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

• ClinicalTrials.gov Identifier: NCT00860899
• Recruitment Status: Completed
• First Posted: March 12, 2009
• Last Update Posted: November 17, 2011
• Sponsor: University Hospital Dubrava
• Information provided by (Responsible Party): Jasminka Persec, MD, PhD, University Hospital Dubrava

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Analgesia; Pain; Systemic Inflammatory Stress Response	Drug: clonidine, levobupivacaine	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Postoperative Pain and Systemic Inflammatory Stress Response (SIRS) After Preoperative Analgesia With Clonidine or Levobupivacaine
• Study Start Date: December 2007
• Actual Primary Completion Date: October 2008
• Actual Study Completion Date: May 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: clonidine; 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.	Drug: clonidine, levobupivacaine; 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.; Other Names: clonidine [Catapres®, Boehringer Ingelheim, Germany]; levobupivacaine [Chirocaine®, Abbott S.p.A., Italy]
Active Comparator: levobupivacaine; Levobupivacaine is long-acting local anesthetic, S-enantiomer of bupivacaine, with identical anesthetic potency.	Drug: clonidine, levobupivacaine; 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.; Other Names: clonidine [Catapres®, Boehringer Ingelheim, Germany]; levobupivacaine [Chirocaine®, Abbott S.p.A., Italy]

Outcome Measures

Primary Outcome Measures :

1. postoperative pain level [ Time Frame: 1 h before surgery, 1 h after start of the surgery, 1 h , 6 h , 12 h and 24 h after surgery ]

Secondary Outcome Measures :

1. systemic inflammatory stress response [ Time Frame: 1 hour before surgery, 1 hour after start of the surgery, 1 h , 6 h , 12 h and 24 h after surgery ]

Eligibility Criteria

• Ages Eligible for Study: 42 Years to 77 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Croatia

University Hospital Dubrava

Zagreb, Croatia, 10000

Sponsors and Collaborators

University Hospital Dubrava

Investigators

• Principal Investigator: Jasminka Persec, MD PhD; Anesthesiology, Resuscitation and Intensive Care Medicine Clinic, University Hospital Dubrava
• Study Chair: Zoran Persec, MD Msc; Department of Urology, University Hospital Dubrava
• Study Director: Ino Husedzinovic, Prof. MD PhD; Anesthesiology, Resuscitation and Intensive Care Medicine Clinic, University Hospital Dubrava

More Information

Publications:

1. Buvanendran A, Kroin JS, Berger RA, Hallab NJ, Saha C et al.Anesthesiology 104(3):403-410, 2006. 2. Katz J. Curr Opin Anaesthesiol 15(4):435-441, 2002. 3. Carr DB. Anesthesiology 85(6): 1498-1499, 1996. 4. Lavand'homme PM, Eisenach JC. Pain 105(1-2):247-254, 2003. 5. Nader ND, Ignatowski TA, Kurek CJ, Knight PR, Spengler RN. Anesth Analg 93(2):363-369, 2001. 6. Wu CT, Jao SW, Borel CO, Yeh CC, Li CY, Lu CH et al. Anesth Analg 99(2):502-509, 2004. 7. Novak-Jankovic V, Bovill JG, Ihan A, Osredkar J. Eur J Anaesthesiology 17(1):50-56, 2000. 8. Kim MH, Hahn TH. Anesth Analg 90(6):1441-1444, 2000. 9. Louizos AA, Hadzilia SJ, Leandros E, Kouroukli IK, Georgiou LG et al. Surg Endosc 19(11):1503-1506, 2005. 10. Meisner M, Brunkhorst FM, Reith HB, Schmidt J, Lestin HG et al. Clin Chem Lab Med 38(10):989-995, 2000. 11. Naeini AE, Montazerolghaem S. Saudi Med J 27(3):422-424, 2006. 12. Sarbinowski R, Arvidsson S, Tylman M, Oresland T, Bengtsson A. Acta Anaesthesiol Scand 49(2):191-196, 2005.

• Responsible Party: Jasminka Persec, MD, PhD, MD PhD, University Hospital Dubrava
• ClinicalTrials.gov Identifier: NCT00860899
• Other Study ID Numbers: 1860; 1861
• First Posted: March 12, 2009
• Last Update Posted: November 17, 2011
• Last Verified: November 2011

Keywords provided by Jasminka Persec, MD, PhD, University Hospital Dubrava:

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

Additional relevant MeSH terms:

Agnosia; Pain, Postoperative; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pain; Clonidine; Levobupivacaine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antihypertensive Agents; Sympatholytics; Autonomic Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anesthetics, Local; Anesthetics; Central Nervous System Depressants