Premedication With Intranasal Dexmedetomidine in Sedation of Patients Undergoing Total Knee Arthroplasty

Study Overview
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Brief Summary
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This study aims to find out if preoperatively given dexmedetomidine is effective analgesic adjuvant for treating postoperative pain in patients undergoing elective total knee arthroplasty (TKA). Another aim is to determine if premedication with intranasal dexmedetomidine could provide sufficient sedation to alleviate anxiety during TKA.

Detailed Description
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Patients undergoing total knee arthroplasty (TKA) under spinal anesthesia often request sedation to alleviate anxiety. Dexmedetomidine may be ideally suited to provide sedation during surgery as it offers sedation and analgesia without causing significant respiratory depression. Furthermore, dexmedetomidine has beneficial synergistic interactions with opioids and sedative drugs. Altogether 80 patients scheduled for elective unilateral TKA under spinal anesthesia will be included in the prospective, randomized and controlled parallel-group study. Patients will be randomized into two groups, forty patients in each group. All patients will receive preoperatively 1000 mg of oral paracetamol as premedication. One group receives a single bolus dose of intranasal 1 ug/kg dexmedetomidine (DEX group) and the other group receives euvolemic dose (10 µL/kg) of saline (PLACEBO-group). Spinal anesthesia will be performed using bupivacaine (5 mg/mL) using 2.0-2.5 mL dose, the amount depending on the clinical judgement of the anesthesiologist responsible for the patient. If patient needs additional analgesic after spinal anesthesia, 50 µg dose of intravenous fentanyl or 3-5 mg of intravenous midazolam may be administered intraoperatively. Postoperative pain management in the surgical ward includes oral paracetamol 1000 mg every 8 hours, and from the first postoperative day onwards patients receive oral naproxen/esomeprazole 500/20 mg twice a day. Oral oxycodone (5-10 mg) will be used, if the pain (measured with visual rating scale, VAS, min 0, max 100, higher scores mean worse outcome) is moderate or intense (VAS>30) after paracetamol and naproxen. Postoperative pain (VAS) and opioid consumption (mg) will be measured and analysed together with intraoperative sedative used (mg, midazolam and/or fentanyl allowed).

Official Title
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Premedication With Intranasal Dexmedetomidine in Sedation of Patients Undergoing Total Knee Arthroplasty

Conditions
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Knee Osteoarthritis, Pain, Postoperative

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is scheduled for elective unilateral total knee arthroplasty (TKA) under spinal anesthesia Fluent skills in finnish language (to understand the given information and to be able to give informed consent and communicate with the study personnel) Age between 35 and 80 years Weight between 50 and 100 kg American Society of Anesthesiologists status 1-3 Written informed consent from the patient Exclusion Criteria: A previous history of intolerance to the study drug or related compounds and additives Disease or condition affecting patient's ability to give written informed consent Existing or recent disease possible affecting absorption, distribution, metabolism, excretion or response to the study drug History of severe cardiac disease (valvular insufficiency, severe left ventricular dysfunction) or abnormal ECG rhythm (bradycardia < 50/min, 2nd or 3rd degree atrioventricular-block, pacemaker) Preoperative systolic blood pressure <110 mmHg Chronic use of strong opioids, pregabalin, gabapentin, amitriptyline or duloxetine Participation in any other study concomitantly or within one month prior to the entry into this study Clinically significant abnormal findings in physical examination or laboratory screening Pregnancy or breastfeeding Use of any drugs known to cause enzyme induction or inhibition for a period of 30 days prior to the study, use of any natural products (including grapefruit products) for at least 14 days prior to the study and caffeine containing products for at least 24 hours prior to the study. The use of regular doses of paracetamol is allowed.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DEX-group<br>intranasal dexmedetomidine 1 µg/kg | Drug: Dexmedetomidine<br>* Intranasal dexmedetomidine 1µg/kg will be administered 30min before the induction of anesthesia using a LMA MAD Nasal-device<br>* Other names: Dexdor;|
| Placebo Comparator: PLACEBO-group<br>intranasal saline 10 µL/kg | Drug: Placebo<br>* Intranasal saline (10 µL/kg) will be administered 30 min before the induction of anesthesia using a LMA MAD NasalTM -device. The dose is euvolemic to 1 µg/mL dexmedetomidine.<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in visual rating scale (VAS 0-100 mm, min 0, max 100, higher score means worse outcome) | Number of patients with visual rating scale value under 30 mm | 24 hours | 
| Change in intraoperative sedatives (mg) administered | Change from baseline midazolam and fentanyl consumption (mg) | From anesthesia induction to the end of surgery. | 
| Change in opioid consumption (mg) postoperatively | Change from baseline opioid consumption (mg) postoperatively at 24 hours | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change (mmHg) in hemodynamic parameter (blood pressure) | More than 30% change from the baseline in the blood pressure (measured in mmHg) | 24 hours | 
| Change (%) in respiratory parameter (peripheral oxygen saturation, SpO2) | More than 10% change from the baseline in the SpO2 (measured %) | 24 hours | 
| Number of patients with adverse events as a measure of safety and tolerability | Number of patients with adverse events as a measure of safety and tolerability | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intranasal, dexmedetomidine, multimodal analgesia