Dexmedetomidine Intra Venous Arthroplasty

Intravenous dexmedetomidine is a drug used in reanimation with sedative, anxiolytic and sympatholytic properties. Recent studies showed useful properties for anaesthesia : decrease of morphine consumption after a various type of surgery, sedative effect on patients under regional anaesthesia, prolongation of central or peripheral regional block. Dose-ranging study for intravenous dexmedetomidine showed that 2 µg/kg is an effective dose to prolong interscalene block. This study aims to determine if intravenous dexmedetomidine at 2 µg/kg allows a longer analgesic duration after a quadri-block (femoral, subgluteal sciatic, obturator and alateral cutaneous nerve blocks) with ropivacaine 0.32% for total knee replacement under regional anaesthesia.

This is a prospective, randomized, double-blind controlled trial with two parallel groups. All patients undergoing total knee arthroplasty under regional anaesthesia and sedation will be screened for inclusion in the protocol. In the pre-anaesthesia room, after the implementation of classical monitoring with an oxygen mask and a peripheral venous catheter, all patients will receive an antibioprophylaxy according to SFAR recommendations and injection of 10 mg of IV dexamethasone.

The patients will be then randomized in 2 groups:

* Dexmedetomidine group (Dex group) : Two administrations of 1 microg/kg of Dexdor® in 250 ml of sodium chloride during 30 min. The first injection will be performed in the pre-anaesthesia unit and the second in the operating room with a free interval of 60 min between the beginning of the 2 injections.
* Control group : Two administrations of 250 ml of sodium chloride during 30 min according to the same former recommendations.

Under ultrasonography guidance and with in-plan technic, a quadri-block (femoral, sciatic subgluteal, obturator and lateral cutaneous nerve blocks) with a maximum of 225 mg of ropivacaine diluted in 70 ml of sodium chloride (ropivacaine 0.32 %) will be performed. If needed, sedation with 5 µg of sufentanil and 1 to 2 mg of midazolam will be performed before regional anaesthesia.

In the operating room, under close monitoring, the patients will receive a bolus of Ketamine 0.3 mg/kg and a propofol bolus of 0.3 mg/kg followed by a continuous infusion if needed. The total dose of propofol used for sedation, conversion to general anaesthesia or any complications concerning anaesthesia or dexmedetomidine (hypotension, bradycardia, arrhythmia, advance cardiac block) will be collected. Postoperative analgesia will be reached with IV 1 g paracetamol and 100 mg ketoprofen starting during surgery and following in the surgical ward by oral paracetamol 1 g / 6 h and oral ibuprofen 400 mg / 8 h. In post anaesthesia care unit all the patients will have oxycodone titration if pain VRS (verbal rating scale) \>3 and oxycodone 10 mg/ 4 h in the surgical ward if pain VRS (verbal rating scale) \>3.

Eligibility Criteria:
Inclusion Criteria:

* 18 years and older
* Patients undergoing elective total knee arthroplasty
* Consent for participation
* Affiliation to the french social security system
* For women of child bearing potential without contraception, beta-HCG negative result

Exclusion Criteria:

* Chronic pain syndrome requiring preoperative morphine use (class 3)
* Hypersensitivity to dexmedetomidine
* Allergy to nonsteroidal anti-inflammatory drugs
* Contraindication for locoregional anesthesia
* Patient wishing a general anesthesia
* Weight\>100 kg, obstructive sleep apnea syndrome or gastrooesophageal reflux complicating the sedation with spontaneous ventilation
* Known acute ischemic disease
* Severe liver failure
* Uncontrolled low blood pressure
* Heart rate \< 60 bpm
* Advanced cardiac block (Level 2 or 3) except if pacemaker
* Pregnant or breastfeeding women
* Communication difficulties or neuropsychiatric disorder
* Patients under protection of the adults (guardianship, curators or safeguard of justice)