Modulation of Remifentanil-induced Postinfusion Hyperalgesia

Sponsor

Ullevaal University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00785863

Collaborator

University of Oslo (Other), Rikshospitalet University Hospital (Other)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In addition to alleviate pain there is growing evidence that µ-opioids enhance pain. This problem is known as opioid induced hyperalgesia(OIH).The NMDA receptor is involved in opioid induced hyperalgesia it may be possible to block OIH by cyclooxygenase inhibitors. This has been demonstrated with parecoxib, a COX-II inhibitor, in a experimental pain model.Both COX-1 and COX-2 are expressed in the spinal cord. It would be of interest to investigate whether a COX-1 preferring inhibitor like ketorolac also can reduce opioid induced hyperalgesic in this experimental pain model.

Condition or Disease	Intervention/Treatment	Phase
Hyperalgesia, Secondary	Other: Placebo Drug: Remifentanil Drug: Ketorolac and remifentanil Drug: Parecoxib and remifentanil	Phase 4

Detailed Description

Remifentanil is an fast acting opioid which has become very popular to use during surgery.

There are studies, both experimental 1-3 and clinical 4;5, which indicate that remifentanil after end of infusion trigger enhanced pain experience and enhanced opioid consumption postoperatively.

Therefore it is important to look at possibilities to block this enhanced pain experience (opioid induced hyperalgesia - OIH). Ketamin has demonstrated to block this effect 5;6 through the NMDA receptor. Unfortunately ketamin has some seriously side-effects like hallucinations, and is therefore not suitable in ordenary clinical use.

Recently, it has been demonstrated that parecoxib (a COX-2 inhibitor) can prevent remifentanil-induced postinfusion hyperalgesia in a study on healthy volunteers.7 COX-2 inhibitors have some disadvantages because of the longterm adverse effects like cardiac arrest. Therefore it would be of interest to look at a COX-1 preferring NSAID, like ketorolac, to see if also non-selective NSAIDs can partly block remifentanil-induced postinfusion hyperalgesia.

To investigate this and to provoke pain and secondary hyperalgesia we use an intradermal electrical pain model which is well established.1;7-9 Detailed description of this model look at reference 7. H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi.

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib or Ketorolac in Humans

Study Start Date :

Dec 1, 2008

Actual Primary Completion Date :

Apr 1, 2009

Actual Study Completion Date :

Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Other: Placebo Placebo IV before placebo infusion
Active Comparator: Remifentanil	Drug: Remifentanil placebo IV and remifentanil infusion Other Names: Ultiva
Active Comparator: Ketorolac and remifentanil	Drug: Ketorolac and remifentanil Ketorolac IV and remifentanil infusion Other Names: Toradol
Active Comparator: Parecoxib and remifentanil	Drug: Parecoxib and remifentanil Parecoxib IV and remifentanil infusion Other Names: Dynastat

Outcome Measures

Primary Outcome Measures

H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi. [during the study]

Secondary Outcome Measures

HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi. [During the study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy volunteers

Exclusion Criteria:

Allergy to the drugs used in the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ullevaal University Hospital	Oslo		Norway	0407

Sponsors and Collaborators

Ullevaal University Hospital
University of Oslo
Rikshospitalet University Hospital

Investigators

Principal Investigator: Harald Lenz, MD, Ullevaal University Hospital
Study Director: Johan Raeder, Prof.,MD,PhD, Ullevaal University Hospital
Study Director: Audun Stubhaug, Prof.,MD,PhD, Rikshospitalet University Hospital