Effects of Intraoperative Magnesium Sulfate on Perioperative Pain Relief After Spine Surgery
Condition: Analgesia; Pain, Postoperative; Spine Disease
MeSH terms: Spinal Diseases; Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      The treatment of postoperative pain is increasingly based on a multimodal approach and
      although opioids remain the drug of choice, they are often used in combination with other
      analgesics (paracetamol, cyclooxygenase inhibitors or non-steroidal anti-inflammatory drugs)
      and co-analgesic agents (clonidine and anti- NMDA such as ketamine or MgSO4). The rationale
      for combined 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 sensitisation. This mechanism is involved in the
      perception of pain and mainly accounts for its persistence during the postoperative period.

      Although magnesium is not a primary analgesic in itself, it enhances the analgesic actions of
      more established analgesics as an adjuvant agent. Magnesium produces a voltage-dependent
      block of NMDA receptors and has been reported to have analgesic properties that might be
      related to this inhibiting property. Magnesium sulfate has been reported to be effective in
      perioperative pain treatment and in blunting somatic, autonomic and endocrine reflexes
      provoked by noxious stimuli.

      When magnesium was used intraoperatively, many researchers reported that it reduced the
      requirement for anesthetics and/or muscle relaxants.

      Intraoperative use of magnesium sulfate can also be associated with decreased incidences of
      nausea and vomiting after surgery, which could have been due to the lower consumption of
      anesthetics (i.e. volatile agents), rather than any antiemetic effect of magnesium sulfate.
      In addition, perioperative i.v. administration of magnesium sulfate has another advantageous
      effect, as it decreases the incidence of shivering by up to 70-90%. Previous studies
      investigating the analgesic efficacy of MgSO4 in general, gynaecological, ophthalmic and
      orthopaedic surgery have shown conflicting results, while reports regarding spine surgery are
      extremely limited.

      Our study was designed to investigate the effects of MgSO4 on perioperative pain relief and
      postoperative quality of recovery after lumbar laminectomy surgery.
    

Detailed description: 
      Each participant will receive standard monitoring (ECG, SpO2, capnography, SBP, oesophageal
      temperature, accelerography) and an intravenous access will be established. The level of
      anaesthesia will be monitored with the bispectral index (BIS), targeting to a BIS level
      40-50.

      Group M patients will receive intravenous magnesium sulfate 20 mg/kg over a 15-min period
      before induction of anaesthesia and 20 mg/kg/h by continuous i.v. infusion during the
      operation. Group C will be given isotonic solution of 0.9% in the same volume as the study
      drug.

      A standard anesthesia protocol will be applied involving propofol 2mg/kg (iv) and fendanyl 2
      μg/kg (iv). Cis-atracurium 0.2 mg/kg (iv) will be given to facilitate endotracheal
      intubation. Anaesthesia will be maintained with air 50% and oxygen 50%, and desflurane
      adjusted to achieve a target BIS between 40 and 50. Remifentanil will be added to the
      anesthesia regimen as needed.

      Hemodynamic parameters will be recorded upon

        -  Baseline: Before the administration of the tested drug

        -  T5: 5 minutes after the administration of the tested drug

        -  T10: 10 minutes after the administration of the tested drug

        -  T15: 15 minutes after the administration of the tested drug

        -  Ts: surgical incision

        -  T30: 30 minutes after the administration of the tested drug

        -  T45: 45 minutes after the administration of the tested drug

        -  T60: 60 minutes after the administration of the tested drug

        -  T90: 90 minutes after the administration of the tested drug

        -  T120: 120 minutes after the administration of the tested drug

        -  T180: 180 minutes after the administration of the tested drug

      Low arterial blood pressure during surgery defined as a mean blood pressure value < 50 mmHg
      will be treated by a bolus of 5 mg ephedrine administered intravenously or phenylephirne civ
      for persistent hypotension.

      Also, time to accelerography recording indicating the appropriateness of neuromuscular block
      for intubation, mean expired desflurane concentration (from 30 min after skin incision to the
      end of surgery), boluses of ephedrine and total intraoperative remifentanil consumption will
      be recorded.

      Postoperative analgesic protocol will involve paracetamol 1 mg (iv), lornoxicam 8mg (iv) and
      morphine 3 mg (upon request).

      Postoperatively pain assessment will be performed by Visual Analogue Scale (VAS), Verbal
      Rating Scale (VRS) and Numerical Rating Scale (NRS) at emergence from anesthesia and 2, 4, 6,
      and 24 h in the study period. 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), will be recorded at emergence and
      thereafter, throughout the study period. Finally, patients' global satisfaction will be
      assessed the first day after surgery using a 5-grade scale (1= worst discomfort ever
      experienced in their life and 5= totally satisfied during the immediate postoperative
      period).
    

Intervention name(s): Magnesium Sulfate; Isotonic saline 0.9%
Intervention type(s): Drug; Drug
Intervention description(s): Intravenous magnesium sulfate 20 mg/kg in 100ml isotonic saline 0.9% over a 15-min period before induction of anesthesia and 20 mg/kg/h by continuous i.v. infusion until surgery completion.; Isotonic saline 0.9% 100ml over a 15-min period before induction of anesthesia and thereafter continuous i.v. infusion until surgery completion in dosage identical to magnesium sulfate group.
Intervention MeSH terms: Magnesium Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: magnesium; analgesia; pain score; opioid consumption; spine surgery