Ketamine as Adjunctive Analgesic With Bupivacaine in Paravertebral Analgesia for Breast Cancer Surgery

• ClinicalTrials.gov Identifier: NCT02462681
• Recruitment Status: Completed
• First Posted: June 4, 2015
• Last Update Posted: July 2, 2017
• Sponsor: Assiut University
• Information provided by (Responsible Party): Shereen Mamdouh, Assiut University

Study Description

Brief Summary:

This study aims to investigate the safety and the analgesic efficacy of adding Ketamine to bupivacaine 0.25% in thoracic PVB in patients undergoing modified radical mastectomy.

Condition or disease	Intervention/treatment	Phase
Acute Pain; Chronic Pain	Drug: paravertebral block	Phase 1; Phase 2

Detailed Description:

Breast cancer is perhaps the most common cancer in women that requires frequent surgical intervention. Nearly 40% of post-operative breast surgery patients experience significant acute post-operative pain, with a pain score above five reflecting inadequacy of conventional pain management. Most of the responses of the human body to post-surgical pain have been proven to be detrimental to the patient's homeostasis and recovery. Moreover, the incidence of chronic postoperative pain in breast surgery patients is as high as 50% and inadequate analgesia is considered as an independent risk factor. Hence, a number of therapeutic measures have been accepted as a part of the "multi-modal" approach to post-operative pain control. Thoracic Paravertebral Block (PVB) is used for pain relief after thoracotomy , and mastectomy. PVB can provide profound, long lasting sensory differentiation. The resulting greater attenuation of surgical stress response may translate into reduced inotropic stimulation of the heart. Additionally, unlike general anesthesia, PVB can provide superior postoperative analgesia, less nausea and vomiting, shorter recovery time; require fewer analgesic, earlier mobilization, and earlier home readiness for discharge. The use of PVB in patients undergoing ambulatory breast surgery has cost-saving potential. There is little systematic research on the efficacy and tolerability of the addition of adjunctive analgesic agent in paravertebral analgesia. The addition of adjunctive analgesics, such as fentanyl and clonidine to local anesthetics has been shown to enhance the quality and duration of sensory neural blockade, and decrease the dose of local anesthetic and supplemental analgesia .

