Bongard Frederic , Darryl Sue. Diagnosis and Treatment Critical Care

Подождите немного. Документ загружается.



BURNS

737

(eg, collagenase, protease, etc.), bacterial motility, and antibi-

otic resistance may be important in the pathogenesis of

eschar penetration and invasion of viable tissues.

Although the use of topical chemotherapeutic agents and

the timely excision and grafting of the burn wound have

decreased the incidence of invasive burn wound infection in

most U.S. burn centers, this problem has not been eliminated

entirely. Invasive burn wound infection is uncommon in sec-

ond-degree burns and in patients with burns of less than

30% of the body surface. Extremes of age and increasing size

of burn strongly influence the risk of developing invasive

burn wound infection.

Clinical Features

A. Symptoms and Signs—Clinical signs of invasive burn

wound infection are often indistinguishable from those

observed in uninfected hypermetabolic burn patients or

burn patients with other sources of sepsis and include

hyper- or hypothermia, tachycardia, tachypnea, ileus, glu-

cose intolerance, and disorientation. Tinctorial and physical

changes in the appearance of the burn wound are more reli-

able signs of invasive burn wound infection (Table 35–5).

The development of clinical signs and symptoms of sepsis in

the thermally injured patient should prompt a thorough

examination of the burn wound to identify areas suspicious

for invasive infection.

B. Laboratory Findings—Surface cultures of the eschar can-

not distinguish colonization from invasive infection.

Quantitative bacteriologic cultures of burn wound tissue

correlate poorly with the presence of invasive burn wound

infection. Quantitative bacteriologic counts less than 10

per

gram of biopsy tissue correlate with absence of invasive burn

wound infection; however, even when quantitative counts

exceed 10

organisms per gram of biopsy tissue, histologic

examination confirms invasive infection in less than half of

biopsy specimens.

Histologic examination of a biopsy of the burn wound

and underlying viable tissue is the most rapid and reliable

method for differentiating microbial colonization of nonvi-

able eschar from microbial invasion of viable subeschar tis-

sue. The latter defines invasive burn wound infection. A burn

wound biopsy is performed as an ICU procedure. A 500-mg

elliptical biopsy (0.5 × 1.0 cm) including subjacent unburned

tissue is obtained by scalpel dissection from the area of the

burn wound identified as suspicious for infection. Hemostasis

is achieved by application of direct pressure or by electroco-

agulation. Half the specimen is cultured for organism identi-

fication and antibiotic sensitivities, and the other half is

submitted for histologic analysis. The presence of microor-

ganisms in viable tissue confirms the diagnosis of invasive

burn wound infection. The histologic staging scheme for

burn wound colonization and infection is presented in

Table 35–6. If only colonization (stage 1A to stage 1C) is pres-

ent, no specific change in antimicrobial therapy is indicated

unless serially obtained specimens document a progression of

colonization stage. If stage 2 (invasion) is reported, prompt

treatment for invasive burn wound infection should begin.

Treatment

When the diagnosis of invasive burn wound infection is

made, local and systemic antimicrobial therapy is initiated.

In the case of bacterial burn wound invasion, topical

chemotherapy should be in the form of twice-daily applica-

tions of mafenide acetate because of its superior eschar pen-

etration. Systemic antibiotic therapy is initiated based on

prior surface cultures or burn center organism prevalence.

Further refinements in therapy are based on biopsy, culture,

and sensitivity results. Customary critical care supportive

measures are employed to maintain hemodynamic and res-

piratory stability. Subeschar antibiotic clysis of the infected

area with a broad-spectrum penicillin is recommended at

12 hours and immediately prior to operation to minimize

the risk of hematogenous seeding and florid septic shock at

the time of eschar excision. Half the daily dose of a broad-

spectrum penicillin (eg, piperacillin or ticarcillin) delivered

in 1 L of normal saline is infused into the subeschar tissues

by means of a no. 20 spinal needle. Excision of the burn

wound to the level of the investing fascia is employed to

ensure removal of all nonviable tissue. The wound is usually

treated with moist dressings of 5% mafenide acetate, 0.5%

silver nitrate, or a biologic dressing. The patient is returned

to the operating room in 24–48 hours for wound inspection

and redebridement or split-thickness skin grafting as needed.

Stage I: Colonization

A. Superficial: Sparse microbial population on burn wound surface.

B. Penetration: Microorganisms present in variable thickness of eschar.

C. Proliferation: Dense population of microorganisms at interface of

nonviable and viable tissue.

Stage II: Invasion

A. Microinvasion: Microscopic foci of microorganisms in viable tissue

immediately subjacent to subeschar space.

B. Generalized: Widespread penetration of microorganisms deep into

viable subcutaneous tissues.

C. Microvascular: Involvement of lymphatics and microvasculature.

Table 35–6. Histologic staging of burn wound infection.

Table 35–5. Clinical signs of burn wound infection.

Conversion of second-degree burn to full-thickness necrosis

Focal dark brown or black discoloration of wound

Degeneration of wound with “neoeschar” formation

Unexpectedly rapid eschar separation

Hemorrhagic discoloration of subeschar fat

Erythematous or violaceous, edematous wound margin

Metastatic septic lesions in unburned tissue



CHAPTER 35

738

In addition to bacteria, fungi and yeasts also cause inva-

sive burn wound infection and have become the predomi-

nant organisms causing burn wound infection because

topical therapy and early excision have reduced the incidence

of bacterial infection. Candida species commonly colonize

wounds but rarely cause invasive burn wound infection.

Aspergillus, the most common filamentous fungus that

causes invasive burn wound infection, usually remains con-

fined to subcutaneous tissues and seldom transverses fascial

planes. Wounds colonized by Candida or Aspergillus can be

treated with topical application of clotrimazole, but histo-

logic evidence of invasion requires surgical burn wound exci-

sion and initiation of systemic amphotericin B therapy. The

Phycomycetes often behave in a manner similar to

Aspergillus; however, these organisms may spread rapidly

along tissue plains, invade blood vessels, and penetrate fascia.

Aggressive wide debridement, including amputation, may be

necessary to control these infections.

