Intrathecal Morphine Versus Morphine-dexmedetomidine Combination for Postoperative Pain Control After Total Knee Replacement: A Randomized Controlled Trial

• Status: Not yet recruiting
• Trial end date: 2023-01-30

Summary

Postoperative pain is the acute inflammatory pain that begins with the trauma of surgery and ends with the healing of the tissue. This pain has deleterious effects on organ systems and may lead to pathophysiological changes in the pulmonary/cardiovascular system. (1) The treatment of postoperative pain is crucial for homeostasis. Additionally, it has a significant impact not only on lowering the cost of treatment but also on shortening the length of both patient's recovery time and, consequently, of her hospital stay. (2) 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. (3) The spinal cord is an important neuronal structure for pain transmission. Nociception is attenuated by local opioids, norepinephrine, and serotonin.(4) The interaction of these systems at the spinal cord level may affect anti-nociception. Opioids administered in the intrathecal or epidural space are widely used for postoperative and chronic nociceptive pain secondary to cancers. (5) Intrathecal injection of morphine to provide postoperative analgesia during the initial 24-h after the operation is a widely used technique,(6) however, opioid therapy is limited because of the side effects (hypotension, pruritus, nausea, urinary retention, respiratory depression) and intolerance.(7) 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. (8) Their anti-nociceptive effect is attributed to the stimulation of a2- adrenoceptors located in the central nervous system. Dexmedetomidine is a highly selective and potent a2-adrenoceptor agonist. Its intrathecal administration leads to anti-nociceptive effects, although it does have some undesired side effects (e.g., hypotension, bradycardia, and sedation). (9, 10) Animal studies demonstrated that there is a synergistic interaction between opioid and alpha-2 adrenergic antinociception in the rat spinal cord. The intrathecal administration of morphine and dexmedetomidine in combination will be found to produce a synergistic effect state magnitude and that the mu, not delta-opioid receptor subtype is responsible for such synergism.(11) The rationale of 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 (12, 13). Human studies on the antinociceptive effects of co-administrated intrathecal morphine (ITM) and dexmedetomidine in postoperative pain are still few.

Liu et al. results revealed that intrathecal administration of dexmedetomidine with morphine reduced the morphine consumption in patients with refractory cancer pain (14) In Huang et al., report, they present a case of a 53-year-old female patient with refractory cancer pain receiving a large dose of intrathecal morphine, whose pain and pain-related depression was significantly improved with the addition of intrathecal DEX. (15) 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.(16) 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.

• Phase: N/A

Details

• Lead Sponsor: Tanta University
• Treatments: Dexmedetomidine; Morphine