Ketamine is an anaesthetic agent with potent analgesic properties. Its mode of action includes noncompetitive antagonism at N-methyl d-aspartate (NMDA) receptors and a local anaesthetic effect. ketamine has been extensively used through epidural and caudal routes with variable results.It possesses some definite advantages over the conventional local anaesthetic agents as it stimulates cardiovascular system and respiratory system.The advantages of ketamine include a good analgesic effect, cardio vascular stability in a hypotensive state, bronchodilatation in asthmatics, and the absence of awareness. Disadvantages include increased heart rate and blood pressure, emergence phenomenon, laryngospasm and apnea, increases in intracranial and intraocular pressure, and the lack of visceral anesthesia.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Ketamine as Adjunctive Analgesic With Bupivacaine in Paravertebral Analgesia for Breast Cancer Surgery
• Study Start Date: May 2015
• Actual Primary Completion Date: December 2016
• Actual Study Completion Date: June 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: bupivacaine group in paravertebral block; patients will be received 20 ml of bupivacaine 0.25% paravertebrally, divided into 3-4 ml in each level	Drug: paravertebral block; Thoracic paravertebral blocks will be performed as described by Moore and Katz. Intradermal lidocaine will be used at the site of the needle insertion. The superior aspect of the spinous processes of T1- T6 will be marked. The skin entry points will 3 cm laterals to the marks. A 22- gauge quincke spinal needle attach to extension tubing to a syringe containing study drugs will be used. The needle will be inserted perpendicular to the skin for a distance of 2 to 4 cm until the transverse process will contact. The needle will be withdrawn and walk cephalad off the transverse process and advance for a further 1.5 to 2 cm.; Other Name: ketamine hydrochloride
Active Comparator: bupivacaine + 0.5 mg/kg ketamine group in paravertebral block; patients will be received 20 ml of bupivacaine 0.25% + 0.5 mg/kg ketamine paravertebrally divide into 3-4 ml in each level	Drug: paravertebral block; Thoracic paravertebral blocks will be performed as described by Moore and Katz. Intradermal lidocaine will be used at the site of the needle insertion. The superior aspect of the spinous processes of T1- T6 will be marked. The skin entry points will 3 cm laterals to the marks. A 22- gauge quincke spinal needle attach to extension tubing to a syringe containing study drugs will be used. The needle will be inserted perpendicular to the skin for a distance of 2 to 4 cm until the transverse process will contact. The needle will be withdrawn and walk cephalad off the transverse process and advance for a further 1.5 to 2 cm.; Other Name: ketamine hydrochloride
Active Comparator: bupivacaine + 1 mg/kg ketamine group in paravertebral block; patients will be received 20 ml of bupivacaine 0.25% + 1mg/kg ketamine paravertebrally divide into 3-4 ml in each level	Drug: paravertebral block; Thoracic paravertebral blocks will be performed as described by Moore and Katz. Intradermal lidocaine will be used at the site of the needle insertion. The superior aspect of the spinous processes of T1- T6 will be marked. The skin entry points will 3 cm laterals to the marks. A 22- gauge quincke spinal needle attach to extension tubing to a syringe containing study drugs will be used. The needle will be inserted perpendicular to the skin for a distance of 2 to 4 cm until the transverse process will contact. The needle will be withdrawn and walk cephalad off the transverse process and advance for a further 1.5 to 2 cm.; Other Name: ketamine hydrochloride

Outcome Measures

Primary Outcome Measures :

1. changes in pain intensity score from baseline [ Time Frame: at 2,4,6,12,24,36and 48 hour postoperatively ]
   Visual analogue scale (VAS) Scored from 0-10 (where 0= no pain and 10= the worst pain imaginable) as it measured as VAS at rest (VAS.R) and during movement or ipsilateral arm abduction (VAS.M)

Secondary Outcome Measures :

1. side effect [ Time Frame: 2,4,6,12,24,36and 48 hour postoperatively. ]
   nausea, vomiting, hypotension, bradycardia, sedation, dizziness and nystagmus will recorded and treated also postoperative complications of the block such as accidental pneumothorax and vascular puncture will be recorded and treated
2. chronic neuropathic pain [ Time Frame: 1st,2nd and 3rd postoperative months ]
   (Douleur Neuropathique 4 questions) (DN4) questionnaire will be used for assessment of development of neuropathic pain

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• all patients scheduled for elective modified radical mastectomy with axillary dissection will be enrolled in the study

Exclusion Criteria:

• patients with a known allergy to the study drugs
• patients with bleeding diathesis
• patients with infection at the site of injection
• patients with central neuropathy
• patients with liver impairment
• patients with renal impairment
• drugs or alcohol abusers
• patients with psychiatric illnesses

Contacts and Locations

Locations

Egypt

Assiut University

Assiut, Egypt, 171516

Sponsors and Collaborators

Assiut University

Investigators

• Principal Investigator: Sahar A. Mohamed, MD; Lecturer of anesthesia, ICU and pain management- South Egypt Cancer Institute- Assuit University

More Information

• Responsible Party: Shereen Mamdouh, lecturer of anesthesia,ICU and pain relief, Assiut University
• ClinicalTrials.gov Identifier: NCT02462681
• Other Study ID Numbers: 211
• First Posted: June 4, 2015
• Last Update Posted: July 2, 2017
• Last Verified: June 2017

Keywords provided by Shereen Mamdouh, Assiut University:

ketamine; adjuvant; paravertebral block

Additional relevant MeSH terms:

Chronic Pain; Acute Pain; Pain; Neurologic Manifestations; 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