PITTSBURGH—Severe sepsis has an annual incidence exceeding three quarters of a million cases, a 28.6% overall hospital mortality rate, and an average cost of $22,100 per case, a major new study of the condition has estimated.[1] “Severe sepsis is primarily a disease of the elderly, and as the nation ages, the incidence is likely to rise,” added lead investigator Derek C. Angus, MD, MPH, in an interview with PULMONARY REVIEWS. Furthermore, “There are as many deaths in patients hospitalized with severe sepsis as [there are] in those with acute myocardial infarction,” said Dr. Angus, an Associate Professor of Critical Care Medicine at the University of Pittsburgh.

The study conducted by Dr. Angus and colleagues adds significantly to existing information on severe sepsis incidence, costs, and outcomes. “However, we do not see it as the be-all and end-all in severe sepsis epidemiology,” stressed Dr. Angus. Rather, along with two other important studies, it gives a better overall picture of the condition’s impact, he said.[2,3]

A LARGE STUDY SPANNING SEVEN STATES

By linking the 1995 discharge files from hospitals in seven states, the investigators formed one enormous patient database. That year, more than 63 million people (about 25% of the US population) lived in the states included in the study: Florida, Maryland, Massachusetts, New Jersey, New York, Virginia, and Washington.

The investigators supplemented the database with hospital and population data from the US Census Bureau, the National Center for Health Statistics, the Centers for Disease Control and Prevention, the American Hospital Association, and the Health Care Financing Administration (which is now known as the Centers for Medicare and Medicaid Services). To identify severe sepsis cases, they selected all acute care hospitalizations with International Classification Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for bacterial or fungal infection and a diagnosis of acute organ dysfunction.

When classifying organ dysfunction, the investigators chose ICD-9-CM codes that suggested new onset dysfunction within six organ systems: the heart, lungs, kidneys, liver, blood, and central nervous system. Non-hepatic gastrointestinal failure was excluded, though, because it is difficult to define.

INCIDENCE

Among the more than 6.6 million hospitalizations recorded in the seven states, the investigators identified 192,980 patients with severe sepsis. After adjustment for age and gender, statistical analysis produced a national incidence estimate of 3.0 cases per 1,000 population, or 751,000 cases annually. Of the patients with severe sepsis, an estimated 68.4% received care in an intensive care, coronary care, or intermediate care unit.

Severe sepsis rates rose sharply with age, from 0.2 cases per 1,000 population among children ages 5 to 14 years to 26.2 cases per 1,000 population among the elderly 85 years or older. After adjustment for age, men generally had higher incidence rates than women. Dr. Angus and his colleagues project that the incidence of sepsis will increase by 1.5% per year. Most of this rise can be attributed to the high incidence of sepsis in the elderly and the overall aging of the population. They estimate that there will be 934,000 cases in the United States in the year 2010 and 1,110,000 cases in 2020.

The overall hospital mortality rate was 28.6%, which translates to 215,000 deaths annually nationwide. Mortality increased with increasing age; the rate was 10% in children and 38.4% in those 85 years or older. However, the impact of age on outcome was most important for patients without comorbidities. Among those who did have comorbid conditions, advancing age conferred little increase in risk. After adjustment for age and site of infection, there was no difference in mortality between men and women.

Total annual costs for severe sepsis were estimated to be $16.7 billion. Per-patient costs for the condition were highest in infants, non-survivors, ICU and surgical patients, and patients with acute dysfunction in four or more organ systems. However, because sepsis affects the elderly disproportionately, more than half of all annual costs—$8.7 billion—were spent on care for patients 65 years or older.

The investigators acknowledge that their study does have some limitations; chief among them is the reliance on ICD-9-CM codes to define infection and organ dysfunction. However, the investigators said, “our approach captured patients similar to those identified using more rigorous prospective screening criteria.” Further, the dataset also did not include information about costs or outcome after hospital discharge. The authors also stressed that these estimates of costs and mortality are not necessarily fully attributable to sepsis.

AN EXCESSIVELY HIGH ESTIMATE?

Some sepsis authorities question the study’s results. For example, the study’s overall mortality estimate is excessively high, “perhaps off by a factor of two to four,” suggested Richard P. Wenzel, MD, MSc, and Michael B. Edmond, MD, MPH, in an accompanying editorial.[4]

“Because total mortality [comprises] mortality owing to underlying disease plus the attributable mortality resulting from infection, not all of the 28.6% mortality rate can be attributed to severe sepsis,” the two physicians explained. They suggested a mortality rate of 14%, or 105,140 deaths per year that result directly from severe sepsis. “Only further data will help add precision to the important goal of accuracy,” Drs. Wenzel and Edmond concluded. Dr. Wenzel is Chairman of the Department of Internal Medicine at the Medical College of Virginia in Richmond; Dr. Edmond is Associate Chairman of Research at that institution.

—Timothy Begany

References
1. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303-1310.
2. Sands KE, Bates DW, Lanken PN, et al. Epidemiology of sepsis syndrome in eight academic medical centers. Academic Medical Center Consortium Sepsis Project Working Group. JAMA. 1997;278:234-240.
3. Rangel-Frausto MS, Pittet D, Costigan M, et al. The natural history of the systemic inflammatory response syndrome (SIRS): a prospective study. JAMA. 1995;273:117-123.
4. Wenzel RP, Edmond MB. Severe sepsis—national estimates. Crit Care Med. 2001;29:1472-1473.

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