Perineural Dexmedetomidine for Ulnar Nerve Block.

Does Perineural Dexmedetomidine Prolong the Duration of an Ulnar Nerve Block When Controlling for Possible Systemic Effects?

The aim of this trial is to investigate if dexmedetomidine prolongs the duration of an ulnar nerve block. By using healthy volunteers the investigators can perform bilateral ulnar nerve blocks and thereby control for a systemic effect to clarify if the effect is actually peripheral or systemic. The investigators hypothesis is that dexmedetomidine as an adjunct to a local anaesthetic prolongs the duration of a peripheral nerve block by a peripheral mechanism.

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Drug: Dexmedetomidine perineurally; Drug: Ropivacaine 5mg/ml; Drug: Dexmedetomidine systemically; Drug: Isotonic saline; Drug: Ropivacaine 7.5mg/ml

Detailed Description

Background:

Efficient pain management promoting mobilization and convalescence is essential in an ideal perioperative course. Regional nerve blocks are a central element in postoperative regimes for many patients and it is therefore important that these nerve blocks are both long lasting and efficient. This trial will investigate whether it is possible to optimize the postoperative pain management when adding dexmedetomidine to the local anaesthetic ropivacaine in peripheral nerve blocks.

The prolonging effect of using dexmedetomidine as adjunct in peripheral nerve blocks have been investigated in several studies. However, it remains uncertain whether the effect is mediated by a systemic-, a peripheral- or a combined systemic/peripheral mechanism. In this trial the adjuvating effect of dexmedetomidine will be investigated using an ulnar nerve block.

Method:

The participants will attend two trial days.

On one trial day the volunteers will receive bilateral ulnar nerve blocks. In one arm they will receive the local anaesthetic ropivacaine 4ml 5mg/ml and placebo (saline) and in the other arm ropivacaine 4ml 5mg/ml and dexmedetomidine 100μg. The dexmedetomidine administered perineurally is absorbed and redistributed and will influence the two nerve blocks equally systemically. On the other trial day the participants will receive ropivacaine 4ml 5mg/ml and placebo (saline) and in the other arm ropivacaine 4ml 7.5mg/ml and placebo (saline). The allocation is blinded to volunteer and investigator.

In this setup we therefore have a perineural- and a systemic dexmedetomidine group and also a placebo group , and a group testing if higher doses of local anesthetics will prolong the duration of a nerve block.

The duration of the nerve block will be measured by 3 different tests: pinprick, temperature test (alcohol) and Pain during tonic heat stimulation. All tests are validated within pain research.

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Køge, Denmark, 4600
    • Recruiting
    • Department of Anesthesiology Zealand University Hospital
    • Contact: Jakob H Andersen, MD; Phone Number: 004560610666; Email: JAHEA@regionsjaelland.dk
    • Principal Investigator: Jakob H Andersen, MD
    • Sub-Investigator: Frederik Vilhelmsen
    • Sub-Investigator: Anja Geisler

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must understand the protocol fully and sign the written in-formed consent.
• ASA 1-2
• BMI > 18 to < 30
• For fertile women: safe contraceptives for the last month and a nega-tive urin HCG.

Exclusion Criteria:

• Participants unable to cooperate in the trial.
• Participants unable to speak or read Danish
• Allergy to study medication.
• Alcohol consumption >21 units for men and >14 for women per week
• Daily intake of prescription painkillers within the last 4 weeks.
• Over the counter painkillers during the last 48 hours.
• Neuromuscular defects or wounds on the arms or hands preventing test performance.
• Diabetes Mellitus
• 2. degree heart block
• Sick sinus node.
• For fertile women a positive urine HCG