Becker WK et al: Fungal burn wound infection: A 10-year experi-

ence. Arch Surg 1991;126:44–8. [PMID: 1985634]

McManus AT: Pseudomonas aeruginosa: A controlled burn

pathogen? Antibiot Chemother 1989;42:103–8. [PMID: 2512832]

McManus WF, Goodwin CW Jr, Pruitt BA Jr: Subeschar treatment

of burn-wound infection. Arch Surg 1983;118:291–4. [PMID:

6824429]

Pruitt BA Jr: The diagnosis and treatment of infection in the burn

patient. Burns Incl Ther Inj 1984;11:79–91. [PMID: 6525539]

Waymack J, Pruitt BA Jr: Burn wound care. Adv Surg 1990;23:

261–89. [PMID: 2403460]



Burn Wound Excision & Grafting

Technique

The current operative management of burns employs tan-

gential excision of eschar to viable dermis or fat and scalpel

excision to the level of the investing fascia for burn wound

removal. Burn wound excision may be performed early in

the postburn course once the patient is hemodynamically

stable and resuscitation is complete.

The operative procedure should be limited to excision of

20% of the body surface area, an area of excision producing

a blood loss equal to the patient’s blood volume, or 2 hours

of operative time. Careful anesthetic management is impera-

tive to avoid hypotension and hypothermia. Hypotension

may impair blood flow to areas of second-degree burn,

resulting in ischemia of the wound and conversion to full-

thickness injury. The depth of excision in tangential and

sequential burn wound removal is governed by the appear-

ance of healthy tissue and punctate bleeding from dermal

beds. Scalpel excision of burns involves removal of the

wound and underlying subcutaneous tissue to the level of the

investing muscle fascia. This may be accomplished more rap-

idly and with significantly less blood loss than tangential or

sequential wound excisions. Once a viable wound surface is

obtained, wound coverage is accomplished with autograft or

biologic dressings.

Conventional skin grafting is achieved with cutaneous

autografts 0.008–0.012 inches thick. These grafts may be

employed as a sheet graft or meshed to provide expansion

ratios ranging from 1.5:1 to 9:1. Expansion ratios of 4:1 or

greater require a prolonged time for interstitial closure, have a

greater propensity for scar formation, and are used only in

patients with massive burns and limited donor sites. Following

grafting, occlusive dressings moistened with topical antibiotic

agents are applied. The wounds are kept moist to prevent des-

iccation until the interstices of the graft have epithelialized.

Skin Substitutes and Biologic Dressings

In massively burned patients, the disparity between donor-

site area and burn-wound area requires the use of temporary

skin substitutes or biologic dressings to effect wound closure

while awaiting donor-site availability. Biologic dressings pre-

vent desiccation of the wound bed, decrease protein and

fluid losses, promote angiogenesis of granulation tissue, and

reduce pain. Viable cadaver allograft currently provides the

best temporary wound coverage. Allograft becomes vascular-

ized from the underlying wound bed and usually remains

adherent until surgically excised or immunologically rejected

by the patient. As a result of the immunosuppression associ-

ated with thermal injury, the allograft may remain intact,

vascularized, and viable for several weeks following applica-

tion. The same theoretical risks of disease transmission (eg,

hepatitis, HIV infection, etc.) associated with organ donation

apply to the use of cadaveric allografts. Appropriate tissue

banking measures are imperative. In addition to fresh

cadaver allograft, frozen and lyophilized allograft is available

from many sources.

Porcine xenograft is also available as a fresh, frozen, or

lyophilized preparation. Advantages include an abundant

supply and lower cost. This biologic dressing, however, does

not become vascularized and adheres to the wound bed by

fibrin bonding. The underside of the graft is nourished by

the plasma circulation, and desiccation and necrosis of the

outer surface usually occur within 1 week. Application of

porcine cutaneous xenografts to superficial partial-thickness

wounds facilitates healing and decreases pain. Porcine

xenografts are of limited usefulness in the coverage of excised

wounds because of their lack of vascularization and the lim-

ited time until desiccation and necrosis occur.

Several synthetic skin substitutes have been developed in

an attempt to avoid the problems of disease transmission and

storage requirements common to biologic dressings. The

most successful materials have been of a bilaminated config-

uration with an outer layer mimicking epidermis that allows

water vapor transmission and prevents bacterial contamina-

tion. The inner dermal layer is designed to promote adher-

ence and fibrovascular ingrowth from the wound bed.

Biobrane is currently the most commonly used synthetic skin



BURNS

739

substitute. The epidermal layer is composed of pliable Silastic,

and the dermal component is derived from porcine collagen.

This product is available with a variety of pore sizes, and its

elastic nature allows freedom of motion and is well adapted to

body contours. Biobrane promotes healing of second-degree

burns and usually provides adequate short-term coverage for

excised wounds, although submembrane suppuration and

lack of adherence cause difficulties. Integra is a synthetic der-

mal substitute that is unique in that a neodermis is formed by

fibrovascular ingrowth into a glycosaminoglycan matrix der-

mal analogue. The epidermal component is Silastic and is

removed once the dermal analogue is vascularized, allowing

definitive closure of the wound with ultrathin split-thickness

autografts. This permits more rapid healing of donor sites for

repeated autograft harvesting. Incomplete adherence, sub-

membrane suppuration, and technical problems with the

application of ultrathin autografts have been observed.

TransCyte is a bilaminated biosynthetic skin substitute

used as a temporary dressing on second-degree burns or

excised full-thickness burns. This product is composed of

Biobrane on which human foreskin-derived neonatal dermal

fibroblasts are seeded and grown to confluence in culture.

The fibroblasts secrete matrix proteins and growth factors

that remain active after the product is frozen. Application of

TransCyte to the wound surface is similar to that of

Biobrane. It also carries the same limitations.

The availability of commercial laboratories capable of

carrying out skin culture techniques has led to the recent

evaluation of cultured autologous keratinocytes for coverage

of wounds in massively burned patients. Current culture

techniques require 3 or more weeks of preparation for a

product six to eight epidermal cells in thickness. These grafts

are quite fragile and susceptible to bacterial colonization of

the recipient wound bed and minimal shear forces. The use

of cultured autologous keratinocytes to effect wound closure

in massively burned patients was studied recently. In a series

of 16 patients with an average burn size greater than 60% of

BSA, definitive final engraftment covered only 4.7% of the

body surface area at a cost of over $9000 per percent of BSA

closed. Wound bed microbial colonization, lack of dermal

elements, and patient age may be significant factors relating

to the failure of culture-derived cells as a definitive form of

burn wound coverage. This technology has the potential for

providing timely coverage of large surface areas but is

presently limited by the aforementioned problems.

