Magnesium and Ketamine in Postoperative Analgesia

Study Overview
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Brief Summary
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90 female patients scheduled for cancer breast surgeries will be assigned to 2 groups, each of 45. Group (K) will receive a bolus of 0.5 mg/kg ketamine with induction of anaesthesia, followed by ketamine infusion 0.12 mg/kg/hour continued till 24 hours after surgery. Group (KM) will receive a bolus of 0.5 mg/kg ketamine added to 50mg/kg magnesium sulfate over 30 minutes after induction of anaesthesia, followed by ketamine infusion 0.12 mg/kg/hour added to 8mg/kg/hour of magnesium sulfate continued till 24 hours after surgery. The same anaesthetic regimen will be applied to all patients. Total intraoperative fentanyl required to maintain mean blood pressure within 20% of its baseline will be recorded. After surgery, all patients will be connected to PCA device containing morphine solution, the amount of morphine consumed during the first 24 hours will be recorded. In the follow-up visits after 3 months, all patients will be assessed for neuropathic pain by DN4 questionnaire.

Detailed Description
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90 female patients aged between 18 and 65 years, scheduled for cancer breast surgeries will be assigned to 2 groups, each of 45. Group (K) will receive a bolus of 0.5 mg/kg ketamine with induction of anaesthesia, followed by ketamine infusion 0.12 mg/kg/hour continued till 24 hours after surgery. Group (KM) will receive a bolus of 0.5 mg/kg ketamine added to 50mg/kg magnesium sulfate over 30 minutes after induction of anaesthesia, followed by ketamine infusion 0.12 mg/kg/hour added to 8mg/kg/hour of magnesium sulfate continued till 24 hours after surgery. The same anaesthetic regimen will be applied to all patients. Total intraoperative fentanyl required to maintain mean blood pressure within 20% of its baseline will be recorded. After surgery, all patients will be connected to PCA device containing morphine solution, the amount of morphine consumed during the first 24 hours will be recorded. In the follow-up visits after 3 months, all patients will be assessed for neuropathic pain by DN4 questionnaire.

Official Title
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Evaluation of the Effect of Adding Magnesium Sulfate Infusion to Ketamine Infusion on Improvement of the Analgesic Efficacy in Cancer Breast Surgeries.

Conditions
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Postoperative Analgesia

Intervention / Treatment
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* Drug: Ketamine
* Drug: ketamine and magnesium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with class II physical status (American Society of Anaesthesiologists) , Age between 18-65 years, Scheduled for breast cancer surgery (e.g. modified radical mastectomy and conservative mastectomy) Exclusion Criteria: Patient refusal, Cardiac dysfunction (ejection fraction <45%), Diabetic patients Patients with uncontrolled hypertension Patients have any degree of heart block Patients have renal impairment (creatinine > 2 mg/dl), Patients have hepatic dysfunction (transaminases > 2 times normal), Patients with preexisting neurological or psychiatric disease, Patients who are allergic to one of the study drugs, Patients with communication difficulties, Inability to use the patient controlled analgesia (PCA) device, Female patients who are pregnant Patients who use preoperative calcium channel blockers or narcotic drugs.

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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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 90 female patients scheduled for cancer breast surgeries will be assigned to 2 groups, each of 45. Group (K) will receive a bolus of 0.5 mg/kg ketamine with induction of anaesthesia, followed by ketamine infusion 0.12 mg/kg/hour continued till 24 hours after surgery. Group (KM) will receive a bolus of 0.5 mg/kg ketamine added to 50mg/kg magnesium sulfate over 30 minutes after induction of anaesthesia, followed by ketamine infusion 0.12 mg/kg/hour added to 8mg/kg/hour of magnesium sulfate continued till 24 hours after surgery.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ketamine group : group (k)<br>-Ketamine group (group K): will receive a bolus of 0.5 mg/kg ketamine during induction of anaesthesia diluted in 100 ml normal saline, followed by ketamine infusion 0.12 mg/kg/hour continued till 24 hours after surgery. The infusion pump concentration will be 0.6mg/ml and the rate of infusion will be 0.2 ml/kg/hour | Drug: Ketamine<br>* Patients will be assigned into 2 groups (each of 45): Ketamine group (group K): will receive a bolus of 0.5 mg/kg ketamine during induction of anaesthesia diluted in 100 ml normal saline, followed by ketamine infusion 0.12 mg/kg/hour continued till 24 hours after surgery. The infusion pump concentration will be 0.6mg/ml and the rate of infusion will be 0.2 ml/kg/hour.<br>|
| Experimental: ketamine and magnesium group: group (KM)<br>- Ketamine and magnesium group (group KM): will receive a bolus of 0.5 mg/kg ketamine added to 50mg/kg magnesium sulfate diluted in 100 ml normal saline over 30 minutes after induction of anaesthesia, followed by ketamine infusion 0.12 mg/kg/hour added to 8mg/kg/hour of magnesium sulfate continued till 24 hours after surgery. Each ml of the administered infusion will contain 0.6mg ketamine and 40mg magnesium and the rate of infusion will be 0.2 ml/kg/hour. | Drug: ketamine and magnesium<br>* Ketamine and magnesium group (group KM): will receive a bolus of 0.5 mg/kg ketamine added to 50mg/kg magnesium sulfate diluted in 100 ml normal saline over 30 minutes after induction of anaesthesia, followed by ketamine infusion 0.12 mg/kg/hour added to 8mg/kg/hour of magnesium sulfate continued till 24 hours after surgery. Each ml of the administered infusion will contain 0.6mg ketamine and 40mg magnesium and the rate of infusion will be 0.2 ml/kg/hour.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the total amount of morphine required during the first postoperative 24 hours | After transferring to post-anaesthesia care unit (PACU), the IV route of each patient will be connected to a PCA device containing morphine solution (1mg/ml). This PCA device will be set to deliver a demand dose of 1ml with a lockout interval of 15 minutes and without a continuous background infusion. The primary outcome in this study will be assessed in the form of the total amount of morphine required during the first postoperative 24 hours. | the first postoperative 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the total amount of intraoperative fentanyl consumption | the total amount of intraoperative fentanyl required to maintain values of mean blood pressure within 20% of their baseline values | during anaesthesia (intraoperative) | 
| (Visual Analogue scale) VAS scores | (VAS) scores during rest and with shoulder movement at 0, 4, 8, 12and 24 post-operative hours | the first postoperative 24 hours | 
| Douleur Neuropathique 4 (DN4 | Chronic post-operative pain will be evaluated in all patients during their outpatient follow-up visit after 3 months. Patients with score of ≥ 4 in the Douleur Neuropathique 4 (DN4) questionnaire will indicate the incidence of neuropathic pain. | 3 months after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnisum sulfate, Ketamine, Analgesia, Breast Cancer Surgeries