1. 2022;25;555-567Immunosuppressive Effect of Intrathecal Morphine, Dexmedetomidine, or Both in Combination with Bupivacaine on Patients Undergoing Major Abdominal Cancer Surgery
   Randomized Trial
   Heba Mohammed Elmasry, ., Rania Mohamed Abdelemam, MD, Khaled Mohamed Fares, MD, Sahar Abdel-Baky Mohamed, MD, Shereen Mamdouh Kamal, MD, and Samar Mansour, ..

BACKGROUND: An impaired immune system in the perioperative period has important clinical implications in patients with cancer. Despite the immunosuppressive properties of opioid therapy, it is still commonly utilized in the intrathecal or epidural space for the treatment of postoperative pain. Also, intrathecal dexmedetomidine has extended analgesic efficacy in postoperative pain; it can significantly affect immune function in perioperative patients.

OBJECTIVE: To investigate the effect of intrathecal morphine, dexmedetomidine, or both in combination with bupivacaine on cellular immunity and cytokine production in cancer surgical patients.

STUDY DESIGN: A prospective randomized clinical study.

SETTING: South Egypt Cancer Institute, Assiut University.

METHODS: Ninety patients were randomly assigned to receive intrathecal morphine 0.5 mg (Group M, n = 30), dexmedetomidine 0.5 µg/kg (Group D, n = 30) or morphine 0.5 mg with dexmedetomidine 0.5 µg/kg (Group MD n = 30); 2 mL bupivacaine 0.5% was added to injected drugs in all groups.  Blood samples were collected preoperative (T0), immediate postoperative (T1), 4 hours postoperative (T2), and 24 hours postoperative (T3) for measurement of CD3, CD4, CD4/CD8 and CD16+56(NK), interleukin(IL)-1beta (IL-1beta), IL-6, IL-10 and tumor necrosis factor alpha (TNF-alpha).

RESULTS: A significant reduction in cellular immunity (CD3, CD4, CD8, CD4/CD8, CD 16+56) was noticed in the 24-hour postoperative period in all 3 studied groups, with a marked reduction in Group M in comparison to Group MD and Group D. Regarding inflammatory mediators, IL-10 and IL-1beta  showed significant reduction in Group M in the first 24-hour postoperative period in comparison to Group MD and Group D, while IL-6 was significantly reduced in Group MD and Group D in comparison to Group M in the same period. TNF-alpha was significantly increased postoperative at T1 and T2 in the 3 studied groups, then at T3 it decreased without a statistically significant difference with the preoperative level.

LIMITATIONS: Our study has some limitations, such as the short period of follow-up and lack of postoperative clinical follow-up of patients to discover the association between immunity and patient outcomes.

CONCLUSION: Intrathecal dexmedetomidine has the least immunosuppressive effect than morphine and morphine-dexmedetomidine, in combination with bupivacaine.

KEY WORDS: Cancer surgery, postoperative, intrathecal, morphine, dexmedetomidine, immunity