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

Effect of Wound Infiltration With Tramadol, Dexmedetomidine, or Magnesium Sulfate as Adjuncts to the Local Anesthetic on Pain Relief After Spine Surgery

Sponsors

Lead Sponsor: Aristotle University Of Thessaloniki

Source 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.

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.

Overall Status Recruiting
Start Date May 10, 2020
Completion Date December 2020
Primary Completion Date November 2020
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Time to first analgesic request in minutes 24 hours after the emergence from anesthesia
Secondary Outcome
Measure Time Frame
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
Enrollment 78
Condition
Intervention

Intervention Type: Drug

Intervention Name: Tramadol with ropivacaine

Description: A solution of tramadol 2mg/kg with ropivacaine hydrochloride 0.5% 100mg mixture making up a total volume of 20ml will be infiltrated in the surgical trauma area before closure.

Arm Group Label: Tramadol with ropivacaine

Other Name: TR

Intervention Type: Drug

Intervention Name: Dexmedetomidine with ropivacaine

Description: A solution of dexmedetomidine 1μg/kg with ropivacaine hydrochloride 0.5% 100mg mixture making up a total volume of 20ml will be infiltrated in the surgical trauma area before closure.

Arm Group Label: Dexmedetomidine with ropivacaine

Other Name: DR

Intervention Type: Drug

Intervention Name: Magnesium with ropivacaine

Description: A solution of magnesium 10 mg/kg with ropivacaine hydrochloride 0.5% 100mg mixture making up a total volume of 20ml will be infiltrated in the surgical trauma area before closure.

Arm Group Label: Magnesium with ropivacaine

Other Name: MR

Intervention Type: Drug

Intervention Name: Ropivacaine plus normal saline

Description: A solution of ropivacaine hydrochloride 0.5% 100mg with 2ml of isotonic saline 0.9% mixture making up a total volume of 20ml will be infiltrated in the surgical trauma area before closure.

Arm Group Label: Placebo with ropivacaine

Other Name: R

Eligibility

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

Gender: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Georgia Tsaousi Principal Investigator Aristotle University Of Thessaloniki
Overall Contact

Last Name: Georgia Tsaousi

Phone: 00302310994855

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: AHEPA University Hospital Georgia Tsaousi, Professor +302310994855 [email protected]
Location Countries

Greece

Verification Date

June 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Aristotle University Of Thessaloniki

Investigator Full Name: Georgia Tsaousi

Investigator Title: Associate Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Tramadol with ropivacaine

Type: Experimental

Description: Tramadol 2mg/kg with ropivacaine 0.5% 100mg for wound infiltration

Label: Dexmedetomidine with ropivacaine

Type: Experimental

Description: Dexmedetomidine 1μg/kg with ropivacaine 0.5% 100mg for wound infiltration

Label: Magnesium with ropivacaine

Type: Experimental

Description: Magnesium sulfate 10 mg/kg with ropivacaine 0.5% 100mg for wound infiltration

Label: Placebo with ropivacaine

Type: Placebo Comparator

Description: Ropivacaine 0.5% 100mg with 2ml isotonic saline 0.9% for wound infiltration

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov