Indwelling catheters should be removed as soon as clinically feasible. Elderly persons are more prone to aspiration pneumonia, which is the leading cause of death due to hospital-acquired infections. Selective decontamination of the digestive tract is not recommended by the Centers for Disease Control and Prevention (72). Simple procedures such as elevation of the head, using sucralfate, and early detection in at-risk patients (chronic lung disease, changing mental status, nasogastric tube, reintubation) are preferred. Old age probably does not increase the risk of intravenous catheter-associated infection, but these occur more frequently in the elderly due to the age-associated increased use of these devices. Appropriate skin care, e.g., using chlorhexidine antiseptic, and probable antibiotic-coated intravascular devices, may decrease the incidence. Hand washing after examining each patient is a simple preventive method that is commonly ignored.
Sepsis is characterized by an imbalance in proinflammatory and anti-inflammatory cytokines. TNF-a and IL-1 are the principal mediators causing most manifestations of sepsis and shock. In animal studies, anti-TNF a antibody and IL-1 receptor antagonists can protect septic animals from death (73,74). Clinical trials, however, have had mixed results. Two multicenter phase II/III trials in patients with sepsis were held evaluating a monoclonal antibody to TNF-a (antiBAY x1351). The North American Sepsis Trial I (NORASEPT 1) showed that septic patients without shock had no benefit from treatment with this monoclonal antibody and in septic patients with shock, the 3-d mortality rate was decreased but not the 28-d mortality. In the International Sepsis Trial (INTERSEPT), the circulating TNF-a levels and the development of organ failure were decreased with the use of the monoclonal antibody, but there was no reduction in the 28-d mortality. Recently, a double-blind, randomized control phase III trial, NORASEPT II, that was conducted in 105 hospitals with 1879 patients, did not find any survival benefit from TNF a blockade (75-77).
Studies on endotoxin blockade have also yielded disappointing results. Clinical studies of two antibodies to the lipid A fraction of lipopolysaccharide and the core region of endotoxin yielded conflicting results. Although the first study showed some clinical benefit in patients not in shock (78), a second randomized large controlled clinical study of a monoclonal antibody to endotoxin found no improvement in survival, although a modest benefit in resolution of organ dysfunction was shown (79).
Despite some early enthusiasm for the use of corticosteroids in patients with septic shock, a meta-analysis has shown that corticosteroids are not beneficial (80). A study on the use of ibuprofen showed that it decreased fever but not survival (81).
A variety of other agents, e.g., interferon-y, N-acetylcysteine, antithrombin III, naloxone, pentoxifylline, and hemofiltration, have been tested in patients with sepsis, but the results are disappointing. The immune response to infection is quite compli cated so that it is unlikely that a single agent will prove beneficial. It is clear that the mortality of sepsis is not improved dramatically despite more intensive therapy. The greater frequency of underlying comorbid conditions in study subjects that included more elderly with chronic illness, immunosuppressive patients, and new innovative and invasive treatment may have contributed to the lack of improvement in survival. There are no published studies focusing on older patients. Whether septic elderly patients would respond differently from younger remains to be answered.
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