The Immune Response of Breast Cancer Patients Treated With Levobupivacaine Using Paravertebral or Superficial Chest Blocks
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Change in measured serum cytokines using an ELISA test after PVB.
研究概览
简要总结
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.
详细描述
Introduction
The human immune system is extremely adaptable and complex. The immune response in the body is often a defense against tumors or infection and maintenance of homeostasis. It includes specific (acquired) and nonspecific (innate) immunity. The immune system is known to be shaped by a complex network of cytokines; interleukins (IL), interferons (IFN), tumor necrosis factor [Eng. Tumor necrosis factor (TNF)] etc. Tumor cells respond differently to cytokines. Certain cytokines stimulate immune reactions and are called pro-inflammatory, while others inhibit the immune system response and are called anti-inflammatory. In previous studies, Il-1, Il-6, TNFα, and IL-10 are common indicators of inflammatory changes in cancer. IL-6 is a potent proinflammatory cytokine with multiple mechanisms of antitumor activity. TNFα stimulates the production of other proinflammatory factors and proteases. IL-10 inhibits the production of pro-inflammatory cytokines.
Surgery and anesthesia change the activity of the immune system quickly and through various processes. Pain, fear, medications, inhalation anesthetics, opioids, tissue injury, blood transfusions, increased stress, and infection activate the immune system during the perioperative period by suppressing the adaptive immune response or enhancing the immune response.
Breast cancer is the most common malignancy in women, second only to lung cancer in mortality. Breast cancer surgery is the primary and most effective treatment, with special emphasis on the minimal release of tumor cells into the vascular and lymphatic systems. Whether the release of tumor cells will result in clinical metastases depends primarily on the balance between antimetastatic immune activity and the ability of the tumor to metastasize to other tissues.
Regional anesthesia is a technique in which the application of a local anesthetic near a nerve or spinal cord inhibits the sensation, pain, and motor stimulation of one region of the body. Applied local anesthetics thus prevent the endocrine-metabolic response to stress. Many studies have shown that the use of neuraxial (spinal and epidural) and perineuroaxial paravertebral block (PVB) regional anesthesia in breast surgery [(propofol / paravertebral block anesthesia - analgesia)] improve postoperative outcome and reduce the development of perioperative immunosuppressive response associated with surgical stress.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Care Provider)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •quadrantectomy with equilateral axillary lymphadenectomy
- •anesthesia preoperative status (American Society of Anesthesiologists (ASA)) 1 and 2
排除标准
- •patient rejection
- •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
研究组 & 干预措施
Group 1 PVB
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.
干预措施: Paravertebral nerve block (PVB) (Procedure)
Group 1 PVB
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.
干预措施: Regional anesthetic technique with ultrasound guidance (Device)
Group 1 PVB
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.
干预措施: Regional anesthetic technique with peripheral nerve stimulation. (Device)
Group 1 PVB
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.
干预措施: Levobupivacaine 0.5% (Drug)
Group 1 PVB
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.
干预措施: General anesthesia (Procedure)
Group 2 PECS
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.
干预措施: Pectoralis and Serratus Plane Nerve Blocks (PECS 2) (Procedure)
Group 2 PECS
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.
干预措施: Regional anesthetic technique with ultrasound guidance (Device)
Group 2 PECS
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.
干预措施: Regional anesthetic technique with peripheral nerve stimulation. (Device)
Group 2 PECS
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.
干预措施: Levobupivacaine 0.5% (Drug)
Group 2 PECS
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.
干预措施: General anesthesia (Procedure)
结局指标
主要结局
Change in measured serum cytokines using an ELISA test after PVB.
时间窗: 1 hour before intervention to 48 hours after surgery
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.
Change in measured serum cytokines using an ELISA test after PECS 2 block.
时间窗: 1 hour before intervention to 48 hours after surgery
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.
Change in cell number of individual lymphocyte subpopulations determined by flow cytometry technique (FACSCalibur) after PVB application.
时间窗: 1 hour before intervention to 48 hours after surgery
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.
Change in cell number of individual lymphocyte subpopulations determined by flow cytometry technique (FACSCalibur) after PECS 2 block application.
时间窗: 1 hour before intervention to 48 hours after surgery
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.
次要结局
- Change in the volume compensation of colloids after the PECS2 block.(From the time of intervention to 24 hours postoperatively)
- 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)
- Mean atrial pressure change after the PECS 2 block.(From time of intervention to 2 hours postoperatively)
- Change in the volume compensation of colloids after the PVB.(From the time of intervention to 24 hours postoperatively)
- Changes in heart rate values after the PECS 2 block.(From the time of intervention to 2 hours postoperatively)
- Change in the perioperative need for vasoactive drugs after PVB.(From the time of intervention to 2 hours postoperatively)
- Changes in heart rate values after the PVB.(From the time of intervention to 2 hours postoperatively)
- Change in the perioperative need for vasoactive drugs after PECS 2 block.(From the time of intervention to 2 hours postoperatively)
研究者
Ivan Ivanovski
Principal investigator; Specialist in anesthesiology, reanimatology and intensive medicine
University of Rijeka