Efficacy and Safety Study of Dexmedetomidine as an Additive to Local Anesthetics in Shoulder Surgery

The Efficacy and Safety of Dexmedetomidine as an Additive to Ropivacaine for Interscalene Brachial Plexus Blocks for Shoulder Surgery

The purpose of this study is to test the efficacy and safety of dexmedetomidine added to ropivacaine in patients undergoing shoulder surgery.

Study Overview

• Status: Completed
• Conditions: Self Efficacy; Drug Safety
• Intervention / Treatment: Drug: dexmedetomidine; Drug: saline

Detailed Description

Peripheral nerve blocks are used throughout the world in lieu of general anesthesia and, more commonly, to provide analgesia and opioid sparing in the postoperative course. Long acting local anesthetics, such as ropivacaine, can provide analgesia for 11.5 ± 5 hours. This leads to many patients reporting their first pain in the evening and nighttime hours when access to healthcare providers and support is most limited. A number of additives to local anesthetics have been studied in humans with limited success. Recent work by a group in Michigan found a dose dependent increase in the duration of analgesia to a thermal stimulus when dexmedetomidine was added to ropivacaine for sciatic nerve blocks in rat.

The goal of the study is to investigate the safety and efficacy of dexmedetomidine added to ropivacaine for interscalene brachial plexus nerve block for shoulder surgery in humans. Provided the initial safety can be established, the trial will continue to evaluate secondary goals including the duration of analgesia, onset of sensory and motor blockade, and opioid-induced side effects. Tertiary outcomes will include subject satisfaction.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Paracelsus Medical University, Department of Anesthesiology, Perioperative and Intensive Care Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA I-III adult subjects
• Age 18-75
• Elective shoulder surgery
• Plan for interscalene brachial plexus block combined with general anesthesia
• Interscalene block
• Willingness to be contacted postoperatively for brief (5-10min) phone call questionnaires
• Written informed consent

Exclusion Criteria:

• Age < 18
• Age > 75
• Inability to understand protocol due to language barrier; difficulty with German language
• Chronic pain requiring daily opioids > 15 mg oral morphine equivalents (equals oral usage of > 10 mg oxycodone/daily; > 5 mg methadone/day; > 4 mg hydromorphone/day)
• Moderate (NRS pain score > 5) daily average pain
• Daily use of gabapentin, pregabalin, tricyclic antidepressant, serotonin- norepinephrine reuptake inhibitor, tramadol
• Hypersensitivity to amide local anesthetics
• History of hypersensitivity or allergic reaction to clonidine or dexmedetomidine
• Uncontrolled anxiety
• Schizophrenia or bipolar disorder
• Preexisting nerve damage (sensory or motor) in the extremity to be blocked
• Peripheral neuropathy
• Significant cardiovascular disease (second (Mobitz II type) or third degree heart block, congestive heart failure, chronic heart failure NYHA III-IV, symptomatic coronary artery disease CSS III-IV)
• BMI > 35
• Uncontrolled diabetes (blood sugar > 250 recorded in last 30 days or HbA1c > 7.5%)
• Chronic clonidine therapy (clonidine patch - Catapres or clonidine tablets)
• Hepatic Impairment (CHILD B or higher)
• Renal Impairment (creatinin > 2.0 mg/dl)
• Ongoing drug or alcohol abuse
• Pregnancy
• Prisoners

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ropivacaine + dexmedetomidine; This group represents the standard of care drug (ropivacaine) plus the new additive to be studied (dexmedetomidine)	Drug: dexmedetomidine; ropivacaine 100 mg + 150 mcg dexmedetomidine, single shot perineural application
Active Comparator: ropivacaine + saline; This group represents the current standard of care in peripheral nerve blockade	Drug: saline; ropivacaine + saline placebo, single shot perineural application

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of dexmedetomidine in perineural application	The time until the patient describes the blockade as completely gone will be analysed and compared between the groups.	24 hrs
Safety of dexmedetomidine in perineural application	Any serious and/or unexpected adverse (AE) events will be assessed on an individual basis by the Principal Investigator and the DSMB. After the first twenty subjects (10 controls and 10 receiving study agent) have completed the study, the data will be reviewed. Provided the DSMB determines the initial safety is established, enrollment will proceed until a total of 62 subjects (31 subjects/group) have been accrued.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analgesia	Analgesia will be assessed based on postoperative pain scores	first 24-48 hrs
Onset of sensory blockade	The subject's sensory function will be measured every 2 minutes for the first 20 minutes, until the loss of sensory function in the dermal distribution of the shoulder.	every 3 minutes for the first 21 minutes
Duration of motor blockade	The time to return of motor strength will be recorded in the subject's postoperative course.	first 24-48 hrs
Opioid-induced side effects	Opioid-induced side effects will be recorded in the subject's postoperative course.	first 24-48 hrs

Collaborators and Investigators

• Sponsor: Prof. Peter Gerner, M.D.
• Investigators: Principal Investigator: Peter Gerner, MD, Paracelsus Medical University Salzburg, Department of Anesthesiology

Publications and helpful links

General Publications

• Brummett CM, Amodeo FS, Janda AM, Padda AK, Lydic R. Perineural dexmedetomidine provides an increased duration of analgesia to a thermal stimulus when compared with a systemic control in a rat sciatic nerve block. Reg Anesth Pain Med. 2010 Sep-Oct;35(5):427-31. doi: 10.1097/AAP.0b013e3181ef4cf0.
• Brummett CM, Hong EK, Janda AM, Amodeo FS, Lydic R. Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the duration of analgesia by blocking the hyperpolarization-activated cation current. Anesthesiology. 2011 Oct;115(4):836-43. doi: 10.1097/ALN.0b013e318221fcc9.
• Brummett CM, Padda AK, Amodeo FS, Welch KB, Lydic R. Perineural dexmedetomidine added to ropivacaine causes a dose-dependent increase in the duration of thermal antinociception in sciatic nerve block in rat. Anesthesiology. 2009 Nov;111(5):1111-9. doi: 10.1097/ALN.0b013e3181bbcc26.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: December 5, 2011
• First Submitted That Met QC Criteria: March 15, 2012
• First Posted (Estimate): March 19, 2012

Study Record Updates

• Last Update Posted (Estimate): December 4, 2012
• Last Update Submitted That Met QC Criteria: December 3, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• 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; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: GernerDex001