especially susceptible to this complication with catheter infection rates reported ranging from 8–57% [10, 11]. Central line sepsis is associated with prolonged indwelling central venous catheters. Meticulous sterile technique is essential during line placement to avoid introduction of potential pathogens. The use of antimicrobial coated catheters and rotation of the catheter site, tubing and apparatus every 72 hours have been reported to have a decrease in catheter infection rates, however these studies are flawed and more valid conclusions would be obtained with a prospective randomized study [12, 13]. All areas should be carefully prepped and draped with Betadine or Chlorhexidine solution and the physician gowned and gloved appropriately prior to insertion [14]. Central line sepsis may be primary in which the central line is the original focus of infection. It also may be secondary, in which case, the catheter tip is seeded and serves as a nidus for continued shedding of microorganisms into the blood stream. Signs of erythema or inflammation around the insertion site should alert the clinician to the potential for a line infection. However, it is important to realize that there may be a significant infection of the catheter tip even when skin surrounding the insertion site appears normal. Central lines can be associated with the development of both gram negative and gram-positive sepsis. The key concept to recognize is that central lines represent a foreign body and as such are prone to microbial seeding. There is significant controversy with regard to the frequency of line changes necessary to avoid catheter-related infection. Frequent line changes may actually increase the risk of central line sepsis. Once a catheter-related infection is suspected, the central venous line should be promptly removed and the tip cultured. Systemic antimicrobial therapy can be initiated for a short time, but generally once the source of infection has been removed the patient should improve quickly. Careful records of previously cannulated sites can allow for sequential venotomy, examination for ultra luminal pus and histologic examination for intimal colonization. Upon confirmation of the diagnosis, immediate operative excision is essential to prevent progressive sepsis. Entire excision of a vein to the port of entry into the central circulation may be required because of the tendency of phlebitis to migrate to vein valves, leaving an ap-

parently normal vein in between the 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 secondary intention.

Urinary tract infection

Urinary tract infections are usually associated with prolonged and often unnecessary catheterization, as it is rarely indicated to leave a catheter in place for more than a few days. Routine monitoring of urine from indwelling catheters should be done by needle aspirates on a regular basis two to three times a week. Urinary tract infections can generally be divided into upper and lower urinary tract infections. True pyelonephritis is very rare in thermally injured patients; however, lower urinary tract infection can occur as a result of a chronic indwelling Foley catheter. The diagnosis should be suspected when there are greater than 1 × 105 organisms cultured from urine specimen. Also urinalysis may reveal white cells and cellular debris associated with active infection. The most common organisms are gram-negative pathogens such as Escherichia coli. The appropriate treatment consists of either exchange or removal of the foley catheter and 7–10 day course of an antimicrobial with good gram-negative coverage. Fluroquinolones such as ciprofloxacin are often very effective for uncomplicated cases. Candiduria is often insignificant but may reflect active infection or septicemia, especially when mycelia can be demonstrated. When present, an active infection with Candida species usually responds well to low doses of fluconazole. If there is suspicion of an ascending infection, more aggressive treatment with prolonged systemic antimicrobials is warranted.

Tracheobronchitis

Smoke inhalation injury is a chemical trancheobronchitis that results from the inhalation of the incomplete products of combustion and is often found in association with severe burn injury. Inhalation injury impairs the mucociliary transport mechanism and predisposes patients to colonization of the tracheobronchial tree by microorganisms. Additionally, direct cellular injury to the respiratory epitheli-

um results in the formation of extensive fibrinous casts composed of inflammatory exudates and sloughed cells. Increased bronchial blood flow leads to increased airway edema. As necrotic debris accumulates and airway edema is increased, patients become susceptible to post-obstructive atelectasis and pneumonia. There is no specific treatment for tracheobronchitis other than aggressive pulmonary toilet and supportive measures. It is important to realize, however, that an upper respiratory infection can quickly turn into a lower respiratory infection with significant mortality. Pneumonia has been shown to independently increase burn mortality by 40%, and the combination of inhalation injury and pneumonia leads to a 60% increase in deaths. Inhalation injury was also found to be associated with a twofold higher risk of developing nosocomial pneumonia than with burns alone. Children and the elderly are especially prone to pneumonia due to a limited physiologic reserve.

Pneumonia

The diagnosis of pneumonia in severely burned patients is exceedingly problematic. During the acute phase of injury these patients demonstrate a hypermetabolic response characterized by increased basal metabolic rate and resetting of their hypothalamic temperature set point. The increased levels of catecholamines result in a hyperdynamic circulation. For these reasons, many of the usual signs and symptoms of pneumonia are unreliable in the severely burn patients. Fever, leucocytosis, tachycardia and tachypnea may all be present even in the absence of an infection. Sputum examination is rarely helpful since specimens are often contaminated with oropharyngeal flora. If sputum expectoration is chosen, examination should include a variety of criteria such as color, amount, consistency and odor of the specimen. Muco-purulent sputum is most commonly found with bacterial pneumonia or bronchitis. Scant or watery sputum is often related to viral and other atypical pneumonias. “Rusty” sputum indicates alveolar involvement and has been most commonly associated with pneumococcal pneumonia. Dark red, mucoid sputum suggests Friedlander’s pneumonia caused by encapsulated K. I. Pneumonia. Foul-smelling sputum is associated with mixed anaerobic infections most commonly seen with as-