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Perineural dexmedetomidine; Ulnar nerve block 4ml ropivacaine 5mg/ml + 1ml 100ug/ml dexmedetomidine perineurally	Drug: Dexmedetomidine perineurally; Dexmedetomidine is added perineurally on one side and will influence the nerve block perineurally on this side. Dexmedetomidine is also absorbed and redistributed systemically and will influence the opposite ulnar nerve block systemically.; Other Names: Dexdor; Drug: Ropivacaine 5mg/ml; Ropivacaine is used in 5mg/ml in the perineural, systemic and placebo nerve blocks.; Other Names: Naropine
Active Comparator: Systemic dexmedetomidine; Ulnar nerve block 4ml ropivacaine 5mg/ml + 1ml isotonic saline (placebo) perineurally + 100ug dexmedetomidine systemically (absorbed and redistributed from the opposite ulnar nerve block)	Drug: Ropivacaine 5mg/ml; Ropivacaine is used in 5mg/ml in the perineural, systemic and placebo nerve blocks.; Other Names: Naropine; Drug: Dexmedetomidine systemically; Dexmedetomidine administered perineurally on one side is absorbed and redistributed systemically and will influence the opposite ulnar nerve block systemically.; Other Names: dexdor; Drug: Isotonic saline; placebo (saline) is administered perineurally in all but the perineural group.; Other Names: Placebo
Placebo Comparator: Placebo; Ulnar nerve block 4ml ropivacaine 5mg/ml + 1ml isotonic saline (placebo) perineurally	Drug: Ropivacaine 5mg/ml; Ropivacaine is used in 5mg/ml in the perineural, systemic and placebo nerve blocks.; Other Names: Naropine; Drug: Isotonic saline; placebo (saline) is administered perineurally in all but the perineural group.; Other Names: Placebo
Active Comparator: High dose Ropivacaine; Ulnar nerve block 4ml ropivacaine 7.5mg/ml + 1ml isotonic saline (placebo) perineurally	Drug: Isotonic saline; placebo (saline) is administered perineurally in all but the perineural group.; Other Names: Placebo; Drug: Ropivacaine 7.5mg/ml; In the high dose ropivacaine group a ropivacaine concentration of 7.5mg/ml is used.; Other Names: Naropine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in duration of sensory nerve block assessed by mechanical discrimination (pinprick) between perineural dexmedetomidine and placebo	Duration of sensory nerve block measured by mechanical discrimination (pinprick) defined as time from block performance (removal of the needle) until the needle feels sharp again.	0-36 hours
Difference in duration of sensory nerve block assessed by mechanical discrimination (pinprick) between systemic dexmedetomidine and placebo	Duration of sensory nerve block measured by mechanical discrimination (pinprick) defined as time from block performance (removal of the needle) until the needle feels sharp again.	0-36 hours
Difference in duration of sensory nerve block assessed by mechanical discrimination (pinprick) between systemic dexmedetomidine and perineural dexmedetomidine	Duration of sensory nerve block measured by mechanical discrimination (pinprick) defined as time from block performance (removal of the needle) until the needle feels sharp again.	0-36 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in duration of sensory nerve block assessed by mechanical discrimination (pinprick) between high dose ropivacaine and placebo	Duration of sensory nerve block measured by mechanical discrimination (pinprick) defined as time from block performance (removal of the needle) until the needle feels sharp again.	0-36 hours
Difference in duration of sensory nerve block assessed by temperature discrimination between perineural dexmedetomidine and placebo	Duration of sensory nerve block measured by temperature discrimination defined as time from block performance (removal of the needle) until the stimulation with an alcohol swab feels cold again.	0-36 hours
Difference in duration of sensory nerve block assessed by temperature discrimination between systemic dexmedetomidine and placebo	Duration of sensory nerve block measured by temperature discrimination defined as time from block performance (removal of the needle) until the stimulation with an alcohol swab feels cold again.	0-36 hours
Difference in duration of sensory nerve block assessed by temperature discrimination between systemic dexmedetomidine and perineural dexmedetomidine	Duration of sensory nerve block measured by temperature discrimination defined as time from block performance (removal of the needle) until the stimulation with an alcohol swab feels cold again.	0-36 hours
Difference in duration of sensory nerve block assessed by temperature discrimination between high dose ropivacaine and placebo	Duration of sensory nerve block measured by temperature discrimination defined as time from block performance (removal of the needle) until the stimulation with an alcohol swab feels cold again.	0-36 hours
Difference in duration of sensory nerve block assessed by pain during tonic heat stimulation between perineural dexmedetomidine and placebo	Duration of sensory nerve block measured by pain during tonic heat stimulation defined as time from block performance (removal of the needle) until a thermode heated to 45C for 30 seconds elicits a painful response again (VAS>0)	0-36 hours
Difference in duration of sensory nerve block assessed by pain during tonic heat stimulation between systemic dexmedetomidine and placebo	Duration of sensory nerve block measured by pain during tonic heat stimulation defined as time from block performance (removal of the needle) until a thermode heated to 45C for 30 seconds elicits a painful response again (VAS>0)	0-36 hours
