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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Double Blind, Placebo Controlled Study for the Study of the Effectiveness of Perioperative Analgesia in Phantom and Stump Pain

Conditions
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Phantom Limb Pain

Intervention / Treatment
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* Procedure: perioperative epidural catheter


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 82 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>perioperative epidural analgesia | Procedure: perioperative epidural catheter<br>* 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)<br>|
| Active Comparator: 2<br>Iv PCA Fentanyl preoperative, Epidural analgesia postoperative | Procedure: perioperative epidural catheter<br>* 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)<br>|
| Active Comparator: 3<br>perioperative IV PCA Fentanyl, epidural anesthesia | Procedure: perioperative epidural catheter<br>* 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)<br>|
| Active Comparator: 4<br>perioperative IV PCA Fentanyl general anesthesia | Procedure: perioperative epidural catheter<br>* 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)<br>|
| Placebo Comparator: 5<br>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<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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