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.