The Immune Response of Breast Cancer Patients Treated With Levobupivacaine Using Paravertebral or Superficial Chest Blocks

NCT05816538 | Active Not Recruiting

• 1 other identifier: 2170-29-02/1-2
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The use of regional anesthesia in breast surgery improves the postoperative outcome, reduces the development of infection, and weakens the perioperative immunosuppressive response associated with the response to surgical stress. The investigators hypothesize that the use of propofol / paravertebral anesthesia and analgesia will be accompanied by a decrease in serum proinflammatory cytokines and/or an increase in anti-inflammatory cytokines compared to propofol / PECS 2 anesthesia and analgesia. The research will be on 100 respondents divided into two groups. 0.5% levobupivacaine will be administered to both groups. Serum concentrations of pro- and anti-inflammatory cytokines, and lymphocyte subpopulations 1h before, 24h, and 48h after surgery will be measured. The investigators aim to compare the effect of propofol / paravertebral and propofol / PECS 2 anesthesia and analgesia on serum perioperative values of pro-inflammatory and anti-inflammatory cytokines to standardize protocols and apply the best method of perioperative analgesia in breast cancer surgery.

Conditions

Paravertebral Block; Pectoralis and Serratus Plane Nerve Blocks; Breast Cancer; Immunologic Suppression; Levobupivacaine

Keywords

Breast Cancer; Levobupivacaine; Immunologic Suppression; Paravertebral block; Pectoralis and Serratus Plane Nerve Blocks

Outcome Measures

Primary Outcomes (4)

• Change in measured serum cytokines using an ELISA test after PVB.

  Venous blood samples will be collected 1 hour before and 24 and 48 hours after surgery. Serum concentrations in picogram per milliliter of pro-inflammatory cytokines Il-1, Il-6, TNFα, and anti-inflammatory cytokine IL-10 will be analyzed using an ELISA test according to the manufacturer's instructions.

  1 hour before intervention to 48 hours after surgery

• Change in measured serum cytokines using an ELISA test after PECS 2 block.

  Venous blood samples will be collected 1 hour before and 24 and 48 hours after surgery. Serum concentrations picogram per milliliter of pro-inflammatory cytokines Il-1, Il-6, TNFα, and anti-inflammatory cytokine IL-10 will be analyzed using an ELISA test according to the manufacturer's instructions.

  1 hour before intervention to 48 hours after surgery

• Change in cell number of individual lymphocyte subpopulations determined by flow cytometry technique (FACSCalibur) after PVB application.

  Venous blood samples will be collected 1 hour before and 24 and 48 hours after surgery. Peripheral blood leukocytes (PBL) will be isolated using a fluorescence-activated single-cell sorting flow cytometry technique on the FACSCalibur Flow Cytometer machine. Flow cytometry is a laser-based technique that detects and analyzes the chemical and physical characteristics of cells or particles. Individual lymphocyte subpopulations: T lymphocytes (helper and cytotoxic), B lymphocytes, NK, Treg (FITC-CD4, APC-CD25, and PE-Foxp3 positive), and NKT cells will be analyzed and determined according to the manufacturer's instructions using specific cell marker antibodies. After gating density plots the results will be presented in the number of cells in a cubic millimeter of blood and compared using scatter graphs.

  1 hour before intervention to 48 hours after surgery

• Change in cell number of individual lymphocyte subpopulations determined by flow cytometry technique (FACSCalibur) after PECS 2 block application.

  Venous blood samples will be collected 1 hour before and 24 and 48 hours after surgery. Peripheral blood leukocytes (PBL) will be isolated using a fluorescence-activated single-cell sorting flow cytometry technique on the FACSCalibur Flow Cytometer machine. Flow cytometry is a laser-based technique that detects and analyzes the chemical and physical characteristics of cells or particles. Individual lymphocyte subpopulations: T lymphocytes (helper and cytotoxic), B lymphocytes, NK, Treg (FITC-CD4, APC-CD25, and PE-Foxp3 positive), and NKT cells will be analyzed and determined according to the manufacturer's instructions using specific cell marker antibodies. After gating density plots the results will be presented in the number of cells in a cubic millimeter of blood and compared using scatter graphs.

  1 hour before intervention to 48 hours after surgery

Secondary Outcomes (12)

• Duration of postoperative analgesia after PVB application measured using visual analgesic scale (VAS).

  24 postoperative hours

• Duration of postoperative analgesia after PECS 2 block application measured using visual analgesic scale (VAS).

  24 postoperative hours

• The total dosage of analgesics in the postoperative period after the PVB application.

  48 postoperative hours

• The total dosage of analgesics in the postoperative period after the PECS 2 block application.

  48 postoperative hours

• Mean atrial pressure change after the PVB.

  From time of intervention to 2 hours postoperatively

Study Arms (2)

Group 1 PVB

ACTIVE COMPARATOR

Group 1 will receive paravertebral block (PVB) as analgesia for breast surgery. PVB is a regional anesthetic technique applied at the thoracic (Th) level of Th2, Th3, and Th4 at a dose of 0.3ml/kg 0.5% levobupivacaine total, divided into levels. Block will be performed with ultrasound-guided in-plane technique and neurostimulation.

