Anesthetic Depth Effects Upon Immune Competent Cells

Study Overview
=================
Brief Summary
-----------------
Anesthesia depth affects the proliferation of lymphocytes to NK-cells and memory T-cells effect and the phagocytosis activity of macrophages in healthy patients. ASA 1-3 subjects undergoing extended shoulder surgery under continuous regional anesthesia randomly were assigned to a deep or a shallow anesthesia level (BIS <35 or >55) for more than an hour. Immune response is measured by lymphocyte proliferation as well as neutrophil and monocyte phagocytosis activity.

Detailed Description
-----------------
Blood samples were taken under minimal stress prior to anesthesia induction (T0), recovery (T1) and 12 weeks following hospital discharge (T2) from the respective anesthesia depth level. Bispectral index monitoring (BIS) was performed from the awake state to complete recovery in all subjects. Hemoglobin concentration, leukocyte and lymphocyte counts were determined by routine automated laboratory techniques. Lymphocyte proliferation was analyzed by SASPA flow cytometry analysis. In brief, 100 µl EDTA blood were stirred with 10 µl FITC and PE marked antibody mixture containing CD3, CD4, CD8, CD 16, CD45, CD28, CD27, CD 56. Monocyte and neutrophil phagocytosis activity was measured separately in macrophages of fresh heparinized whole blood using flow cytometric test kits. Proteomics of monocytes was done synchronously.

Official Title
-----------------
Hypnotic Depth Reduces Lymphocyte Proliferation to Natural Killer Cells, B-cells, Memory T-cells, Depresses Intracellular Oxidative Burst and Changes Protein Expression Pattern of Monocytes

Conditions
-----------------
Immunotoxicity, Anesthesia, Inert Gas Narcosis

Intervention / Treatment
-----------------
* Drug: High dose propofol, fentanyl and sevoflurane
* Drug: Low dose propofol, fentanyl and sevoflurane


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: enrolment for longer shoulder surgery consent for the standard anesthesia form in combination with the interscalene plexus block ASA Status 1-3 Exclusion Criteria: sedative premedication severe immune deficiency (diabetes, steroid or antihistamine medication, cancer, chemotherapy, status post transplantation, drug and alcohol abuse), recent surgery (1 month) or blood transfusion

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deep Anesthesia<br>Standard anesthesia with fentanyl, propofol for shoulder surgery together with a interscalene plexus block was performed. The anesthesiologist only was informed about the group allocation by the study director and tried to control best for maintenance on target anesthesia level BIS 45 (group 1, deep anesthesia). Anesthesia depth was measured by BIS monitors (BIS Vista, Aspect) for every minute and the minutes below or equal to a BIS level of 45 were counted. | Drug: High dose propofol, fentanyl and sevoflurane<br>* Deep Anesthesia<br>* Other names: BIS lower than or equal to 45;|
| Experimental: Shallow Anesthesia<br>Standard anesthesia with fentanyl, propofol for shoulder surgery together with a inter scalene plexus block was performed. The anesthesiologist only was informed about the group allocation by the study director and tried to control best for maintenance on target anesthesia level BIS ≥ 55 (group 2, shallow anesthesia). Anesthesia depth as measured by BIS monitors (BIS Vista, Aspect) for every minute and the minutes above a BIS level of 45 were counted. | Drug: Low dose propofol, fentanyl and sevoflurane<br>* Shallow Anesthesia<br>* Other names: BIS above 45;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression of lymphocyte proliferation by CD expression pattern in SASPA-Test as given in a percentage from before anesthesia | before and following anesthesia period over 60 min | 70-90 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of phagocytosis activity as a percentage of base line (prior to anesthesia) | before and following anesthesia period over 60 min | 70-90 min | 
| Protein expression pattern of monocytes by proteomics analysis and mass spectrometry | before and following anesthesia period over 60 min | 70-90 min |