title: Is worsening multiple organ failure the cause of death in patients with severe sepsis?
abstract: OBJECTIVE
  Although the mortality of severe sepsis is easily quantified, the actual cause and timing of death from severe sepsis are less defined. We used the INDEPTH (International Integrated Database for the Evaluation of Severe Sepsis and Drotrecogin alfa activated) database to investigate the reported cause of death in patients with severe sepsis.
  
  
  METHODS
  Retrospective database analysis.
  
  
  METHODS
  Data from 4459 patients with severe sepsis (drotrecogin alfa activated, n = 3228; placebo, n = 1231) included in five clinical trials conducted in tertiary care institutions in 28 countries.
  
  
  RESULTS
  We examined the cause of death and the pattern of Sequential Organ Failure Assessment scores near the time of death. We also evaluated the time course of biomarker levels at this late stage. A total of 1201 (27.0%) patients died during the 28-day study period. The main causes of death were as follows: sepsis-associated multiple organ failure (43.1%), refractory septic shock (22.6%), and respiratory failure (13.0%). There were no significant differences in the distributions of cause of death between drotrecogin alfa activated and placebo patients, so that all patients were combined for analysis. The mean cardiovascular Sequential Organ Failure Assessment score increased from 2.4, 4 days before death, to 2.9, 1 day before death, and the mean respiratory Sequential Organ Failure Assessment score increased from 2.6, 4 days before death, to 2.9, 1 day before death. The increase in these individual Sequential Organ Failure Assessment scores was more prominent in patients who died early (day 0-5). Protein C levels decreased and interleukin-6 levels increased in the days before death.
  
  
  CONCLUSIONS
  Patients with severe sepsis typically die of multiple organ failure, refractory shock, or respiratory failure. Persistent, more than worsening, organ failure is the more common pattern before death.
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Belgium. jlvincen@ulb.ac.be
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Mark D
authors.initials: MD
authors.lastname: Williams
mesh_terms: D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use; D002423:Cause of Death; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D016638:Critical Illness / Q000401:mortality; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D009102:Multiple Organ Failure / Q000139:chemically induced* / Q000401:mortality* / Q000628:therapy; D011486:Protein C / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012131:Respiratory Insufficiency / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D012189:Retrospective Studies; D018570:Risk Assessment; D018805:Sepsis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D012772:Shock, Septic / Q000139:chemically induced / Q000401:mortality / Q000503:physiopathology / Q000628:therapy
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated