Adrenal insufficiency, heart rate variability, and complex biologic systems: a study of 1,871 critically ill trauma patients

BACKGROUND: Reduction in integer heart rate variability (HRVi), one potential measurement of complex biologic systems, is common in ICU patients and is strongly associated with hospital mortality. Adrenal insufficiency (AI) and reduced HRVi are associated with autonomic dysfunction. Failure of the autonomic nervous system can be associated with loss of biologic complexity. We hypothesize decreased HRVi is associated with AI, and HRVi improves after treatment of AI, suggesting "recomplexification" (resumption of normal stress response to injury). STUDY DESIGN: Of 4,116 trauma ICU admissions from December 2000 to November 2005, 1,871 patients had sufficient physiologic, laboratory, pharmacy, and demographic data for analysis. Seventy-five patients failing cosyntropin-stimulation testing were defined as AI; the remaining 1,796 were defined as no AI. HRVi was calculated as integer heart rate standard deviation over 5-minute intervals. HRVi 10th, 50th (median), and 90th percentiles were calculated over the 72 hours pre-, or poststeroid, or both administration (AI). HRVi percentiles in non-AI patients were evaluated at the same interval and compared with AI using Wilcoxon's rank-sum test. In patients with AI, daily HRVi was computed 3 days before and after steroid administration, and compared between survivors and nonsurvivors. RESULTS: There were 2.9 million heart-rate intervals measured. HRVi stratified patients with AI (cosyntropin failure), and without AI. HRVi was similar in AI survivors and nonsurvivors before steroid treatment, but differed after treatment. HRVi increased substantially in survivors after steroid administration, yet did not change in nonsurvivors. HRVi does not increase in patients who are unresponsive to steroids and die. CONCLUSIONS: Reduced heart-rate variability, a potential measurement of complex biologic systems, is associated with cosyntropin-confirmed AI; improved in patients responding to steroid therapy; and is a noninvasive, real-time biomarker suggesting AI.