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PAIN MEDICINE

The Effect of Epidural Clonidine on Perioperative Cytokine Response, Postoperative Pain, and Bowel Function in Patients Undergoing Colorectal Surgery

Ching-Tang Wu, MD^*, Shu-Wen Jao, MD, Cecil O. Borel, MD, Chun-Chang Yeh, MD^*, Chi-Yuan Li, MD^*, Chueng-He Lu, MD^*, and Chih-Shung Wong, MD PhD^*

Departments of *Anesthesiology and Colon and Rectal Surgery, Tri-Service General Hospital and National Defense Medical Center, National Defense University, Taipei, Taiwan, Republic of China; and Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina

Address correspondence and reprint requests to Ching-Tang Wu, MD, Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, National Defense University, #325, Section 2, Chenggung Rd., Neihu 114, Taipei, Taiwan, Republic of China. Address e-mail to wuchingtang{at}msn.com

The postoperative period is associated with an increased production of cytokines, which augment pain sensitivity. We investigated the hypothesis that epidural clonidine premedication and postoperative patient-controlled epidural analgesia (PCEA) including clonidine would decrease the release of proinflammatory (interleukin (IL)-6, IL-1ß, IL-8, and tumor necrosis factor (TNF)-) and antiinflammatory (IL-1 receptor antagonist (RA)) cytokines in patients who underwent elective colorectal surgery and that they would provide better postoperative analgesia. Forty patients were randomly assigned to 1 of 2 groups of 20 each: the control group received normal saline 10 mL, whereas the clonidine group received epidural clonidine 150 µg diluted with 9 mL of normal saline 30 min before surgery. Venous blood samples for cytokine levels were obtained before induction, at the end of surgery, and after surgery at 12 and 24 h. After surgery, the clonidine group patients received PCEA with morphine (0.1 mg/mL) and clonidine (1.5 µg/mL) in 0.2% ropivacaine 100 mL, whereas control group patients received only PCEA morphine and ropivacaine. Patients in the clonidine group exhibited longer PCEA trigger times, lower pain scores at rest and while coughing, less morphine consumption, and a faster return of bowel function throughout the 72-h postoperative observation period, compared with patients in the control group. For patients in the clonidine group, production of IL-1RA, IL-6, and IL-8 was significantly less increased at the end of the surgical procedure and at 12 and 24 h after surgery. However, the concentrations of IL-1ß and TNF- were not significantly increased.

IMPLICATIONS: The combination of preoperative epidural clonidine with postoperative patient-controlled analgesia morphine, ropivacaine, and clonidine provides preemptive analgesia and results in reduced pain intensity, diminished opioid consumption, a faster return of bowel function, and attenuated production of interleukin (IL)-6, IL-8, and IL-1 receptor antagonist (RA) in the perioperative period, without any complications. The lower levels of IL-6, IL-8, and IL-1RA could diminish pain transmission and central nervous system sensitization, thus improving postoperative pain and allowing a faster return of bowel function.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999