Local Anesthetic Concentration and Nerve Block Duration

Local Anesthetic Concentration and Nerve Block Duration: A Randomized, Blinded Study in Healthy Volunteers

Background: Local anesthetic (LA) concentration and nerve block duration is sparsely described in a heterogenic study mass.

Aim: To investigate the effect of LA concentration on peripheral nerve block duration in healthy volunteers.

Methods: Randomization of 60 healthy volunteers who will receive 1 of 5 different volumes of LA (ropivacaine) using a constant dose.

Primary endpoint: Sensory nerve block defined by insensitivity towards cold.

Study Overview

• Status: Completed
• Conditions: Peripheral Nerve Block
• Intervention / Treatment: Drug: Ropivacaine

Detailed Description

Background:

Important factors for a safe and successful nerve block include volume, dose and concentration of local anesthetic (LA). Knowing the duration of peripheral nerve blocks is important to prevent pain breakthrough. With the advancements in ultrasound (US)-guided nerve block techniques it has been possible to substantially reduce the amount of LA required to perform a successful nerve block. This has reduced the risk of systemic toxicity. However, lowering LA volume may reduce nerve block duration, but the extent of this is sparsely described in a heterogenic study mass.

Diluted and large volumes of LA seem to correlate with nerve block duration. Furthermore, increasing LA concentration seems to increase the level of motor block, but not the block duration. A long-lasting nerve block without dense motor block is preferable for optimized pain control and better opportunities to rehabilitate/ambulate.

Aim:

To investigate the effect of LA concentration on common peroneal nerve block duration in healthy volunteers.

Methods:

Randomization of 60 healthy volunteers who will receive 1 of 5 different volumes of LA (ropivacaine) using a constant dose (10mg).

Primary outcome: Duration of sensory nerve block defined by insensitivity towards cold.

Secondary outcome: Duration of motor nerve block defined by either paresis or paralysis.

Explorative outcomes: Degrees of sensory and motor nerve block; Onset times of sensory and motor nerve block; Length of neural exposure to LA.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Danmark
    • Hillerød, Danmark, Denmark, 3400
      • Nordsjællands Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Male or female from and above 18 years of age
2. ASA classification ≤ II

Exclusion criteria

1. BMI below 18 kg/m2
2. Former surgery to the lower extremity in which intervention is planned and surgery which may have caused neural damage to the common peroneal nerve/affected the sensory distribution area of the common peroneal nerve
3. Peripheral nerve disease
4. Allergy to LA
5. Pregnancy or breastfeeding
6. Enrolment in other investigational drug studies or recent clinical trials that may interfere with this study
7. Habitual use of any kind of analgesic treatment
8. Anatomic abnormalities preventing successful US-guided peripheral nerve catheter insertion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Volume: 2.5 mL; Perineural injection of ropivacaine 10 mg, 2.5 mL. Concentration: Ropivacaine 4 mg/mL.	Drug: Ropivacaine; Perineural injection using a peripheral nerve block catheter and a constant infusion rate (10mL/h); Other Names: Isotonic saline (natriumchloride)
Experimental: Volume: 5 mL; Perineural injection of ropivacaine 10 mg, 5 mL. Concentration: Ropivacaine 2 mg/mL	Drug: Ropivacaine; Perineural injection using a peripheral nerve block catheter and a constant infusion rate (10mL/h); Other Names: Isotonic saline (natriumchloride)
Experimental: Volume: 10 mL; Perineural injection of ropivacaine 10 mg, 10 mL Concentration: Ropivacaine 1 mg/mL	Drug: Ropivacaine; Perineural injection using a peripheral nerve block catheter and a constant infusion rate (10mL/h); Other Names: Isotonic saline (natriumchloride)
Experimental: Volume: 15 mL; Perineural injection of ropivacaine 10 mg, 15mL Concentration: Ropivacaine 0.67 mg/mL	Drug: Ropivacaine; Perineural injection using a peripheral nerve block catheter and a constant infusion rate (10mL/h); Other Names: Isotonic saline (natriumchloride)
Experimental: Volume: 20 mL; Perineural injection of ropivacaine 10 mg, 20mL Concentration: Ropivacaine 0.5 mg/mL	Drug: Ropivacaine; Perineural injection using a peripheral nerve block catheter and a constant infusion rate (10mL/h); Other Names: Isotonic saline (natriumchloride)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of sensory nerve block	Insensitivity towards cold. Testing will start after onset of sensory nerve block and will be done in intervals of 60 minutes hereafter and continue until return of normal sensation.	1-24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of motor nerve block	Paresis or paralysis of ankle dorsiflexion. Testing will start after onset of sensory nerve block and will be done in intervals of 60 minutes hereafter and continue until return of normal sensation.	1-24 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of neural exposure to local anesthetic	Ultrasound-guided measurement of the perineural spread of local anesthetic. From the most distal to the most proximal point. Measured in millimetres.	10 minutes
Onset of sensory nerve block	Insensitivity towards cold. Testing will start 10 minutes after end of LA infusion and continue every 5 minutes until onset is apparent.	10-180 minutes
Onset of motor nerve block	Paresis or paralysis of ankle dorsiflexion. Testing will start 10 minutes after end of LA infusion and continue every 5 minutes until onset of sensory nerve block is apparent.	10-180 minutes
Degree of sensory nerve block	Grading system using a 4-level scale and compared to the contralateral leg: 1) normal; 2) different; 3) warmth; 4) no sensation. Testing will start after onset of sensory nerve block and will be done in intervals of 60 minutes hereafter and continue until return of normal sensation.	1-24 hours
Degree of motor nerve block	Grading system using a 3-level scale and compared to the contralateral leg: 1) normal; 2) paresis; 3) paralysis. Testing will start after onset of sensory nerve block and will be done in intervals of 60 minutes hereafter and continue until return of normal sensation.	1-24 hours

Collaborators and Investigators

• Sponsor: Nordsjaellands Hospital
• Collaborators: Innovation Fund Denmark
• Investigators: Principal Investigator: Claus B Christiansen, MD, Nordsjællands Hospital

Publications and helpful links

General Publications

• Christiansen CB, Madsen MH, Molleskov E, Rothe C, Lundstrom LH, Lange KHW. The effect of ropivacaine concentration on common peroneal nerve block duration using a fixed dose: A randomised, double-blind trial in healthy volunteers. Eur J Anaesthesiol. 2020 Apr;37(4):316-322. doi: 10.1097/EJA.0000000000001112.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2017
• Primary Completion (Actual): December 8, 2017
• Study Completion (Actual): January 5, 2018

Study Registration Dates

• First Submitted: September 29, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Actual): January 8, 2018
• Last Update Submitted That Met QC Criteria: January 5, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Ropivacaine
• Other Study ID Numbers: H-17022555

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