piration [14]. More invasive sampling techniques such as brochoalveolar lavage have been advocated; however, these have also been shown to be less than ideal for establishing a diagnosis of pneumonia. Radiographic findings can be helpful if they reveal lobar consolidation. Unfortunately, concomitant inhalation injury and changes in pulmonary vascular permeability more often result in diffuse nonspecific radiographic changes consistent with noncardiogenic pulmonary edema. Pneumonias can result from descending infection and have clearly been shown to increase the incidence and the mortality of nosocomial pneumonia in the burn population. Generally, patients with a significant inhalation injury and pneumonia develop atelectasis, ventilationperfusion mismatch, arterial hypoxia and respiratory failure. Prolonged mechanical ventilation leads to inevitable barotraumas and further worsening of pulmonary status in these patients. Ventilator-asso- ciated pneumonia (VAP) specifically refers to pneumonia that develops more than 48 hours after intubation (late-onset VAP) in mechanically ventilated patients who had no clinical evidence suggesting the presence or likely development of pneumonia at the time of intubation. VAP that occurs within 48 hours of intubation is frequently the result of aspiration and usually yields a better prognosis than late-onset VAP, which is more often caused by antibioticresistant bacteria. While broncho-alveolar lavage has been to correlate better with the presence of trancheobronchitis than with radiographic evidence of true pneumonia, it is the best available tool. For this reason, a positive lavage in the appropriate clinical context mandates aggressive intervention. These nosocomial pneumonias are generally gram-negative infections and systemic antimicrobial therapy with multiple agents is generally required until the infection resolves clinically. Amikacain and piperacillin with tazobactam or ceftazidime are generally recommended for serious infections, but antibiotics should be selected on the basis of susceptibility patterns in each hospital. Once cultures are returned, antimicrobial coverage may be narrowed appropriately.

Sepsis in the burn patient

Sepsis is one of the leading causes of morbidity and mortality in critically ill patients [15]. Severely burned

patients are markedly susceptible to a variety of infectious complications [16]. Sepsis may result from seeding of the bloodstream from the burn wound, the respiratory tract, the gastrointestinal tract, and the urinary tract and central venous catheters. The burn wound and the lungs account for the vast majority of cases. The immunocompromised state of the burned patient is associated with multiple defects of the humoral and cellular components of both the nonspecific host defense system and the specific immune defense system and is markedly contributing to the increased susceptibility to infection. It is important to differentiate bacteremia from septicemia. Bacteremia refers to the presence of bacteria in the blood stream and may occur transiently after burn wound manipulation or excision. This transient bacteremia generally resolves and is not associated with any significant morbidity. Septicemia, however, implies a widespread response at the tissue level to bacteria or their products and toxins. Traditionally sepsis is categorized as gram-posi- tive or gram-negative. Gram-negative sepsis is by far the most predominant in severely burned patients.

There are excellent criteria for the diagnosis of infection and sepsis in most patients, but the standard diagnoses for infection and sepsis really do not apply to burn patients 17. Burn patients lose their primary barrier to microorganism invasion so they are constantly and chronically exposed to the environment. In response to this exposure, inflammatory mediators that change the baseline metabolic profile of the burn patient are continuously released. The baseline temperature is reset to about 38.5°C, and tachycardia and tachypnea persist for months in patients with extensive burns. Continuous exposure leads to significant changes in the white blood cell (WBC) count, making leukocytosis a poor indicator of sepsis.

The burn sepsis definition must therefore distinguish changes in patient status as the result of infection due to a microbial entity from the alterations secondary to the burn injury itself or associated events (such as inhalation injury). Several of these global changes are based on the fact that patients with extensive burns develop a hypermetabolic state that surpasses that of any other patient group.

Current definitions for sepsis and infection have many criteria (fever, tachycardia, tachypnea, leuko-

cytosis) that are routinely found in patients with extensive burns, making these current definitions less applicable to the burn population. The diagnosis of sepsis is aclinical diagnosis. Laboratory studies are supportive. A patient who is adequately resuscitated and becomes hemodynamically unstable should alert the clinician to the possibility of either active bleeding or the development of septic shock. The five cardinal signs of sepsis are hyperventilation, thrombocytopenia, hyperglycemia, obtundation and hypothermia. Leucocytosis and fever are also important, but must be interpreted with caution in this setting. Based on the American Burn Association Consensus Conference to Define Sepsis and Infection in Burns, sepsis is defined by the criteria depicted in Tables 1 and 2 [17, 18].

A septic source can be documented as:

1) Burn wound biopsy with > 105 organisms/gm tissue and/or histologic evidence of viable tissue invasion

2) Positive blood culture

3) Urinary tract infection with > 105 organisms/ ml urine of

4) Pulmonary infection

Local evidence of invasive wound infection includes black or brown patches of wound discoloration, rapid eschar separation, conversion of wounds to full thickness, spreading peri-wound erythema, punctate hemorrhagic subeschar lesions, and violaceous

Table 1. Definition of sepsis

Hart et al. (2000) Determinants of skeletal muscle catabolism after severe burn. Ann Surg 233(4): 455–465