Effects of Perioperative Transauricular Vagus Nerve Electrical Stimulation on POD, POCD and CPSP

Postoperative Delirium Clinical Trial

Official title:

Effects of Perioperative Transauricular Vagus Nerve Electrical Stimulation on Postoperative Delirium, Postoperative Cognitive Dysfunction and Chronic Postsurgical Pain in Patients Undergoing Arthroplasty.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05439707
• Other study ID #: XuzhouCH20220620
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 1, 2022
• Est. completion date: September 1, 2024

Study information

• Verified date: June 2022
• Source: Xuzhou Central Hospital
• Contact: Yangzi Zhu, Doctor
• Phone: +86 18168779150
• Email: zhuyz[@]188.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) occur in 11-51% of patients after surgery, and its prevalence increases with age. The occurrence of delirium is associated with increased morbidity and mortality, prolonged hospital stay, worse functional recovery. Orthopedic procedures and specifically joint replacements have been considered as a major risk for development of chronic postsurgical pain (CPSP). Approximately 13-44% of patients will develop CPSP after knee or hip arthOpioid abuseroplasty. CPSP may cause the discomfort, distress, disability and opioid abuse. Mounting evidence has revealed that inflammation triggered by surgical trauma plays a key role in POD, POCD and CPSP. Recent studies found that vagus nerve stimulation showed the suppression of inflammation. In this study, the effect of perioperative transauricular vagus nerve stimulation on the prognosis of patients undergoing arthroplasty will be investigated, providing potential solutions for the prevention and treatment of postoperative cognitive dysfunction, postoperative delirium and chronic postsurgical pain.

Description:

The investigators assessed POD by the Confusion Assessment Method for the ICU twice daily for 7 days after surgery. Participants' cognitive function was assessed with neuropsychological battery tests. The tests included digit span (forward and backward), Corsi block, paired associate verbal learning, digit symbol test, trail-making test and so on.The investigators make a CPSP diagnosis based on the 11th revision of the International Classification of Diseases.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 600
• Est. completion date: September 1, 2024
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

Inclusion Criteria:

• 50 to 80 years old.
• ASA grade I-?.
• elective knee or hip replacement.

Exclusion Criteria:

• Mini-Mental State Examination (MMSE) score < 23.
• Education years<7.
• Peptic ulcer disease, serious cardiac-cerebral vascular disease.
• Neurological or psychiatric disorders.
• History of drug and alcohol abuse.
• Hepatic and/or kidney dysfunction.
• BMI>35.
• Patients on antidepressants.
• ASA >?.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Delirium
• Pain, Postoperative
• Postoperative Cognitive Complications
• Postoperative Cognitive Dysfunction
• Postoperative Delirium

Intervention

Device:
• transaricular vagus nerve stimulation
The transaricular vagus nerve stimulator was placed in the left ear trunk, which is dominated only by the auricular branch of the vagus nerve. Continuous stimulation was performed at a frequency of 25Hz with pulse width of 300 µs. The stimulation was adjusted to be higher than the perception threshold and lower than the pain threshold. Each stimulation lasted for 30 minutes, three times per day (morning, noon, evening), from 1 day before surgery to 7 days after surgery, and the treatment lasted for 9 consecutive days.
• fake transaricular vagus nerve stimulation
The transaricular vagus nerve stimulator was placed in the same position as the experimental group, covered with an insulating film and placed at the site of the stimulation, so that the patient could not actually receive the electrical stimulation. Continuous stimulation was performed at a frequency of 25Hz and pulse width of 300 µs, and the stimulation was adjusted to be higher than the perception threshold and lower than the pain threshold. Each stimulation lasted for 30 minutes, three times per day (morning, noon, evening), from 1 day before surgery to 7 days after surgery, for 9 consecutive days.

Locations

Country	Name	City	State
China	Xuzhou Central Hospital	Changzhou	Jiangsu

Sponsors (3)

Lead Sponsor	Collaborator
Xuzhou Central Hospital	The Affiliated Hospital of Xuzhou Medical University, The First People's Hospital of Xuzhou

Country where clinical trial is conducted

China, 

References & Publications (11)

Eckenhoff RG, Maze M, Xie Z, Culley DJ, Goodlin SJ, Zuo Z, Wei H, Whittington RA, Terrando N, Orser BA, Eckenhoff MF. Perioperative Neurocognitive Disorder: State of the Preclinical Science. Anesthesiology. 2020 Jan;132(1):55-68. doi: 10.1097/ALN.00000000 — View Citation

Farmer AD, Strzelczyk A, Finisguerra A, Gourine AV, Gharabaghi A, Hasan A, Burger AM, Jaramillo AM, Mertens A, Majid A, Verkuil B, Badran BW, Ventura-Bort C, Gaul C, Beste C, Warren CM, Quintana DS, Hämmerer D, Freri E, Frangos E, Tobaldini E, Kaniusas E, — View Citation

Glare P, Aubrey KR, Myles PS. Transition from acute to chronic pain after surgery. Lancet. 2019 Apr 13;393(10180):1537-1546. doi: 10.1016/S0140-6736(19)30352-6. Review. — View Citation

