鞘内吗啡、右美托咪定或两者与布比卡因联合用于行大型腹部癌症手术患者的免疫抑制作用。

Immunosuppressive Effect of Intrathecal Morphine, Dexmedetomidine, or Both in Combination with Bupivacaine on Patients Undergoing Major Abdominal Cancer Surgery.

机构信息

Anesthesia, Intensive Care, and Pain Management Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

Oncologic Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

出版信息

Pain Physician. 2022 Nov;25(8):555-567.

PMID:36375185

Abstract

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.

摘要

背景

围手术期免疫系统受损对癌症患者具有重要的临床意义。尽管阿片类药物具有免疫抑制作用，但它仍常用于鞘内或硬膜外腔治疗术后疼痛。此外，鞘内给予右美托咪定可延长术后疼痛的镇痛效果；它可显著影响围手术期患者的免疫功能。

目的

研究鞘内给予吗啡、右美托咪定或两者联合布比卡因对癌症手术患者细胞免疫和细胞因子产生的影响。

研究设计

前瞻性随机临床试验。

设置

南埃及癌症研究所，艾斯尤特大学。

方法

90 名患者被随机分配接受鞘内注射吗啡 0.5mg（M 组，n=30）、右美托咪定 0.5µg/kg（D 组，n=30）或吗啡 0.5mg 联合右美托咪定 0.5µg/kg（MD 组，n=30）；所有组均在注射药物中加入 2mL 布比卡因 0.5%。在术前（T0）、术后即刻（T1）、术后 4 小时（T2）和术后 24 小时（T3）采集血液样本，以测量 CD3、CD4、CD4/CD8 和 CD16+56（NK）、白细胞介素（IL）-1β（IL-1β）、IL-6、IL-10 和肿瘤坏死因子-α（TNF-α）。

结果

在所有 3 个研究组中，术后 24 小时内细胞免疫（CD3、CD4、CD8、CD4/CD8、CD16+56）显著降低，M 组与 MD 组和 D 组相比，降低更为显著。关于炎症介质，与 MD 组和 D 组相比，M 组在术后前 24 小时内 IL-10 和 IL-1β显著降低，而在同一时期，MD 组和 D 组的 IL-6 显著降低。TNF-α在 3 个研究组中的 T1 和 T2 时明显升高，然后在 T3 时降低，但与术前水平无统计学差异。