May 22, 2002 The incidence of sepsis — a severe, whole-body immune response to infection — is increasing by an average of 16% a year in the U.S., according to research by investigators at Emory University School of Medicine and the Centers for Disease Control and Prevention (CDC). During the 20-year period from 1979 to 1999, the incidence of sepsis increased by more than 329%, from 78 to 259 cases per 100,000 people. Sepsis is a major public health problem, consuming more than $15 billion in healthcare costs annually in the U.S.
Emory pulmonologist and intensivist Greg Martin, M.D., in collaboration with Marc Moss, M.D., of Emory and David Mannino, M.D., of the CDC presented results of their analysis of data from the U.S. National Hospital Discharge Survey at the annual meeting of the American Thoracic Society in Atlanta on Tuesday. The study is the most comprehensive survey of sepsis epidemiology to date because it includes statistics from the entire country over a long period of time.
The scientists used selected groupings of clinical disease classification codes to identify patients with sepsis. The incidence of sepsis increased in both children and adults during the 20-year period. Males, African-Americans, and other non-Caucasians had the highest rates of hospitalization due to sepsis, although the incidence in females and Caucasians increased more rapidly. The study also indicated an increase in gram-positive infections, which by 1999 represented the majority of cases of sepsis (56%), while gram-negative infections, anaerobic, fungal and viral infections were less common. Although relatively uncommon, the greatest increase was in sepsis cases with fungal infections as their source.
Although sepsis begins with an identifiable infection, when patients become septic their immune systems are intensely activated, setting off a cascade of events that may result in uncontrolled inflammation throughout the body. Sepsis also activates the coagulation system by promoting thrombosis and inhibiting fibrinolysis, which is how the body breaks up clots. These changes may contribute to multiple organ failure, which is a major cause of mortality from sepsis.
Following years of research on sepsis, scientists last year introduced the first effective specific therapy — the drug Xigris, which is activated protein C, a recombinant form of a natural anticoagulant. Xigris is effective because it is an anti-coagulant that also reduces inflammation. Before Xigris, the mainstay of therapy was general, broad-spectrum antibiotics and supportive care.
Physicians must be able to recognize sepsis quickly in order to treat it. "Studies show that if you wait even four to eight hours to begin antibiotic therapy, the mortality from sepsis worsens considerably," notes Dr. Martin. "And antibiotics must be appropriate. Patients with severe sepsis are in shock, with organ failure, respiratory failure, and renal failure. Although the mortality with severe sepsis is approximately 30% to 40%, Xigris reduces that to approximately 25%.
Although there has been no scientific study to identify the reasons for the increase in sepsis, Dr. Martin offers several explanations. "Physicians are identifying more cases of sepsis because they are aware of how sepsis differs from other infections," he says. "And sepsis is actually occurring more frequently due to the overuse of antibiotics and the development of resistant organisms. This is apparent in the shift towards gram-positive organisms as the cause of sepsis and the increase in fungal causes. Improvements in care among individuals with altered immunities also could be leading to an increase in sepsis. For example, antiretroviral therapy has led to increased longevity for HIV patients, and we have more patients receiving organ transplants, bone marrow transplants, and high-dose chemotherapy who are vulnerable to infection. An increase in medical and surgical procedures that breach body barriers also predisposes more patients to sepsis."
According to earlier research, 80% of patients with sepsis develop it outside the hospital, while only 20% develop it while in a hospital or nursing home. Although the incidence of sepsis is increasing, with more than 700,000 cases per year, the mortality appears to be decreasing, from 29% of cases in 1979 to 17.4% in 1999. Because of the increased incidence, however, more people continue to die each year.
Physicians have become much more adept at diagnosing sepsis, according to Dr. Martin, partly because of a consensus definition that includes criteria such as changes in temperature, heart rate, respiratory function, and white blood cell count. Sepsis is defined as being an initial infection plus at least two of these four additional criteria.
"This makes it much easier for physicians to walk to the bedside and identify patients with sepsis, including those at highest risk," Dr. Martin says. "If a patient has sepsis with organ failure, physicians need to be very aggressive with treatment.
"Not only do we need to treat sepsis promptly and aggressively, we also need to educate the entire physician community about how to recognize sepsis early or prevent sepsis in high-risk patients, We also need to examine how antibiotics, medical procedures, and an increase in immune-compromised patients and elderly patients represent increased risk for sepsis. A new understanding of sepsis could have a major impact on patients and healthcare resources," Dr. Martin emphasizes.
The study was funded by Emory University and the National Institutes of Health.
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