Intravenous endotoxin administration in healthy volunteers caused a significant loss of heart rate variability and an increase in heart rate regularity, even with ibuprofen pretreatment.
RCT
Single-blind
Crossover
No
Does intravenous endotoxin reduce heart rate variability in healthy volunteers?
Experimental human endotoxemia causes a loss of heart rate variability and an increase in heart rate regularity, which may serve as an early marker for sepsis.
OBJECTIVE: To determine whether human endotoxemia is associated with a loss of the physiologic beat-to-beat variability of heart rate. DESIGN: Prospective, randomized, crossover, single-blind study. SETTING: Clinical research center in a federal, nonuniversity hospital. SUBJECTS: Healthy volunteers. INTERVENTIONS: Intravenous administration of reference (Escherichia coli) endotoxin or saline placebo, with or without previous administration of oral ibuprofen. MEASUREMENTS AND MAIN RESULTS: Electrocardiograms were continuously recorded and digitized using series of 1000 beat epochs of R-R intervals over 8 hrs. Analyses included measures in the time domain (standard deviation), frequency domain (power spectra), and a measure of regularity (approximate entropy). Endotoxin administration was associated with loss of variability by all measures. This loss of variability remained significant even with administration of ibuprofen, which blocked the development of fever and endotoxin-related symptoms. CONCLUSIONS: Infusion of endotoxin into human volunteers causes loss of heart rate variability, as measured by standard deviation and power spectra, as well as an increase in heart rate regularity, as measured by approximate entropy. Changes in approximate entropy occurred earlier than changes in other heart rate variability measures and may be a useful means of detecting early sepsis. This reduction in regularity is consistent with a model in which the pathogenesis of multiple organ system dysfunction syndrome involves the physiologic uncoupling of vital organ systems.
Godin et al. (Mon,) conducted a rct in Healthy volunteers. Intravenous Escherichia coli endotoxin with or without oral ibuprofen vs. Saline placebo was evaluated on Heart rate variability (standard deviation, power spectra) and regularity (approximate entropy). Intravenous endotoxin administration in healthy volunteers caused a significant loss of heart rate variability and an increase in heart rate regularity, even with ibuprofen pretreatment.