Sepsis and sepsis-related deaths are on the increase in U.S., according to Emory and CDC study

April 16, 2003

ATLANTA-- The incidence of sepsis -- a severe, whole-body immune response to infection -- has increased by an annualized average of 8.7% a year in the U.S. over the past 22 years, according to research by investigators at Emory University School of Medicine and the Centers for Disease Control and Prevention (CDC). The study was conducted on discharge data from 750 million patient hospitalizations in 500 non-federal hospitals nationwide between 1979 and 2000. The results were reported in the April 17 issue of The New England Journal of Medicine.

The study, conducted by Emory physicians Greg Martin, MD, Marc Moss, MD and Stephanie Eaton, MD from the Division of Pulmonary and Critical Care Medicine, and by CDC scientist David Mannino, MD, was the most comprehensive investigation of sepsis epidemiology to date, because it included statistics from the entire country over a long period of time, with equal representation from all geographic regions. Data was from the National Hospital Discharge Survey conducted by the National Center for Health Statistics.

During the study period, an estimated 10,319,418 cases of sepsis were identified from across the United States,, with an increase from about 164,000 cases a year (82.7 per 100,000 population) in 1979 to nearly 660,000 cases a year (240.4 per 100,000) in 2000. Sepsis was more common among men than among women (approximately 1.28 times) and more common among nonwhite persons than among white persons (approximately 1.81 times). The rate of sepsis due to fungal organisms increased by 207% over the 22-year period, accompanied by a shift towards gram-positive bacteria after 1987.

During the 22-year period, the average age of patients with sepsis increased continually, from 57.4 years in the first study period (1979 to 1984) to 60.8 years in the last study period (1995-2000). Although the in-hospital mortality rate fell from 27.8% during the first five-year period to 17.9% during the last five-year period, and the average length of hospital stay decreased, the total number of in-hospital deaths from sepsis nearly tripled, from 43,579 in 1979 to 120,491 in 2000.Sepsis is a major public health problem, consuming more than $17 billion in healthcare resources annually in the United States. According to the National Center for Health Statistics, sepsis is the 10th leading cause of death overall in the United States -- a number that has steadily risen in the past two decades.

Physicians define sepsis through a combination of infection and physiologic conditions referred to collectively as "systemic inflammatory response syndrome" criteria. These criteria, including changes in temperature, heart rate, respiratory function, and white blood cell count, permit rapid identification of patients with sepsis. Using hospital disease classification codes, sepsis is defined by the presence of either septicemia (pathogens or their toxins in the blood); bacteremia (bacteria in the blood); or disseminated fungal or Candida infection. More severe forms of sepsis may include acute organ dysfunction or shock.

Although the pathway to 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.

Before the drug Xigris became available in 2001 as the first effective therapy for sepsis, the mainstay of treatment was broad-spectrum antibiotics and supportive care. Xigris is activated protein C -- a recombinant form of a natural anticoagulant -- and is effective because of its anti-coagulant and anti-inflammatory properties. Although the mortality from severe sepsis is approximately 30% to 40%, use of Xigris may reduce mortality to approximately 25%.

Although no scientific study has yet uncovered the reasons for the increase in sepsis, Dr. Martin offers several explanations, including an increase in antibiotic resistance, an increase in invasive procedures, transplantation, chemotherapy, and immunosuppressive drugs, and improvements in care among individuals with altered immunities, including antiretroviral therapy for HIV patients. He notes, however, that "because these data are collected from a large database, it is important to realize that changes in medical coding and billing practices may influence the appearance of disease."

"Racial and gender disparities in sepsis incidence are significant, and are cause for additional investigation," said Dr. Martin. "Simple changes in coding practice would not account for such a difference in risk, where nonwhite patients develop sepsis at nearly twice the rate of white patients. The most striking difference is among black men, in which sepsis occurs at the youngest ages and results in the highest mortality. Once we better understand why such differences exist, we can not only work to narrow the gap, but understanding the mechanism for such a difference may improve care for all sepsis patients."

The study also noted changes in post-hospital care, including a progressive increase in the likelihood of being discharged from the hospital to a transitional medical facility for rehabilitation or other non-acute medical care. Dr. Martin explains that such increases, "while not surprising given the changes in hospitals and reimbursement over the past two decades, portends a major public health problem. With the number of people developing sepsis on the rise, and mortality rates falling, even greater numbers of patients are expected to require such care in the foreseeable future."

Although new consensus definitions have made diagnosing sepsis much more feasible for physicians at the bedside, says Dr. Martin, rapid recognition, with appropriate use of antibiotics, is still crucial for effective treatment. "Not only do we need to treat sepsis aggressively, we also must focus on early identification of septic patients to maximize their benefits from available therapies. Studies show that if you wait even four to eight hours to begin antibiotic therapy, the mortality from sepsis worsens considerably. Physicians need to be able to walk to the bedside and identify patients with sepsis, including those at highest risk. If a patient has sepsis with organ failure, physicians need to be very aggressive with treatment."

Examining how antibiotics, medical procedures, and an increase in immune-compromised patients and elderly patients represent increased risk for sepsis also is important, Dr. Martin says. "A new understanding of sepsis could have a major impact on patients and on the provision of healthcare resources," he emphasizes.
The study was funded by Emory University, the Centers for Disease Control and Prevention and the National Institutes of Health.

Emory University Health Sciences Center

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