title: Hydrocortisone at stress-associated concentrations helps maintain human heart rate variability during subsequent endotoxin challenge.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH. athos.rassias@hitchcock.org
authors.forename: Athos J
authors.initials: AJ
authors.lastname: Rassias
authors.forename: Paul M
authors.initials: PM
authors.lastname: Guyre
authors.forename: Mark P
authors.initials: MP
authors.lastname: Yeager
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011292:Premedication; D013312:Stress, Physiological / Q000187:drug effects; D018746:Systemic Inflammatory Response Syndrome / Q000517:prevention & control*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D006854:Hydrocortisone