Caruso DM et al: Randomized clinical study of Hydrofiber dressing

with silver or silver sulfadiazine in the management of partial-

thickness burns. Burn Care Res 2006;27:298–309. [PMID:

16679897]

Hansbrough JF: Current status of skin replacements for coverage

of extensive burn wounds. J Trauma 1990;30:S155–60. [PMID:

2254975]

Hansbrough JF et al: Burn wound closure with cultured autolo-

gous keratinocytes and fibroblasts attached to a collagen-

glycosaminoglycan substrate. JAMA 1989;262:2125–30.

Heimbach D et al: Artificial dermis for major burns: A multicenter

randomized clinical trial. Ann Surg 1988;208:313–20.

Pruitt BA Jr, Levine NS: Characteristics and uses of biologic dress-

ings and skin substitutes. Arch Surg 1984;119:312–22. [PMID:

6365034]

Pruitt BA Jr, McManus WF, McDougal WS: Surgical management

of burns. In Nora FP (ed), Operative Surgery: Principles and

Techniques. Philadelphia: Saunders, 1990.



Inhalation Injury

ESSENTIALS OF DIAGNOSIS



Facial burns.



Intraoral burns or carbonaceous sputum.



Edema, erythema, mucosal ulcerations on laryngoscopy.



Increased

133

Xe retention.



Decreased Pao

and expiratory flow rates.

General Considerations

Pulmonary injury from smoke inhalation is frequently

observed in patients with thermal injury who require admis-

sion to a burn center. In a recent series, 33% of patients had

concomitant inhalation injury. The injury caused by the

inhalation of smoke or toxic gases may include chemical

damage to the respiratory system, carbon monoxide toxicity,

and infrequently, direct thermal injury to the tracheo-

bronchial tree. Patients most likely to have inhalation injury

are those with burns sustained in a closed space and those

who were burned during a period of depressed conscious-

ness secondary to head trauma or drug intoxication.

Direct thermal injury to the airway is encountered rarely

in patients who survive a fire and are hospitalized for treat-

ment. However, autopsy series of patients dying at the scene

of a fire frequently reveal devastating direct thermal injury to

the airways. The effective cooling capabilities of the

nasopharynx and oropharynx prevent significant heat expo-

sure of the lower respiratory system; however, direct thermal

injury to the supraglottic airway does occur and may lead to

upper airway obstruction. An exception is burns caused by

exposure to steam because water has a heat-carrying capac-

ity 4000 times greater than that of air.

Smoke inhalation—particularly when the injury occurred

in a closed space—may be associated with carbon monoxide

poisoning, which may impair tissue oxygenation. The pres-

ence of carboxyhemoglobin or the chemical alteration of the

cytochrome system by carbon monoxide does not affect the

amount of dissolved oxygen in the blood; thus the Pa

will

remain normal. However, saturation of hemoglobin by oxy-

gen may be markedly reduced, impairing oxygen delivery.

The inhalation of smoke (incomplete products of combus-

tion) is manifest by deleterious effects on both the airway and



CHAPTER 35

740

the pulmonary vasculature. The anatomic location of pul-

monary injury depends on the size of the inhaled particle.

When the particle diameter is less than 0.05 μm, the larger,

endoscopically visible airways may appear normal in the pres-

ence of severe alveolar and terminal bronchiolar inflammatory

damage. Alternatively, the larger airways may be severely

inflamed, leading to mucosal ulceration or necrosis in the pres-

ence of relatively normal gas exchange and alveolar function.

In various animal models of inhalation injury, increased

pulmonary microvascular permeability and peribronchial

edema have been reproduced. Thromboxane A

levels have

been found to increase within 5 minutes of inhalation injury,

with levels correlating with increases in lung lymph flow and

extravascular lung water. The role of the neutrophil in the

pathophysiology of smoke inhalation is currently under

investigation. Both the preinjury induction of a neutropenic

state by administration of mechlorethamine and postinjury

treatment with pentoxifylline have been reported to attenu-

ate pulmonary artery hypertension, reduce pulmonary vas-

cular resistance, and decrease the severity of pulmonary

insufficiency following smoke exposure in animals. Although

alterations in surfactant function have been described fol-

lowing smoke inhalation, surfactant replacement has not

been shown to improve pulmonary function in animal mod-

els of inhalation injury.

Clinical Features

A. Symptoms and Signs—Smoke inhalation should be sus-

pected in patients with facial burns, singed facial hair and

nasal fibrissae, intraoral burns or carbonaceous deposits in the

oropharynx, or a history of being burned in a closed space.

B. Bronchoscopy—The diagnosis of inhalation injury is

made by examination of the upper airway and tracheo-

bronchial tree by fiberoptic bronchoscopy. Direct laryn-

goscopy also may be used to visualize the upper airway. The

presence of carbonaceous material, edema, erythema, or

mucosal ulcerations below the vocal cords confirms the diag-

nosis. An endotracheal tube of appropriate size should be

placed over the fiberoptic bronchoscope before the examina-

tion so that intubation may be readily achieved if the appear-

ance of upper airway edema threatens airway patency.

False-negative bronchoscopic examinations occur occasion-

ally and usually are secondary to the failure to observe

inflammation and erythema in the hypovolemic patient with

impaired tracheal mucosa perfusion.

C. Radionuclide Studies—

133

Xe ventilation-perfusion lung

scans may be performed in patients in whom the clinical sus-

picion of inhalation injury is high yet the bronchoscopic

examination appears relatively normal. After intravenous

injection of 10 μCi of

133

Xe, serial chest scintigraphs are

obtained. Retention of the gas in the lungs for over 90 seconds

following injection or an unequal distribution of radiation

density is considered diagnostic of inhalation injury. The false-

negative and false-positive rates from this study are 5% and 8%,

respectively. False-negatives result from marked hyperventila-

tion and false-positives from preexisting chronic obstructive

pulmonary disease (COPD), bronchitis, or atelectasis.

D. Respiratory Function Studies—Measurements of pul-

monary function also may be helpful in establishing the

diagnosis of inhalation injury. Burn patients with inhalation

injury may have a decreased Pa

and peak expiratory flow

and an increased ventilation-perfusion gradient, airway

resistance, and nitrogen washout slope. Static and dynamic

compliance tends to be normal in the early phase of inhala-

tion injury. The complexity of some pulmonary function

tests and the requirement for full patient cooperation often

limit their clinical usefulness as aids to the early diagnosis of

inhalation injury.