Procedure: Paravertebral nerve block (PVB); Device: Regional anesthetic technique with ultrasound guidance; Device: Regional anesthetic technique with peripheral nerve stimulation.; Drug: Levobupivacaine 0.5%; Procedure: General anesthesia

Group 2 PECS

EXPERIMENTAL

Group 2 will receive Pectoralis and Serratus Plane Nerve blocks (PECS 2) as analgesia for breast surgery. PECS 2 block is a regional anesthetic technique applied in the space between the large and small pectoral muscles (10 ml of 0.5% levobupivacaine), and in the space between the small pectoralis muscle and the serratus anterior muscle (with 15 ml of 0.5% levobupivacaine). Block will be performed with ultrasound-guided in-plane technique and neurostimulation.

Procedure: Pectoralis and Serratus Plane Nerve Blocks (PECS 2); Device: Regional anesthetic technique with ultrasound guidance; Device: Regional anesthetic technique with peripheral nerve stimulation.; Drug: Levobupivacaine 0.5%; Procedure: General anesthesia

Interventions

Paravertebral nerve block (PVB) PROCEDURE

PVB is a regional anesthetic technique applied at the thoracic (Th) level of Th2, Th3, and Th4 at a dose of 0.3ml/kg 0.5% levobupivacaine total, divided into levels. Block will be performed with ultrasound-guided in-plane technique and neurostimulation.

Group 1 PVB

Pectoralis and Serratus Plane Nerve Blocks (PECS 2) PROCEDURE

Pectoralis and Serratus Plane Nerve blocks (PECS 2) is a regional anesthetic technique applied in the space between the large and small pectoral muscles (10 ml of 0.5% levobupivacaine), and in the space between the small pectoralis muscle and the serratus anterior muscle (with 15 ml of 0.5% levobupivacaine). Block will be performed with ultrasound-guided in-plane technique and neurostimulation.

Group 2 PECS

Regional anesthetic technique with ultrasound guidance DEVICE

The device that will be used is an ultrasound with an 8 Hz ultrasonic linear probe for both regional anesthetic techniques.

Group 1 PVB; Group 2 PECS

Regional anesthetic technique with peripheral nerve stimulation. DEVICE

The 22G neurostimulator needle (Stimuplex D®, B. Braun Melsungen AG)\], and neurostimulator (Stimuplex HNS 12, B. Braun, Melsungen AG, Germany) will be used for both regional anesthesias.

Group 1 PVB; Group 2 PECS

Levobupivacaine 0.5% DRUG

Local anesthetic levobupivacaine 0.5% will be used for regional anesthetic technique with ultrasound guidance and peripheral nerve stimulation. For the paravertebral block at a dose of 0.3ml/kg total, applied at the thoracic (Th) level of Th2, Th3, and Th4 and divided into levels. For the PECS 2 block levobupivacaine 0.5% 10 ml will be applied in the space between the large and small pectoral muscles and 15 ml in the space between the small pectoralis muscle and the serratus anterior muscle.

Group 1 PVB; Group 2 PECS

General anesthesia PROCEDURE

In both groups for induction of general anesthesia we will use 1% propofol 2 - 2.5 mg/kg (10 mg/ml, Fresenius), sufentanil (Sufentanil® Altamedics) 0.2 μg / kg, rocuronium \[Zemuron®, Schering - Plow\] 0.8 mg/kg. We will use a laryngeal mask (I - gel supraglottic airway) of appropriate sizes for airway maintenance. All subjects will be ventilated by controlled mechanical ventilation with a volume of 8 ml/kg, a frequency of about 12 breaths per min with a mixture of oxygen and air in a 40: 60% ratio. Maintenance of anesthesia and sedation in group 1 will be performed with continuous infusion of 1% propofol (10 mg / ml, Fresenius) (25 - 150 mcg / kg / min.) and rocuronium \[Zemuron®, Schering - Plow\] 0.01 mg / kg / min per perfusor.

Group 1 PVB; Group 2 PECS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• quadrantectomy with equilateral axillary lymphadenectomy
• anesthesia preoperative status (American Society of Anesthesiologists (ASA)) 1 and 2

You may not qualify if:

• patient rejection
• ASA\> 3
• contraindication for local anesthetic
• contraindications for planned regional anesthesia and analgesia
• immunosuppressive therapy including corticosteroids
• acute infection
• history of chronic opioid use
• presence of autoimmune disease
• obese definite body mass index BMI) greater than 29.9 kg/m2

Sponsors & Collaborators

• University of Rijeka: lead

Study Sites (1)

University hospital centre Rijeka

Rijeka, 51000, Croatia

Location

Related Publications (21)

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MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anesthesia, General

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Anesthesia; Anesthesia and Analgesia

Study Officials

• Ivan Ivanovski, M.D.

  Faculty of Medicine, University of Rijeka

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator; Specialist in anesthesiology, reanimatology and intensive medicine

Study Record Dates

• First Submitted: January 16, 2023
• First Posted: April 18, 2023
• Study Start: January 18, 2024
• Primary Completion: May 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1)