Anesthesia Depth Increases the Degree of Postoperative Dementia, Delirium, and Cognitive Dysfunction

Study Overview
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Brief Summary
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Anesthetics and anesthesia are suspicious to induce dementia or aggravate preexistent cognitive deficits with or without evoking postoperative delirium. In animal trials various anesthetics induce increased levels of misfolded amyloid beta and protein tau, the molecular substance of pathophysiologic brain tissues of demented patients. The amount of those markers seems to correlate well with the degree of dementia [1]. In contradiction, a single study indicates that the incidence of postoperative cognitive deficit (POCD) decreases if hypnotic depth is deep [2]. Unfortunately the study did not sum up the amount of anesthetic drug load, since this would have clarified if the amount of anesthetics used is associated to POCD and dementia. Another possibility is that stress and noxious stimulation induced by light anesthesia results in POCD, whereas deep anesthesia protects from it or inhibits implicit memory. The investigators' prospective randomized trial is underway to verify the impact of anesthetics and narcotic depth upon grade of dementia and incidence of early postoperative cognitive dysfunction on postoperative day 1 as well as the incidence of delirium within a 90 day period. The investigators' hypothesis is that the incidence of POCD and delirium and the degree of early cognitive dysfunction is less when anesthetic and vasoactive drug load is less in the BIS- guided anesthesia group with the superficial but sufficient anesthesia level.

Official Title
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Anesthesia Depth Increases the Degree of Postoperative Dementia, Delirium, and Cognitive Dysfunction by a Higher Load of Neurotrophic Drugs

Conditions
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Anesthesia, Delirium, Dementia, Bispectral Index Monitor

Intervention / Treatment
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* Device: Anesthesia depth monitor
* Device: Sham control
* Drug: propofol and sevoflurane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adults older than 70 years major surgery ( spine, orthopedic, urologic, gynecology, abdominal) Exclusion Criteria: adults younger than 71 years major blood loss surgery allergy to soja oil, nuts, other ingredients of propofol patient wants to have spinal or regional anesthesia only

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 110 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anesthesia depth monitor<br>Anesthesia depth is aimed to be between BIS 50-60 | Device: Anesthesia depth monitor<br> <br> * Other names: Aim at an anesthesia level of BIS 50-60 titrating propofol and sevoflurane in the experimental;Drug: propofol and sevoflurane<br> <br> |
| Sham Comparator: Control group<br>Anesthesia depth is monitored but blinded to the anesthesiologist | Device: Sham control<br>* Standard care as usual. Bis m Standard care as usual. Bispectral index monitor is not visible for anesthesia provider.<br>Drug: propofol and sevoflurane<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative cognition and mental capacity of elderlies following major surgery | Mini Mental State Test (MMSE) and automated Memory and Attention Test (MAT) were performed on the day before and after the surgery. The MAT is a validated computerized test for the discrimination of short and long time memory, for visual and auditory comprehension and attention capacity. | One day after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of mental and other complications (serious adverse events) | Incidences of delirium and mental dysfunction until hospital discharge is counted. Delirium was postoperatively diagnosed by the NUDESC, postoperative cognitive dysfunction (POCD) by the MAT, other serious adverse events in the course of the hospital stay were noted. | 90 postoperative days |