Metabolomic Profiling of Erector Spinae Plane Block* for Breast Cancer Surgery

Study Overview
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Brief Summary
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Worldwide, breast cancer is the most common cancer among women, and its incidence and mortality rates are expected to increase significantly in the next years. It remains a major health problem. There is a vast area on breast cancer and immunity that still needs to be researched. Do anesthetic techniques and medication preferences effect immune responses? If so how they effect breast cancer outcomes is unclear. On this trial, the investigators are searching anesthetic techniques affect on inflammatory and immune responses.

Detailed Description
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Breast cancer is the most frequently encountered surgery among all cancer surgeries. Although it is a well known procedure for anesthesiologists, it is still unclear whether anesthesiology effects immune responses. Cancer therapies often use immune therapies such as Bevacizumab (a monoclonal antibody which targets Vascular Endothelial Growth Factor), Trastuzumab(a monoclonal antibody for Herceptin (HER2/Neu) mutation) how anesthetics effect VEGF stays unclear. Opioids are commonly used to provide analgesia for cancer pain, and functional opioid receptors have been identified on natural killer (NK) cells, the lymphocytes responsible for surveillance and elimination of cancer cells.[4] Anesthesiologists have well founded concerns about using morphine during cancer surgeries. Regional anesthetic techniques commonly used on cancer surgeries.The activation of sensory neurons during pain enhances tumor progression and metastatic potential. Regional anesthesia blocks somatic nociception and inhibits sympathetic preganglionic outflow (functional sympathectomy) during surgery. Moreover regional anesthesia, by blocking sympathetic nervous system output, induces a prevalence of parasympathetic tone. Local anesthetics can also modulate autonomic receptors. For these reasons, more studies are needed to investigate the action of regional anesthetic neuromodulation on cancer progression.[11] The Erector Spinae Plane Block (ESP block) is most often performed on thoracic paraspinal levels, causes sympathetic blockage. Sympathetic block has been studied on central neuraxial blocks but the sympathetic block caused by the ESP block and immune responses remain unclear. Sympathetic block inhibits hyperbolic immune responses after surgery, therefore enhances postoperative rate of acceleration on cytokine levels. The investigators propose that ESP block improves immune responses and improved immune responses have better clinical outcomes for patients with breast cancer. Improved immune responses decrease length of stay (LOS), enhance postoperative recovery, analgesia and quality of life. Therefore allows better patient experience about procedures. The investigators will take 90 patients who will undergo a breast cancer operation and compare vitals (heart rate, blood pressure, oxygen saturation), Numeric Rating Scales (NRS), Vascular Endothelial Growth Factor (VEGF) responses, systemic immune inflammatory indexes, cortisol levels, CRP and Procalcitonin levels between three groups; opioid analgesia group(group M), ESP block group(group E), non-opioid non-ESP group (group P). The investigators' main focus is immune alterations after anesthesia techniques. Anesthesiologist keep track of pain scores after surgery. this trials secondary outcome focuses on pain management after surgery.

Official Title
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Metabolomic Profiling of Erector Spinae Plane Block for Breast Cancer Surgery

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Morphine
* Procedure: Erector Spinae Block
* Drug: Control


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Should be female Should be between 18-65 years old Diagnosed with unilateral primary breast cancer Are decided to have mastectomy surgery Stage 1-2 breast cancer (T0-1-2, N0-1, M0) Exclusion criteria from the: Being allergic to the anesthetics Previously had breast operation other than diagnostic biopsy Presence of a malignancy history on the other breast Diagnosed with Inflammatory breast cancer Having a risk score of The American Society of Anaesthesiologists (ASA) risk score 3 and above Contraindications for regional block(Allergies for local anesthetics, Anatomic application difficulties, Coagulopathies) Hormone usage NRS score greater than 3 before the operation Opioid or steroid usage before the operation Rheumatologic history Sickness or drug usage that might cause immunosuppression Chemotherapy and/or radiotherapy history Concomitant history of previous malignancy History of Coronary Artery Disease, Peripheral Vascular Disease that may affect VEGF Chronic smoking Chronic obstructive pulmonary disease Presence of infection at the time of surgery Hypothalamus, Pituitary, adrenal gland dysfunction Autoimmune diseases