The diagnosis of inhalation injury can be made with 96%

accuracy when the results of fiberoptic bronchoscopy, venti-

lation-perfusion scanning, and pulmonary function testing

are combined. Overdiagnosis of inhalation injury accounts

for the 4% error.

Treatment

A. General Measures—The current treatment of inhalation

injury is primarily supportive because no specific agent has

been identified that minimizes the severity of the insult. The

aim of treatment, therefore, is to correct the underlying pul-

monary insufficiency while minimizing further iatrogenic

pulmonary insults. The amount of intervention required is

guided by the severity of pulmonary insufficiency.

B. Respiratory Support—Patients with mild disease require

only administration of humidified oxygen-enriched air (usu-

ally 40%) and noninvasive pulmonary physiotherapy. Severe

injury may require maximal mechanical ventilatory support

and frequent flexible fiberoptic or rigid bronchoscopy to

clear the airways of sloughed mucosal debris and secretions.

Small-airways disease may produce significant atelectasis

requiring increased oxygen administration and institution of

positive end-expiratory pressure. Systemic administration of

steroids has not decreased morbidity or mortality rates in

patients with inhalation injury, and such treatment has been

reported to increase infectious complications.

A recent clinical trial of the prophylactic use of high-fre-

quency percussive ventilation in patients with inhalation

injury demonstrated significant improvements in morbid-

ity and mortality rates compared with conventional volume

ventilation. Fifty-four burn patients with documented

inhalation injury were managed by this type of ventilation

within 24 hours of intubation. Fourteen patients (25.9%)

developed pneumonia, compared with a predicted histori-

cal frequency of 45.8%. The observed mortality rate was

18.5% compared with a historical frequency of 35%. Only

4 of the 10 deaths were attributable to pulmonary failure.

Although the exact mechanism by which high-frequency

percussive ventilation improves outcome is not known, the

ability to maintain ventilation and oxygenation at lower peak



BURNS

741

airway pressures and inspired oxygen concentrations may

reduce the iatrogenic injury associated with the use of

volume-controlled ventilators. The high frequency percussive

breaths also improve clearance of secretions—similar to results

obtained with high-frequency oscillators and jet ventilators.

C. Antimicrobial Therapy—Bronchopneumonia is the most

common cause of morbidity and death in patients with

inhalation injury. The daily chest roentgenograph should be

examined carefully. Appropriate antimicrobial therapy is ini-

tiated based on the presence of pulmonary infiltrates and

sputum leukocytosis. Pneumonia occurring after inhalation

injury usually is caused by gram-positive organisms. Gram-

negative pneumonias, which now occur infrequently, usually

develop later in the hospital course. Therapy is initiated

based on the results of the sputum Gram stain, with refine-

ments of antibiotic choice depending on endobronchial cul-

ture and microbial sensitivity testing.

Prognosis

Smoke inhalation, in the absence of cutaneous thermal

injury, is almost always treated successfully by supportive

measures. The tracheobronchial mucosa typically heals com-

pletely in 2–3 weeks. However, when smoke inhalation

occurs in the presence of moderate to severe cutaneous burn,

mortality rates are increased by as much as 20% over those

predicted by the age of the patient and the extent of injury.

When pneumonia complicates inhalation, the mortality rate

may rise to 60% above the predicted level.

Cioffi WG et al: High-frequency percussive ventilation in patients

with inhalation injury. J Trauma 1989;29:350–4. [PMID:

2926848]

Cioffi WG et al: Prophylactic use of high-frequency percussive ven-

tilation in patients with inhalation injury. Ann Surg

1991;213:575–80. [PMID: 2039288]

Huang Y, Li A,Yang Z: Effect of smoke inhalation injury on throm-

boxane levels and platelet counts. Burns Incl Therm Inj

1988;14:440–6. [PMID: 3250716]

Pruitt BA Jr et al: Evaluation and management of patients with

inhalation injury. J Trauma 1990;30:S63–8. [PMID: 2254994]

Shirani KZ, Moylan JA Jr, Pruitt BA Jr: Diagnosis and treatment of

inhalation injury. In Loke J (ed), Pathophysiology and Treatment

of Inhalation Injuries. New York: Marcel Dekker, 1988.

Shirani KZ, Pruitt BA Jr, Mason AD Jr: The influence of inhalation

injury and pneumonia in burn mortality. Ann Surg

1987;205:82–7. [PMID: 3800465]

POSTRESUSCITATION PERIOD



Prevention & Treatment of Complications

1. Infection Control

Infectious complications always have been the predominant

determinant of outcome in thermally injured patients.

Improved care of critically ill patients and the control of

burn wound sepsis through effective topical antimicrobial

agents and timely excision and grafting have resulted in the

salvage of more burn patients who previously would have

died in the early postburn period. The hospital course of

nonsurvivors also has been prolonged. Since infection con-

tinues as the leading cause of morbidity and death in burn

patients, prolonged hospitalization increases the risk of col-

onization and infection by nosocomial organisms that are

predominantly true fungi, yeasts, and multiply-antibiotic-

resistant bacteria.

A strict infection control program can minimize the clin-

ical impact of exposure to nosocomial pathogens during a

prolonged hospital stay in an immunocompromised patient.

Such a program might employ scheduled microbial surveil-

lance, an actively functioning infection control committee,

environmental monitoring procedures, biopsy monitoring of

the burn wound, and cohort patient care as deemed neces-

sary. The surveillance program includes thrice-weekly cul-

tures of sputum and the burn wound surface and

twice-weekly culturing of urine and stool. Multiple antibiotic

sensitivities are determined for all staphylococci as well as all

Pseudomonas species and other gram-negative organisms

recovered from routine cultures. Reports are provided on a

daily basis, enabling initial empirical selection of antibiotics

to be made more precisely should an infection be diagnosed.

Cohort patient care is initiated if a patient is admitted

and found to be colonized or infected with an organism of

broad antibiotic resistance or if this resistance pattern devel-

ops during broad-spectrum antibiotic therapy.

Cross-contamination is minimized by strict enforce-

ment of hand washing, gowning, and gloving policies. The

establishment of patient care teams to provide care for

only one specific patient or a limited number of patients

and restriction of the traffic of convalescing patients (often

colonized with resistant organisms) are imperative in

reducing cross-contamination and eradicating endemic

microorganisms.

