Magnesium Sulphate Versus Ketamine as an Adjuvant to Bupivacaine in Pectoral Nerve Block During Mastectomy

Study Overview
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Brief Summary
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There are no published article that compare magnesium sulfate and ketamine as adjuvants to bupivacaine in PECS block , so the aim of this study is to evaluate the efficacy of Magnesium sulfate versus ketamine when added to local anesthetic ( Bupivacaine) in pectoral nerve block during mastectomy and detect which of these drugs has the more effective analgesic effect and decrease opioid consumption .

Detailed Description
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Breast cancer is the most common malignancy in females, and its incidence increases with increase the age of the patients and it is the most expected cause of death in the world . Surgery is the main treatment of breast cancer and other treatments include chemotherapy, radiotherapy , hormonal therapy and biological therapy or combination treatment and this depends on the type of the cancer and its stage . Breast surgery is usually associated with significant postoperative pain. Poorly controlled postoperative pain has a negative physiological and psychological impacts as it is associated with an increase in hospital stay , medical care cost, significant postoperative nausea and vomiting , development of chronic pain syndrome and impaired quality of life . Several methods have been involved in postoperative pain control including multi modal analgesia using multiple medication with different mechanism of action as intravenous and oral opioids , non-steroidal anti-inflammatory drugs and local anesthetic infiltration also has an important role in pain control . Regional anesthetic procedures have an effective role in acute pain control as thoracic epidural and thoracic paravertebral block are considered the gold standard procedures for postoperative pain management for breast cancer surgery, but not every anesthesiologist is comfortable making these invasive procedures . Recently, the pectoral nerves blocks (PECS I and PECS II) are recommended for providing intraoperative and postoperative pain control during and after breast surgery. These blocks may be more effective when compared to other regional anesthetic procedures . Pectoral nerves blocks includes 2 types (PECS I and PECS II). The PECS block type I is a easy and reliable performed by injection an interfacial plane between the pectoralis major and pectoralis minor muscles to block the lateral region of the breast to provide analgesia for breast surgery . The PECS block type II modified Pecs's block'' is performed by injection at the interfascial plane between the pectoralis minor muscle and serratus anterior muscle . It aims at blocking the pectoral nerves, the intercostobrachial , intercostals (III, IV, V, and VI), and the long thoracic nerve and these are required to block the axilla also provides analgesia to mammary glands and the skin from the T2-T6 dermatomes extending into the mid-axillary line providing complete analgesia during breast surgery and several types of mastectomies . Pectoral nerve block is usually performed using an in-line needling technique by ultrasound guidance, which is essential to identify the plane between the pectoralis major, minor muscles, and serratus anterior as well as the anatomical landmarks associated with them . Hematoma and local anesthetic toxicity and risk of pneumothorax are adverse effects in pectoral nerve block especially PECS II block which may be reduced by using ultrasound guidance and decreasing anesthetic drug concentrations . Various adjuvants, as fentanyl, morphine, tramadol, epinephrine, α2 agonists, dexamethasone, midazolam, neostigmine and sodium bicarbonate have been added to local anesthetics agents to prolong the time and potency of postoperative analgesia and this is may be associated with adverse effects, and the outcomes have been inadequate. An understanding of pain mechanisms points to the role of central sensitization and N-methyl-D-aspartate (NMDA) receptor activation by excitatory amino acid transmitters in postsurgical pain . Magnesium sulfate (MgSO4) is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the central and peripheral nervous system, and is found to decrease the intraoperative and postoperative analgesic consumption and also it increases the duration and potency of analgesia when combined with different local anesthetics. Magnesium augments local anesthetics (LA) action in the peripheral nerves by increasing the firing threshold in both myelinated and unmyelinated axons increasing the transmembrane potential causing hyperpolarization and adding of magnesium to bupivacaine produces an enhancement of nerve blocking . Ketamine is also a non-competitive antagonist of the N-methyl-D-aspartate NMDA receptor antagonist commonly used for its analgesic and anesthetic effect . Ketamine decreases the intensity of postoperative pain, reduces 24-hour opioid consumption, and delays the time to first request of analgesic therapy . Bupivacaine is an amide local anesthetic with a slow onset, long duration of action and high potency. The maximum recommended single bolus dose of bupivacaine is 2.5 mg/Kg, bupivacaine exert its action through impairing sodium influx across the neuronal membrane by blocking the sodium channels .

Official Title
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Efficacy Of Magnesium Sulphate Versus Ketamine as an Adjuvant to Bupivacaine in Pectoral Nerve Block During Mastectomy : Comparative Controlled , Randomized Double-Blind Study

Conditions
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Cancer, Breast

Intervention / Treatment
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* Drug: Use of Bupivacaine in pectoral nerve block in mastectomy
* Drug: use of Ketamine as adjuvants to bupivacaine in pectoral nerve block in mastectomy
* Drug: Use of Magnesium Sulfate as adjuvants to bupivacaine in pectoral nerve block in mastectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patient Age from 30 to 70 years old American Society of Anesthesiologists (ASA) I-II Exclusion Criteria: Cognitive impairment History of alcohol or drug abuse Allergy to the studied drugs Patients with coagulation disorders Block site infection Uncontrolled diabetes mellitus Uncontrolled hypertension Body Mass Index( BMI) more than 30 kg/m2

