Neurotoxicity of Anesthesia in Middle Aged Patients

Evaluation of Possible Neurotoxicity of Anesthesia Guided by Olfactory Changes in Middle-aged Patients

for the last 20 years, the increasing reports from non-human studies have raised suspicion that general anesthetics may cause neurotoxic changes in the developing brain that lead to adverse neurodevelopmental outcomes later in life.there are several case reports of reversible smell and taste dysfunction following exposure to general anesthesia suggesting a possible relationship between anesthetic agents and olfactory dysfunction.

this study is to assess the possible neurotoxicity of sevoflurane,isoflurane,and propofol based anesthesia guided by olfactory changes

Study Overview

• Status: Active, not recruiting
• Conditions: Anesthesia; Adverse Effect
• Intervention / Treatment: Drug: Anesthesia Agent

Detailed Description

the primary inhibitory neurotransmitter GABA is found in neuronal synapses involving olfactory bulb. So, the involvement of common GABA pathway implies a possible interaction of general anesthetics with olfactory function.

olfactory identification is an associative memory which is found to be facilitated by action of melatonin. involvement of GABA receptor in the transfer of light information from suprachiasmatic nuclei to pineal gland suggests possible interaction of melatonin and anesthetic agents.

the aim of the study is to evaluate the possible neurotoxicity of sevoflurane,isoflurane,and propofol based anesthesia guided by olfactory changes

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

Study Locations

• Egypt
  • Tanta, Egypt, 31527
    • tanta university, faculty of medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

middle aged patients, of both sex, undergoing elective surgical procedures other than major surgeries, of duration 90-120 minutes, and of American Society of Anesthesiologists' physical status I and II will be enrolled in the study

Description

Inclusion Criteria:

• patients aged 18-50 years
• both sex
• American society of Anesthesiologists' physical status I and II
• elective surgery of duration 90-120 minutes

Exclusion Criteria:

• patients's refusal
• recent airway infection
• allergic rhinitis
• nasal polyps
• history of alcoholism
• smoking
• pregnancy
• menstruating female
• mental retardation
• psychiatric illness
• neurosurgical or oto-rhino-laryngeal surgery
• history of olfactory deficits or cognitive impairment
• CNS disease e.g. epilepsy
• history of first degree relative with alzheimer's disease,dementia, or cognitive dysfunction
• those who are unable to answer the tests themselves

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
regional anesthesia; surgical procedures which will be performed under intrathecal anesthesia without sedation	Drug: Anesthesia Agent; various anesthetic agents used in both general and regional anesthesia; Other Names: Propofol infusion; Sevoflurane; Isoflurane
sevoflurane; surgical procedures which will be performed under general anesthesia and sevoflurane will be used for maintenance of anesthesia	Drug: Anesthesia Agent; various anesthetic agents used in both general and regional anesthesia; Other Names: Propofol infusion; Sevoflurane; Isoflurane
isoflurane; surgical procedures which will be performed under general anesthesia and isoflurane will be used for maintenance of anesthesia	Drug: Anesthesia Agent; various anesthetic agents used in both general and regional anesthesia; Other Names: Propofol infusion; Sevoflurane; Isoflurane
propofol; surgical procedures which will be performed under general anesthesia and propofol infusion will be used for maintenance of anesthesia	Drug: Anesthesia Agent; various anesthetic agents used in both general and regional anesthesia; Other Names: Propofol infusion; Sevoflurane; Isoflurane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
olfactory threshold	we will use (10 dilutions) of 4% n-butyl alcohol. The odorant and a blank will be presented to the participant. The test will be progressed from weaker-to-stronger concentrations of odorant. Two bottles will be presented to each participant, an odorant bottle and an identical bottle filled with distilled water. The participant will sniff each one for 9 seconds and then will chose which one smelled stronger. If the participant is incorrect at one concentration, the next higher concentration will be presented. When the correct choice is made, the same concentration of odorant will be presented to the participant until four consecutive correct responses are given.	olfactory threshold will be measured at 12 hours preoperative then at 6, 24 and 48 hours postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
olfactory identification	We will use UPSIT test.	Smell identification will be measured at 12 hours preoperative then at 6, 24 and 48 hours postoperative
cognitive dysfunction	cognitive dysfunction will be evaluated by mini-mental state examination	Cognitive dysfunction will be evaluated at 12 hours preoperative then at 6, 24 and 48 hours postoperative
serum melatonin concentrations	Melatonin levels will be measured in plasma by the enzyme-linked immunosorbent assay (ELISA)	serum melatonin will be measured at 12 hours preoperative then at 6, 24 and 48 hours postoperative

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Principal Investigator: Mona R Elghamry, MD, tanta university, faculty of medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: February 11, 2020
• First Submitted That Met QC Criteria: February 15, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Poisoning; Neurotoxicity Syndromes; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Platelet Aggregation Inhibitors; Hypnotics and Sedatives; Anesthetics, Inhalation; Anesthetics; Propofol; Sevoflurane; Isoflurane
• Other Study ID Numbers: neurotoxicity of anesthesia

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: statistics of demographic data,type of surgeries, olfactory dysfunction tests,mini-mental state examination, and serum melatonin
• IPD Sharing Time Frame: Individual patient data will be shared after finishing and publication of the study and it will be available for 6 months.
• IPD Sharing Access Criteria: the individual patient data will be available for scientific research only up on email request. request will be sent to email of principal investigator (drmonagh19802000@gmail.com)
• IPD Sharing Supporting Information Type: Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No