Exploration of autonomic regulation reflecting on pathophysiological change of sepsis: a prospective observational study

Abstract

Aim: It remains unclear how autonomic regulation modulates pathophysiological changes of sepsis. This study aims to analyze and clarify those in patients with suspected sepsis.

Methods: In this single-centered, prospective, observational study, adult patients who had an infection, a quick Sequential Organ Failure Assessment score of 2 or more at the emergency department, and underwent intensive care were screened. Heart rate variability (HRV) and serum adrenaline were measured immediately after arrival. The primary outcome was defined as vasopressor dependence during 48 h after arrival.

Results: A total of 63 patients were included. All the patients had SOFA score of 2 or more on admission. Vasopressor dependence, renal replacement therapy, and in-hospital mortality were associated with higher adrenaline (which reflects sympathetic adrenergic system activity). Bacteremia was associated with lower high-frequency components of HRV (parasympathetic nerve activity). The HRV parameter of sympathetic nerve activity had no significant association with the outcomes. In the multivariate logistic regression model adjusted for age and sex, vasopressor dependence remained associated with higher adrenaline (cut-off 0.11 ng/mL, odds ratio 9.71, 95% confidence interval 2.55-37; P = 0.000874), and lower high-frequency components with bacteremia (17.2 ms², odds ratio 4.86, 95% confidence interval 1.36-17.4; P = 0.0152). There were no significant correlations between parameters of HRV and serum adrenaline.

Conclusion: Hypoperfusion, organ dysfunction, and in-hospital mortality were associated with an increased sympathetic adrenergic activity. Bacteremia was associated with decreased parasympathetic nerve activity. The autonomic regulator may involve a multilayered and differentiated modulating process for sepsis.

Keywords: Adrenaline; autonomic nervous system; bacteremia; sepsis; septic shock.

Fig. 1

Flowchart of the study population. COVID‐19, coronavirus disease 2019; ED, emergency department; ICU: intensive care unit; q‐SOFA: quick Sequential Organ Failure Assessment.

Fig. 2

Correlation between (A) (LF to HF + LF) – HF, (B) (LF to HF + LF) – adrenaline, and (C) HF – adrenaline. CI, confidence interval; HF, high frequency; LF, low frequency.