Non-opioid Analgesic Combination With Morphine for Postoperative Analgesia.
- Conditions
- Post Operative Analgesia
- Interventions
- Registration Number
- NCT01882530
- Lead Sponsor
- Rennes University Hospital
- Brief Summary
The combination of different analgesic drugs and/or analgesia techniques is part of the standard management of postoperative analgesia. The analysis of the literature reveals a lack of comparison of the associations of non-opioid analgesic (NOA) with morphine for postoperative analgesia.
The objectives of this study are :
* comparing the morphine sparing effect of different combination of 3 NOA (paracetamol, nefopam, ketoprofen) for postoperative analgesia.
* determining whether the morphine-sparing effect is associated with or without a reduction in the incidence of morphine side effects.
* evaluating the effects of NOA on postoperative hyperalgesia.
- Detailed Description
Since the description of the concept of balanced analgesia in the early 90's, the combination of different analgesic drugs and/or analgesia techniques is part of the standard management of postoperative analgesia. A recent survey conducted in France by Fletcher et al. showed that patients often received one or more NOA associated with an opioid. The benefit and risk of the use of opioids associated with NOA were recently reassessed as part of a formal recommendation of experts and detailed in a recent review. The analysis of the literature reveals a lack of comparison of the combinations of NOA with morphine for postoperative analgesia. For example, paracetamol and morphine in combination does not always allow a significant morphine-sparing effect compared with morphine alone and does not reduce the incidence of morphine side effects. A number of definitive answers has therefore yet to be found: Does NOA -morphine association allow an effective morphine-sparing effect? Is there an interest in prescribing several NOAs in association? If yes, what are the most interesting combinations in terms of morphine-sparing effect and safety?
Another question concerns the effects of NOA on postoperative hyperalgesia. This hyperalgesia, which results from surgery-related inflammation, is increased by consumption of morphine and not only contributes to the overall experience of postoperative pain but also to the chronicisation of postoperative pain. Since in clinical practice, hyperalgesia can be measured using specific tools (Von Frey filament type), our study will evaluate the anti-hyperalgesic effects of NOA on a subgroup of patients enrolled in the centers used to evaluate nociceptive thresholds.
The objectives of this study are :
* comparing the morphine sparing effect of different combination of 3 NOA (paracetamol, nefopam, ketoprofen) for postoperative analgesia.
* determining whether the morphine-sparing effect is associated with or without a reduction in the incidence of morphine side effects.
* evaluating the effects of NOA on postoperative hyperalgesia.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 223
- Adults older than 18 years
- Receiving scheduled surgery requiring the use of a PCA to treat postoperative pain
- Patients with a written informed consent
- Patients with a written informed consent for the sub-study on hyperalgesia (patients in the centers concerned)
- Affiliate to a social security system
- Allergy to morphine, paracetamol, nefopam or ketoprofen or to any of their excipients
- Absorption of morphine and / or NOA within 24 hours before surgery
- Absorption of methadone within 48 hours before surgery
- History of epilepsy
- Renal insufficiency (creatinin clearance <30 ml / min MDRD)
- Hepatic insufficiency
- Severe respiratory insufficiency
- Pregnancy or breastfeeding women
- History of seizures
- Symptomatic urethroprostatic disorders
- Angle-closure glaucoma
- Gastrointestinal, cerebrovascular or other evolving bleedings
- Active peptic ulcer or active gastritis
- Severe heart failure
- History of asthma triggered by taking ketoprofen or similar substances
- Disable adult person under guardianship
- Use of nitrous oxide during anesthesia protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Group N: Nefopam Morphine All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group P: Paracetamol Paracetamol All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group N: Nefopam Nefopam All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group K: Ketoprofen Ketoprofen All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group K: Ketoprofen Morphine All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group NK: nefopam and ketoprofen Ketoprofen All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group NK: nefopam and ketoprofen Morphine All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group PNK: paracetamol, nefopam and ketoprofen Nefopam All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group PNK: paracetamol, nefopam and ketoprofen Ketoprofen All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group PNK: paracetamol, nefopam and ketoprofen Morphine All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group P: Paracetamol Morphine All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group PN: paracetamol and nefopam Paracetamol All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Control group C: Placebo Morphine All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group PK: paracetamol and ketoprofen Paracetamol All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group PN: paracetamol and nefopam Morphine All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group PK: paracetamol and ketoprofen Ketoprofen All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group PK: paracetamol and ketoprofen Morphine All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group PNK: paracetamol, nefopam and ketoprofen Paracetamol All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group PN: paracetamol and nefopam Nefopam All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours. Group NK: nefopam and ketoprofen Nefopam All patients will receive treatment intraoperatively (IV) in 30 minutes, 60 minutes before the end of the intervention, then postoperatively every 6 hours for 48 hours.
- Primary Outcome Measures
Name Time Method Morphine consumption (mg), accumulated over 24 hours, measured by patient controlled analgesia (PCA). Day 1
- Secondary Outcome Measures
Name Time Method Incidence of side effects associated with morphine: nausea, vomiting, sedation, urinary retention, pruritus. Day 3 Global satisfaction (measured after treatment) Day 3 Morphine consumption (mg) measured by patient controlled analgesia (PCA). Day 2, day 3 Incidence of chronic pain assessed by a telephone questionnaire 3 months after surgery (sub-study in 3 centers). Month 3 Area of hyperalgesia measured using a von Frey filament expressed in cm2, 48 hours after surgery (sub-study in 3 centers). Day 2
Trial Locations
- Locations (19)
Marcel Chauvin
🇫🇷Boulogne, France
Xavier Capdevila
🇫🇷Montpellier, France
Hawa Keita-Meyer
🇫🇷Colombes, France
Dominique Fletcher
🇫🇷Garches, France
Jacques Ripart
🇫🇷Nîmes, France
Jean-Xavier Mazoit
🇫🇷Paris, France
Anissa Belbachir
🇫🇷Paris, France
Karim Asehnoune
🇫🇷Nantes, France
Frédéric Aubrun
🇫🇷Lyon, France
Jean-Marc Malinovsky
🇫🇷Reims, France
Marc Gentili
🇫🇷St Grégoire, France
Marc Beaussier
🇫🇷Paris, France
Hervé Bouaziz
🇫🇷Nancy, France
Karine Nouette-Gaulain
🇫🇷Bordeaux, France
Pierre Albaladejo
🇫🇷Grenoble, France
Marc Raucoules
🇫🇷Nice, France
Sébastien Bloc
🇫🇷Quincy sous Sénart, France
Vincent Minville
🇫🇷Toulouse, France
Emmanuel Marret
🇫🇷Paris, France