The infection control committee monitors infections

occurring in the burn unit to identify changes in microbial

prevalence, the incidence of infection, and evidence of cross-

contamination. Strict criteria for the definition and identifi-

cation of infections that occur in burn patients are necessary

to avoid unnecessary and inappropriate antibiotic adminis-

tration. Antibiotics are used only for specific indications to

minimize the emergence of microbial resistance. Effective

infection control policies require continual reevaluation of

surveillance culture results and correlation with the sites and

treatment of infections.

2. Infectious Complications: Prevention,

Diagnosis, & Treatment

With the decrease in fatal burn wound sepsis and improved

survival of patients with massive burns, infections in other

sites have shown a relative increase as principal causes of



CHAPTER 35

742

death. Dense bacterial colonization of the burn wound and

the presence of immunosuppression associated with burn

injury increase the likelihood of development of infectious

complications.

Pneumonia

Pneumonia is the most frequent septic complication follow-

ing thermal injury. As the occurrence of invasive burn

wound infection has decreased, bronchopneumonia has

surpassed hematogenous pneumonia as the predominant

form. The increase in airborne pneumonia also may be

attributable to improved survival in patients with severe

inhalation injury. Atelectasis is often present prior to the

development of infection. The appearance of an ill-defined

irregular infiltrate on chest x-ray mandates Gram stain, cul-

ture, and sensitivity testing of endobronchial secretions.

Empirical antibiotic treatment is begun as determined by

microbiologic surveillance and Gram stain of the secretions.

Subsequent antibiotic therapy is adjusted on the basis of

sensitivity testing.

Compared with bronchopneumonia, hematogenous

pneumonia usually occurs later in the hospital course.

Remote septic foci such as invasive wound infection,

endocarditis, and suppurative thrombophlebitis are com-

mon causes. The radiographic hallmark is a solitary nodu-

lar pulmonary infiltrate, but progression to multiple

nodular infiltrates throughout the lungs may occur. All

possible sites of infection must be evaluated if a character-

istic nodular pulmonary infiltrate appears. The primary

infection must be identified and treated. The pneumonic

process is treated by systemic administration of antibi-

otics directed against the causative organism and ventila-

tory support as needed. Aggressive pulmonary toilet

to prevent atelectasis may help to decrease the occurrence

of pneumonia, although most routine measures have little

proved benefit.

Suppurative Thrombophlebitis

The loss of skin integrity, the presence of dense bacterial col-

onization of the burn wound, and the frequent need for

long-term venous access increase the likelihood that suppu-

rative thrombophlebitis will develop in burn patients.

Limiting the duration of cannulation of a vein to 3 days or

less in patients with thermal injury has reduced the inci-

dence of this complication from 4.3% to less than 1.4% in

recent years. Local signs of thrombophlebitis are present in

less than half of patients with this complication because of

the presence of the overlying burn wound and the systemic

immunosuppression accompanying burn injury. With the

increased use of central venous cannulation, these patients

are also at risk for development of central vein suppurative

thrombophlebitis.

The diagnosis of peripheral vein suppurative throm-

bophlebitis is made by operative exploration, excision, histologic

analysis, and culture of the suspected phlebitic vein.

Identification of bacteria within the vein necessitates excision

of the entire length of involved vein to a level of patent normal

vein and the administration of systemic antibiotics to which

the causative microorganism is sensitive. The diagnosis of cen-

tral venous thrombophlebitis is more difficult. Indium-

111–labeled leukocyte scanning, CT scanning, and contrast

venography may help to establish the diagnosis. This rare com-

plication is treated with systemic antibiotics directed against

the organism isolated by blood culture and anticoagulation

with heparin. The efficacy of thrombolytic therapy in the treat-

ment of central venous thrombosis is unclear. The failure of

antibiotics and anticoagulation to eradicate the infectious focus

mandates surgical exploration and vein excision.

The true incidence of intravascular catheter–related bac-

teremia in thermally injured patients is unknown. Vascular

access through a densely colonized wound in those with

extensive surface area burns limits the use and effectiveness

of standard catheter care policies employed for other criti-

cally ill patients. Presumably, as a result of contamination by

removal through colonized eschar and skin, catheter tip cul-

tures frequently are positive even in the absence of sepsis or

bacteremia. Exchanging catheters over guidewires, an

accepted practice in most ICUs, is discouraged because the

catheters and guidewires often transverse heavily contami-

nated open wounds or intact eschar. Consequently, central

venous and pulmonary artery catheters are removed and a

new catheter inserted at a different site every 3 days. This pol-

icy has resulted in a low incidence of bacteremia and sepsis

clinically attributable to catheter-related infections.

Endocarditis

Acute infective endocarditis is an infrequent but consistent

source of morbidity and mortality in burn patients (1.3%)

owing to the bacteremias associated with wound manipula-

tion, prolonged intravenous cannulation, and septic throm-

bophlebitis. Preventive measures include effective topical

antimicrobial therapy, timely excision and closure of the

burn wound, and early discontinuation or frequent replace-

ment of intravenous cannulas.

Staphylococcus aureus is the most common causative

organism, and the right side of the heart is affected most fre-

quently. Recurrent staphylococcal bacteremia in a burn

patient with sepsis and no other apparent identifiable source

of infection should suggest the diagnosis. Heart murmurs

are difficult to detect in hyperdynamic, tachycardiac

patients. Transesophageal echocardiography is the pre-

ferred examination to detect valvular lesions, but small veg-

etations may remain undetected. On occasion, cardiac

catheterization—to identify valvular vegetations or valvular

incompetence—may be required for definitive diagnosis if

echocardiographic findings are equivocal. Systemic maximal-

dose antibiotic therapy is directed against the causative

organism. Antibiotic therapy is continued for 6 weeks after

the last positive blood culture.



BURNS

743

Sinusitis

The true incidence of sinusitis in burn patients is unclear, but

patients requiring prolonged transnasal intubation of both

the airway and stomach are at increased risk. One study

reported an incidence of 36% in transnasally intubated ICU

burn patients. Sinusitis is most often clinically undetectable

and requires radiographic examination by plain films or CT

scanning to establish the diagnosis. These studies help to

direct sinus aspiration to differentiate between congestion

and infection. Treatment involves topical mucosal vasocon-

strictors to improve patency of the sinus ostia and removal of

transnasal tubes. Appropriate systemic antibiotic therapy

should be initiated. Surgical drainage is required in cases not

responsive to these procedures. Tracheostomy or gastros-

tomy may be necessary if prolonged ventilatory support and

enteral nutrition are required.

