Can Dexmedetomidine For Procedural Sedation In Knee Arthroplasty Reduce Postoperative Pain? A Randomized Control Study

Dexmedetomidine has been often used for procedural sedation. It has also has been shown to have a pain sparing effect. Therefore the investigators propose that if Dexmedetomidine is used for sedation in total knee replacements done under spinal anesthetic, the patients will have less pain up to 24 hours after the procedure.

Study Overview

• Status: Completed
• Conditions: Total Knee Arthroplasty
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Normal Saline Placebo

Detailed Description

Randomization will occur prior to patient being brought into operating room (by pharmacy or by the anesthesia research coordinator). A third anesthetist not involved in the project will mix up the syringe based on instructions in an opaque envelope, and provide the syringe to the attending anesthetist.

The current standard of care entails patients receiving a midazolam bolus for sedation during the operation. The investigators propose to substitute a syringe of dexmedetomidine or saline to be run as an infusion throughout the case for sedation. A midazolam bolus will be available at anesthetist discretion to achieve a moderate sedation score as defined by the American Society of Anesthesia.

Standardized Medication Protocol

Pre-op:

Tylenol and Naproxen

Spinal:

Marcaine .75%, 1.7cc (12.75mg) Fentanyl 10 micrograms

Sedation

1. st arm- Dexmedetomidine, drawn up into a 50cc syringe of saline, thereby making it 5ug/ml.
2. nd arm- Receives Normal Saline syringe

Plan for bolus of 0.5microgram/kg over 10 minutes, and then infusion of 0.5 microgram/kg/hr (Can be titrated from 0.2-0.7 microgram per kg per hr to achieve moderate sedation as defined by the ASA

Both groups will have a midazolam 0.5mg prn q 5minutes to be used as a rescue to achieve moderate sedation.

Post op- Initial setting of patient-controlled-analgesia pump to be set at morphine 1 mg, lockout of 8 minutes, to be increased to 1.5 mg with lockout of 6 minutes if pain not controlled. The investigators will increase the pump dose by 0.5 mg/dose/1 hr until pain controlled.

Risks The most common treatment-emergent adverse reactions for dexmedetomidine, occurring in 2% of patients in both ICU and procedural sedation studies, include- Hypotension, Bradycardia and Dry mouth. To minimize the risks to participants, an anesthesiologist will always be present in the room while the infusion is running, will monitor the patient, and will be allowed to treat as they see fit any of these risks.

Data Collection Data collection will be performed primarily by Ian Chan, anesthesiology resident.

Primary Outcome:

Total morphine consumption in the first 24 hours

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4P 0W5
      • Regina General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Total Knee arthroplasty American Society of Anesthesiologist score of 1-3 Age 18-85 Elective total knee arthroplasty under spinal anesthetic.

Exclusion Criteria:

• Contraindication to Dexmedetomidine. (second or third degree heart block, renal or hepatic dysfunction) Contraindication to Spinal Anesthetic Pain being treated by opioids prior to operation Contraindication to premedication Previous total knee arthroplasty

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dexmedetomidine arm; Standardized pre-op meds and spinal anesthetic. Once the patient's spinal is performed, patient will receive the following: Start with bolus of 0.5micrgram/kg over 10 minutes, and then infusion of 0.5 microgram/kg/hr Infusion will be stopped after the last staple or suture is performed on the incision. Both groups will have a midazolam 0.5mg prn q 5minutes to be used as a rescue to achieve moderate sedation as defined by ASA.	Drug: Dexmedetomidine
PLACEBO_COMPARATOR: Saline Placebo; Patients will receive the standardized pre-op meds and spinal anesthetic. Once the spinal anesthetic is performed, Patient will receive the same infusion rates as in the Dexmedetomidine arm, however with Normal Saline as a Placebo. midazolam 0.5mg prn q 5minutes to be used as a rescue to achieve moderate sedation.	Drug: Normal Saline Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine Consumption	Patients will be provided with a patient-controlled-analgesia in which they will have morphine available for pain scores greater than 3.	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Time of First Analgesia Request	time of first analgesia request from closure of skin up to 24 hours.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS Scores	Patients will be asked to chart their VAS pain score at the 6, 12 , and 24 hour mark.	6, 12 and 24 hour marks.

Collaborators and Investigators

• Sponsor: University of Saskatchewan
• Investigators: Principal Investigator: Ian A Chan, MD, Department of Anesthesia, University of Saskatchewan, Canada; Principal Investigator: Jurgen Maslany, MD, FRCPC, University of Saskatchewan; Principal Investigator: Kyle Gorman, MD, FRCPC, University of Saskatchewan

Publications and helpful links

General Publications

• Chan IA, Maslany JG, Gorman KJ, O'Brien JM, McKay WP. Dexmedetomidine during total knee arthroplasty performed under spinal anesthesia decreases opioid use: a randomized-controlled trial. Can J Anaesth. 2016 May;63(5):569-76. doi: 10.1007/s12630-016-0597-y. Epub 2016 Jan 29.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: December 29, 2013
• First Submitted That Met QC Criteria: December 30, 2013
• First Posted (ESTIMATE): January 1, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): June 20, 2016
• Last Update Submitted That Met QC Criteria: May 10, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: UofS 13-232