Magnesium and Ketamine in Postoperative Analgesia

• ClinicalTrials.gov Identifier: NCT04111848
• Recruitment Status: Completed
• First Posted: October 1, 2019
• Last Update Posted: March 2, 2021
• Sponsor: National Cancer Institute, Egypt
• Information provided by (Responsible Party): National Cancer Institute, Egypt

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Postoperative Analgesia	Drug: Ketamine; Drug: ketamine and magnesium	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The study medications were prepared by a pharmacist who was not involved in the patient management or the data collection. Both the patients and the stuff involved in their management were unaware of the group assignment. Equal rates of the drug infusion and equal volumes of the administered drugs were applied to all patients to ensure double blinding of the study.
• Primary Purpose: Supportive Care
• Official Title: Evaluation of the Effect of Adding Magnesium Sulfate Infusion to Ketamine Infusion on Improvement of the Analgesic Efficacy in Cancer Breast Surgeries.
• Actual Study Start Date: November 1, 2019
• Actual Primary Completion Date: November 1, 2020
• Actual Study Completion Date: December 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: ketamine group : group (k); -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; 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.
Experimental: ketamine and magnesium group: group (KM); - 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; 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.

Outcome Measures

Primary Outcome Measures :

1. the total amount of morphine required during the first postoperative 24 hours [ Time Frame: 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.

Secondary Outcome Measures :

1. the total amount of intraoperative fentanyl consumption [ Time Frame: during anaesthesia (intraoperative) ]
   the total amount of intraoperative fentanyl required to maintain values of mean blood pressure within 20% of their baseline values
2. (Visual Analogue scale) VAS scores [ Time Frame: the first postoperative 24 hours ]
   (VAS) scores during rest and with shoulder movement at 0, 4, 8, 12and 24 post-operative hours
3. Douleur Neuropathique 4 (DN4 [ Time Frame: 3 months after surgery ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Egypt

National Cancer Institute

Cairo, Egypt

Sponsors and Collaborators

National Cancer Institute, Egypt

Investigators

• Principal Investigator: Mohamed Hassan, MD; Ass Prof- Anesthesia Dept- National Cancer Institute - Cairo University

More Information

• Responsible Party: National Cancer Institute, Egypt
• ClinicalTrials.gov Identifier: NCT04111848
• Other Study ID Numbers: AP1904-50102
• First Posted: October 1, 2019
• Last Update Posted: March 2, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by National Cancer Institute, Egypt:

Magnisum sulfate; Ketamine; Analgesia; Breast Cancer Surgeries

Additional relevant MeSH terms:

Agnosia; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Ketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action