Intrathecal Morphine Versus Morphine-dexmedetomidine Combination for Postoperative Pain Control After Total Knee Replacement
Condition: Intrathecal Morphine; Intrathecal Morphine-dexmedetomidine Combination; Postoperative Pain Control; Total Knee Replacement
MeSH terms: Pain, Postoperative
Study type: Interventional

Summary: 
      Total knee replacement is one of the most painful orthopedic surgical procedures. Patients
      who undergo total knee replacement are usually older and have limited cardiac and pulmonary
      reserves. The increased sensitivity of elderly patients to drugs makes it necessary to choose
      postoperative analgesia agents and methods that have minimal side effects.

      Intrathecal injection of morphine to provide postoperative analgesia during the initial 24-h
      after the operation is a widely used technique, however, opioid therapy is limited because of
      the side effects (hypotension, pruritus, nausea, urinary retention, respiratory depression)
      and intolerance.

      Alpha-2 adrenergic agonists (clonidine and dexmedetomidine) have pharmacologic
      characteristics (sedation, hypnosis, anxiolysis, sympatholytic, and analgesia) that make them
      suitable as adjuvants to multimodal analgesia.

      Their anti-nociceptive effect is attributed to the stimulation of a2- adrenoceptors located
      in the central nervous system.

      The rationale for combining analgesics that produce similar therapeutic effects or
      synergistic interactions is to accentuate the analgesic efficacy and decrease the side
      effects by permitting dose reduction of each agent. Human studies on the antinociceptive
      effects of co-administrated intrathecal morphine (ITM) and dexmedetomidine in postoperative
      pain are still few.

      On the other hand, Abdel-Ghaffar et al., results do not support improved analgesia with the
      combination of intrathecal morphine and dexmedetomidine, despite the absence of significant
      adverse effects.

      We hypothesized that the addition of dexmedetomidine to ITM would improve the quality of
      perioperative pain control and decrease the side effects of postoperative systemic opioid
      use.
    

Detailed description: 
      105 patients, aged >50 years, with ASA Physical Status Class II and III, scheduled for TKR
      under spinal anesthesia will be included in this study.

      105 Patients will be randomly allocated into three equal groups (35 patients each):

        -  Group morphine (35 patients): patients will be received given 0.5% heavy bupivacaine
           (3.5 ml) plus 0.1 mg of morphine.

        -  Group morphine-Dex (35 patients): patients will be received given 0.5% heavy bupivacaine
           (3.5 ml) plus 0.1 mg of morphine plus 5 mcg of dexmedetomidine.

      Group Dex (35 patients): patients will be received given 0.5% heavy bupivacaine (3.5 ml) plus
      5 mcg of dexmedetomidine

      Measurements:

        1. Demographic data as age, BMI, ASA status, duration of surgery

        2. During surgery, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart
           rate (HR) will be recorded at the 1st, 5th, 15th, 30th, and 60th minutes.

        3. Postoperative pain severity assessed by the visual analog score for pain at rest
           (ranging from 0 to 10, where 0 no pain and 10 maximum pain) will be evaluated
           postoperatively at 30 min and 2, 4, 6, 12, and 24 h postoperative. Accordingly, the
           patient is requested to verbally express his degree of pain using this scale. Patients
           with the visual analog score≥ 4 will be received 3 mg morphine IV and will be recorded.
           Patients who complained of pain (the visual analog score< 3) and needed analgesics will
           be treated intravenous infusion every six to eight hours with Diclofenac Na(75mg).

        4. The total dose of morphine used postoperatively will be observed and recorded for the
           1st, 2nd, 6th, 12th, and 24th postoperative hours.

        5. The period from the moment the intrathecal injection will be made postoperatively until
           the first analgesic became necessary will be recorded

        6. Any recorded postoperative complication as sedation, nausea and vomiting, respiratory
           depression.

        7. The patient's level of sedation will be assessed at the same time points using Ramsay
           Sedation Scale (score 3-4 mean adequate sedation). (17)
    

Intervention name(s): Dexmedetomidine; Morphine; Dexmedetomidine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Group morphine-Dex (35 patients): patients will be received given 0.5% heavy bupivacaine (3.5 ml) plus 0.1 mg of morphine plus 5 mcg of dexmedetomidine.; Group morphine (35 patients): patients will be received given 0.5% heavy bupivacaine (3.5 ml) plus 0.1 mg of morphine.; Group Dex (35 patients): patients will be received given 0.5% heavy bupivacaine (3.5 ml) plus 5 mcg of dexmedetomidine.
Other intervention name(s): morphine
Intervention MeSH terms: Dexmedetomidine; Morphine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention