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

NCT01594047 | Completed Results

• 1 other identifier: metadone
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 1

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.

Conditions

Post Operative Pain; Hyperalgesia

Keywords

hyperalgesia; Patient controlled analgesia; morphine; methadone; ketamine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Pain Intensity Measured by a Numeric Rating Scale (NRS)

  24 and 48 hours after surgery

• Opioid Consumption

  48 hours

Study Arms (4)

zero/morphine

NO INTERVENTION

Patient received a standard balance anaesthesia and morphine for post operative pain.

ketamine/morphine

EXPERIMENTAL

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

zero/metadone

EXPERIMENTAL

Methadone PCA

Drug: Methadone PCA

ketamine/methadone

EXPERIMENTAL

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; Drug: Methadone PCA

Interventions

ketamine infusion DRUG

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

Also known as: hyperalgesia-blocker

ketamine/methadone; ketamine/morphine

Methadone PCA DRUG

Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)

Also known as: hyperalgesia-blocker

ketamine/methadone; zero/metadone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients undergoing open colo-rectal surgery

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Related Publications (1)

• Tognoli E, Proto PL, Motta G, Galeone C, Mariani L, Valenza F. Methadone for postoperative analgesia: contribution of N-methyl-D-aspartate receptor antagonism: A randomised controlled trial. Eur J Anaesthesiol. 2020 Oct;37(10):934-943. doi: 10.1097/EJA.0000000000001217.

  PMID: 32516227 DERIVED

MeSH Terms

Conditions

Pain, Postoperative; Hyperalgesia

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Somatosensory Disorders; Sensation Disorders; Nervous System Diseases

Limitations and Caveats

We chose to analyse mechanical static punctuate hyperalgesia along three lines lateral to the surgical wound, as it is the most common test used to characterise the effect of ketamine and others NMDAr blockers on neuroplasticity in surgical patients. We are aware that there is increasing evidence that the quantitative sensory testing may be more effective and specific in detecting and defining hyperalgesia, both in acute and chronic settings.

Results Point of Contact

• Title: Tognoli Emiliano MD
• Organization: Fondazione IRCCS Istituto nazionale dei Tumori

Emiliano.Tognoli@istitutotumori.mi.it

+39 0223902282

Study Officials

• Emiliano Tognoli

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: medical doctor

Study Record Dates

• First Submitted: May 5, 2012
• First Posted: May 8, 2012
• Study Start: December 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: August 1, 2014
• Last Updated: October 1, 2025
• Results First Posted: October 2, 2023

Record last verified: 2025-09

Locations

IT (1)