Hydrocortisone at stress-associated concentrations helps maintain human heart rate variability during subsequent endotoxin challenge

• Published in: Journal of critical care Vol. 26; no. 6; pp. 636.e1 - 636.e5
• Main Authors: Rassias, Athos J., Guyre, Paul M., Yeager, Mark P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2011; Elsevier Limited
• Subjects: Adolescent; Adult; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Critical Care; Dose-Response Relationship, Drug; Endotoxins - blood; Escherichia coli; Experimental endotoxemia; Female; Glucocorticoid; Heart rate; Heart Rate - drug effects; Heart rate variability; Human; Humans; Hydrocortisone - administration & dosage; Hydrocortisone - pharmacology; Male; Middle Aged; Premedication; Sepsis; Stress, Physiological - drug effects; Studies; Systemic Inflammatory Response Syndrome - prevention & control; Time series; Treatment Outcome; Young Adult; Human; Sepsis; Heart rate variability; Glucocorticoid; Experimental endotoxemia
• ISSN: 0883-9441; 1557-8615; 1557-8615
• DOI: 10.1016/j.jcrc.2011.01.009

We evaluated the differential impact of stress-associated vs high pharmacologic concentrations of hydrocortisone pretreatment on heart rate variability (HRV) during a subsequent systemic inflammatory stimulus. Healthy volunteers were randomized to receive placebo (Control) and hydrocortisone at 1.5 μg/kg per minute (STRESS) or at 3.0 μg/kg per minute (PHARM) as a 6-hour infusion. The STRESS dose was chosen to replicate the condition of physiologic adrenal cortical output during acute systemic stress. The PHARM dose was chosen to induce a supraphysiologic concentration of cortisol. The next day, all subjects received 2 ng/kg Escherichia coli endotoxin (lipopolysaccharide). Heart rate variability was analyzed with the statistic approximate entropy (ApEn). A lower ApEn correlates with decreased HRV. At the 3-hour nadir, the decrease in ApEn in the STRESS group was significantly less compared to placebo ( P < .03), whereas ApEn in the PHARM group was not statistically different. We also found that the maximal decrease in ApEn preceded maximal increase in heart rate in all groups. The decrease in R-R interval was maximal at 4 hours, whereas the ApEn nadir was 1 hour earlier at 3 hours. Pretreatment with a stress dose of hydrocortisone but not a higher pharmacologic dose maintained a significantly higher ApEn after endotoxin exposure when compared to a placebo. In addition, decreases in ApEn preceded increases in heart rate.