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

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ClinicalTrials.gov Identifier: NCT04391855
Recruitment Status : Recruiting
First Posted : May 18, 2020
Last Update Posted : February 15, 2022
Sponsor:
Information provided by (Responsible Party):
Georgia Tsaousi, Aristotle University Of Thessaloniki

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.


Condition or disease Intervention/treatment Phase
Analgesia Pain, Postoperative Spinal Stenosis Spinal Disease Drug: Tramadol with ropivacaine Drug: Dexmedetomidine with ropivacaine Drug: Magnesium with ropivacaine Drug: Ropivacaine plus normal saline Phase 4

Detailed Description:

Each participant will receive standard monitoring (ECG, SpO2, capnography, SBP, oesophageal temperature) and intravenous access will be established. A standard anesthesia protocol will be applied involving propofol 2mg/kg (iv) and remifentanil in TCI (target-controlled infusion). Cis-atracurium 0.2 mg/kg (iv) will be given to facilitate endotracheal intubation. Anesthesia will be maintained with desflurane in a 50% air/O2 mixture A standard anesthesia protocol will be applied involving propofol 2mg/kg (iv) and remifentanil in TCI (target-controlled infusion). Cis-atracurium 0.2 mg/kg (iv) will be given to facilitate endotracheal intubation. Anesthesia will be maintained with air to oxygen mixture of 50%, and desflurane adjusted to achieve a target BIS between 40 and 50. Remifentanil target level will be titrated according to analgesic demands defined by a > 20% change of heart rate or blood pressure compared with baseline. The duration of both anesthesia and surgical procedure will be registered. Furthermore, the level of sedation upon anesthesia emergence will be recorded using the Ramsey sedation scale.

Postoperatively pain assessment will be performed by the Visual Analogue Scale (VAS) and Numerical Rating Scale (NRS) at anesthesia emergence and at 2, 4, 6, 12, 18, and 24 h after surgery conclusion. Time to first analgesic request and total analgesics consumption postoperatively (morphine equivalents) will be recorded.

Episodes of shivering, as well as episodes of nausea and vomiting (PONV) and other postoperative adverse events, will be recorded at emergence and 24 hours thereafter.

Finally, patients' global satisfaction will be assessed the second day and one month after surgery using the Quality of Recovery Scale(QoR-40). In the meantime, blood samples will be taken at the time before the surgical stimulus, 6 hours and 24 hours after wound infiltration to measure cortisol, TNF-a, and IL-6 plasma concentration.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Wound Infiltration With Tramadol, Dexmedetomidine, or Magnesium Sulfate as Adjuncts to the Local Anesthetic on Pain Relief After Spine Surgery
Actual Study Start Date : May 10, 2020
Estimated Primary Completion Date : August 30, 2022
Estimated Study Completion Date : September 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tramadol with ropivacaine
Tramadol 2mg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration
Drug: Tramadol with ropivacaine
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.
Other Name: TR

Experimental: Dexmedetomidine with ropivacaine
Dexmedetomidine 1μg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration
Drug: Dexmedetomidine with ropivacaine
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.
Other Name: DR

Experimental: Magnesium with ropivacaine
Magnesium sulfate 10 mg/kg with ropivacaine (10mg/ml) 100mg for wound infiltration
Drug: Magnesium with ropivacaine
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.
Other Name: MR

Placebo Comparator: Placebo with ropivacaine
Ropivacaine (10mg/ml) 100mg with 5ml isotonic saline for wound infiltration
Drug: Ropivacaine plus normal saline
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.
Other Name: R




Primary Outcome Measures :
  1. Time to first analgesic request in minutes [ Time Frame: 24 hours after the emergence from anesthesia ]
    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%


