The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: a safety study

Author:

Tan Gansheng12ORCID,Huguenard Anna L1,Donovan Kara M12,Demarest Phillip12,Liu Xiaoxuan12,Li Ziwei12,Adamek Markus3,Lavine Kory1,Vellimana Ananth K14,Kummer Terrance T4,Osbun Joshua W14,Zipfel Gregory J1,Brunner Peter12ORCID,Leuthardt Eric C12

Affiliation:

1. Department of Neurosurgery, Washington University School of Medicine

2. Department of Biomedical Engineering, Washington University in St. Louis

3. Department of Neuroscience, Washington University in St. Louis

4. Department of Neurology, Washington University in St. Louis

Abstract

Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. 3,10,13 However, the effects of taVNS on cardiovascular dynamics in critically ill patients like those with SAH have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population 5 . Therefore, we assessed the impact of both acute taVNS and repetitive taVNS on cardiovascular function in this study.In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a Sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram (ECG) readings and vital signs. We compared long-term changes in heart rate, heart rate variability, QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored rapidly responsive cardiovascular biomarkers in patients exhibiting clinical improvement.We found that repetitive taVNS did not significantly alter heart rate, corrected QT interval, blood pressure, or intracranial pressure. However, taVNS increased overall heart rate variability and parasympathetic activity from 5–10 days after initial treatment, as compared to the sham treatment. Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, intracranial pressure, or heart rate variability. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than 1 point in their Modified Rankin Score at the time of discharge.Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment.Trial registration: NCT04557618

Publisher

eLife Sciences Publications, Ltd

Reference47 articles.

1. Inflammation in Subarachnoid Hemorrhage and Delayed Deterioration Associated with Vasospasm: A Review;Provencio;Acta Neurochirurgica Supplement,2012

2. Transcutaneous auricular vagus nerve stimulation reduces cytokine production in sepsis: An open double-blind, sham-controlled, pilot study;Wu;Brain Stimulation,2023

3. Inflammatory Events Following Subarachnoid Hemorrhage (SAH);Schneider;Current Neuropharmacology,2018

4. Impact of Acute Cardiac Complications After Subarachnoid Hemorrhage on Long-Term Mortality and Cardiovascular Events;Norberg;Neurocritical Care,2018

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