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Ultrasound guided pectoral nerve block will be performed after induction of general anaesthesia . Starting from the lateral third of the clavicle and moving distally and laterally to the mid axillary line. The needle will be inserted in plane with ultrasound probe between 2 pectoralis muscles and 10 mL of bupivacaine 0.25% alone or with ketamine or magnesium will be injected between the 2 pectoral after negative aspiration for blood (PECS I) then the ultrasound probe will be moved towards axilla until identification of the serratus anterior then the needle will be inserted between pectoralis minor and serratus anterior muscles and 20 mL of bupivacaine 0.25% alone or with ketamine or magnesium will be injected after negative aspiration. Skin incision will be performed 15 minutes after the block will be given . After extubation , all patients will be transferred to the post anesthesia care unit for postoperative monitoring and observation
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A (control group )<br>Patients will be given 30 mL of 0.25% bupivacaine hydrochloride in pectoral nerve block . | Drug: Use of Bupivacaine in pectoral nerve block in mastectomy<br>* Pectoral nerve block will be performed and patients will be given 30 mL of 0.25% bupivacaine hydrochloride and It will be divided into 10 mL injected between the 2 pectoral muscles on the interfascial plane, and 20 mL will be injected between the pectoralis minor and the serratus anterior muscles<br>* Other names: marcain;|
| Active Comparator: Group B ( Ketamine group)<br>Patients will be given 30 mL of 0.25% bupivacaine hydrochloride plus ketamine hydrochloride (1 mg/kg) in pectoral nerve block . | Drug: use of Ketamine as adjuvants to bupivacaine in pectoral nerve block in mastectomy<br>* Pectoral nerve block will be performed and Patients will be given 30 mL of 0.25% bupivacaine hydrochloride plus ketamine hydrochloride (1 mg/kg) and It will be divided into 10 mL injected between the 2 pectoral muscles on the interfascial plane, and 20 mL will be injected between the pectoralis minor and the serratus anterior muscles<br>* Other names: ketalar;|
| Active Comparator: Group C (Magnesium sulfate group)<br>Patients will be given 30 mL 0.25% bupivacaine hydrochloride plus magnesium sulfate ( 28 ml bupivacaine 0.25% plus 2ml magnesium sulfate (50%) in pectoral nerve block | Drug: Use of Magnesium Sulfate as adjuvants to bupivacaine in pectoral nerve block in mastectomy<br>* Pectoral nerve block will be performed and Patients will be given 30 mL 0.25% Bupivacaine hydrochloride plus Magnesium Sulfate ( 28 ml Bupivacaine 0.25% plus 2ml magnesium sulfate 50%) and It will be divided into 10 mL injected between the 2 pectoral muscles on the interfascial plane, and 20 mL will be injected between the pectoralis minor and the serratus anterior muscles<br>* Other names: Mgso4;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The postoperative time to first request of analgesia | the aim of this study is to evaluate the efficacy of Magnesium sulfate versus ketamine when added to local anesthetic (Bupivacaine) in pectoral nerve block during mastectomy and the first time of request of analgesia postoperative in hours is the primary outcome | up to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Scale (VAS) , the scale is determined by measuring the distance in millimeter (mm) on the 10 centimeter (cm) line between the 0 (no pain ) and the mark of the patient . | All patients will be followed up and assessed at baseline, one hour, 2 hours, 4 hours, 8 hours, 12 hours and 24 hours, postoperative for Visual Analogue Scale (VAS) to assess the pain intensity ,The Visual Analogue Scale VAS consists of a 10 cm line with two end points representing 0(no pain ) and 10 (worst pain ) | up to 24 hours | 
| Postoperative analgesic requirements( ( pethidine in milligram/ kilogram (mg/kg) ) | All patients will be followed up and assessed at baseline, one hour, 2 hours, 4 hours, 8 hours, 12 hours and 24 hours, postoperative for visual analogue scale to assess pain intensity and pethidine will be given 0.2-0.5 mg/kg if visual analogue scale (VAS) scale ≥ 3) | up to 24 hours | 
| Postoperative heart rate (Beat/minute) | All patients will be followed up and assessed at baseline, one hour, 2 hours, 4 hours, 8 hours, 12 hours and 24 hours, postoperative for heart rate measurement (Beat/minute) | up to 24 hours | 
| Postoperative non-invasive arterial blood pressure in millimeters of mercury (mmHg) | All patients will be followed up and assessed at baseline, one hour, 2 hours, 4 hours, 8 hours, 12 hours and 24 hours, postoperative for non invasive blood pressure measurement in millimeters of mercury (mmHg) | up to 24 hours | 
| Postoperative respiratory rate (breath/minute) | All patients will be followed up and assessed at baseline, one hour, 2 hours, 4 hours, 8 hours, 12 hours and 24 hours, postoperative for respiratory rate measurement in (breath/minute) | up to 24 hours | 
| Postoperative nausea and vomiting | All patients will be followed up and assessed at baseline, one hour, 2 hours, 4 hours, 8 hours, 12 hours and 24 hours, postoperative for postoperative Nausea and Vomiting (PONV) score (0=no nausea and vomiting, 1=mild nausea, 2=severe nausea, 3=vomiting once, and 4=repeated vomiting) . | up to 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnesium sulphate, ketamine, PECS block, Mastectomy