Optimized Perioperative Analgesia Reduces the Prevalence and the Intensity of Phantom Pain in Lower Limb Amputation

• ClinicalTrials.gov Identifier: NCT00443404
• Recruitment Status: Completed
• First Posted: March 6, 2007
• Last Update Posted: November 6, 2011
• Sponsor: University of Patras
• Information provided by: University of Patras

Study Description

Brief Summary:

Severe pre-amputation pain is associated with phantom pain development, and phantom pain models assign major importance to central and peripheral nervous system changes related to pre-amputation pain. Several interventions have been evaluated for phantom pain prevention, including continuous brachial plexus blockade5, intravenous6 or epidural ketamine administration, postoperative perineural ketamine/clonidine infusion8 and oral gabapentin9, but their true effect remains unclear.

Condition or disease	Intervention/treatment	Phase
Phantom Limb Pain	Procedure: perioperative epidural catheter	Phase 2; Phase 3

Detailed Description:

In a prospective, randomized, double-blind trial, 65 patients undergoing elective lower limb amputation were assigned to one of five analgesic regimens. Patients in groups 1-4 had lumbar epidural catheter placed 48 hours before amputation, and received epidural bupivacaine/fentanyl or saline infusion before and/or after amputation. Patients receiving epidural saline also had IV Fentanyl Patient-Control Analgesia, whereas patients receiving epidural analgesia also had IV saline. Group 5 (control) received IM meperidine and oral codeine/acetaminophen. VAS and McGill Pain Questionnaire (MPQ) scores (for ischemic, phantom and stump pain) were recorded starting 48 hours before, continuing until 48 hours after amputation, and at 4 days, 10 days, 1 and 6 months after amputation. Phantom and stump pain intensity and frequency were the main study endpoints.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Double Blind, Placebo Controlled Study for the Study of the Effectiveness of Perioperative Analgesia in Phantom and Stump Pain
• Study Start Date: December 2003
• Actual Primary Completion Date: May 2008
• Actual Study Completion Date: May 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1; perioperative epidural analgesia	Procedure: perioperative epidural catheter; Perioperative epidural catheter in groups 1-4. Pre- and postoperative epidural analgesia in group 1. Preoperative IV PCA Fentanyl and postoperative epidural analgesia in group 2. Perioperative IV PCA Fentanyl in groups 2,3. IM meperidine p.o. codeine/acetaminophen, IV acetaminophen and IV parecoxib in group 5 (control)
Active Comparator: 2; Iv PCA Fentanyl preoperative, Epidural analgesia postoperative	Procedure: perioperative epidural catheter; Perioperative epidural catheter in groups 1-4. Pre- and postoperative epidural analgesia in group 1. Preoperative IV PCA Fentanyl and postoperative epidural analgesia in group 2. Perioperative IV PCA Fentanyl in groups 2,3. IM meperidine p.o. codeine/acetaminophen, IV acetaminophen and IV parecoxib in group 5 (control)
Active Comparator: 3; perioperative IV PCA Fentanyl, epidural anesthesia	Procedure: perioperative epidural catheter; Perioperative epidural catheter in groups 1-4. Pre- and postoperative epidural analgesia in group 1. Preoperative IV PCA Fentanyl and postoperative epidural analgesia in group 2. Perioperative IV PCA Fentanyl in groups 2,3. IM meperidine p.o. codeine/acetaminophen, IV acetaminophen and IV parecoxib in group 5 (control)
Active Comparator: 4; perioperative IV PCA Fentanyl general anesthesia	Procedure: perioperative epidural catheter; Perioperative epidural catheter in groups 1-4. Pre- and postoperative epidural analgesia in group 1. Preoperative IV PCA Fentanyl and postoperative epidural analgesia in group 2. Perioperative IV PCA Fentanyl in groups 2,3. IM meperidine p.o. codeine/acetaminophen, IV acetaminophen and IV parecoxib in group 5 (control)
Placebo Comparator: 5; IV PCA with saline 0.9% and sc saline 0.9%in the L3-L4 area. IM meperidine, po codeine/acetaminophen, IV acetaminophen and IV parecoxib	Procedure: perioperative epidural catheter; Perioperative epidural catheter in groups 1-4. Pre- and postoperative epidural analgesia in group 1. Preoperative IV PCA Fentanyl and postoperative epidural analgesia in group 2. Perioperative IV PCA Fentanyl in groups 2,3. IM meperidine p.o. codeine/acetaminophen, IV acetaminophen and IV parecoxib in group 5 (control)

Outcome Measures

Primary Outcome Measures :

1. VAS and McGill PRI(R)2 scores for phantom and stump pain are recorded 48 and 24 hours before, and 4 and 10 days, 1 and 6 months after amputation. Phantom and stump pain intensity are the endpoints of the study. [ Time Frame: six months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 82 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age >18, Visual Analog. Scale (VAS) pain score >70mm which was frequent or continuous one week before scheduled major (above or below knee) amputation, and patient consent.

Exclusion Criteria:

• No written patient consent
• Age < 18 years
• Age > 82 years
• Antiplatelet medication
• Mental status not acceptable
• Exclusion criteria were age >85
• Emergency amputation
• Ipsilateral re-amputation
• Foot or toe amputation
• Inability to complete a detailed pain questionnaire
• History of chronic pain or substance abuse
• Active psychiatric disease requiring treatment
• Any contraindication to epidural catheter placement (anticoagulation, anti-platelet medications, previous lumbar spine surgery).

Contacts and Locations

Locations

Greece

Patras, Greece

Sponsors and Collaborators

University of Patras

Investigators

• Principal Investigator: Diamanto N. Aretha, MD; University of Patras, School of Medicine, University Hospital of Patras, Rion, 26500, Department of Anaesthesiology and Critical Care Medicine
• Study Director: Menelaos Karanikolas, MD, MPH; University of Patras, School of Medicine, University Hospital of Patras, Rion, 26500, Department of Anaesthesiology and Critical Care Medicine
• Study Chair: Kriton S Filos, MD Professor; University of Patras, School of Medicine, University Hospital of Patras, Rion, 26500, Department of Anaesthesiology and Critical Care Medicine
• Principal Investigator: Georgia Monantera, MD; University of Patras, School of Medicine, University Hospital of Patras, Rion, 26500, Department of Anaesthesiology and Critical Care Medicine
• Study Director: Ioannis Tsolakis, MD Professor; University of Patras, School of Medicine, University Hospital of Patras, Rion, 26500, Department of Surgery

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Karanikolas M, Aretha D, Tsolakis I, Monantera G, Kiekkas P, Papadoulas S, Swarm RA, Filos KS. Optimized perioperative analgesia reduces chronic phantom limb pain intensity, prevalence, and frequency: a prospective, randomized, clinical trial. Anesthesiology. 2011 May;114(5):1144-54. doi: 10.1097/ALN.0b013e31820fc7d2.

• Responsible Party: Diamanto Aretha, University Hospital of Patras
• ClinicalTrials.gov Identifier: NCT00443404
• Other Study ID Numbers: phantom pain-UPatras; There are no secondary Id
• First Posted: March 6, 2007
• Last Update Posted: November 6, 2011
• Last Verified: September 2009

Keywords provided by University of Patras:

phantom; amputation; analgesia; pain; preemptive; perioperative; lower limb amputation; intensity of phantom limb pain; preemptive analgesia reduces phantom pain; perioperative analgesia reduces phantom pain; Severe Phantom Limb Pain (VAS>70 mm); resistant to medical treatment one week before amputation

Additional relevant MeSH terms:

Phantom Limb; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain