Effects of Transcutaneous Vagal Nerve Stimulation on Post-Surgical Return to Consciousness, Delirium, and Depression

Overview

This study will examine whether noninvasive, transcutaneous vagal nerve stimulation (tcVNS) can help restore consciousness in patients in the operating room and the Post Anesthesia Care Unit (PACU). The study will also investigate if tcVNS can expedite discharge from the PACU and examine whether tcVNS administerd in the PACU helps reduce delirium and depression after surgery. The study will also evaluate whether tcVNS speeds cognitive recovery from emergence of anesthesia and surgery.

Interventions

• Device Transcutaneous vagal nerve stimulation
  The tcVNS device utilized in this study is not an implanted device, but rather is solely operated outside of the body by affixing it around the patient's ear. The device delivers stimulation of the vagus nerve at designated intensity, interval, and frequency.
• Device Sham (No Treatment)
  The stimulator is flipped upside down so that the participant does not receive stimulation of the vagal nerve.

Primary outcome measures

• Aim 1: Primary Endpoint 1: Determine if administering auricular tcVNS enhances the speed of recovery of anesthesia. [Time frame: 24 Hours]
• Aim1:Primary Endpoint 2 : Richmond Agitation Sedation Scale (RASS Score) [Time frame: 1 Hour]
• Aim 2: Primary Endpoint 1: Post Anesthesia Care Unit Discharge (PACU) [Time frame: 3 Hours]
• Aim 2: Primary Endpoint 2: Discharge from Hospital [Time frame: From PACU discharge (average of two hours post-surgical end time) to study completion (average of two days)]
• Aim 3: Primary Endpoint 1: Post Anesthesia Care Unit delirium [Time frame: From PACU arrival to one hour post-PACU arrival]
• Aim 3: Primary Endpoint 1a: Post Anesthesia Care Delirium [Time frame: 30 Days after discharge]
• Aim3:Primary Endpoint 1b: PHQ-9 [Time frame: 30 days]

Secondary outcome measures (7)

• Aim 3: Secondary Endpoint 1:EEG Monitoring Data [Time frame: From pre-surgical EEG placement (i.e. approximately 30 minutes before surgery) through study completion (an average of 2 days)]
• The Montreal Cognitive Assessment (MoCA) evaluations [Time frame: 48 hours]
• SF-36 Survey [Time frame: 30 days]
• Neuro Qol Cognition Function Short Form [Time frame: 30 Days]
• Neuro- QOL [Time frame: 30 Days]
• DRS-R-98 [Time frame: 48 hours]
• DigitSpan Test [Time frame: 48 Hours]

Eligibility criteria

Inclusion criteria

• Aged > 18 years of age
• Patients undergoing lumbar surgery for degenerative disc disease or spinal stenosis involving two or more levels
• Montreal Cognitive Assessment (MoCA) score ≥ 18 - accept mild
• Ability to use a keyboard
• Able to understand and communicate in English
• Be able to consent independently
• Women of child-bearing age must be comfortable confirming a negative pregnancy prior to participating in the study.
• Must not be involved in any other research intervention study testing neurobehavioral functioning

Exclusion criteria

• Age < 18 years of age
• History of vagotomy (cutting the vagus nerve)
• History of bradycardia, heart block, prolonged QT syndrome, brugada syndrome, heart failure with ejection fraction less than 35% and/or New York Heart Association symptoms
• MoCA < 18
• History of seizure disorder or intracranial hemorrhage
• Patients with carotid stenosis
• Patients with aneurysms
• Other neurological diagnoses or a diagnosis of severe psychiatric disorder (e.g., psychosis) or a reported childhood learning disability
• Pregnancy, breastfeeding
• Active addiction history
• ECG adhesive allergy
• Severe aphasia, preventing subject from understanding the protocol and giving written consent
• Patients will be excluded postoperatively if there is neck swelling at the proposed site of left tcVNS.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Northwestern University Feinberg School of Medicine — Chicago

Publications

• Assenza G, Tombini M, Lanzone J, Ricci L, Di Lazzaro V, Casciato S, Morano A, Giallonardo AT, Di Bonaventura C, Beghi E, Ferlazzo E, Gasparini S, Giuliano L, Pisani F, Benna P, Bisulli F, De Falco FA, Franceschetti S, La Neve A, Meletti S, Mostacci B, Sartucci F, Striano P, Villani F, Aguglia U, Avanzini G, Belcastro V, Bianchi A, Cianci V, Labate A, Magaudda A, Michelucci R, Verri A, Zaccara G, P PMID 32524324
• Ben-Menachem E, Revesz D, Simon BJ, Silberstein S. Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Eur J Neurol. 2015 Sep;22(9):1260-8. doi: 10.1111/ene.12629. Epub 2015 Jan 23. PMID 25614179
• Han S, Kim M, Kim H, Shin H, Youn I. Ketamine Inhibits Ultrasound Stimulation-Induced Neuromodulation by Blocking Cortical Neuron Activity. Ultrasound Med Biol. 2018 Mar;44(3):635-646. doi: 10.1016/j.ultrasmedbio.2017.11.008. Epub 2017 Dec 21. PMID 29276137
• Redgrave J, Day D, Leung H, Laud PJ, Ali A, Lindert R, Majid A. Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. Brain Stimul. 2018 Nov-Dec;11(6):1225-1238. doi: 10.1016/j.brs.2018.08.010. Epub 2018 Aug 23. PMID 30217648
• Hachem LD, Wong SM, Ibrahim GM. The vagus afferent network: emerging role in translational connectomics. Neurosurg Focus. 2018 Sep;45(3):E2. doi: 10.3171/2018.6.FOCUS18216. PMID 30173606
• Rufener KS, Geyer U, Janitzky K, Heinze HJ, Zaehle T. Modulating auditory selective attention by non-invasive brain stimulation: Differential effects of transcutaneous vagal nerve stimulation and transcranial random noise stimulation. Eur J Neurosci. 2018 Sep;48(6):2301-2309. doi: 10.1111/ejn.14128. Epub 2018 Sep 9. PMID 30144194
• Ruffoli R, Giorgi FS, Pizzanelli C, Murri L, Paparelli A, Fornai F. The chemical neuroanatomy of vagus nerve stimulation. J Chem Neuroanat. 2011 Dec;42(4):288-96. doi: 10.1016/j.jchemneu.2010.12.002. Epub 2010 Dec 16. PMID 21167932
• George MS, Aston-Jones G. Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Neuropsychopharmacology. 2010 Jan;35(1):301-16. doi: 10.1038/npp.2009.87. PMID 19693003

Identifiers

NCT: NCT07610655 · STU00223307

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