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

September 18, 2025 updated by: Emiliano Tognoli, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

not desired

Study Type

Interventional

Enrollment (Actual)

113

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: zero/morphine
Patient received a standard balance anaesthesia and morphine for post operative pain.
Experimental: ketamine/morphine
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
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
Other Names:
  • hyperalgesia-blocker
Experimental: zero/metadone
Methadone PCA
Drug: Methadone PCA
Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
Other Names:
  • hyperalgesia-blocker
Experimental: ketamine/methadone

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
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
Other Names:
  • hyperalgesia-blocker
Drug: Methadone PCA
Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
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
Time Frame: 24 and 48 hours after surgery

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)
Time Frame: 24 and 48 hours after surgery
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
Time Frame: 48 hours
Cumulative opioid consumption at 48 hours from surgery ( end of the study)
48 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Investigators

  • Principal Investigator: Emiliano Tognoli, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2009

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

May 5, 2012

First Submitted That Met QC Criteria

May 7, 2012

First Posted (Estimated)

May 8, 2012

Study Record Updates

Last Update Posted (Estimated)

October 1, 2025

Last Update Submitted That Met QC Criteria

September 18, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • metadone

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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