Modulation of Remifentanil-induced Postinfusion Hyperalgesia

Ullevaal University Hospital

Status and phase: Completed; Phase 4

Conditions: Hyperalgesia, Secondary

Treatments: Drug: Parecoxib and remifentanil; Drug: Ketorolac and remifentanil; Other: Placebo; Drug: Remifentanil

Study type: Interventional

Funder types: Other

Identifiers

NCT00785863

2008-000904-10

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: Male

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy volunteers

Exclusion criteria

• Allergy to the drugs used in the study

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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16 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Other: Placebo

Remifentanil

Active Comparator group

Treatment:

Drug: Remifentanil

Ketorolac and remifentanil

Active Comparator group

Treatment:

Drug: Ketorolac and remifentanil

Parecoxib and remifentanil

Active Comparator group

Treatment:

Drug: Parecoxib and remifentanil