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.

HMGB-1 as a Useful Prognostic Biomarker in Sepsis-Induced Organ Failure in Patients Undergoing PMX-DHP

“…Tracey reported that stimulation of the vagus nerve prevents the damaging effects of cytokine release in experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, arthritis, and other inflammatory syndromes [24]. Consistent with this report, data from Tateishi et al indicates that reduction in heart rate variability (HRV) indices is associated with hypercytokinemia [25]. We have previously found an HRV in patients with septic shock, and that this is favorably influenced by PMX-DHP (reported at the 7th World Congress on Trauma, Shock, Inflammation, and Sepsis, 2007, Munich, Germany).…”

Experimental examination of anti-inflammatory effects of a 5-HT3 receptor antagonist, tropisetron, and concomitant effects on autonomic nervous function in a rat sepsis model

“…Recently, many investigators have attempted to utilize HRV analysis [16][17][18] for non-invasive, prompt, and objective assessment of autonomic nervous activity. HRV analysis in various animal models of [15,19,20] and patients with [21][22][23][24] sepsis has been documented in several published articles. While tropisetron induced a significant increase in HF, an index of parasympathetic nervous activity, in the sham-operated animals, the HF value in the CLP + tropisetron group tended to be higher than that in the CLP group, though not to a significant extent.…”

Variability in Cardiovascular Control: The Baroreflex Reconsidered

“…From medical practice it is a well-known fact that extremely stable recordings of heart rate and blood pressure are signs of a severe disease, often with a poor outcome (e.g. Bigger et al 1992;Winchell and Hoyt 1997;Aronson et al 2004;Tateishi et al 2007). Since clinical monitoring systems are becoming more and more intelligent, enabled to do online analysis of the incoming continuous vital signals, one would expect the development of newer software to go more towards tracking of short-term variability, in an attempt to give early warning of impending deterioration of the patient's condition.…”