Clinical trial NCT00785863: Modulation of Remifentanil-induced Postinfusion Hyperalgesia
Official title: Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib or Ketorolac in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hyperalgesia, Secondary
Keywords: hyperalgesia
remifentanil
ketorolac
parecoxib
COX-1 inhibitor
COX-2 inhibitor
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: University of Oslo
name: Rikshospitalet University Hospital
First posted: 2008-11-05
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteers

Exclusion Criteria:

* Allergy to the drugs used in the study

Primary outcomes:
measure: H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi.
timeFrame: during the study
Secondary outcomes:
measure: HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi.
timeFrame: During the study
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Ullevaal University Hospital
Study officials:
affiliation: Ullevaal University Hospital
name: Harald Lenz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ullevaal University Hospital
name: Johan Raeder, Prof.,MD,PhD
role: STUDY_DIRECTOR
affiliation: Rikshospitalet University Hospital
name: Audun Stubhaug, Prof.,MD,PhD
role: STUDY_DIRECTOR
References: