Wound Infiltration With Tramadol, Dexmedetomidine, or Magnesium Plus Ropivacaine for Pain Relief After Spine Surgery
Condition: Analgesia; Pain, Postoperative; Spinal Stenosis; Spinal Disease
MeSH terms: Spinal Stenosis; Spinal Diseases; Pain, Postoperative
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Tramadol with ropivacaine; Dexmedetomidine with ropivacaine; Magnesium with ropivacaine; Ropivacaine plus normal saline
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 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.; 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.; 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.; 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 intervention name(s): TR; DR; MR; R
Intervention MeSH terms: Dexmedetomidine; Tramadol; Ropivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: analgesia; pain score; tramadol; dexmedetomidine; magnesium; opioid consumption; spine surgery