Premedication with Intranasal Dexmedetomidine in Sedation of Patients Undergoing Total Knee Arthroplasty (TKADEX)

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.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Knee Osteoarthritis
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Placebo

Detailed Description

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 numerical rating scale, NRS, min 0, max 100, higher scores mean worse outcome) is moderate or intense (NRS>30) after paracetamol and naproxen.

Postoperative pain (NRS) and opioid consumption (mg) will be measured and analysed together with intraoperative sedative used (mg, midazolam and/or fentanyl allowed).

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland
    • Perioperative Services, Intensive Care and Pain Therapy, Turku University Hospital and University of Turku

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The patient is scheduled for elective unilateral total knee arthroplasty (TKA) under spinal anesthesia
2. Fluent skills in finnish language (to understand the given information and to be able to give informed consent and communicate with the study personnel)
3. Age between 35 and 80 years
4. Weight between 50 and 100 kg
5. American Society of Anesthesiologists status 1-3
6. Written informed consent from the patient

Exclusion Criteria:

1. A previous history of intolerance to the study drug or related compounds and additives
2. Disease or condition affecting patient's ability to give written informed consent
3. Existing or recent disease possible affecting absorption, distribution, metabolism, excretion or response to the study drug
4. 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)
5. Preoperative systolic blood pressure <110 mmHg
6. Chronic use of strong opioids, pregabalin, gabapentin, amitriptyline or duloxetine
7. Participation in any other study concomitantly or within one month prior to the entry into this study
8. Clinically significant abnormal findings in physical examination or laboratory screening
9. Pregnancy or breastfeeding
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DEX-group; intranasal dexmedetomidine 1 µg/kg	Drug: Dexmedetomidine; Intranasal dexmedetomidine 1µg/kg will be administered 30min before the induction of anesthesia using a LMA MAD Nasal-device; Other Names: Dexdor
Placebo Comparator: PLACEBO-group; intranasal saline 10 µL/kg	Drug: Placebo; 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.; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change in numerical rating scale (NRS 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

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

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Suvi-Maria Tiainen, MD, Turku University Hospital, University of Turku

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2022
• Primary Completion (Actual): September 15, 2023
• Study Completion (Actual): January 20, 2025

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: April 21, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: intranasal; dexmedetomidine; multimodal analgesia
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Hypnotics and Sedatives; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Dexmedetomidine
• Other Study ID Numbers: TKADEX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No