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

Pain, Postoperative Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04391855
• Other study ID #: SpinInf
• Status: Completed
• Phase: Phase 4
• Start date: May 10, 2020
• Est. completion date: December 10, 2022

Study information

• Verified date: December 2022
• Source: Aristotle University Of Thessaloniki
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: December 10, 2022
• Est. primary completion date: November 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Analgesia
• Pain, Postoperative
• Spinal Disease
• Spinal Diseases
• Spinal Stenosis

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Greece	AHEPA University Hospital	Thessaloniki

Sponsors (1)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patients' sedation level after emergence	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).	At 5 minutes after emergence from anesthesia
Other	Postoperative adverse effects	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%	24 hours after the emergence from anesthesia
Other	Quality of Recovery	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.	At 48 hours postoperatively and one month after hospital discharge
Primary	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	Pain intensity postoperatively	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%	At 10 minutes after emergence from anesthesia, and 2, 4, 6, 12, 18 and 24 hours after the emergence from anesthesia
Secondary	Analgesics consumption postoperatively in morphine equivalents	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%	24 hours after the emergence from anesthesia
Secondary	Plasma concentration of TNF-a and IL-6	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.	Before wound infiltration, and at 6 and 24 hours thereafter
Secondary	Plasma concentration of cortisol	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.	Before wound infiltration, and at 6 and 24 hours thereafter