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

Sponsor

University Hospital Dubrava (Other)

Overall Status

Completed

CT.gov ID

NCT00860899

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.5

Patients Per Site Per Month

Study Details

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

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 :

Dec 1, 2007

Actual Primary Completion Date :

Oct 1, 2008

Actual Study Completion Date :

May 1, 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]

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

Other Names:

clonidine [Catapres®, Boehringer Ingelheim, Germany]

levobupivacaine [Chirocaine®, Abbott S.p.A., Italy]

Outcome Measures

Primary Outcome Measures

postoperative pain level [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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

42 Years to 77 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	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