Clinical efficacy and mechanisms of transcutaneous auricular vagus nerve stimulation targeting the gut-brain axis for postoperative complications of aortic dissection: study protocol for a randomized controlled trial

经皮耳迷走神经刺激靶向肠脑轴治疗主动脉夹层术后并发症的临床疗效及机制:一项随机对照试验的研究方案

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Abstract

BACKGROUND: Aortic dissection (AD) is a life-threatening cardiovascular emergency characterized by rapid onset and high mortality. While surgery intervention, the primary treatment, improves short-term survival, it frequently leads to postoperative complications including systemic inflammatory response syndrome, gastrointestinal dysfunction, and anxiety/depression. These complications may be exacerbated by dysregulation of the gut-brain axis (GBA). Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique known to exert anti-inflammatory, prokinetic, and neuroregulatory effects in various conditions; however, its application for managing postoperative complications in AD remains unexplored. This study aims to evaluate the efficacy and safety of taVNS in regulating the GBA among postoperative AD patients through a randomized controlled trial. METHODS: This is a single-center, randomized, investigator-blinded, sham-controlled randomized controlled trial. A total of 50 patients aged 18-75 years with postoperative Stanford Type A or B AD will be enrolled and randomly assigned in a 1:1 ratio to either the active taVNS group or the sham control group. Both groups will receive standard postoperative care. The experimental group will additionally receive active taVNS targeting the vagus nerve-innervated auricular area (15 Hz, 200 μs pulse width), while the control group will receive sham stimulation at a non-vagus innervated site without electrical current. The intervention will be administered for 30 min, twice daily, over 7 consecutive days, with follow-up assessments continuing until 24 weeks post-surgery. Primary outcomes include changes in gut microbiota diversity/abundance and brain function (assessed via functional near-infrared spectroscopy). Secondary outcomes encompass inflammatory markers, plasma neurotransmitter levels, intestinal function recovery, and relevant psychometric scale scores. Safety will be monitored through vital signs, laboratory tests, and recording of any adverse events. DISCUSSION: This study is the first to innovatively integrate taVNS with the GBA theory, investigating its multi-target mechanisms through a comprehensive set of biomarkers and clinical endpoints. If proven effective, taVNS could offer a safe and cost-effective non-pharmacological adjunctive therapy for managing postoperative complications in AD. Furthermore, the findings have the potential to elucidate the role of the GBA in the recovery trajectory of patients following major cardiovascular surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR, http://www.chictr.org.cn), No. ChiCTR2500102345, Date: May 13, 2025.

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