DEPRESSED HEART RATE VARIABILITY IS ASSOCIATED WITH HIGH IL-6 BLOOD LEVEL AND DECLINE IN THE BLOOD PRESSURE IN SEPTIC PATIENTS

Abstract
Depressed heart rate variability (HRV) in septic patients is known to be associated with poor outcome. However, neither etiology of depression of HRV nor its clinical significance has been clearly determined. Because hypercytokinemia plays an important role in sepsis, we investigated the relationships between depressed HRV and IL-6 blood level. The subjects of this study were 45 septic patients treated in our intensive care unit. IL-6 blood level upon admission exhibited significant negative correlations with two HRV indices, low-frequency power (LF) (r = −0.76; P < 0.01) and high-frequency power (HF) (r = −0.53; P < 0.01). Multivariate analysis revealed strong correlations between IL-6 blood level and LF (P = 0.01) and HF (P = 0.01), respectively, even when the effects of patient background factors and therapeutic intervention were taken into account. Among the patients who developed septic shock, a high IL-6 blood level and a low LF were observed in both the survivor and nonsurvivor groups on the day of admission. The HF was lower than normal at the same time points in both groups. However, the HF was significantly higher in the nonsurvivor group than in the survivor group. By the time of discharge from the intensive care unit, both IL-6 blood level and HRV indices had become significantly closer to the normal ranges in the survivor group, but not in the nonsurvivor group. A significant negative correlation was observed between LF upon admission and percent decline in blood pressure (r = −0.76, P < 0.01). These findings indicate that reduction in HRV indices is associated with hypercytokinemia, indicating that the autonomic nervous system and the inflammatory response mediated by the cytokine network affect each other. These results also suggest that depression of HRV is closely related to rapid changes in blood pressure. Thus, heart rate variability indices are associated with both the severity and poor outcome of sepsis.