title: Measurement of endotoxin activity in critically ill patients using whole blood neutrophil dependent chemiluminescence.
abstract: BACKGROUND
  Lipopolysaccharide (endotoxin) from the cell wall of Gram-negative bacteria is a potent trigger for the release of host-derived inflammatory mediators. The relationship between endotoxaemia, Gram-negative infection and the clinical syndrome of sepsis has been difficult to establish, in part because of the limitations of available endotoxin assays.
  
  
  METHODS
  We performed an observational cohort study in critically ill patients in the medical/surgical intensive care unit (ICU) of a tertiary care hospital. Whole blood endotoxin levels on the day of ICU admission were measured using a novel chemiluminescent assay--the endotoxin activity assay (EAA)--and the chromogenic modification of the limulus amoebocyte lysate (LAL) assay.
  
  
  RESULTS
  We studied 74 consecutive admissions. Endotoxin levels were higher in patients with a diagnosis of sepsis (470 +/- 57 pg/ml) than in patients admitted with a diagnosis other than sepsis (157 +/- 140 pg/ml; P < 0.001). Endotoxaemia was significantly associated with Gram-negative infection (P < 0.05); no patient with a Gram-negative infection had an endotoxin level below 50 pg/ml. White blood cell counts of patients with EAA-detected endotoxaemia were significantly higher (15.7 +/- 9.1 x 10(9) cells/l for endotoxaemic patients versus 10.8 +/- 6.2 x 10(9) cells/l for patients without endotoxaemia; P < 0.05).
  
  
  CONCLUSIONS
  Endotoxaemia is associated with Gram-negative infection from any source, and with a diagnosis of sepsis and leukocytosis. These correlations were not apparent using the LAL method. The EAA may be a useful diagnostic tool for the investigation of invasive Gram-negative infection and incipient sepsis.
authors.affiliation: Medical/Surgical Intensive Care Unit, University Health Network, Toronto, Ontario, Canada. John.Marshall@UHN.on.ca
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.forename: Paul M
authors.initials: PM
authors.lastname: Walker
authors.forename: Debra M
authors.initials: DM
authors.lastname: Foster
authors.forename: David
authors.initials: D
authors.lastname: Harris
authors.forename: Melanie
authors.initials: M
authors.lastname: Ribeiro
authors.forename: Jeff
authors.initials: J
authors.lastname: Paice
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Romaschin
authors.forename: Anastasia N
authors.initials: AN
authors.lastname: Derzko
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D019446:Endotoxemia / Q000145:classification* / Q000378:metabolism / Q000401:mortality; D004731:Endotoxins / Q000097:blood*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000382:microbiology
chemical_list: D004731:Endotoxins