Neurotoxicity of Anesthesia in Middle Aged Patients

Study Overview
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Brief Summary
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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

Detailed Description
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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

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

Conditions
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Anesthesia; Adverse Effect

Intervention / Treatment
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* Drug: Anesthesia Agent


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| regional anesthesia<br>surgical procedures which will be performed under intrathecal anesthesia without sedation | Drug: Anesthesia Agent<br>* various anesthetic agents used in both general and regional anesthesia<br>* Other names: Propofol infusion;|
| sevoflurane<br>surgical procedures which will be performed under general anesthesia and sevoflurane will be used for maintenance of anesthesia | Drug: Anesthesia Agent<br>* various anesthetic agents used in both general and regional anesthesia<br>* Other names: Propofol infusion;|
| isoflurane<br>surgical procedures which will be performed under general anesthesia and isoflurane will be used for maintenance of anesthesia | Drug: Anesthesia Agent<br>* various anesthetic agents used in both general and regional anesthesia<br>* Other names: Propofol infusion;|
| propofol<br>surgical procedures which will be performed under general anesthesia and propofol infusion will be used for maintenance of anesthesia | Drug: Anesthesia Agent<br>* various anesthetic agents used in both general and regional anesthesia<br>* Other names: Propofol infusion;|

What is the study measuring?
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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 |