Inhalational Anesthesia and Precipitation of Dementia: is There a Link?

December 1, 2022 updated by: University Health Network, Toronto

Inhalational Anesthesia and Precipitation of Dementia: is There a Link? A Prospective, Multicenter, Randomized, Controlled Clinical Trial Comparing Two Different Anesthetic Techniques in Elderly Patients

Many elderly patients undergoing surgical procedures already have impaired cognitive (memory/concentration) status. Patients with pre-existing cognitive impairment, or dementia, may benefit from modified anesthesia techniques. It is estimated that one in eight people age 65 and older has Alzheimers disease. More so, nearly half of people that are 85 years or older have Alzheimers disease. Currently, both spinal (regional) and inhalational (general) anesthesia, are used in patients undergoing common urological, orthopedic, and general surgical procedures. Inhalational anesthesia has been associated with higher risk of memory impairment in experimental (animal) and human studies. However, currently, there are simply no large or good enough studies to be sure that inhalational anesthesia is responsible for causing dementia and Alzheimers disease.The proposed study investigates if elderly patients (65 years and older) undergoing spinal anesthesia (patient is awake or slightly sedated) are less likely to develop dementia and Alzheimers disease for up to 2 years after surgery, when compared to inhalational anesthesia (patient is kept asleep with gas anesthetic). The investigators will also test all patients for the presence of apolipoprotein (ApoE-Îμ4 type of gene that is present in 15-20% of patients), and beta-amyloid tau protein (present in cerebrospinal fluid) that are known risk factors for Alzheimers disease. The particular strength of this study is that it takes into account whether the frequency and/or severity of dementia and Alzheimers disease is different in patients with and without these markers. The investigators believe that this study will make a major contribution to better understanding of development of Alzheimers disease.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

500

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Toronto General Hospital, University Health Network
      • Toronto, Ontario, Canada, M9V 1R8
        • William Osler Health Centre
  • Latvia
      • Riga, Latvia, LV 1002
        • Pauls Stradins Clinical University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • >65 yrs of age
  • Male or female
  • Scheduled to undergo urologic procedures (e.g., transurethral resection of prostate, transurethral resection of bladder tumor), orthopedic (e.g., total knee replacement, total hip replacement) general (e.g., femoral hernia repair, lower abdominal surgery) or vascular surgery procedures (e.g. lower limb reperfusion amputations) and qualifies to be randomized to receive either local (spinal) or general anesthetic

Exclusion Criteria:

  • Diagnosis of severe dementia
  • Diagnosis of any other significant neurological disease such as Parkinson's, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain or spinal abnormalities.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Spinal anesthesia group
Spinal anesthesia group will receive bupivacaine 10-15mg anesthesia according to the standard practice. Supplemental sedation with intravenous anesthetics (midazolam/propofol) will be optional.
Drug: Spinal anesthesia group: bupivacaine 10-15mg
Genetic: Blood test
DNA will be tested for the presence of ε4 allele of the apolipoprotein E gene
Other: Lumbar spinal tap
1ml of cerebrospinal fluid (CSF) removed and stored for further analysis of amyloid tau protein after completion of the study
Behavioral: Montreal Cognitive Assessment (MOCA) and MMSE
ACTIVE_COMPARATOR: General anesthesia group
Induction of anesthesia will be achieved with propofol 1.5-2mg/kg and fentanyl 1-3g/kg. Anesthesia will be maintained with inhalational anesthesia (isoflurane or sevoflurane) at the discretion of anesthesiologist in charge of the case. A mixture of Air/O2 will be used to maintain adequate oxygenation. Nitrous oxide will not be used.
Genetic: Blood test
DNA will be tested for the presence of ε4 allele of the apolipoprotein E gene
Other: Lumbar spinal tap
1ml of cerebrospinal fluid (CSF) removed and stored for further analysis of amyloid tau protein after completion of the study
Behavioral: Montreal Cognitive Assessment (MOCA) and MMSE
Drug: General anesthesia group: induction propofol 1.5-2mg/kg and fentanyl 1-3g/kg, maintained with isoflurane or sevoflurane

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Assessing the incidence of early dementia
Time Frame: Change from baseline, hospital discharge (3 day average), 3 months, 1 year, and 2 years
Change from baseline, hospital discharge (3 day average), 3 months, 1 year, and 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 1, 2014

Primary Completion (ACTUAL)

November 1, 2019

Study Completion (ANTICIPATED)

July 1, 2023

Study Registration Dates

First Submitted

July 11, 2013

First Submitted That Met QC Criteria

July 18, 2013

First Posted (ESTIMATE)

July 19, 2013

Study Record Updates

Last Update Posted (ACTUAL)

December 5, 2022

Last Update Submitted That Met QC Criteria

December 1, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-6122

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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