Decreased physiologic variability as a generalized response to human endotoxemia*

Abstract

OBJECTIVE: To test the effect in normal human volunteers of transient systemic inflammation on the variability in time-series behaviors of widely divergent physiologic measures of the human inflammatory response. DESIGN: Prospective study of human volunteers who were tested on 2 consecutive days, a control day and a treatment day. Each participant served as his or her own control. SETTING: Critical care facility of a university medical center. SUBJECTS: Subjects were eight healthy human volunteers. INTERVENTIONS: Participant subjects were tested on both a baseline day with no intervention and on a treatment day when they received 4 ng/kg intravenous Escherichia coli endotoxin. MEASUREMENTS AND MAIN RESULTS: Continuous electrocardiographic recordings and serial blood sampling (performed every 5 mins) were used to create time-series of heart rate (R-R intervals), neutrophil function (phagocytosis), and plasma cortisol concentrations. For each primary measure, we recorded a significant increase in the regularity (decreased variability) of the functional measurement as assessed by the statistical entity, approximate entropy. CONCLUSIONS: Increased regularity, or decreased variability, of organ functions is a generalized response to systemic inflammation that occurs in widely divergent systems during endotoxemia.