.
References
1. National Burn Repository Chicago 2015.
2. 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.
3. Greenhalgh DG, Saffle JR, Holmes JHT, et al. American Burn Asso­
ciation consensus conference to define sepsis and infection in burns.
J Burn Care Res. 2007;28(6):776-790.
4. Teplitz C, Davis D, Mason AD Jr, Moncrief JA. Pseudomonas burn
wound sepsis. I Pathogenesis of experimental Pseudomonas burn
wound sepsis. J Surg Res. 1964;4:200-216.
5. Robson MC, Krizek TJ, Heggers JP. Biology of surgical infection. Curr
Probl Surg. 1973;1–62.
6. Pruitt BA Jr, McManus AT, Kim SH, Goodwin CW. Burn wound infec­
tions: current status. World J Surg. 1998;22(2):135-145.
7. Robson MC. Bacterial control in the burn wound. Clin Plast Surg.
1979;6(4):515-522.
8. Barret JP, Herndon DN. Effects of burn wound excision on bacterial
colonization and invasion. Plast Reconstr Surg. 2003;111(2):744-
750, discussion 751-752.
9. Altoparlak U, Erol S, Akcay MN, Celebi F, Kadanali A. The time-
related changes of antimicrobial resistance patterns and predomi­
nant bacterial profiles of burn wounds and body flora of burned
patients. Burns. 2004;30(7):660-664.
10. Rutala WA, Weber DJ. Are room decontamination units needed to
prevent transmission of environmental pathogens? Infect Control
Hosp Epidemiol. 2011;32(8):743-747.
11. Trick WE, Vernon MO, Hayes RA, et al. Impact of ring wearing on
hand contamination and comparison of hand hygiene agents in a
hospital. Clin Infect Dis. 2003;36(11):1383-1390.
12. Karabay O, Kocoglu E, Tahtaci M. The role of mobile phones in the
spread of bacteria associated with nosocomial infections. J Infect Dev
Ctries. 2007;1:72-73.
13. Snyder GM, Thom KA, Furuno JP, et al. Detection of methicillin-
resistant Staphylococcus aureus and vancomycin-resistant entero­
cocci on the gowns and gloves of healthcare workers. Infect Control
Hosp Epidemiol. 2008;29(7):583-589.
14. Taddonio TE, Thomson PD, Smith DJ Jr, Prasad JK. A survey of
wound monitoring and topical antimicrobial therapy practices in the
treatment of burn injury. J Burn Care Rehabil. 1990;11(5):423-427.
15. Kwei J, Halstead FD, Dretzke J, Oppenheim BA, Moiemen NS. Protocol
for a systematic review of quantitative burn wound microbiology in
the management of burns patients. Syst Rev. 2015;4:150.
16. Miles AA, Misra SS, Irwin JO. The estimation of the bactericidal
power of the blood. J Hyg (Lond). 1938;38(6):732-749.
17. Steer JA, Papini RP, Wilson AP, McGrouther DA, Parkhouse N. Quanti­
tative microbiology in the management of burn patients. II. Relation­
ship between bacterial counts obtained by burn wound biopsy culture
and surface alginate swab culture, with clinical outcome following
burn surgery and change of dressings. Burns. 1996;22(3):177-181.
18. Mayhall CG. The epidemiology of burn wound infections: then and
now. Clin Infect Dis. 2003;37(4):543-550.
19. White MC, Thornton K, Young AE. Early diagnosis and treatment
of toxic shock syndrome in paediatric burns. Burns. 2005;31(2):
193-197.
20. Pruitt BA Jr, Foley FD. The use of biopsies in burn patient care.
Surgery. 1973;73(6):887-897.
21. Robson MC, Krizek TJ. Predicting skin graft survival. J Trauma.
1973;13(3):213-217.
22. Napolitano LM. Severe soft tissue infections. Infect Dis Clin North Am.
2009;23(3):571-591.
23. Heggers JP, Sazy JA, Stenberg BD, et al. Bactericidal and wound-heal­
ing properties of sodium hypochlorite solutions: the 1991 Lindberg
Award. J Burn Care Rehabil. 1991;12(5):420-424.
24. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ
failure and guidelines for the use of innovative therapies in sepsis.
The ACCP/SCCM Consensus Conference Committee. American
College of Chest Physicians/Society of Critical Care Medicine. Chest.
1992;101(6):1644-1655.
25. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/
ATS/SIS International Sepsis Definitions Conference. Crit Care Med.
2003;31(4):1250-1256.
26. Calandra T, Cohen J. The international sepsis forum consensus con­
ference on definitions of infection in the intensive care unit. Crit Care
Med. 2005;33(7):1538-1548.

113.e2 11  •  Treatment of Infection in Burn Patients
79. Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines
for the management of candidiasis: 2009 update by the Infectious
Diseases Society of America. Clin Infect Dis. 2009;48(5):503-535.
