Introduction: rationale for using drotrecogin alfa (activated) in patients with severe sepsis

Abstract

Sepsis associated with acute organ dysfunction (severe sepsis) remains a leading cause of mortality despite ongoing improvements in critical care. In the United States and Europe, it is estimated that there are at least 1 million cases of severe sepsis annually [ 1 Angus D.C. Linde-Zwirble W.T. 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 Crossref PubMed Scopus (6566) Google Scholar , 2 Davies A, Green C, Hutton J, Chinn C. Severe sepsis: a European estimate of the burden of disease in ICU. Intensive Care Med 2001;27(suppl):S284. Abstract 581 Google Scholar ]. Linde-Zwirble et al [ [3] Linde-Zwirble W.T. Angus D.C. Carcillo J. et al. Age-specific incidence and outcome of sepsis in the US. Crit Care Med. 1999; 27 ([abstract]): A33 Crossref Scopus (48) Google Scholar ] estimated that >750,000 cases of severe sepsis are reported each year in the United States, of which 28% to 50% will be fatal; this unacceptably high mortality rate has remained essentially unchanged for several decades [ [4] Natanson C. Esposito C.J. Banks S.M. The sirens’ songs of confirmatory sepsis trials selection bias and sampling error. Crit Care Med. 1998; 26: 1927-1931 Crossref PubMed Scopus (133) Google Scholar ]. Consequently, >600 patients in the United States die daily of this disorder, a rate approximately equal to that of deaths after acute myocardial infarction [ 1 Angus D.C. Linde-Zwirble W.T. 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 Crossref PubMed Scopus (6566) Google Scholar , 4 Natanson C. Esposito C.J. Banks S.M. The sirens’ songs of confirmatory sepsis trials selection bias and sampling error. Crit Care Med. 1998; 26: 1927-1931 Crossref PubMed Scopus (133) Google Scholar , 5 Murphy S.L. Deaths final data for 1998. Natl Vital Stat Rep. 2000; 48: 1-105 PubMed Google Scholar ]. Because of a number of factors (including age, human immunodeficiency virus infection, and transplant procedures) and an increasing frequency of nosocomial infection, the incidence of severe sepsis is expected to increase at a rate of 1.5% per year well into this century [ 1 Angus D.C. Linde-Zwirble W.T. 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 Crossref PubMed Scopus (6566) Google Scholar , 3 Linde-Zwirble W.T. Angus D.C. Carcillo J. et al. Age-specific incidence and outcome of sepsis in the US. Crit Care Med. 1999; 27 ([abstract]): A33 Crossref Scopus (48) Google Scholar ]. Moreover, severe sepsis is expensive. In the United States, healthcare costs associated with this disorder exceed $16.7 billion annually, with an estimated cost of $22,100 per patient [ [1] Angus D.C. Linde-Zwirble W.T. 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 Crossref PubMed Scopus (6566) Google Scholar ]. Therefore, interventions that reduce the incidence and mortality of this deadly disorder are urgently needed.