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

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Morphine<br>30 patients who received intravenous morphine intraoperatively, without regional block application | Drug: Morphine<br>* PREOPERATIVE ANALGESIA: None INTRAOPERATİVE ANALGESIA: Paracetamol 1000 mg IV Morphine 0,1 mg/kg IV POSTOPERATIVE ANALGESIA IV Morphine Patient-Controlled Analgesia (PCA) Rescue analgesic: IV paracetamol<br>* Other names: Opioid;|
| Erector Spinae Block<br>30 patients who had preoperative esp block but did not use morphine during or after surgery | Procedure: Erector Spinae Block<br>* PREOPERATIVE ANALGESIA: Ultrasonography (USG) guided ESP block:T4 spinal level, %0,25 concentration 20 ml, single injection INTRAOPERATİVE ANALGESIA: Paracetamol 1000 mg IV dexketoprofen 50 mg IV POSTOPERATIVE ANALGESIA IV PCA with tramadol Rescue analgesic: IV paracetamol<br>* Other names: Plane block;|
| Control<br>30 patients who received multimodal analgesia methods other than ESP block or IV morphine | Drug: Control<br>* PREOPERATIVE ANALGESIA: none INTRAOPERATİVE ANALGESIA: Paracetamol 1000 mg IV Dexketoprofen 50 mg IV POSTOPERATIVE ANALGESIA IV PCA with tramadol Rescue analgesic: IV paracetamol<br>* Other names: other;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolomic profiling of ESP block for breast cancer surgery | Metabolomic profiling of 3 groups will be performed with liquid chromatography mass spectrometrt (LCMS) and Quadrupole time-of-flight (Q-TOF). | 24 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Defining the change in preoperative (baseline), postoperative hour 24 Vascular Endothelial Growth Factor (VEGF) levels between the morphine group (group M), the ESP block group (group E), and the control group (group c). | The investigators will measure VEGF preoperative(baseline), postoperative hour 24 from blood analysis. Normal ranges of serum VEGF were 62-707 pg/ml. | change from baseline VEGF at 24 hours postoperatively | 
| Defining the change in preoperative (baseline), postoperative hour 1, postoperative hour 24 cortisol levels between the morphine group (group M), the ESP block group (group E), and the control group (group c). | The investigators will measure cortisol preoperative(baseline),postoperative hour 1, postoperative hour 24 from blood analysis. Serum cortisol normal range for adults 8 am to 4pm: 5-25 mcg/dL | change from baseline cortisol up to 24 hours postoperatively | 
| Defining the change in preoperative (baseline), postoperative hour 1, postoperative hour 24 C-reactive Protein levels between the morphine group (group M), the ESP block group (group E), and the control group (group c). | The investigators will measure CRP preoperative(baseline), postoperative hour 1, postoperative hour 24 from blood analysis. CRP normal reading is less than 10mg/L. | change from baseline CRP up to 24 hours postoperatively | 
| Defining analgesic effects between the morphine group (group M), the ESP block group (group E), and the control group (group c) on patients who had breast cancer surgery. | The investigators will evaluate patients' pain score with numeric rating scale (NRS) postoperative hour 1, 2, 12, 24 and compare NRS between the control group (group c), the ESP block group (group E) and intravenous morphine group (group M) The investigators will compare NRS between two groups at postoperative hour 1, 2, 12, 24. The most common form of NRS is a horizontal line with an eleven point numeric range, from 0 (patient with no pain) to 10 (patient with the worst pain possible). | End of surgery up to 24 hours postoperatively | 
| Tramadol consumption between the ESP block group and the control group | The investigators will record total opioid consumption via Patient-Controlled Analgesia devices. | End of surgery up to 24 hours postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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erector spinae plane block, breast cancer, anesthesia and cancer, nerve block and cancer, cancer prognosis