1. Advances in burn critical care
Kyros Ipaktchi, MD; Saman Arbabi, MD, MPH
Background: Management of burn patients requires a complex of burn patients includes strategies to minimize iatrogenic injury with
interaction of surgical, medical, critical care, and rehabilitation low tidal volume ventilation, to improve ventilation/perfusion mis-
approaches. Severe burn patients are some of the most challeng- match, and to diagnosis pneumonia. Many aspects of burn resusci-
ing critically ill patients who may have multiple-system organ tation remain controversial, and the best form of fluid resuscitation
failure with life-threatening complications. has yet to be identified. Recent research in the metabolic response to
Objective: To review and highlight some of the recent ad- thermal injury has identified many potentially beneficial treatments.
vances in burn critical care. We focused on some of the new Although immunomodulation therapy is promising, currently most of
treatment modalities in the management of respiratory complica- these treatments are not clinically viable, and further clinical and
tions, advances in burn resuscitation, management of the meta- translational research is warranted. (Crit Care Med 2006; 34[Suppl.]:
bolic response to burns, and recent ideas in burn immunotherapy. S239 –S244)
Data Source: A search of the MEDLINE database and manual
KEY WORDS: burn; critical care; inflammation; signal transduc-
review of published articles and abstracts from national and
tion; mitogen-activated protein kinase (MAPK); adrenergic recep-
international meetings.
tors; immunotherapy
Data Syntheses and Conclusions: The respiratory management
T reating patients with burn patients face complex critical care issues. bating acute lung injury. Institution of
injuries requires a complex, The present article will be a brief report low tidal volume ventilation, allowing
multidimensional approach. on some of the new advances in burn permissive hypercapnia, was shown to re-
Burn patients may have exten- critical care. Rather than being all inclu- duce the development of ventilator-
sive damage to skin, which may require sive, we focused on four critical care issues: associated lung injury and significantly
multiple surgical interventions, burn new approaches in management of respira- improve outcomes (4). In addition, use of
wound management, physical and occu- tory complications, advances in the resus- alternate ventilation strategies such as
pational therapy, and scar management. citation strategies, complex management high-frequency oscillatory ventilation
In the last decade, there have been major of the metabolic response to burns in- and high-frequency percussive ventila-
advances in this aspect of burn care, cluding nutritional support, and recent tion may be beneficial in selected burn
which includes early excision and graft- ideas and approaches in immunotherapy. patients (5). Although there are limited
ing with autologous or allogeneic skin or comparative data regarding these two
biosynthetic dermal substitutes (1). Al- AIRWAY MANAGEMENT AND strategies, it seems that high-frequency
though this approach has decreased mor- VENTILATORY STRATEGIES percussive ventilation is especially useful
bidity and mortality, burn patients con- in inhalation injuries (6). Extracorporeal
tinue to face many serious complications. Most severely burn-injured patients
are intubated early for airway manage- membrane oxygenation is described by
Thermal insult may induce a major distur- some authors as an ultimate salvage op-
bance in the homeostatic mechanisms, ment and respiratory support. Pulmonary
insufficiency and failure in severely tion in the pediatric population (7). For
with severe disturbance in hemodynamic, adult patients, extracorporeal membrane
respiratory, and metabolic pathways (2). burned patients is multifactorial. The
pathogenesis can be differentiated into oxygenation is to be considered when pa-
Potential postburn complications are se- tients face respiratory death from inhala-
vere systemic inflammatory response direct pulmonary and upper airway inha-
lation injury and indirect or secondary tion injury (8).
