ABSTRACT: High blood levels of endotoxin on admission to the intensive care unit are predictive of adverse outcomes, including organ failure and death. However, the significance of changes in endotoxin levels over time has not been evaluated. We examined whether dynamic daily changes in endotoxin levels resulted in the development of greater organ dysfunction over time in critically ill patients. The study was a retrospective analysis of data from the longitudinal phase of a prospective observational multicenter cohort study of endotoxin levels in patients admitted to the intensive care unit. We analyzed 345 patients. Daily variation in endotoxin levels was assessed by calculating the number of inflections in the curve generated by plotting endotoxin levels against time. The degree of organ dysfunction over time was analyzed using a calculation of the total area under the curve generated by plotting the Multi Organ Dysfunction Score against time. From 1,301 endotoxin activity assay results, patients with dynamic daily variation in endotoxin levels as measured by a greater number of inflections had a greater degree of total organ dysfunction as measured by Multi Organ Dysfunction Score against time (P < 0.05). The arithmetic mean standard deviation of endotoxin activity assay results increased stepwise in the zero, one, and two inflection groups supporting the association between inflections and variability. Endotoxin activity assay variability was found to be independent of infection status (P = 0.52). Daily dynamic variation in endotoxin levels is a marker of increased severity of illness as measured by burden of total organ dysfunction over time. Further studies are warranted to assess the role of daily variation in endotoxin levels in the pathogenesis and potential therapy of organ failure in the critically ill.
*St. Michael's Hospital, University of Toronto; †Spectral Diagnostics, Toronto; and ‡Ottawa Hospital, University of Ottawa, Ottawa, Canada
Received 13 Dec 2006; first review completed 2 Jan 2007; accepted in final form 22 Feb 2007
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