Postoperative Pain and SIRS After Preoperative Analgesia With Clonidine or Levobupivacaine (PPSAPACL)

Postoperative Pain and Systemic Inflammatory Stress Response (SIRS) After Preoperative Analgesia With Clonidine or Levobupivacaine

The purpose of this study was to investigate hypothesis that preoperative administration of epidural clonidine will reduce postoperative pain and systemic inflammatory stress response better than epidural levobupivacaine.

Investigations showed that upregulation of prostaglandin E2 and interleukin-6 at central sites is an important component of surgery induced inflammatory response in patients. Postoperative period is associated with an increased production of cytokines, which augment pain sensitivity. With adequate perioperative pain control it is possible to control central and peripheral inflammatory response to surgery, and influence on patient outcomes. Use of analgetics before the pain stimulus (preventive analgesia) prevent development of neuroplastic changes in central nervous system, and reduces pain. Clonidine is an alpha2-adrenergic agonist with sedative, analgesic and hemodynamic properties. It inhibits transmission of nociceptive stimuli in the dorsal horn of the spinal cord, acting on the inhibitory descending pathways. According to recent experimental investigations clonidine lowers proinflammatory cytokine level, and prevents hypersensitization acting through adrenoreceptors alpha-2A. Levobupivacaine is a long-acting local anesthetic, S-enantiomer of bupivacaine, with identical anesthetic potency. When administered intraperitoneally or by local infiltration of operation site, levobupivacaine produced analgesia and reduction of proinflammatory cytokines. Investigations of epidural and intrathecal levobupivacaine provide evidence for improved postoperative analgesia with reduced analgesic consumption. But, it remains unknown if that analgesia is sufficient enough to blockade inflammatory stress response during perioperative time.We want to investigate and compare analgesic and immunomodulation efficacy of this two frequently used analgesics.

clonidine, levobupivacaine, preoperative analgesia, postoperative pain, systemic inflammatory stress response, epidural analgesia, Anesthetics, Local

Clonidine is an alpha2-adrenergic agonist with sedative, analgesic and hemodynamic properties. It inhibits transmission of nociceptive stimuli in the dorsal horn of the spinal cord, acting on the inhibitory descending pathways.

Levobupivacaine is long-acting local anesthetic, S-enantiomer of bupivacaine, with identical anesthetic potency.

clonidine [Catapres®, Boehringer Ingelheim, Germany], levobupivacaine [Chirocaine®, Abbott S.p.A., Italy]

One hour prior to skin incision, on epidural catheter, patients received 5 µg/kg of clonidine [Catapres®, Boehringer Ingelheim, Germany], 7 mL of 0.25% levobupivacaine [Chirocaine®, Abbott S.p.A., Italy] or 7 mL of saline.The study was designed to compare clonidine and levobupivacaine, and than both with the control group, in order to asses their analgesic and immunomodulation efficacy.

Inclusion Criteria: colorectal resection surgery patients preoperative risk of anesthesia and operation, ASA (American Society of Anesthesiologists) physical status I or II Exclusion Criteria: diabetes mellitus renal insufficiency liver insufficiency autoimmune disease corticosteroid and immunosuppressive use operation time exceeding six hours

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