syndrome, sepsis, acute respiratory dis-
acute lung injury due to activation of the Adjunct therapies such as inhaled ni-
tress syndrome, multiple-system organ
systemic inflammatory response. There is tric oxide have gained momentum in
failure, and death. Addition of inhalation
also secondary delayed pulmonary injury treating hypoxic vasoconstriction in burn
injury may double the mortality rate and
due to sepsis and pneumonia. In addition, patients, improving ventilation/perfusion
act as a synergistic insult on the pulmo-
ventilator-associated lung injury has mismatches and thereby tissue oxygen-
nary system (3). Physicians treating burn
been described as an important iatro- ation (9, 10). In an animal model of in-
genic factor contributing to the second- halation injury, aerosolized heparin at-
ary accentuation of pulmonary injury (4). tenuated cellular infiltrates, lung edema,
From the University of Michigan Burn Center, Ann
Arbor, MI. The reduced pulmonary compliance and congestion, and cast formation and im-
Copyright © 2006 by the Society of Critical Care chest wall rigidity of burn patients can proved oxygenation (11). In a study of 90
Medicine and Lippincott Williams & Wilkins lead to aggressive ventilatory manage- consecutive burn pediatric patients who
DOI: 10.1097/01.CCM.0000232625.63460.D4 ment and high airway pressures, exacer- had inhalation injury, there was a signif-
Crit Care Med 2006 Vol. 34, No. 9 (Suppl.) S239

2. icant decrease in reintubation rates, in the accurate diagnosis of infectious compli- Crystalloid solutions, such as lactated
prevalence of atelectasis, and in mortality cations such as pneumonia. The National Ringers solution and normal saline, are
for patients treated with the regimen of Infection Surveillance System uses phys- still first-line fluid replacements in burn
aerosolized heparin and N-acetylcysteine iologic data, laboratory evaluation, and resuscitation. Due to reduced intravascu-
when compared with controls (12). radiographic data to define pneumonia. lar fluid retention, large volumes have
Although most recent studies demon- Recognizing the difficult diagnosis of to be infused, which accentuate tissue
strate improved outcomes with early tra- ventilator-associated pneumonia in the edema, and the development of tissue
cheostomy, controversy still exists on the injured patients (21), many investigators edema can lead to worsening outcomes
general “optimal” tracheostomy tech- have demonstrated the improved sensi- (30). Hypertonic saline (HTS) resuscita-
nique and timing (13). A retrospective tivity and specificity by including quanti- tion (7.5% NaCl) has been promoted for
study of pediatric burn patients demon- tative cultures obtained via bronchoal- its efficient intravascular volume resusci-
strated that early tracheostomy was safe, veolar lavage (22, 23). In a retrospective tation, rapid restoration of blood pressure
provided a secure airway, and improved review of adult burn patients, the use of and cardiac output with improved cere-
the ventilatory management of patients bronchoalveolar lavage eliminated the bral perfusion, and potential for expand-
(14); but there was no significant change unnecessary antibiotic treatment of 21% ing circulating volume by reabsorption of
in oxygenation, minute ventilation, or pH of patients and was associated with a fluid from the interstitial space (31).
after tracheostomy. In a retrospective re- lower rate of ventilator-associated pneu- More recently, HTS has been studied as a
view of adult patients with severe burn monia (24). fluid with significant modulation of sys-
injury, there were no differences in ven- temic inflammatory response secondary
tilatory support, length of stay, preva- RESUSCITATION to reperfusion injury, which may be ben-
lence of pneumonia, or survival (15); eficial in patients with shock (32, 33). In
however, patients with tracheostomy had Burn trauma leads to a combination animal models of trauma and burn, use of
a significantly shorter time to extubation. of hypovolemic and distributive shock HTS resuscitation has been associated
Although there is controversy regarding on the basis of generalized microvascu- with decreased edema and improved or-
improved pneumonia rate and mortality, lar injury and interstitial third-spacing gan perfusion and outcomes (34 –36).
most researchers agree that tracheos- through collagen and matrix degenera- Data on the effectiveness of HTS to pre-
tomy offers some advantages in terms of tion. Burn injury is marked by dynamic vent organ damage in the clinical setting
patient comfort and security. Regarding and ongoing fluid shifts, which have led are inconsistent (37). Some of the studies
the preferred tracheostomy technique, re- to the development of fluid resuscitation in burn patients have demonstrated that
cent studies demonstrate that percutane- formulas based on percentage of total HTS may have decreased the fluid load,
ous tracheostomy may be safe in burn pa- body surface area burn and weight. Fluid tissue edema, and complications such as
tients (16, 17). Addition of fiberoptic resuscitation based on the Parkland burn abdominal compartment syndrome (38 –
assistance may avoid rare but serious com- formula is extensively used in burn cen- 40). But others have noted no benefit in
plications (18). The enthusiasm for percu- ters and has helped minimize the occur- fluid requirement and potential increase
taneous tracheostomy should be tempered rence of burn shock (25). However, a risk of renal failure (41). It seems that the
in patients with severe facial and neck recent survey of 28 burn centers found benefit of HTS is seen in early resuscita-
burns or upper airway edema because loss that in 58% of patients, actual fluid re- tion (42), and some researchers have rec-
of airway in these patients may be associ- suscitation exceeded the 4 mL/kg recom- ommended stopping HTS infusion when
ated with significant complications. mended by Baxter and Shires (26). Over- serum sodium concentration exceeds 160
resuscitation has been shown to correlate mEq/L (29, 43). Currently, HTS is not
Pneumonia. Pneumonia is still one of directly with increasing intraabdominal routinely used in burn patients, and fur-
the most common infectious complica- pressure and the development of abdom- ther research is required to better define
tions in severe burn patients. Ventilator- inal compartment syndrome (27). Apart potential benefits, the timing, and the
associated pneumonia is very common in from the well-described extremity com- optimal volume.