Other Complications

A. Ocular—Thermal injury of the ocular adnexa is common

in patients sustaining facial burns, but actual injury to the

cornea and globe is uncommon because of the ble-

pharospasm induced by heat, noxious gases, and smoke.

Exceptions occur in patients with altered sensoria at the

time of burning and incomplete protection of the globe.

Shortly after admission, fluorescein staining of the cornea

and examination with a Wood’s lamp should be performed

to detect loss of epithelial integrity. If epithelial defects are

noted, prophylactic topical antibiotic therapy, for example,

bacitracin zinc–neomycin sulfate–polymyxin B sulfate oph-

thalmic ointment, should be initiated. Ophthalmologic con-

sultation should be obtained and the defects examined daily

to document resolution or progression of the epithelial

defects, the major hazard of which is bacterial infection.

Minor corneal abrasions that become infected may progress

rapidly to corneal ulceration and globe perforation.

Infections caused by Pseudomonas species are particularly

prone to this complication.

Frequent ocular examination, adequate eye lubrication,

prophylactic and therapeutic use of topical antibiotics, and

timely performance of eyelid releases are paramount in the

prevention of ocular complications. With severe burns of the

eyelids, ectropion or loss of lid margin may occur. If the

cornea is no longer protected, operation is indicated in the

form of an eyelid release with split-thickness skin grafting.

Release of one or both lids may be required, and in severe

cases, repeated release of the same lid may be made necessary

by progressive skin graft contracture. A temporary tarsorrha-

phy is sometimes useful to protect the cornea from exposure,

but severe ectropion or loss of the lid margin limits the use-

fulness of this technique.

B. Gastrointestinal—Many GI complications have been

documented following thermal injury and include pancreati-

tis, acalculous cholecystitis, gastroduodenal stress ulceration,

and Ogilvie’s syndrome. Stress ulceration of the upper GI

tract has been controlled effectively by prophylactic antacid

or H

-receptor antagonist therapy. Hemorrhage or perfora-

tion requiring operative management occurred in only five

patients (0.1%) during a 14-year series. In a recent study, the

prophylactic administration of sucralfate has been found

equally effective in stress ulcer prevention. Gastric colonization

with gram-negative organisms occurred later among patients

receiving sucralfate than among those receiving antacids, but

this did not change the incidence or type of pneumonia

occurring following burn injury.

Superior mesenteric artery syndrome may occur in

patients who sustain profound weight loss during their hos-

pital course. This condition results in compression and

obstruction of the transverse duodenum by the superior

mesenteric artery from weight loss–induced changes in the

anatomic position of this vessel. Current nutritional prac-

tices have nearly eliminated this complication. If diagnosed,

initial management should be directed toward nutritional

repletion and nasogastric decompression. Nasoenteral feed-

ing tubes may be guided past the obstruction under fluoro-

scopic guidance and are preferred over parenteral alimentation.

Operation is rarely necessary.

The management of GI complications in thermally

injured patients is the same as in other critically ill patients.

If operation is required, retention sutures should be used in

closing any abdominal incision in burn patients owing to the

increased risk of postoperative wound infection and fascial

dehiscence.

Bowers BL, Purdue GF, Hunt JL: Paranasal sinusitis in burn

patients following nasotracheal intubation. Arch Surg

1991;126:1411–12. [PMID: 1747055]

Pruitt BA Jr: The diagnosis and treatment of infection in the burn

patient. Burns Incl Therm Inj 1984;11:79–91. [PMID: 6525539]

Pruitt BA Jr, McManus AT, Kim SH: Burns. In Gorbach SL, Bartlet

JG, Blacklow HR (eds), Infectious Diseases in Medicine and

Surgery. Philadelphia: Saunders, 1992.

Shirani KZ et al: Effects of environment on infection in burn

patients. Arch Surg 1986;121:31–36. [PMID: 3942497]

NUTRITION



Postburn Hypermetabolism

Extensive thermal injury may cause metabolic rates to rise

to levels one and one-half to two times normal, far exceed-

ing the hypermetabolism observed in other critically ill

patients. The hypermetabolic response is linearly related to

the extent of burn, and the actual physiologic response is

influenced by environmental temperature, the patient’s age,

physical activity, pain and anxiety, and the presence of

infection. The hypermetabolic response to burn injury,

common to other forms of critical illness and trauma, is

partially driven by the neurohumoral milieu produced by



CHAPTER 35

744

the hypothalamic-pituitary and autonomic nervous system

responses. Activation of the former results in increased release

of antidiuretic hormone, adrenocorticotropic hormone

(ACTH), and β-endorphins, whereas stimulation of the latter

results in the release of catecholamines, glucagon, and corti-

sol. Postburn hypermetabolism is manifested by increased

oxygen consumption, a hyperdynamic circulation, increased

core temperature, wasting of lean body mass, and increased

urinary nitrogen excretion. An increase in CO

production

follows that parallels oxygen consumption. Hypermetabolism

is temperature-sensitive in patients with burns involving over

50% of the BSA, and a 10% decrease in metabolic rate may be

achieved by maintaining ambient temperatures above 30°C.

Blood flow to the burn wound is markedly increased com-

pared with the blood flow to other organs and tissues. This

explains to some extent the relationship of extent of burn to

hypermetabolism.



Substrate Utilization

Glucose metabolism is altered following thermal injury.

Hepatic gluconeogenesis and total glucose flow increase.

However, owing to relative insulin insensitivity, glucose uptake

by insulin-dependent tissues is decreased.An exaggerated frac-

tion of nutrient flow is directed to the burn wound. Through

anaerobic, insulin-independent means, large quantities of glu-

cose are required to support the immune cellular functions of

necrotic tissue removal and microbial containment and

destruction. Cellular proliferation and wound healing are also

glucose-dependent. The predominance of anaerobic metabo-

lism in the burn wound results in increased lactate production

with subsequent hepatic conversion of lactate to glucose via

the Cori cycle.

Marked catabolism resulting in muscle protein breakdown

and loss of lean body mass is observed following thermal

injury. Catabolism of muscle protein provides amino acid glu-

coneogenic precursors (converted to glucose by liver and gut)

and supplies amino acid substrates for synthesis of acute-phase

proteins. Significant nitrogen loss occurs, with 80–90%

excreted as urea. The metabolism of glutamine, a preferred

substrate for gut metabolism and a precursor for renal ammo-

nia production, is also increased during the hypermetabolic

phase. Glutamine is converted by the gut into alanine, which

subsequently enters the gluconeogenic pathway.

