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The autonomic nervous system in septic shock and its role as a future therapeutic target: a narrative review.

ABSTRACT: The autonomic nervous system (ANS) regulates the cardiovascular system. A growing body of experimental and clinical evidence confirms significant dysfunction of this regulation during sepsis and septic shock. Clinical guidelines do not currently include any evaluation of ANS function during the resuscitation phase of septic shock despite the fact that the severity and persistence of ANS dysfunction are correlated with worse clinical outcomes. In the critical care setting, the clinical use of ANS-related hemodynamic indices is currently limited to preliminary investigations trying to predict and anticipate imminent clinical deterioration. In this review, we discuss the evidence supporting the concept that, in septic shock, restoration of ANS-mediated control of the cardiovascular system or alleviation of the clinical consequences induced by its dysfunction (e.g., excessive tachycardia, etc.), may be an important therapeutic goal, in combination with traditional resuscitation targets. Recent studies, which have used standard and advanced monitoring methods and mathematical models to investigate the ANS-mediated mechanisms of physiological regulation, have shown the feasibility and importance of monitoring ANS hemodynamic indices at the bedside, based on the acquisition of simple signals, such as heart rate and arterial blood pressure fluctuations. During the early phase of septic shock, experimental and/or clinical studies have shown the efficacy of negative-chronotropic agents (i.e., beta-blockers or ivabradine) in controlling persistent tachycardia despite adequate resuscitation. Central α-2 agonists have been shown to prevent peripheral adrenergic receptor desensitization by reducing catecholamine exposure. Whether these new therapeutic approaches can safely improve clinical outcomes remains to be confirmed in larger clinical trials. New technological solutions are now available to non-invasively modulate ANS outflow, such as transcutaneous vagal stimulation, with initial pre-clinical studies showing promising results and paving the way for ANS modulation to be considered as a new potential therapeutic target in patients with septic shock.

SUBMITTER: Carrara M

PROVIDER: S-EPMC8128952 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective: Re-hospitalization after sepsis can lead to impaired quality of life. Predictors of re-hospitalization could help identify sepsis survivors who may benefit from targeted interventions. Our goal was to determine whether low heart rate variability (HRV), a measure of autonomic nervous system dysfunction, is associated with re-hospitalization in pediatric septic shock survivors. Materials and Methods: This was a retrospective, observational cohort study of patients admitted between 6/2012 and 10/2020 at a single institution. Patients admitted to the pediatric intensive care unit with septic shock who had continuous heart rate data available from the bedside monitors and survived their hospitalization were included. HRV was measured using age-normalized z-scores of the integer HRV (HRVi), which is the standard deviation of the heart rate sampled every 1 s over 5 consecutive minutes. The 24-h median HRVi was assessed on two different days: the last 24 h of PICU admission ("last HRVi") and the 24-h period with the lowest median HRVi ("lowest HRVi"). The change between the lowest and last HRVi was termed "delta HRVi." The primary outcome was re-hospitalization within 1 year of discharge, including both emergency department encounters and hospital readmission, with sensitivity analyses at 30 and 90 days. Kruskal-Wallis, logistic regression, and Poisson regression evaluated the association between HRVi and re-hospitalizations and adjusted for potential confounders. Results: Of the 463 patients who met inclusion criteria, 306 (66%) were re-hospitalized, including 270 readmissions (58%). The last HRVi was significantly lower among re-hospitalized patients compared to those who were not (p = 0.02). There was no difference in the lowest HRVi, but patients who were re-hospitalized showed a smaller recovery in their delta HRVi compared to those who were not re-hospitalized (p = 0.02). This association remained significant after adjusting for potential confounders. In the sensitivity analysis, a smaller recovery in delta HRVi was consistently associated with a higher likelihood of re-hospitalization. Conclusion: In pediatric septic shock survivors, a smaller recovery in HRV during the index admission is significantly associated with re-hospitalization. This continuous physiologic measure could potentially be used as a predictor of patients at risk for re-hospitalization and lower health-related quality of life.

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The autonomic nervous system in septic shock and its role as a future therapeutic target: a narrative review.

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