Perioperative Opioid-induced Hyperalgesia and Its Prevention With Ketamine and Methadone

Study Overview
=================
Brief Summary
-----------------
Background: In perioperative period inhibition of N-Methyl-D-Aspartate receptor prevents opioid-induced hyperalgesia and reduce postoperative opioid requirement after abdominal surgery. Methadone is both a µ-opioid receptor agonist like Morphine and a N-Methyl-D-Aspartate antagonist. Study Aim. To evaluate the efficacy of intraoperative Ketamine and postoperative Methadone analgesia in preventing opioid-induced hyperalgesia after abdominal surgery.

Detailed Description
-----------------
not desired

Official Title
-----------------
Perioperative Opioid-induced Hyperalgesia and Its Prevention With Ketamine and Methadone

Conditions
-----------------
Post Operative Pain, Hyperalgesia

Intervention / Treatment
-----------------
* Drug: ketamine infusion
* Drug: Methadone PCA


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients undergoing open colo-rectal surgery Exclusion Criteria: ASA status more than II, history of chronic pain, ischemic heart disease or chronic pulmonary disease, allergy to any drugs used in the protocol. Body Max Index more than 35.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: zero/morphine<br>Patient received a standard balance anaesthesia and morphine for post operative pain. | |
| Experimental: ketamine/morphine<br>Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery. | Drug: ketamine infusion<br>* Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery<br>* Other names: hyperalgesia-blocker;|
| Experimental: zero/metadone<br>Methadone PCA | Drug: Methadone PCA<br>* Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)<br>* Other names: hyperalgesia-blocker;|
| Experimental: ketamine/methadone<br>Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery. Methadone administered by a PCA system (dose 2 mg, lock-out 12min.). | Drug: ketamine infusion<br>* Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery<br>* Other names: hyperalgesia-blocker;Drug: Methadone PCA<br>* Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)<br>* Other names: hyperalgesia-blocker;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Extent of Hyperalgesia Area Proximal to Surgical Wound | Hyperalgesia is determined by stimulating with a won Fray hair N°16 along three lines at a right angle to the top, middle, and bottom sides of the surgical incision. Each line starts from the edge of the abdomen to the surgical incision. Stimulation continue from the edge toward the surgical incision until the patients reported a worsening in sensation The distance from the incision to where sensation change was measured. The mean of the three assessments was used as a measure of the extent of the hyperalgesia area. | 24 and 48 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity Measured by a Numeric Rating Scale (NRS) | A Numerical Rating Scale (NRS) from 0 to 10 is used as a measure of pain intensity. Zero indicates the absence of any pain and 10 the worse pain never felt. | 24 and 48 hours after surgery | 
| Opioid Consumption | Cumulative opioid consumption at 48 hours from surgery ( end of the study) | 48 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hyperalgesia, Patient controlled analgesia, morphine, methadone, ketamine