Anesthetic Depth Effects Upon Immune Competent Cells (BIS-MA)

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

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.

Study Overview

• Status: Completed
• Conditions: Anesthesia; Immunotoxicity; Inert Gas Narcosis
• Intervention / Treatment: Drug: High dose propofol, fentanyl and sevoflurane; Drug: Low dose propofol, fentanyl and sevoflurane

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany, 68163
    • University Medicine of Mannheim, Dept. Anesthesiology and Critical Care Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Deep Anesthesia; 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; Deep Anesthesia; Other Names: BIS lower than or equal to 45
EXPERIMENTAL: Shallow Anesthesia; 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; Shallow Anesthesia; 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

Collaborators and Investigators

• Sponsor: Heidelberg University
• Investigators: Principal Investigator: Thomas Frietsch, MD, PhD, University of Mannheim

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (ACTUAL): March 1, 2012
• Study Completion (ACTUAL): March 1, 2013

Study Registration Dates

• First Submitted: May 12, 2016
• First Submitted That Met QC Criteria: June 8, 2016
• First Posted (ESTIMATE): June 9, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Occupational Diseases; Poisoning; Gas Poisoning; Inert Gas Narcosis; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anesthetics, Inhalation; Fentanyl; Propofol; Sevoflurane
• Other Study ID Numbers: Anesthetic depth-MA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: per request