Modulation of Remifentanil-induced Postinfusion Hyperalgesia

Phase 4

Completed

• Conditions: Hyperalgesia, Secondary
• Interventions: Drug: Ketorolac and remifentanil; Drug: Parecoxib and remifentanil; Other: Placebo; Drug: Remifentanil

• Registration Number: NCT00785863
• Lead Sponsor: Ullevaal University Hospital

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.

Study Timeline

• Status Verified: 2008-11
• Study First Submitted: 2008-11-04
• Study First Submitted QC: 2008-11-04
• Study First Posted: 2008-11-05
• Study Start: 2008-12
• Primary Completion: 2009-04
• Study Completion: 2009-04
• Last Update Submitted: 2011-06-30
• Last Update Posted: 2011-07-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 16

Inclusion Criteria

• Healthy volunteers

Exclusion Criteria

• Allergy to the drugs used in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Ketorolac and remifentanil	Ketorolac and remifentanil	-
Parecoxib and remifentanil	Parecoxib and remifentanil	-
Placebo	Placebo	-
Remifentanil	Remifentanil	-

Primary Outcome Measures

Name	Time	Method
H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi.	during the study

Secondary Outcome Measures

Name	Time	Method
HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi.	During the study

Trial Locations

Locations (1)

Ullevaal University Hospital; 🇳🇴 Oslo, Norway