The ability to oxidize fat as a source of nonprotein calo-

ries depends on the extent of injury and the degree of

hypermetabolism. In patients with relatively small burns,

carbohydrate and fat may be used interchangeably as effec-

tive nonprotein calorie sources. In patients with larger

burns, carbohydrate is more effective than fat in maintain-

ing body protein stores when each is used as a sole energy

source.



Estimation of Caloric Needs

Many formulas exist for the estimation of caloric needs in

thermally injured patients. Some of the more common ones

based on body size, age, and sex are presented in Table 35–7.

The increase in calories required to support the metabolic

demand following burn injury is computed by either adding

predetermined stress or injury factors to standard formulas or

by incorporating the measured extent of burn into those for-

mulas specifically derived for burn patients. The use of for-

mulas to predict caloric requirements in individual patients

may result in overestimation or underestimation of caloric

needs. Since most formulas are derived by patient measure-

ments in the resting state, activity factors are customarily

applied and range from 10–50%. Serial measurements by

indirect calorimetry provide the most accurate determination

of energy requirements for patients with major burns; how-

ever, there is no current consensus regarding the most appro-

priate formula to use when requirements must be estimated.

The best method to calculate the protein requirements of

thermally injured patients remains controversial; however,

supplying 12–18 g of nitrogen per square meter of body sur-

face area or 1.5–2 g of protein per kilogram of body weight

Based on Harris-Benedict equation Basal metabolic rate × Activity factor × Injury factor

BMR male = 66.47 + 13.75 (kg BW) + 5.00 (cm ht) – 6.76 (age yr)

BMR female = 65.51 + 9.56 (kg BW) + 1.85 (cm ht) – 4.68 (age yr)

Activity factor = 1.2 bed rest, 1.3 out of bed

Injury factor = 2.1 for severe burn

Curreri (25 kcal × kg BW) + 40 kcal × % burn

Shriner’s (Galveston)

1800 kcal/m

BSA + 2200 kcal/m

of burn

USAISR

Basal in kcal/m

BSA per hour x Factor

Factor = 2.33764 – (1.33764

[–0.0286 × % burn]

)

USAISR = U.S. Army Institute of Surgical Research.

Table 35–7. Formulas for estimating energy requirements in thermally injured patients.



BURNS

745

has been recommended. Nonprotein kilocalorie-to-nitrogen

ratios of 100:1 to 150:1 are acceptable. Only enough fat to

prevent essential fatty acid deficiency is required. Some burn

patients may tolerate up to 9 mg/kg per minute of carbohy-

drate administration. However, carbohydrate delivery

exceeding 5 mg/kg per minute occasionally results in hepatic

fat deposition and excessive CO

production. This may cause

retention in patients unable to compensate by increas-

ing minute ventilation.

Once the optimal delivery rate of carbohydrates is deter-

mined, balancing the remainder of the caloric requirements

with fat may be achieved safely if the fraction of calories

delivered as fat does not exceed one-third of the total.

Triglyceride clearance usually is increased following thermal

injury, but triglyceride levels should be followed weekly in

patients whose nutritional regimens contain a significant

percentage of calories supplied as fat. Hypertriglyceridemia,

usually from parenteral infusion of fat emulsions, may result

in coagulation abnormalities, hepatic dysfunction, and

altered pulmonary diffusion capacity. Triglyceride levels

above 200 mg/dL should prompt a decrease in lipid admin-

istration. The combination of medium- and long-chain

triglycerides provided in most enteral formulas is the pre-

ferred form of dietary fat supplementation and rarely results

in hypertriglyceridemia.



Delivery of Nutritional Support

Administration of nutrition by the enteral route is pre-

ferred to preserve enterohepatic delivery of substrates and

maintain mucosal function and integrity. Enteral intake

may be initiated safely when the ileus associated with ther-

mal injury has resolved. Patients with burns exceeding

30–40% of BSA may not be capable of meeting nutritional

goals by oral intake alone, and supplementation with any of

the commercially available enteral formulas with an appro-

priate calorie-to-nitrogen ratio may be used. Nasogastric

and nasojejunal feedings are commonly employed based on

institutional preference. Nasojejunal feedings have the

added advantage of providing continuous nutrition

throughout the perioperative and intraoperative periods

with a low risk of aspiration.

Parenteral nutrition is reserved for patients with pro-

longed ileus or conditions prohibiting effective GI motility

or absorption. Glucose intolerance is a more common com-

plication of parenteral nutrition and necessitates frequent

monitoring of blood glucose levels.



Monitoring Nutritional Therapy

Careful monitoring of nutritional therapy is imperative if the

high metabolic demand associated with thermal injury is to

be met and adequate nutrition maintained throughout the

hospital course. Useful indices include body weights, calo-

rie counts, nitrogen balance studies, and measurement of

respiratory quotients. In other critically ill patients, measure-

ment of serum albumin, transferrin, prealbumin, and

retinol-binding protein are commonly employed to monitor

the adequacy of nutritional support; however, these bio-

chemical markers have been shown to be poor predictors of

temporal changes in nitrogen balance in thermally injured

patients, and their use is not recommended. Nitrogen bal-

ance calculations based on urinary urea nitrogen (UUN)

excretion measurements should be modified to include

wound losses and other nonurea protein losses. Wound

losses, in grams per day, may be estimated as 0.1 × BSA in m

× percent BSA of unhealed burn wound. Total urinary nitro-

gen excretion exceeds UUN in thermally injured patients.

Increasing the measured 24-hour UUN by 25% will provide

an accurate estimate of total urinary nitrogen losses. The

daily nitrogen loss is increased by adding 2 g to account for

stool and normal integumentary losses. The formula derived

for daily nitrogen loss following thermal injury is as follows:

Total nitrogen loss (g/day) = 24-hour UUN

× 1.25 + [0.1 × BSA (m

)] + 2

If indirect calorimetric measurements are available, mon-

itoring the respiratory quotient (RQ) provides useful infor-

mation regarding substrate utilization. An RQ of greater than

1.0 indicates carbohydrate oxidation and overfeeding, which

may result in hepatic fat deposition. An RQ of less than 0.7

indicates fat oxidation and is consistent with the delivery of

insufficient carbohydrate calories. Routine serum chemistries,

liver function tests, and serum calcium, phosphorus, magne-

sium, and triglyceride determinations should be monitored

once or twice a week during nutritional therapy. Most meta-

bolic complications can be avoided by appropriate adjust-

ment of the elemental and nutrient composition of the

formula administered.