Hovens IB, Schoemaker RG, van der Zee EA, Absalom AR, Heineman E, van Leeuwen BL. Postoperative cognitive dysfunction: Involvement of neuroinflammation and neuronal functioning. Brain Behav Immun. 2014 May;38:202-10. doi: 10.1016/j.bbi.2014.02.002. Epub 2 — View Citation

Huffman WJ, Subramaniyan S, Rodriguiz RM, Wetsel WC, Grill WM, Terrando N. Modulation of neuroinflammation and memory dysfunction using percutaneous vagus nerve stimulation in mice. Brain Stimul. 2019 Jan - Feb;12(1):19-29. doi: 10.1016/j.brs.2018.10.005. — View Citation

Jin Z, Hu J, Ma D. Postoperative delirium: perioperative assessment, risk reduction, and management. Br J Anaesth. 2020 Oct;125(4):492-504. doi: 10.1016/j.bja.2020.06.063. Epub 2020 Aug 11. Review. — View Citation

Lavand'homme P. Transition from acute to chronic pain after surgery. Pain. 2017 Apr;158 Suppl 1:S50-S54. doi: 10.1097/j.pain.0000000000000809. Review. — View Citation

Liu CH, Yang MH, Zhang GZ, Wang XX, Li B, Li M, Woelfer M, Walter M, Wang L. Neural networks and the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation in depression. J Neuroinflammation. 2020 Feb 12;17(1):54. doi: 10.1186/s12974 — View Citation

Mohanty R, Lindroth H, Twadell S, Nair VA, Prabhakaran V, Sanders RD. A pilot study of neural correlates of perioperative executive function associated with noncardiac surgery in the elderly. Br J Anaesth. 2019 Nov;123(5):e517-e518. doi: 10.1016/j.bja.201 — View Citation

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 2 — View Citation

Zhu Y, Zhou M, Jia X, Zhang W, Shi Y, Bai S, Rampes S, Vizcaychipi MP, Wu C, Wang K, Ma D, Yang Q, Wang L. Inflammation Disrupts the Brain Network of Executive Function After Cardiac Surgery. Ann Surg. 2021 Jul 2. doi: 10.1097/SLA.0000000000005041. [Epub — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Postoperative cognitive function	The incidence of POCD was compared between the experimental group and the control group.The preoperative and postoperative differences of the following scales were calculated and compared: Digit Span (forward and backward), Visual Retention and Paired Associate Verbal Learning subtests of the Wechsler Memory Scale, Digit Symbol subtest of the Wechsler Adult Intelligence ScaleRevised, Halstead-Reitan Trail Making Test (Part A), Corsi Block Test and Grooved Pegboard Test (favored and unfavored hand). The standard deviation (SD) for each test was computed from the preoperative scores. A participant whose postoperative performance declined by =1 SD as compared to each preoperative test score on =2 tests was classified as POCD.	1 month after the surgery.
Primary	Postoperative cognitive function	The incidence of POCD was compared between the experimental group and the control group.The preoperative and postoperative differences of the following scales were calculated and compared: Digit Span (forward and backward), Visual Retention and Paired Associate Verbal Learning subtests of the Wechsler Memory Scale, Digit Symbol subtest of the Wechsler Adult Intelligence ScaleRevised, Halstead-Reitan Trail Making Test (Part A), Corsi Block Test and Grooved Pegboard Test (favored and unfavored hand). The standard deviation (SD) for each test was computed from the preoperative scores. A participant whose postoperative performance declined by =1 SD as compared to each preoperative test score on =2 tests was classified as POCD.	3 months after the surgery.
Primary	Postoperative delirium	The incidence of POD was compared between the experimental group and the control group.Postoperative delirium was assessed by the Delirium Assessment Scale (CAM-ICU)	Consecutive 7 days after the surgery
Primary	Acute postoperative pain	The incidence of acute postoperative pain was compared between the experimental group and the control group.Acute postoperative pain was assessed by Visual Analogue Scale(VAS) for 7 consecutive days within 1 week after surgery.	Consecutive 7 days after the surgery for acute pain
Primary	Chronic Postsurgical pain	The incidence of chronic postoperative pain (CPSP) was assessed by the Short Form McGill Pain Questionnaire (SF-MPQ) and Neuropathic Pain Scale (NPS).The incidence of CPSP was compared between the experimental group and the control group.	3 months after the surgery for chronic pain
Secondary	TNF-a level in peripheral venous blood	The incidence of TNF-a level (pg/ml) in peripheral venous blood was compared between the experimental group and the control group	1 day before the surgery, Postoperative day 1, 3, 5
Secondary	IL-6 level in peripheral venous blood	The incidence of IL-6 level (pg/ml) in peripheral venous blood was compared between the experimental group and the control group	1 day before the surgery, Postoperative day 1, 3, 5
Secondary	IL-1ß level in peripheral venous blood	The incidence of IL-1ß level (pg/ml) in peripheral venous blood was compared between the experimental group and the control group	1 day before the surgery, Postoperative day 1, 3, 5
Secondary	cortisol level in peripheral venous blood	The incidence of cortisol level (µg/dL) in peripheral venous blood was compared between the experimental group and the control group	1 day before the surgery, Postoperative day 1, 3, 5