80. Pappas PG, Kauffman CA, Andes DR, et al. Executive summary:
Clinical Practice Guideline for the Management of Candidiasis: 2016
Update by the Infectious Diseases Society of America. Clin Infect Dis.
2016;62(4):409-417.
81. Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline
for the Management of Candidiasis: 2016 Update by the Infectious
Diseases Society of America. Clin Infect Dis. 2016;62(4):e1-e50.
82. Alangaden GJ. Nosocomial fungal infections: epidemiology,
infection control, and prevention. Infect Dis Clin North Am.
2011;25(1):201-225.
83. Hope W, Morton A, Eisen DP. Increase in prevalence of nosocomial
non-Candida albicans candidaemia and the association of Candida
krusei with fluconazole use. J Hosp Infect. 2002;50(1):56-65.
84. Malani AN, Kerr LE, Kauffman CA. Voriconazole: how to use this
antifungal agent and what to expect. Semin Respir Crit Care Med.
2015;36(5):786-795.
85. Boucher HW, Groll AH, Chiou CC, Walsh TJ. Newer systemic
antifungal agents: pharmacokinetics, safety and efficacy. Drugs.
2004;64(18):1997-2020.
86. Saliba F, Dupont B. Renal impairment and amphotericin B for­
mulations in patients with invasive fungal infections. Med Mycol.
2008;46(2):97-112.
87. Ellis D. Amphotericin B: spectrum and resistance. J Antimicrob Che­
mother. 2002;49(suppl 1):7-10.
88. Murray PRBE. Manual of Clinical Microbiology. 8th ed. Washington,
DC: American Society for Microbiology; 2003.
89. Cook N. Methicillin-resistant Staphylococcus aureus versus the burn
patient. Burns. 1998;24(2):91-98.
90. de Macedo JL, Rosa SC, Castro C. Sepsis in burned patients. Rev Soc
Bras Med Trop. 2003;36(6):647-652.
91. Edwards-Jones V, Greenwood JE. What’s new in burn microbiology?
James Laing Memorial Prize Essay 2000. Burns. 2003;29(1):15-24.
92. Prasanna M, Thomas C. A profile of methicillin resistant Staphylo­
coccus aureus infection in the burn center of the Sultanate of Oman.
Burns. 1998;24(7):631-636.
93. Thabet L, Turki A, Ben Redjeb S, Messadi A. Profil bacteriologique et
resistance aux antibiotiques des bacteries isolees dans un service de
reanimation des brules durant deux ans. [Bacteriological profile and
antibiotic resistance of bacteria isolates in a burn department]. Tunis
Med. 2008;86(12):1051-1054.
94. Wilson GR, French GW, Sully L. Loss of split thickness skin grafts due
to non-group A beta-haemolytic streptococci. Ann R Coll Surg Engl.
1988;70(4):217-219.
95. von Baum H, Ober JF, Wendt C, Wenzel RP, Edmond MB. Antibiotic-
resistant bloodstream infections in hospitalized patients: specific risk
factors in a high-risk population? Infection. 2005;33(5-6):320-326.
96. Gonzalez MR, Fleuchot B, Lauciello L, et al. Effect of human burn
wound exudate on Pseudomonas aeruginosa virulence. mSphere.
2016;1(2).
97. McManus AT, Mason AD Jr, McManus WF, Pruitt BA Jr. Twenty-five
year review of Pseudomonas aeruginosa bacteremia in a burn center.
Eur J Clin Microbiol. 1985;4(2):219-223.
98. Walton MA, Villarreal C, Herndon DN, Heggers JP. The use of aztreo­
nam as an alternate therapy for multi-resistant Pseudomonas aerugi­
nosa. Burns. 1997;23(3):225-227.
99. Zarrilli R, Crispino M, Bagattini M, et al. Molecular epidemiology of
sequential outbreaks of Acinetobacter baumannii in an intensive care
unit shows the emergence of carbapenem resistance. J Clin Microbiol.
2004;42(3):946-953.
100. Chim H, Tan BH, Song C. Five-year review of infections in a burn
intensive care unit: high incidence of Acinetobacter baumannii in a
tropical climate. Burns. 2007;33(8):1008-1014.
101. Corbella X, Montero A, Pujol M, et al. Emergence and rapid spread
of carbapenem resistance during a large and sustained hospital
outbreak of multiresistant Acinetobacter baumannii. J Clin Microbiol.
2000;38(11):4086-4095.
102. Albrecht MC, Griffith ME, Murray CK, et al. Impact of Acineto­
bacter infection on the mortality of burn patients. J Am Coll Surg.
2006;203(4):546-550.
103. Friedman ND, Korman TM, Fairley CK, Franklin JC, Spelman DW.
Bacteraemia due to Stenotrophomonas maltophilia: an analysis of 45
episodes. J Infect. 2002;45(1):47-53.
52. Heggers J. The use of antimicrobial agents. Clin Plast Surg. 1979;6(4):
545-551.
53. Aziz Z, Abu SF, Chong NJ. A systematic review of silver-containing
dressings and topical silver agents (used with dressings) for burn
wounds. Burns. 2012;38(3):307-318.
