The Neuroprotective Effect of Dexmedetomidine Preserving Brain Functional Connectivity in Elderly Patients

NCT04973124 | Completed DMC

• 1 other identifier: 200618004
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Older patients are more prone to adverse cognitive outcomes such as postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). Both conditions are associated with an increased risk of death, functional decline, and health care costs. The presence of pro-inflammatory cytokines in the central nervous system has detrimental effects on the regulation of neurotransmitter signaling in different areas of the brain, especially the hippocampus, ultimately resulting in neuronal dysfunction and cognitive decline. Neuroimaging studies have provided important information on the structural and functional networks involved in the pathogenesis of POD and POCD. Strong evidence has shown a decrease in the integrity of the default mode network (DMN), along a continuum from normal aging to mild cognitive impairment and Alzheimer's disease. Dexmedetomidine is a highly selective alpha-2 adrenergic agonist with sedative and analgesic properties but minimal respiratory effects. Several studies have shown that dexmedetomidine reduces serum pro-inflammatory cytokines and POCD. The expected results are to analyze the change in the integrity of the DMN from the preoperative period to the first weeks after discharge given by the two anesthetic strategies (SEVO vs SEVODEX). In addition, it seeks to evaluate (1) Changes in the integrity of the DMN at 3 months. (2) Modulation of structural changes in white matter integrity as measured by DTI. (3) Patient performance in specific cognitive function tests and serum inflammation biomarkers between the pre- and postoperative period. For the analysis, the Generalized Linear Model (GLM) will be used, in which the integrity of the DMN is the dependent variable. As predictors will use the anesthetic groups (SEVO and SEVODEX) and the measurement time (preoperative, 1 to 3 weeks after discharge and 3 months later as levels). With this work we aim to provide a mechanistic explanation of the observed neuroprotective effects of dexmedetomidine in anesthesia protocols for elderly patients. Furthermore, this work will possibly promote functional connectivity as a possible clinical biomarker of cognitive impairment in this vulnerable population.

Conditions

Anesthesia; Dexmedetomidine; Aging

Keywords

Aged; Dexmedetomidine; Anesthesia

Outcome Measures

Primary Outcomes (1)

• Reduction of the alteration of the NDM due to the effect of dexmedetomidine associated with sevoflouran in elderly patients under general anesthesia

  To assess the effect of the administration of dexmedetomidine, together with sevoflurane, in reducing the disruption of the default mode network (DMN) after surgery in elderly patients through functional magnetic resonance imaging( f-MRI)of the brain.

  f-MRI before surgery (t0), f-MRI two to four weeks post discharge (t1), Three months post discharge (t2)

Secondary Outcomes (5)

• The relationship among the indicators of systemic inflammation and Cognition

  Pre and postoperative levels of IL-6, TNFα and pre and postoperative score of the MoCa test up to 3 month.

• The relationship among the indicators of systemic inflammation and Delirum

  Pre and postoperative levels of IL-6, TNFα and pre and postoperative score of CAM up to 7 days.

• The relationship among the indicators of systemic inflammation and frailty .

  Pre and postoperative levels of IL-6, TNFα and pre and postoperative score of frail scale up to 7 days.

• The association between poor cognitive outcomes and potential markers brain injury.

  Pre Operative score MoCa test, CAM and f-MRI (t0) and Post Operative score MoCa test, CAM and f-MRI (t2) up to 3 months.

• The association between postoperative neuroinflammation and images of brain structure

  Post operative IL-6, TNFα and f-MRI (t2) up to 3 months.

Study Arms (2)

SEVODEX Group

ACTIVE COMPARATOR

The SEVODEX group will receive intraoperative dexmedetomidine at a fixed infusion rate of 0.25 mcg/kg/h

Drug: Dexmedetomidine

SEVO Group

PLACEBO COMPARATOR

The SEVO group will not receive dexmedetomidine during surgery.

Drug: Placebo

Interventions

Dexmedetomidine DRUG

These participants will receive intraoperative dexmedetomidine.

