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A Prospective Study

M. Sigfrido Rangel-Frausto, MD, MSc; Didier Pittet, MD; Michele Costigan, RN, BSN; Taekyu Hwang, MS; Charles S. Davis, PhD; Richard P. Wenzel, MD, MSc

JAMA. 1995;273(2):117-123.

Abstract
Objective.
—Define the epidemiology of the four recently classified syndromes describing the biologic response to infection: systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock.

Design.
—Prospective cohort study with a follow-up of 28 days or until discharge if earlier.

Setting.
—Three intensive care units and three general wards in a tertiary health care institution.

Methods.
—Patients were included if they met at least two of the criteria for SIRS: fever or hypothermia, tachycardia, tachypnea, or abnormal white blood cell count.

Main Outcomes Measures.
—Development of any stage of the biologic response to infection: sepsis, severe sepsis, septic shock, end-organ dysfunction, and death.

Results.
—During the study period 3708 patients were admitted to the survey units, and 2527 (68%) met the criteria for SIRS. The incidence density rates for SIRS in the surgical, medical, and cardiovascular intensive care units were 857,804, and 542 episodes per 1000 patient-days, respectively, and 671,495, and 320 per 1000 patient-days for the medical, cardiothoracic, and general surgery wards, respectively. Among patients with SIRS, 649 (26%) developed sepsis, 467 (18%) developed severe sepsis, and 110 (4%) developed septic shock. The median interval from SIRS to sepsis was inversely correlated with the number of SIRS criteria (two, three, or all four) that the patients met. As the population of patients progressed from SIRS to septic shock, increasing proportions had adult respiratory distress syndrome, disseminated intravascular coagulation, acute renal failure, and shock. Positive blood cultures were found in 17% of patients with sepsis, in 25% with severe sepsis, and in 69% with septic shock. There were also stepwise increases in mortality rates in the hierarchy from SIRS, sepsis, severe sepsis, and septic shock: 7%, 16%, 20%, and 46%, respectively. Of interest, we also observed equal numbers of patients who appeared to have sepsis, severe sepsis, and septic shock but who had negative cultures. They had been prescribed empirical antibiotics for a median of 3 days. The cause of the systemic inflammatory response in these culture-negative populations is unknown, but they had similar morbidity and mortality rates as the respective culture-positive populations.

Conclusions.
—This prospective epidemiologic study of SIRS and related conditions provides, to our knowledge, the first evidence of a clinical progression from SIRS to sepsis to severe sepsis and septic shock.

(JAMA. 1995;273:117-123)

Author Affiliations
From the Division of General Medicine, Clinical Epidemiology, and Health Services Research, Department of Internal Medicine (Drs Rangel-Frausto and Wenzel and Ms Costigan), and Division of Biostatistics, Department of Preventive Medicine (Dr Davis and Mr Hwang), University of Iowa College of Medicine, Iowa City; and Infection Control Group, Division of Infectious Diseases, Department of Internal Medicine, University Hospital, Geneva, Switzerland (Dr Pittet). Dr Wenzel has served as a consultant for Pfizer Roerig, New York, NY.

Footnotes
Reprint requests to Division of General Medicine, C-41 GH, University of Iowa Hospitals and Clinics, Iowa City, IA 52242 (Dr Wenzel).

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