Modulation of Remifentanil-induced Postinfusion Hyperalgesia
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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 | Intervention | Phase |
|---|---|---|
|
Hyperalgesia, Secondary |
Other: Placebo Drug: Remifentanil Drug: Ketorolac and remifentanil Drug: Parecoxib and remifentanil |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Basic Science |
| Official Title: | Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by Parecoxib or Ketorolac in Humans |
- H0 : Parecoxib prevents remifentanil postinfusion secondary hyperalgesi. Ketorolac does not prevent remifentanil postinfusion secondary hyperalgesi. [ Time Frame: during the study ] [ Designated as safety issue: No ]
- HA : Parecoxib and ketorolac prevent remifentanil postinfusion secondary hyperalgesi. [ Time Frame: During the study ] [ Designated as safety issue: No ]
| Enrollment: | 16 |
| Study Start Date: | December 2008 |
| Study Completion Date: | April 2009 |
| Primary Completion Date: | April 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Placebo Comparator: Placebo |
Other: Placebo
Placebo IV before placebo infusion
Other Name: Placebo
|
| Active Comparator: Remifentanil |
Drug: Remifentanil
placebo IV and remifentanil infusion
Other Name: Ultiva
|
| Active Comparator: Ketorolac and remifentanil |
Drug: Ketorolac and remifentanil
Ketorolac IV and remifentanil infusion
Other Name: Toradol
|
| Active Comparator: Parecoxib and remifentanil |
Drug: Parecoxib and remifentanil
Parecoxib IV and remifentanil infusion
Other Name: Dynastat
|
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| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders 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| Norway | |
| Ullevaal University Hospital | |
| Oslo, Norway, 0407 | |
| 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 |
More Information
No publications provided
| Responsible Party: | Ullevaal University Hospital |
| ClinicalTrials.gov Identifier: | NCT00785863 History of Changes |
| Other Study ID Numbers: | 2008-000904-10 |
| Study First Received: | November 4, 2008 |
| Last Updated: | June 30, 2011 |
| Health Authority: | Norway:National Committee for Medical and Health Research Ethics Norway: Norwegian Medicines Agency Norway: Norwegian Social Science Data Services Norway: Directorate of Health |
Keywords provided by Oslo University Hospital:
|
hyperalgesia remifentanil ketorolac |
parecoxib COX-1 inhibitor COX-2 inhibitor |
Additional relevant MeSH terms:
|
Hyperalgesia Somatosensory Disorders Sensation Disorders Neurologic Manifestations Nervous System Diseases Signs and Symptoms Ketorolac Ketorolac Tromethamine Parecoxib Remifentanil Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents |
Physiological Effects of Drugs Pharmacologic Actions Anti-Inflammatory Agents Therapeutic Uses Antirheumatic Agents Cyclooxygenase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Central Nervous System Agents Analgesics, Opioid Central Nervous System Depressants Hypnotics and Sedatives Anesthetics, Intravenous Anesthetics, General Anesthetics |
ClinicalTrials.gov processed this record on June 17, 2013