Difference in duration of sensory nerve block assessed by pain during tonic heat stimulation between perineural dexmedetomidine and systemic dexmedetomidine	Duration of sensory nerve block measured by pain during tonic heat stimulation defined as time from block performance (removal of the needle) until a thermode heated to 45C for 30 seconds elicits a painful response again (VAS>0)	0-36 hours
Difference in duration of sensory nerve block assessed by pain during tonic heat stimulation between high dose ropivacaine and placebo	Duration of sensory nerve block measured by pain during tonic heat stimulation defined as time from block performance (removal of the needle) until a thermode heated to 45C for 30 seconds elicits a painful response again (VAS>0)	0-36 hours
Difference in duration of motor nerve block assessed by maximum voluntary isometric contraction between perineural dexmedetomidine and placebo	Duration of motor nerve block measured by maximum voluntary isometric contraction is defined as time from block performance (removal of the needle) until fifth finger abduction maximal voluntary isometric contraction (MVIC) > 75% of baseline value, or the participant indicates return of normal motor funktion.	0-36 hours
Difference in duration of motor nerve block assessed by maximum voluntary isometric contraction between systemic dexmedetomidine and placebo	Duration of motor nerve block measured by maximum voluntary isometric contraction is defined as time from block performance (removal of the needle) until fifth finger abduction maximal voluntary isometric contraction (MVIC) > 75% of baseline value, or the participant indicates return of normal motor funktion.	0-36 hours
Difference in duration of motor nerve block assessed by maximum voluntary isometric contraction between systemic dexmedetomidine and perineural dexmedetomidine	Duration of motor nerve block meassured by maximum voluntary isometric contraction is defined as time from block performance (removal of the needle) until fifth finger abduction maximal voluntary isometric contraction (MVIC) > 75% of baseline value, or the participant indicates return of normal motor funktion.	0-36 hours
Difference in duration of motor nerve block assessed by maximum voluntary isometric contraction between high dose ropivacaine and placebo	Duration of motor nerve block measured by maximum voluntary isometric contraction is defined as time from block performance (removal of the needle) until fifth finger abduction maximal voluntary isometric contraction (MVIC) > 75% of baseline value, or the participant indicates return of normal motor funktion.	0-36 hours
Difference in onset of sensory nerve block assessed by mechanical discrimination (pinprick) between perineural dexmedetomidine and placebo	Onset of sensory nerve block assessed by mechanical discrimination (pinprick) is defined as time from block performance (removal of the needle) until the needle stops feeling sharp.	0-36 hours
Difference in onset of sensory nerve block assessed by mechanical discrimination (pinprick) between systemic dexmedetomidine and placebo	Onset of sensory nerve block assessed by mechanical discrimination (pinprick) is defined as time from block performance (removal of the needle) until the needle stops feeling sharp.	0-36 hours
Difference in onset of sensory nerve block assessed by mechanical discrimination (pinprick) between perineural dexmedetomidine and systemic dexmedetomidine	Onset of sensory nerve block assessed by mechanical discrimination (pinprick) is defined as time from block performance (removal of the needle) until the needle stops feeling sharp.	0-36 hours
Difference in onset of sensory nerve block assessed by mechanical discrimination (pinprick) between high dose ropivacaine and placebo	Onset of sensory nerve block assessed by mechanical discrimination (pinprick) is defined as time from block performance (removal of the needle) until the needle stops feeling sharp.	0-36 hours

Collaborators and Investigators

• Sponsor: Zealand University Hospital
• Investigators: Principal Investigator: Jakob H Andersen, M.D., Department of Anesthesiology, Zealand University Hospital

Publications and helpful links

General Publications

• Andersen JH, Jaeger P, Grevstad U, Estrup S, Geisler A, Vilhelmsen F, Dahl JB, Laier GH, Ilfeld BM, Mathiesen O. Systemic dexmedetomidine is not as efficient as perineural dexmedetomidine in prolonging an ulnar nerve block. Reg Anesth Pain Med. 2019 Mar;44(3):333-340. doi: 10.1136/rapm-2018-100089. Epub 2019 Jan 23.

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2017
• Primary Completion (Anticipated): January 1, 2018
• Study Completion (Anticipated): April 1, 2018

Study Registration Dates

• First Submitted: July 17, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 19, 2017

Study Record Updates

• Last Update Posted (Actual): July 31, 2017
• Last Update Submitted That Met QC Criteria: July 26, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: volunteers
• Additional Relevant MeSH Terms: 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; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Anesthetics, Local; Dexmedetomidine; Ropivacaine
• Other Study ID Numbers: REG-158-2016; 2016-004883-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No