A Sequential Allocation Study to Determine the ED50 of Dexmetedomidine as an Adjuvant to Lidocaine Intravenous Regional Anesthesia

Intravenous Regional Anesthesia (IVRA) is an easy and reliable anesthetic technique for hand and forearm surgery. Its use is however limited by the presence of tourniquet pain during the surgery and the absence of postoperative analgesia. Many adjuvants to local anesthetics have been studied in order to overcome these shortcomings, including α2 adrenergic agonists. Clonidine has been shown to be efficacious when used with IVRA at a dose of 1µg/kg. Dexmetedomidine (DEX) is a recent more selective α2 adrenergic agonist that has been used successfully during IVRA at a dose of 0.5µg/kg. However when comparing potency ratios of Clonidine and DEX (8 to 1), the investigators hypothesize that a lower DEX dose would provide patients with adequate anesthesia.

We will determine the population average dose of DEX (ED50) that provides 50 minutes of tolerance to the tourniquet during a Lidocaine IVRA by a sequential Dixon up-down allocation study.

Eligible patients will be enrolled after obtaining informed consent. Patients will receive a standardized IVRA with Lidocaine and DEX adjuvant following a sequential allocation scheme. The first patient will receive a dose of 0.5 µg/kg of DEX. The dose will be then adjusted in 0.1 µg/kg increments for the following patients dependent on the success of the previous patients block. If a patient experiences tourniquet pain prior to 50 minutes after inflation of the distal tourniquet the next patient will receive a higher dose, if he does not experience pain prior to 50 minutes after inflation of the distal tourniquet the dose for the following patient will be decreased.

Recruitment will continue until 6 independent crossovers are observed with a minimum of 20 patients. The mean and the standard deviation of the ED50 of DEX will be calculated using the modified up-down method.

This study will help determine the ED50 of DEX used as an adjuvant in IVRA. Based on the potency ratios of Clonidine vs. DEX, the investigators hypothesize that the dose of DEX needed to achieve 50 minutes of pain free tourniquet time will be closer to 0.125 µg/kg rather than 0.5 µg/kg, a 75% reduction in the dose studied.

Study Overview

• Status: Completed
• Conditions: Dexmedetomidine; Carpal Tunnel; Tourniquet Pain; Bier Block; Tendon Release; Tendn Transfer
• Intervention / Treatment: Drug: Dexmedetomidine

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients 18 to 70 years of age, ASA physical status I-II, undergoing unilateral hand or forearm surgery (that require 30 minutes or more) under IVRA.

Exclusion Criteria:

•Patients with Raynaud's disease, sickle cell anemia, heart block, allergy to any of the anesthetic drugs used, patients on α-adrenergic agonists, ASA III or IV, emergency surgery and pregnant patients., Weight greater than 100Kg.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dexmedetomidine

Drug: Dexmedetomidine; Following a sequential allocation scheme, the dexmedetomidine dose for each patient was determined by the Dixon up-and-down method. The dexmedetomidine dose for the first patient was 0.5 µg/kg. The dose was then adjusted in 0.1 µg/kg increments for the following patients depending on the success of the previous patient's block. If a patient experienced tourniquet pain prior to T0 + 50 minutes the next patient received a higher dose. If a patient did not experience pain at T0 + 50 minutes of tourniquet time the dose for the following patient was decreased. Identical syringes containing the solution mix were prepared by the principal investigator and handed to the blinded anesthesiologist in the room. Stopping rules were set at 6 independent crossovers in the same direction (no pain to pain or pain to no pain), with a minimum number of 20 patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median effective dose of dexmedetomidine	The dexmedetomidine dose for the first patient was 0.5 µg/kg, the minimum tourniquet time chosen for our study was 50 minutes. The dose was then adjusted in 0.1 µg/kg increments for the following patients depending on the success of the previous patient's block. If a patient experienced tourniquet pain prior to T0 + 50 minutes the next patient received a higher dose. If a patient did not experience pain at T0 + 50 minutes of tourniquet time the dose for the following patient was decreased. Stopping rules were set at 6 independent crossovers in the same direction (no pain to pain or pain to no pain), with a minimum number of 20 patients. The mean and standard deviation of the ED50 of dexmedetomidine were calculated using the modified up-and-down method, which uses the average dexmedetomidine dose of all independent pairs of patients involved a crossover to calculate the ED50	During the procedure

Collaborators and Investigators

• Sponsor: American University of Beirut Medical Center

Publications and helpful links

General Publications

• Karam C, Al Assadi S, Kanazi G, Zeeni C. A sequential allocation study to determine the ED(50) of Dexmedetomidine as an adjuvant to lidocaine intravenous regional anesthesia. BMC Anesthesiol. 2022 May 27;22(1):165. doi: 10.1186/s12871-022-01702-9.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 25, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 20, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Wounds and Injuries; Neuromuscular Diseases; Mononeuropathies; Peripheral Nervous System Diseases; Median Neuropathy; Nerve Compression Syndromes; Cumulative Trauma Disorders; Sprains and Strains; Carpal Tunnel Syndrome; 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: ANES.CZ.01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The datasets used and/or analysed during the current study are not publicly available because the publicity policy is not yet generated by our institutional review board but are available from the corresponding author on reasonable request.

Drug and device information, study documents

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