Secondary Outcome Measures :
  1. Pain intensity postoperatively [ Time Frame: At 10 minutes after emergence from anesthesia, and 2, 4, 6, 12, 18 and 24 hours after the emergence from anesthesia ]
    The difference in pain intensity postoperatively assessed by Visual Analogue Scale (graded from 0 defining absence of pain to 10 meaning extreme pain) or Numerical Pain Scale (graded from 0 defining no pain to 10 the worst pain ever experienced) after wound infiltration with tramadol plus ropivacaine, tramadol plus ropivacaine, magnesium sulfate plus ropivacaine or ropivacaine plus isotonic saline 0.9%

  2. Analgesics consumption postoperatively in morphine equivalents [ Time Frame: 24 hours after the emergence from anesthesia ]
    The difference in analgesic consumption (assessed as mg of morphine equivalents) postoperatively after wound infiltration with tramadol plus ropivacaine, tramadol plus ropivacaine, magnesium sulfate plus ropivacaine or ropivacaine plus isotonic saline 0.9%

  3. Plasma concentration of TNF-a and IL-6 [ Time Frame: Before wound infiltration, and at 6 and 24 hours thereafter ]
    Levels of TNF-a and IL-6 in pg/ml will be measured from blood samples at the times before surgical stimulus, at 6 hours and 24 hours after wound infiltration, as stress-response biomarkers.

  4. Plasma concentration of cortisol [ Time Frame: Before wound infiltration, and at 6 and 24 hours thereafter ]
    Levels of cortisol (in mcg/dL) will be measured from blood samples at the times before surgical stimulus, at 6 hours and 24 hours after wound infiltration, as stress-response biomarkers.


Other Outcome Measures:
  1. Patients' sedation level after emergence [ Time Frame: At 5 minutes after emergence from anesthesia ]
    The level of sedation will be assessed after emergence using the Ramsey sedation scale in each participant, which ranges between 1 (anxious and restless patient) to 6 (unresponsive patient).

  2. Postoperative adverse effects [ Time Frame: 24 hours after the emergence from anesthesia ]
    The incidence of shivering, pruritus, nausea /vomiting, or any other adverse effect postoperatively after wound infiltration with tramadol plus ropivacaine, tramadol plus ropivacaine, magnesium sulfate plus ropivacaine or ropivacaine plus isotonic saline 0.9%

  3. Quality of Recovery [ Time Frame: At 48 hours postoperatively and one month after hospital discharge ]
    The quality of recovery and overall satisfaction of each participant will be assessed using the Quality of Recovery Scale (QoR-40) ranging from 0 the worst to 200 the best value.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04391855


Contacts
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Contact: Georgia Tsaousi 00302310994855 tsaousig@otenet.gr
Contact: Anastasia Nikopoulou 00302310994862 anastasian1991@windowslive.com

Locations
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Greece
AHEPA University Hospital Recruiting
Thessaloniki, Greece, 54636
Contact: Georgia Tsaousi, Professor    +302310994855    tsaousig@otenet.gr   
Contact: Anastasia Nikopoulou, Dr    +302310994855    anastasian1991@windowslive.com   
Sponsors and Collaborators
Aristotle University Of Thessaloniki
Investigators
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Principal Investigator: Georgia Tsaousi Aristotle University Of Thessaloniki
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Responsible Party: Georgia Tsaousi, Associate Professor, Aristotle University Of Thessaloniki
ClinicalTrials.gov Identifier: NCT04391855    
Other Study ID Numbers: SpinInf
First Posted: May 18, 2020    Key Record Dates
Last Update Posted: February 15, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Georgia Tsaousi, Aristotle University Of Thessaloniki:
analgesia
pain score
tramadol
dexmedetomidine
magnesium
opioid consumption
spine surgery
Additional relevant MeSH terms:
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Spinal Stenosis
Spinal Diseases
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Neurologic Manifestations
Bone Diseases
Musculoskeletal Diseases
Dexmedetomidine
Tramadol
Ropivacaine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anesthetics, Local
Anesthetics
Analgesics, Opioid
Narcotics