burn patients, and similar to other criti- partment syndrome, orbital compart- Theoretically, the use of colloids in
cally ill patients, it is associated with in- ment syndrome requiring canthotomy in resuscitation of hypovolemic patients
creased risk of fatal outcome (19, 20). patients receiving supranormal resuscita- may be associated with preservation of
Several factors prime burn victims for tion was recently described (28). The cur- plasma osmotic pressure, more efficient
increased susceptibility for pneumonia: rent high-volume fluid regimens have plasma volume expansion, and decreased
relative immunosuppression, dysfunc- shifted postburn resuscitation complica- tissue and pulmonary edema. However,
tional ciliary movement in inhalational tions from renal failure to pulmonary clinical studies have not demonstrated a
injuries leading to impaired secretory edema, with increased requirement for significant improvement in patient out-
clearance, pulmonary inflammatory acti- ventilatory support, the need for fascioto- comes with colloid resuscitation (31, 44,
vation with acute lung injury, and in- mies in unburned limbs, and the occur- 45). In burn patients, treatment with al-
creased leakage of nutrient-rich plasma rence of the abdominal compartment bumin did not improve outcomes (44).
into lung parenchyma. Due to severe un- syndrome (29). The increased use of sed- A prospective randomized study dem-
derlying inflammatory pulmonary pa- ative and analgesic medication may have onstrated that a restrictive strategy of
thology, accurate clinical diagnosis of contributed to increased fluid volumes red-cell transfusion (hemoglobin concen-
ventilator-associated pneumonia can be given to burn patients. In essence, the tration maintained at 7.0 –9.0 g/dL) may
very difficult in burn patients. The recent pendulum may have swung from insuffi- be superior to a liberal transfusion strat-
emergence of multi– drug-resistant bac- cient resuscitation to excessive volume egy (hemoglobin concentration main-
terial pathogens has mandated a more loading. tained at 10.0 –12.0 g/dL) in critically ill
S240 Crit Care Med 2006 Vol. 34, No. 9 (Suppl.)

3. patients, with the possible exception of there is significant increase in energy ex- ment of surgical patients. In elective non-
patients with acute myocardial infarction penditure after burns, high-calorie nutri- cardiac operations, perioperative
and unstable angina (46). A recent mul- tional support was thought to decrease treatment with beta-blockers has been as-
tiple-center cohort analysis found an in- muscle catabolism. However, aggressive sociated with reduced mortality and prev-
creased mortality in burn patients asso- high-calorie feeding with a combination alence of cardiovascular complications
ciated with blood transfusions (47). of enteral and parenteral nutrition was (61, 62). In burn patients, beta-blockers
Therefore, there is a push to decrease associated with increased mortality (56). can blunt the catecholamine effect by at-
blood transfusion in burn patients. Re- Increasing enteral feeding beyond the tenuating hypermetabolism, decreasing
combinant human erythropoietin has body energy expenditure, 20 – 40% above oxygen demand and resting energy ex-
been shown to be useful in treatment of the resting energy expenditure, does not penditure, and decreasing heart rate and
chronic anemia and, theoretically, may improve lean body mass and is associated cardiac oxygen demand (54). Beta-
decrease the need for blood transfusion in with complications such as fatty liver blockers may also attenuate catechol-
the ICU. However, in a prospective, dou- (51). Most authors recommend adequate amine-induced muscle catabolism and li-
ble-blind, randomized study of 40 se- calorie intake via enteral feeding and polysis (63, 64). Moreover, there are data
verely burned patients, recombinant hu- avoidance of overfeeding (54). to suggest that beta-blockers can modify
man erythropoietin did not prevent the High carbohydrate diets compared catecholamine-mediated defect in lym-
development of postburn anemia or de- with high fat diets may improve the net phocyte activation and improve immune
crease transfusion requirements (48). In- balance of skeletal muscle protein (57). response with decreased infectious com-
terestingly, a recent animal study dem- Increased endogenous insulin may con- plications (65). Various studies have dem-
onstrated that recombinant human tribute to improved muscle metabolism. onstrated the potential beneficial effect of
erythropoietin improved healing of burn In a study of six adult patients with beta-blockers in burn patients. Adminis-
wound through increased epithelial pro- 40% total body surface area burn, treat- tration of propranolol (nonselective beta-
liferation, maturation of the extracellular ment with insulin and metformin were antagonist) to burned children reduces
matrix, and angiogenesis (49). Currently, associated with improved muscle kinetic the release of free fatty acids from adipose
most centers do not use erythropoietin in (58). However, high carbohydrate diet tissue and decreases hepatic triacylglyc-
treatment of burn patients, and further may be associated with elevated glucose, erol storage and fat accumulation (66,
clinical study is required before routine which may be detrimental in critically ill 67). In a randomized study of 25 children
clinical use. patients. In a study of 58 pediatric burn with severe burns, treatment with pro-
patients, there was a significant associa- pranolol attenuated hypermetabolism
METABOLIC RESPONSE tion between poor glucose control and and reversed muscle protein catabolism
complications such as increased bactere- (68). In a retrospective study of adult
During the flow phase postburn, there mia, reduced skin graft take, and in- burn patients, use of beta-blockers was
is an impressive hyperdynamic response. creased mortality (59). In another study, associated with decreased mortality,
For pediatric patient with 40% total tight glucose control in severe burn pa- wound infection rate, and wound healing
body surface area burn, the resting met- tients seemed to be safe and associated time (69). Although these data strongly
abolic rate is increased in the ranges be- with decreased risk of infection and im- support the use of beta-blockers in burn
tween 160% and 200% (50). This global proved survival (60). Therefore, aggres- patients, there are no large randomized
hypermetabolism is associated with sive monitoring and treatment of hyper- studies looking at mortality and wound
tachycardia, fever, muscle protein catab- glycemia is recommended. healing in burn patients. Nevertheless,
olism, and derangement in hepatic pro- Similar to all critically ill patients, ad- many burn units use beta-blockers such
tein synthesis (51, 52). This response may equate protein intake is required. Be- as propranolol or metoprolol as the most
be associated with significant complica- cause there is an increased oxidation rate effective catabolic treatment in burn pa-
tions such as immunodeficiency, im- of amino acids in burn patients, the pro- tients.
