Immunotherapy in burn patients

Abstract

Infection remains the leading cause of death following hospitalization of patients with major burn injury. This susceptibility is due not only to the loss of the skin barrier, but also, and perhaps more importantly, to acquired immunodeficiencies. Virtually every variable of immunologic resistance to infection has been studied and reported to be abnormal following severe thermal injury (5). Neutrophils have been reported to show impairment in chemotaxis, phagocytosis, and intracellular killing of bacteria. T lymphocytes show a diminished response both to specific and nonspecific activators, such as phytohemagglutinin (PHA), and suppressor T cells show increased activity in the thermally injured patient. B-cell function, as measured by antibody synthesis, has been shown to be diminished in severely burned patients. Complement levels are variable, depending on the complement factor measured. Certain inhibitory complement degradation products, such as C3b and C5a, are markedly elevated following severe thermal injury, and the opsonic index also is markedly depressed. The fixed macrophages of the reticuloendothelial system (RES) demonstrate a markedly diminished phagocytic ability within 24 hr of burn injury. To determine which of these abnormalities was most predictive of the development of an infection, a sequential prospective analysis of immunologic abnormalities in infections following severe thermal injuries was undertaken at this institution (4). Twenty consenting patients with burn injuries involving more than 45% of the total body surface area (TBSA) were studied. The average burn size x~Tas 59.5% TBSA, and 44.0% were third degree burns. All patients received routine therapy, including topical antibiotics; systemic antibiotics were administered only on specific indications, primarily bacteremia. The caloric needs were met using nasogastric tube feedings, if necessary, to meet the requirements. Blood samples were obtained on all patients three times per week until the patient's wounds were totally closed, or until the patient died. The following tests were run on all samples: measurements of antibacterial function of neutrophils using Staphylococcus attretts and Escherichia coli, chemotaxis of neutrophils, serum levels of C3 and IgG, measurement of opsonic activity of the serum, and lymphocyte response to PHA. For analysis, all patients were divided into two groups, infected and noninfected, based on the presence or absence of a positive blood culture during the period of the study. Of the 20 patients, 13 developed positive blood cultures at some time during the period of observation. The average burn size for these patients was 62% TBSA. The seven patients without positive blood cultures had an average 54% TBSA burn. All tests showed an impairment of function, both in those patients who developed bacteremias and in those who did not. There were no differences between the infected and noninfected patients in any of these variables, except for the neutrophil bactericidal index (NBI). NBI is a measurement of the neutrophil's ability to phagocytose and kill bacteria, with numbers greater than one indicating impairment in these abilities. Infected patients had significantly worse neutrophil function (p < 0.01) against S. aureus, overall, than noninfected patients (Fig. 1). The NBI for E. coli in the infected group was worse compared with the noninfected group, but not significantly so.