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

NCT ID: NCT04859283

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-10
• Study Completion Date: 2025-01-20

Brief Summary

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

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).

Conditions

Knee Osteoarthritis; Pain, Postoperative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

DEX-group

intranasal dexmedetomidine 1 µg/kg

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type: DRUG

Intranasal dexmedetomidine 1µg/kg will be administered 30min before the induction of anesthesia using a LMA MAD Nasal-device

PLACEBO-group

intranasal saline 10 µL/kg

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

Dexmedetomidine

Intranasal dexmedetomidine 1µg/kg will be administered 30min before the induction of anesthesia using a LMA MAD Nasal-device

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Dexdor; Saline

Eligibility Criteria

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.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Turku University Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Teijo Saari, MD, PhD

Professor and Head Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Suvi-Maria Tiainen, MD

Role: PRINCIPAL_INVESTIGATOR

Turku University Hospital, University of Turku

Locations

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

Turku, , Finland

Countries

Finland

References

Tiainen SM, Heinonen H, Koskinen A, Makela S, Laitio R, Loyttyniemi E, Makela K, Saari TI, Uusalo P. Premedication with intranasal dexmedetomidine in patients undergoing total knee arthroplasty under spinal anaesthesia (TKADEX)-a prospective, double-blinded, randomised controlled trial. BJA Open. 2025 Mar 3;13:100382. doi: 10.1016/j.bjao.2025.100382. eCollection 2025 Mar.

Reference Type: DERIVED

PMID: 40114985 (View on PubMed)

Other Identifiers

TKADEX

Identifier Type: -

Identifier Source: org_study_id