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

Tracking Information

• First Submitted Date: September 30, 2019
• First Posted Date: October 1, 2019
• Last Update Posted Date: March 2, 2021
• Actual Study Start Date: November 1, 2019
• Actual Primary Completion Date: November 1, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 30, 2019)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 30, 2019)

• 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
• (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
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Magnesium and Ketamine in Postoperative Analgesia
• Official Title: Evaluation of the Effect of Adding Magnesium Sulfate Infusion to Ketamine Infusion on Improvement of the Analgesic Efficacy in Cancer Breast Surgeries.
• 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.
• 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 Type: Interventional
• Study Phase: Phase 4

Study Design

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

• Condition: Postoperative Analgesia

Intervention

• 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.

• 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.

Study Arms

• 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
  Intervention: Drug: Ketamine
• 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.
  Intervention: Drug: ketamine and magnesium

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 30, 2019): 90
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 1, 2020
• Actual Primary Completion Date: November 1, 2020 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Egypt

Administrative Information

• NCT Number: NCT04111848
• Other Study ID Numbers: AP1904-50102
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: National Cancer Institute, Egypt
• Study Sponsor: National Cancer Institute, Egypt
• Collaborators: Not Provided

Investigators

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

• PRS Account: National Cancer Institute, Egypt
• Verification Date: February 2021