Complications

The mechanical, septic, and metabolic complications associ-

ated with enteral and parenteral nutrition in thermally

injured patients are the same as those common to all critically

ill patients. However, the quantity and duration of nutritional

supplementation required in thermally injured patients are

such that strict attention to the amount, composition, and

safe delivery of nutrition is required to avoid complications.

Burke JF et al: Glucose requirements following burn injury:

Parameters of optimal glucose infusion and possible hepatic

and respiratory abnormalities following excessive glucose

intake. Ann Surg 1979;190:274–85. [PMID: 485602]

Carlson DE, Jordan BS: Implementing nutritional therapy in the

thermally injured patient. Crit Care Nurs Clin North Am

1991;3:221–35. [PMID: 1905139]

Carlson DE et al: Resting energy expenditure in patients with ther-

mal injuries. Surg Gynecol Obstet 1992;174:270–76. [PMID:

1553604]



CHAPTER 35

746

Demling RH, Lalonde C: Nutritional support. In Blaisdell FW,

Trunkey DD (eds), Burn Trauma. New York: Thieme, 1989.

Saffle JR et al: Use of indirect calorimetry in the nutritional man-

agement of burned patients. J Trauma 1985;25:32–9. [PMID:

3965736]

Waxman K et al: Protein loss across burn wounds. J Trauma

1987;27:136–40. [PMID: 3820350]

Wilmore DW et al: Catecholamines: Mediator of the hypermeta-

bolic response to thermal injury. Ann Surg 1974;180:653–69.

[PMID: 4412350]

Wilmore DW: Pathophysiology of the hypermetabolic response to

burn injury. J Trauma 1990;30:S4–6. [PMID: 2254989 ]

Current Controversies & Unresolved Issues

Postburn Hemodynamics

Resuscitation of patients to provide supranormal levels of

oxygen delivery in states of severe illness or injury has been

popularized recently. At present, this goal is impractical in

the acute resuscitation of thermally injured patients. Even

though large volumes of fluid may be required to maintain

urine output, burned patients have decreased oxygen deliv-

ery and consumption during the initial phase of resuscita-

tion. Attempts to improve oxygen delivery would result in

massive fluid administration leading to excessive edema for-

mation and subsequent morbidity. The goal of fluid resusci-

tation in thermally injured patients is to maintain vital organ

function at the lowest physiologic cost. A more physiologic

restoration of intravascular volume and oxygen delivery

would seem beneficial.

Several approaches to reduction of edema formation and

restoration of circulatory integrity are under investigation.

Early intervention to block production of or to scavenge

superoxide and oxygen free radicals has been shown to

decrease edema formation. Administration of a soluble com-

plement receptor that blocks the classic and alternative com-

plement pathways has attenuated postburn edema formation

in animals. Fluid resuscitation with deferoxamine has been

shown to diminish the systemic effects of burn-induced oxi-

dant injury, and an inositol phosphate derivative, 1,2,6-

myoinositol triphosphate, has been shown to decrease burn

wound edema and resuscitation fluid requirements by an

unknown mechanism. Vitamin C, which has been shown in

various animal models to reduce burn wound edema and

resuscitation volume, was administered to burn patients in a

prospective, randomized, controlled manner. The patients

were resuscitated according to the Parkland formula. The 24-

hour total fluid infusion volumes were 5.5 mL/kg per percent

burn in the control group and 3.0 mL/kg per percent burn in

the vitamin C group. The vitamin C group had an initial

weight gain of 9.2% of pretreatment weight compared with a

17.8% weight increase in controls. The results of this initial

small study are encouraging. Urinary outputs were main-

tained between 0.5 and 1.0 mL/kg per hour during the first

24 hours postburn, and total 24-hour urine volumes were

not different between groups. Inhibition of lipid peroxida-

tion accomplished by antioxidant administration may be an

important adjunct in limiting fluid resuscitation volume and

edema formation following burn injury.

The inclusion of osmotically active macromolecules,

such as pentafraction, that have a decreased propensity for

transcapillary leakage during resuscitation also could improve

early circulatory integrity. Until mechanisms of edema forma-

tion are better understood and means of limiting transvascu-

lar fluid loss are developed, “supranormal” resuscitation is

neither appropriate nor feasible for burn patients.

Inhalation Injury

The mechanism by which inhalation of smoke and products of

incomplete combustion injure the tracheobronchial mucosa,

distal airways, and lung parenchyma is not completely under-

stood. In part, injury is governed by particle size, which deter-

mines the anatomic region where injury will occur. Toxicities

of noxious gases produced by combustion of synthetic and

natural materials also contribute to the tissue injury of

smoke inhalation but are at present impossible to quantify in

patients following exposure. Most animal models used to

study the effects of smoke inhalation fail to reproduce the

clinical and histologic changes associated with inhalation

injury in humans. Problems with smoke composition, car-

bon monoxide poisoning, and smoke delivery systems are

common. In a recent study of smoke inhalation injury in non-

human primates, high-frequency percussive ventilation was

found to be superior to conventional volume ventilation and

high-frequency oscillatory ventilation in decreasing baro-

trauma and the histopathologic severity of injury.

Pharmacologic intervention to modulate the response to

smoke inhalation may prove beneficial in decreasing pul-

monary vascular changes and improving lung aeration.

Recent studies in sheep have shown improved alveolar venti-

lation and diminished inflammatory response to smoke

inhalation following postexposure treatment with pentoxi-

fylline. The use of inhaled nitric oxide—which does not alter

the normal inflammatory response—to ameliorate pul-

monary artery hypertension following smoke inhalation is

also being studied. Other treatments, including complement

depletion and antioxidant therapy, are being investigated and

may prove beneficial. Any attempt to modulate the host

response to inhalation injury must proceed with caution to

avoid impairing the normal mechanisms of cellular repair

and immunologic defense.

A nebulized cocktail of heparin and a mucolytic agent,

N-acetylcystine, has been shown to reduce pulmonary failure

and ameliorate airway cast formation in both an animal

model and a case-controlled human study in 47 children. A

blinded, randomized study or studies in adults have not

been reported; however, decreases in reintubation rates

and mortality rates for patients treated with this regimen

were noted when compared with historical controls.

Further information is also needed in this arena; however,