Dexmedetomidine,Ketamine and Their Combination to Bupivicaine on Thoracic Epidural Analgesia

Effect of Adding Dexmedetomidine, Ketamine and Their Combination to Bupivicaine in Thoracic Epidural Analgesia on Post-mastectomy Pain

This study investigate the effect of addition dexmedetomidine, ketamine or their combination to bupivacaine in thoracic epidural analgesia on acute postoperative pain after breast cancer surgery.

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: Drug: Ketamine, bupivacine,dexmedetomidine

Detailed Description

Breast cancer is the most common cancer diagnosed in Egyptian women. Many modalities are used in the treatment of breast cancer including chemotherapy, radiotherapy or surgical intervention. Nowadays, surgical intervention is more conservative.Modified radical mastectomy (MRM) is the standard surgical procedure of choice in these patients. MRM is usually performed under general anesthesia, almost always combining intravenous and inhalational agents.The drawback of general anesthesia includes inadequate pain control due to lack of analgesia, high incidence of nausea and vomiting, stress of anesthesia and surgery, and increasing the length of hospital stay.Post mastectomy pain is a pain which occur following breast cancer procedures, particularly those operations that remove tissues in upper outer quadrant of breast and/or axilla. This pain can be severe enough to cause long term disabilities and interfere with sleep, performance of daily activities. Also, it can seriously affect the patient mood, and social functions.

Thoracic epidural analgesia (TEA) faces growing interest as adjuvant anesthetic and post-operative analgesic regimen. the use of adjuvant drug with local anesthetic is essential as it prolongs the duration of action, gives better success rate and increases patient satisfaction.

Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, not only abolishes peripheral afferent noxious stimulation, but it can also prevent the central sensitization of nociceptors. When added to epidural local anesthetics, ketamine appears to have adjuvant effects. Dexmedetomedine is a selective, α2-adrenoceptor agonist with analgesic potency, sedative properties, and minimal respiratory depression when used as an adjuvant to regional anesthesia.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Assuit, Egypt
    • South Egypt Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients scheduled for modified radical mastectomy.
• ASA Physical status I, II and III.

Exclusion Criteria:

• Patients' refusal.
• Uncooperative patients & severe psychiatric illness (cannot evaluate their own pain intensity using visual analogue scale (VAS).
• Patients with history of drug allergy.
• severe renal or liver impairment, unstable ischemic heart disease
• Any contraindications to epidural analgesia (coagulopathy, recent -less than 1 week-treatment with thrombolytic or potent antiplatelet drugs as clopidogrel, and local infection).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: bupivacine group; preoperative insertion of thoracic epidural at T4-5 and adminstration of 12 ml bupivacine 0.125% as one shot 15 minutes before general anesthesia postoperative analgesia done by infusion of bupivacaine 0.125% (5ml/hour through thoracic epidural catheter for 12 hours).	Drug: Ketamine, bupivacine,dexmedetomidine; thoracic epidural catheter insertion at T4-5
Active Comparator: ketamine group; preoperative insertion of thoracic epidural at T4-5 and adminstration of 12 ml bupivacine 0.125% plus ketamine in a dose 0.5 mg/kg 15 minutes before general anesthesia postoperative analgesia will be preformed by infusion of mixture of (bupivacaine 0.125% plus ketamine 0.5 mg/ml ml) in a rate of 5ml/hour through thoracic epidural catheter for 12 hours	Drug: Ketamine, bupivacine,dexmedetomidine; thoracic epidural catheter insertion at T4-5
Active Comparator: dexmedetomidine group; preoperative insertion of thoracic epidural at T4-5 and adminstration of 12 ml bupivacine 0.125% plus dexmedetomidine in a dose 1 ug/kg 15 minutes before general anesthesia Postoperative analgesia will be performed using infusion of mixture of (bupivacaine 0.125% plus dexmedetomedine 2μg/ ml) in a rate of 5ml/hour through thoracic epidural catheter for 12 hours.	Drug: Ketamine, bupivacine,dexmedetomidine; thoracic epidural catheter insertion at T4-5
Active Comparator: ketamine-dexmedetomidine group; preoperative insertion of thoracic epidural at T4-5 and adminstration of 12 ml bupivacine 0.125% plus both ketamine in a dose 0.3 mg/kg and dexmedetomidine in a dose 0.1 ug/kg 15 minutes before general anesthesia Postoperative analgesia will be performed using infusion of mixture of (bupivacaine 0.125% plus dexmedetomedine 2μg/ ml and and ketamine 0.5 mg/ml) in a rate of 5ml/hour through thoracic epidural catheter for 12 hours.	Drug: Ketamine, bupivacine,dexmedetomidine; thoracic epidural catheter insertion at T4-5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
total dose of intravenous morphine consumption in the first 48 hours post operatively	total dose of intravenous morphine comsumption	48 hours postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual analogue scale	Visual analogue scale will be assessed at rest and on movement (abduction of the ipsi-lateral arm).	0, 2,4,6,8,18,36,48 hours
MAP	mean arterial blood pressure	0,30,60,120,150 minutes
HR	heart rate	0,30,60,120,150 minutes
sedation score	sedation sore using sedation scale where; 0 = aware - 1 = drowsy - 2 = asleep/easily respond to verbal command - 3 = asleep/difficulty responding to verbal command -4 = asleep/no respond to verbal command	0, 2,4,6,8,18,36,48 hours

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: February 21, 2017
• First Submitted That Met QC Criteria: February 21, 2017
• First Posted (Actual): February 24, 2017

Study Record Updates

• Last Update Posted (Actual): June 28, 2019
• Last Update Submitted That Met QC Criteria: June 27, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: postmastectomy pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Ketamine; Dexmedetomidine
• Other Study ID Numbers: 110

Drug and device information, study documents

• 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