Also known as: Sevoflorane

SEVODEX Group

Placebo DRUG

These participants will not receive intraoperative dexmedetomidine.

SEVO Group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• ASA I, II or III.
• Body mass index (BMI) \<35 kg/m2.
• Scheduled at least 6 days prior to surgery to allow adequate time for the baseline assessment.
• Planned admission to the hospital for at least 2 days.

You may not qualify if:

• Active delirium diagnosed with the Confusion Assessment Method (CAM).
• Mild cognitive impairment or dementia diagnosed with the Spanish-language version of the Montreal Cognitive Assessment MoCA-S1-2 score (score \<20 points).
• In case the patient cannot answer the MoCA test, the instrument AD8-Ch will be applied.
• Hospitalization within 3 months prior to enrollment to minimize risk of recent delirium history.
• Severely frail condition defined with the Clinical Frailty Scale (CFS ≥7).
• Inability to perform cognitive tests due to legal blindness or severe deafness
• History of schizophrenia or psychosis.
• Harmful alcohol use or alcohol dependence (AUDIT score ≥16 considering the standard drink equivalent determined by MINSAL).
• History of benzodiazepines or marihuana consumption (more than 3 days per week).
• Unable to pass assessment for capacity to provide informed consent.
• Claustrophobia.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Pontificia Universidad Catolica de Chile

Santiago, Santiago Metropolitan, 450881, Chile

Location

Related Publications (6)

• Brown EN, Purdon PL. The aging brain and anesthesia. Curr Opin Anaesthesiol. 2013 Aug;26(4):414-9. doi: 10.1097/ACO.0b013e328362d183.

  PMID: 23820102 BACKGROUND

• Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, Gravenstein JS. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008 Jan;108(1):18-30. doi: 10.1097/01.anes.0000296071.19434.1e.

  PMID: 18156878 BACKGROUND

• Rudolph JL, Inouye SK, Jones RN, Yang FM, Fong TG, Levkoff SE, Marcantonio ER. Delirium: an independent predictor of functional decline after cardiac surgery. J Am Geriatr Soc. 2010 Apr;58(4):643-9. doi: 10.1111/j.1532-5415.2010.02762.x. Epub 2010 Mar 22.

  PMID: 20345866 BACKGROUND

• Jiang L, Hu M, Lu Y, Cao Y, Chang Y, Dai Z. The protective effects of dexmedetomidine on ischemic brain injury: A meta-analysis. J Clin Anesth. 2017 Aug;40:25-32. doi: 10.1016/j.jclinane.2017.04.003. Epub 2017 Apr 17.

  PMID: 28625441 BACKGROUND

• Armstrong R, Xu F, Arora A, Rasic N, Syed NI. General anesthetics and cytotoxicity: possible implications for brain health. Drug Chem Toxicol. 2017 Apr;40(2):241-249. doi: 10.1080/01480545.2016.1188306. Epub 2016 Jun 2.

  PMID: 27252089 BACKGROUND

• Kant IMJ, de Bresser J, van Montfort SJT, Slooter AJC, Hendrikse J. MRI Markers of Neurodegenerative and Neurovascular Changes in Relation to Postoperative Delirium and Postoperative Cognitive Decline. Am J Geriatr Psychiatry. 2017 Oct;25(10):1048-1061. doi: 10.1016/j.jagp.2017.06.016. Epub 2017 Jun 28.

  PMID: 28760515 BACKGROUND

MeSH Terms

Interventions

Dexmedetomidine

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ignacio Cortinez, MD

  Titular Profesor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Each participant will be assigned an identifier that the research team will use from enrollment to follow-up.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned to any of the groups: Control Group and DEX Group

Study Record Dates

• First Submitted: June 24, 2021
• First Posted: July 22, 2021
• Study Start: November 16, 2021
• Primary Completion: August 30, 2024
• Study Completion: November 1, 2024
• Last Updated: May 31, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)