Wound Infiltration With Tramadol, Dexmedetomidine, or Magnesium Plus Ropivacaine for Pain Relief After Spine Surgery

NCT04391855 | Completed Phase 4

• 1 other identifier: SpinInf
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The rationale for multimodal analgesia is to achieve additive or synergistic analgesic properties while decreasing the incidence of side effects by reducing the dose of each agent. Nociceptive stimuli are known to activate the release of the excitatory amino acid glutamate in the dorsal horn of the spinal cord. The resultant activation of NMDA receptors causes calcium entry into the cell and triggers central sensitization. This mechanism is involved in the perception of pain and mainly accounts for its persistence during the postoperative period. Peri-incisional injection of local anesthetics is an effective method for pain relief after many surgical procedures, as it can reduce postoperative analgesic consumption. Ropivacaine is a propyl analog of bupivacaine with a longer duration of action with a much safer cardiotoxicity profile than bupivacaine. Thus, a combination of local anesthetic with other analgesic factors, such as opioids, dexmedetomidine, clonidine, ketamine, magnesium sulfate, dexamethasone is suggested for a better analgesic outcome. Dexmedetomidine, a highly selective a2-adrenergic receptor agonist, has been the focus of interest for its broad spectrum (sedative, analgesic, and anesthetic sparing) properties, making it a useful and safe adjunct in many clinical applications. The intravenous, intramuscular, intrathecal, epidural, and perineural use of this agent enhances analgesic effects. Tramadol hydrochloride is a synthetic analog of codeine that acts on both opioid (weak m receptor agonist) and nonopioid receptors (inhibits the reuptake of noradrenaline and serotonin as well as release stored serotonin from nerve endings) which play a crucial role in pain inhibition pathway. It also blocks nerve conduction which imparts its local anesthetics like action on peripheral nerves. It was reported that NMDA antagonists could prolong the analgesic effect of bupivacaine to even a week, as well as inhibit hyperalgesia. Magnesium sulfate (MGS) is a non-competitive antagonist of N-methyl, D-aspartate (NMDA) receptors with an analgesic effect and is essential for the release of acetylcholine from the presynaptic terminals and, similar to calcium channel blockers (CCB), can prevent the entry of calcium into the cell. Aim of the study is to evaluate and compare the postoperative analgesic efficacy of tramadol, dexmedetomidine, and magnesium when added to ropivacaine as an adjuvant for wound infiltration following spine surgery.

Conditions

Analgesia; Pain, Postoperative; Spinal Stenosis; Spinal Disease

Keywords

analgesia; pain score; tramadol; dexmedetomidine; magnesium; opioid consumption; spine surgery

Outcome Measures

Primary Outcomes (1)

• Time to first analgesic request in minutes

  The difference in the time frame (minutes) for analgesia request after emergence from anesthesia after wound infiltration with tramadol plus ropivacaine, tramadol plus ropivacaine, magnesium sulfate plus ropivacaine or ropivacaine plus isotonic saline 0.9%

  24 hours after the emergence from anesthesia

Secondary Outcomes (4)

• Pain intensity postoperatively

  At 10 minutes after emergence from anesthesia, and 2, 4, 6, 12, 18 and 24 hours after the emergence from anesthesia

• Analgesics consumption postoperatively in morphine equivalents

  24 hours after the emergence from anesthesia

• Plasma concentration of TNF-a and IL-6

  Before wound infiltration, and at 6 and 24 hours thereafter

• Plasma concentration of cortisol

  Before wound infiltration, and at 6 and 24 hours thereafter

Other Outcomes (3)

• Patients' sedation level after emergence

  At 5 minutes after emergence from anesthesia

• Postoperative adverse effects

  24 hours after the emergence from anesthesia

• Quality of Recovery

  At 48 hours postoperatively and one month after hospital discharge

Study Arms (4)

Tramadol with ropivacaine

EXPERIMENTAL

Tramadol 2mg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration

Drug: Tramadol with ropivacaine

Dexmedetomidine with ropivacaine

EXPERIMENTAL

Dexmedetomidine 1μg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration

Drug: Dexmedetomidine with ropivacaine

Magnesium with ropivacaine

EXPERIMENTAL

Magnesium sulfate 10 mg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration

Drug: Magnesium with ropivacaine

Placebo with ropivacaine

PLACEBO COMPARATOR

Ropivacaine (10mg/ml) 100mg with 5ml isotonic saline for wound infiltration

Drug: Ropivacaine plus normal saline

Interventions

Tramadol with ropivacaine DRUG

A solution of tramadol 2mg/kg with ropivacaine hydrochloride (10mg/ml) 100mg mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure.

Also known as: TR

Tramadol with ropivacaine

Dexmedetomidine with ropivacaine DRUG

A solution of dexmedetomidine 1μg/kg with ropivacaine hydrochloride (10mg/ml) 100mg mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure.

Also known as: DR

Dexmedetomidine with ropivacaine

Magnesium with ropivacaine DRUG

A solution of magnesium 10 mg/kg with ropivacaine hydrochloride (10mg/ml) 100mg mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure.

Also known as: MR

Magnesium with ropivacaine

Ropivacaine plus normal saline DRUG

A solution of ropivacaine hydrochloride (10mg/ml) 100mg with 5ml of isotonic saline 0.9% mixture making up a total volume of 15ml will be infiltrated in the surgical trauma area before closure.

Also known as: R

Placebo with ropivacaine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients aged between 18 and 80 years
• ASA Physical status 1 to 3
• Elective or semi-elective one-level lumbar laminectomy or discectomy surgery
• Signed informed consent

You may not qualify if:

• Chronic use of opioids
• Drugs or alcohol abuse
• Neurological disorders
• Local anesthetics toxicity
• Myopathy
• Cardiac conductance disturbances
• Hepatic failure
• Renal failure
• Pregnancy

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead

Study Sites (1)

AHEPA University Hospital

Thessaloniki, 54636, Greece

Location

MeSH Terms

Conditions

Agnosia; Pain, Postoperative; Spinal Stenosis; Spinal Diseases

Interventions

Tramadol; Ropivacaine; Dexmedetomidine; Magnesium; Saline Solution

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Pathologic Processes; Pain; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Dimethylamines; Methylamines; Amines; Lipids; Anilides; Amides; Aniline Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals, Light; Metals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Georgia Tsaousi

  Aristotle University Of Thessaloniki

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 13, 2020
• First Posted: May 18, 2020
• Study Start: May 10, 2020
• Primary Completion: November 8, 2022
• Study Completion: December 10, 2022
• Last Updated: December 20, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)