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

NCT ID: NCT04391855

Last Updated: 2022-12-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-10
• Study Completion Date: 2022-12-10

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.

Conditions

Analgesia; Pain, Postoperative; Spinal Stenosis; Spinal Disease

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Tramadol with ropivacaine

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

Group Type: EXPERIMENTAL

Tramadol with ropivacaine

Intervention Type: 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.

Dexmedetomidine with ropivacaine

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

Group Type: EXPERIMENTAL

Dexmedetomidine with ropivacaine

Intervention Type: 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.

Magnesium with ropivacaine

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

Group Type: EXPERIMENTAL

Magnesium with ropivacaine

Intervention Type: 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.

Placebo with ropivacaine

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

Group Type: PLACEBO_COMPARATOR

Ropivacaine plus normal saline

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

TR; DR; MR; 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aristotle University Of Thessaloniki

OTHER

Sponsor Role: lead

Responsible Party

Georgia Tsaousi

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Georgia Tsaousi

Role: PRINCIPAL_INVESTIGATOR

Aristotle University Of Thessaloniki

Locations

AHEPA University Hospital

Thessaloniki, , Greece

Countries

Greece

Other Identifiers

SpinInf

Identifier Type: -

Identifier Source: org_study_id