54. Chattopadhyay A, Chang K, Nguyen K, et al. An inexpensive bis­
muth-petrolatum dressing for treatment of burns. Plast Reconstr
Surg Glob Open. 2016;4(6):e737.
55. Diggle FH. The value of “Bipp” in primary operations for gunshot
wounds of joints. Br Med J. 1919;1(3045):572-573.
56. Nigam A, Allwood MC. BIPP: how does it work? Clin Otolaryngol
Allied Sci. 1990;15(2):173-175.
57. Atwal A, Cousin GC. Bismuth toxicity in patients treated with bismuth
iodoform paraffin packs. Br J Oral Maxillofac Surg. 2016;54(1):
111-112.
58. Ovaska H, Wood DM, House I, et al. Severe iatrogenic bismuth poi­
soning with bismuth iodoform paraffin paste treated with DMPS
chelation. Clin Toxicol (Phila). 2008;46(9):855-857.
59. Mendelson JA. Topical mafenide hydrochloride aqueous spray in
initial management of massive contaminated wounds with devital­
ized tissue. Prehosp Disaster Med. 2001;16(3):172-174.
60. Mulcahy LR, Isabella VM, Lewis K. Pseudomonas aeruginosa biofilms
in disease. Microb Ecol. 2014;68(1):1-12.
61. Denning DW, Haiduven-Griffiths D. Eradication of low-level methi­
cillin-resistant Staphylococcus aureus skin colonization with topical
mupirocin. Infect Control Hosp Epidemiol. 1988;9(6):261-263.
62. Strock LL, Lee MM, Rutan RL, et al. Topical Bactroban (mupirocin):
efficacy in treating burn wounds infected with methicillin-resistant
staphylococci. J Burn Care Rehabil. 1990;11(5):454-459.
63. Tao L, Zhou J, Gong Y, et al. Risk factors for central line-associated
bloodstream infection in patients with major burns and the efficacy
of the topical application of mupirocin at the central venous catheter
exit site. Burns. 2015;41(8):1831-1838.
64. Barret JP, Ramzy PI, Heggers JP, et al. Topical nystatin powder in
severe burns: a new treatment for angioinvasive fungal infections
refractory to other topical and systemic agents. Burns. 1999;25
(6):505-508.
65. White CE, Renz EM. Advances in surgical care: management of
severe burn injury. Crit Care Med. 2008;36(7 suppl):S318-S324.
66. Enoch S, Roshan A, Shah M. Emergency and early management of
burns and scalds. Br Med J. 2009;338:b1037.
67. Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign
guidelines for management of severe sepsis and septic shock. Crit
Care Med. 2004;32(3):858-873.
68. Martyn J. Clinical pharmacology and drug therapy in the burned
patient. Anesthesiology. 1986;65(1):67-75.
69. McEvoy GK. AHFS Drug Information Essentials. Bethesda, MD: Ameri­
can Society of Health-System Pharmacists; 2004.
70. Rybak MJ. The pharmacokinetic and pharmacodynamic properties
of vancomycin. Clin Infect Dis. 2006;42(suppl 1):S35-S39.
71. Branski LK, Al-Mousawi A, Rivero H, et al. Emerging infections in
burns. Surg Infect (Larchmt). 2009;10(5):389-397.
72. Arizpe A, Reveles KR, Patel SD, Aitken SL. Updates in the manage­
ment of cephalosporin-resistant gram-negative bacteria. Curr Infect
Dis Rep. 2016;18(12):39.
73. Vigliarolo L, Ramirez MS, Centron D, Lopardo H. Influencia de la con­
centracion inhibitoria minima de penicilina en la accion sinergica de
su combinacion con gentamicina frente a estreptococos del grupo
viridans. [Influence of penicillin minimum inhibitory concentration
in the synergy between penicillin and gentamicin in viridans-group
streptococci]. Rev Argent Microbiol. 2007;39(2):107-112.
74. Liao CH, Huang YT, Tsai HY, Hsueh PR. In vitro synergy of ampicillin
with gentamicin, ceftriaxone and ciprofloxacin against Enterococcus
faecalis. Int J Antimicrob Agents. 2014;44(1):85-86.
75. Roberts DM. The relevance of drug clearance to antibiotic dosing
in critically ill patients. Curr Pharm Biotechnol. 2011;12(12):2002-
2014.
76. Kunin CM, Bugg A. Recovery of tissue bound polymyxin B and colis­
timethate. Proc Soc Exp Biol Med. 1971;137(3):786-790.
77. Kunin CM, Bugg A. Binding of polymyxin antibiotics to tissues: the
major determinant of distribution and persistence in the body. J Infect
Dis. 1971;124(4):394-400.
78. Leroy O, Mira JP, Montravers P, Gangneux JP, Lortholary O. Compari­
son of albicans vs. non-albicans candidemia in French intensive care
units. Crit Care. 2010;14(3):R98.