paired wound healing, sepsis, loss of lean tein requirement is increased to 1.5–2.0 Oxandrolone. Oxandrolone is an ana-
body and muscle mass, cardiac ischemia, g/kg per day in treatment of severely log of testosterone, which is an anabolic
and potential death. Primary treatment burned patients (54). hormone. It has been used to treat mus-
modalities include avoidance of infec- cle wasting in various disease processes
tious complications such as sepsis and Modulation of Hormonal and such as acquired immune deficiency syn-
early excision of full-thickness burns, Endocrine Response drome (70). In a study of 14 severely
which is associated with attenuation of burned children, oxandrolone improved
hypermetabolism (52–54). Several other Burn injury is associated with in- muscle protein metabolism through en-
approaches have been used to attenuate creased levels of catecholamines and cat- hanced protein synthesis efficiency (71).
the burn-induced hypermetabolism (54). abolic hormones. Therefore, it is logical In adult burn patients, oxandrolone sig-
This article will focus on early nutritional to assume blockade of catecholamine re- nificantly decreased weight loss and net
support and modulation of hormonal/ sponse or use of anabolic steroids may nitrogen loss and increased donor site
endocrine response. attenuate hypermetabolism or blunt cat- wound healing compared with placebo
abolic response after burn injury. In this controls (72). In a prospective random-
Nutritional Support review, we will focus on beta-adrenergic ized study of 81 patients, 10 mg of oxan-
receptor blockade and oxandrolone. drolone every 12 hrs was associated with
The use of early enteral feeding in Beta-Adrenergic Receptor Blockade. decreased hospital stay (73). Although
burn patients may attenuate catabolic re- There has been a recent increased enthu- there was no hepatic insufficiency, a sig-
sponse after thermal injury (55). Because siasm for use of beta-blockers in treat- nificant increase in hepatic transami-
Crit Care Med 2006 Vol. 34, No. 9 (Suppl.) S241

4. nases was observed. The authors recom- experimental burn-injured sheep was as- may attenuate systemic inflammatory re-
mended monitoring liver function tests sociated with decreased edema and fluid sponse and acute lung injury (93, 94). In
in patients treated with oxandrolone. requirement (83). In a randomized trial these studies, topical application of p38-
Enthusiasm to use oxandrolone should of critically ill surgical patients, a combi- mitogen–activated protein kinase inhibi-
also be tempered by the findings of po- nation of ascorbic acid and -tocopherol tor to the burn wound decreased dermal
tential increase in ventilatory days; in a reduced the prevalence of organ failure inflammation, postburn skin apoptosis,
study of trauma patients, oxandrolone and ICU length of stay (84). Early use of systemic inflammatory response, and sec-
was associated with increased ventila- high-dose antioxidant therapy in the in- ondary pulmonary complications. Topical
tory days (74). The authors suggested jured patients seems to be beneficial; inflammatory modulation in severe burns
that oxandrolone may enhance collagen however, further clinical trials are re- is attractive because it can be readily used
deposition in acute respiratory distress. quired to confirm this potential effect and in patients who are already receiving top-
Overall, it seems that oxandrolone may better define the timing and the required ical antimicrobial agents, and it may
be beneficial in patients with large body dose (85, 86). avoid some of the systemic complica-
surface area burns. Recombinant Human Activated Pro- tions. However, currently there are no
tein C. Recombinant activated protein C clinically approved topical immuno-
IMMUNOTHERAPY (activated drotrecogin alfa) is the first modulators for burn patients.
agent approved by the Food and Drug
Severe dermal burns are known to in- Administration for treatment of severe
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