A Randomized, Double-blind Study to Compare the Efficacy of Intravenous Dexmedetomidine Infusion, Oral Gabapentin and Their Combination on Postoperative Analgesia in Cancer Patients Undergoing Modified Radical Mastectomy

Introduction:

Breast cancer is the most common malignant tumour among females with an incidence of about 2.1 million women every year. It is the greatest cancer-related mortality among women approximately 15% of all cancer mortality. In addition to that, Egypt follows the international incidence with breast cancer being the most common malignancy among females with 18,660 patients each year.¹ Modified Radical Mastectomy (MRM) is one of the main surgical treatments of breast cancer. Accordingly, it is an account for 31% of all breast surgery cases.² The common modality for anaesthesia for MRM is general anaesthesia with or without regional blocks.³

Nearly about 40-60% of breast surgery patients develop severe acute postoperative pain.⁴ Opioids are the current best standard drugs for postoperative pain relief, however, exposure to large doses of opioids leads to multiple side effects like prolonged sedation, respiratory depression, nausea, and vomiting.⁵ Moreover, the use of opioids inhibits cell-mediated immunity with an increase in tumour angiogenesis, cell migration, and metastasis in addition to the progression of the cell cycle. Therefore, plans other than opioids are recommended without losing proper and effective analgesia, especially in breast cancer patients who are more sensitive to develop opioid tolerance and addiction.⁶ So it became a necessity to find safe analgesic techniques for these patients by using different techniques like adjuvant therapies or multimodal analgesia by combining different drugs with different mechanisms of action together to increase the quality of postoperative analgesia and to decrease the need for high doses of systemic opioids and their related side addiction.⁷'⁸

Alpha-2 agonists including clonidine and dexmedetomidine have been used perioperatively. Dexmedetomidine is different from clonidine in two properties. It has more affinity for the alpha-2 receptor (8 times that of clonidine) and is easier to titrate.⁹ Also, dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that has sedative, analgesic, anaesthetic-sparing properties without causing any respiratory depression.¹⁰ Dexmedetomidine can be a good anaesthetic premedication because of its sympatholytic effect to attenuate the sympathetic stress response to perioperative stresses like laryngoscopy and intubation.¹¹ The analgesic effect provided by dexmedetomidine is mediated mainly through interaction at alpha-2a within the spinal cord, where drug activity attenuates nociceptive signal transduction. And although dexmedetomidine when given alone has been documented to reduce pain, it has a synergistic or additive effect when combined with opioids.¹²

Another promising drug for postoperative pain management is gabapentin. It binds to the α-2 δ subunit of voltage-gated calcium channels and preventing the release of nociceptive neurotransmitters like glutamate, substance P, and noradrenaline.¹³ Evidence suggests that, in addition to its effectiveness as an analgesic for patients with neuropathic pain and chronic pain syndromes, gabapentin also provides effective postoperative analgesia when given before an operation.¹⁴'¹⁵ Therefore the combination of IV dexmedetomidine and oral gabapentin due to their analgesic effects would be more effective in reducing postoperative analgesic consumption and providing prolonged postoperative analgesia after a modified radical mastectomy.