Preoperative Dexmedetomidine & EC50 of Propofol (PreopDXM)

Preoperative Dexmedetomidine Reduces the EC50 of Propofol for Successful i-gelTM Insertion Without Muscle Relaxants

Dexmedetomidine is a useful anaesthetic adjuvant for general anaesthesia. In this prospective randomised study, we determined whether preoperative dexmedetomidine administration could reduce the half maximal effective concentration (EC50) of propofol for successful i-gelTM insertion without muscle relaxants.

Study Overview

• Status: Completed
• Conditions: Urologic Surgery
• Intervention / Treatment: Drug: Group D : Dexmedetomidine + propofol group; Drug: Group C : Saline + propofol group

Detailed Description

Propofol is a useful induction agent for LMA insertion without muscle relaxants because it profoundly inhibits pharyngeal and laryngeal reactivity. A previous report showed that the effect-site concentration of propofol for successful classic LMA insertion in 50% of adults (EC50) without muscle relaxants in healthy male patients was 8.72 (0.55) µg ml-1. The EC50 of propofol may be dependent on the type of LMA used. A previous study comparing the EC50 of the propofol concentration between classic and proseal LMA insertions demonstrated that the EC50 of propofol needed for proseal LMA insertion was 35% greater than that needed for classic LMA insertion. Unfortunately, no investigation has been performed to determine the EC50 of the propofol concentration required for i-gel insertion without muscle relaxants.

Dexmedetomidine (DEX), a selective alpha-2 agonist, has sympatholytic, sedative, and analgesic properties. Such beneficial characteristics make DEX a useful anaesthetic adjuvant for general anaesthesia. Many reports have revealed the beneficial effects of DEX in terms of reducing intraoperative anaesthetic requirements, postoperative analgesic demand, and increased haemodynamic responses to noxious stimuli such as endotracheal intubation. A previous investigation showed that preoperative clonidine, an alpha-2 agonist, decreased the EC50 required for LMA insertion.

We hypothesised that preoperative DEX administration can reduce the propofol concentration required for i-gel insertion. In this study, we compared the EC50 of propofol needed for successful i-gel insertion without muscle relaxants between DEX and placebo groups

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-799
    • Seoul National University of Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA physical status I-II patients who were 20-65 years old and scheduled for general anaesthesia for urologic surgery

Exclusion Criteria:

• Patients with an allergy to alpha-2 adrenergic agonists or propofol
• Patients who anticipated difficult airway (cervical spinal disease, Mallampati score of III or IV, a mouth opening of <2.5 cm, and/or body mass index of >30 kg m-2), unstable teeth
• Patients with bradycardia of <50 beats/min, heart block greater than first degree, severe cardiorespiratory dysfunction
• Patients with symptoms of upper respiratory infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group D : Dexmedetomidine + propofol group; In Group D, DEX (1 µg kg-1) was intravenously loaded for 10 min before induction of anaesthesia.	Drug: Group D : Dexmedetomidine + propofol group; All patients were pre-oxygenated with 100% oxygen with spontaneous breathing for 3 min before the end of loading of dexmedetomidine. Anaesthesia was induced with predetermined effect-site propofol concentrations using a target-controlled infusion device (Orchestra; Fresenius-Vial, Brezins, France). The first patient in Group D received an effect-site propofol concentration of 3 and 5 µg mL-1, respectively, over 5 min. After equilibration of the plasma and effect-site propofol concentrations, i-gel (size 4 for patients weighing 50-90 kg, size 3 for patients weighing 30-50 kg) was inserted using the standard technique by a single anaesthesiologist staff member with expertise in i-gel insertion and who entered the operating room immediately before i-gel insertion to blind him to the group assignment.
Placebo Comparator: Group C : Saline + propofol group; In Group C, 0.9% of normal saline (1 µg kg-1) was loaded 10 min before induction of anaeshtesia.	Drug: Group C : Saline + propofol group; All patients were pre-oxygenated with 100% oxygen with spontaneous breathing for 3 min before the end of loading of normal saline. Anaesthesia was induced with predetermined effect-site propofol concentrations using a target-controlled infusion device (Orchestra; Fresenius-Vial, Brezins, France). The first patient in Group C received an effect-site propofol concentration of 3 and 5 µg mL-1, respectively, over 5 min. After equilibration of the plasma and effect-site propofol concentrations, i-gel (size 4 for patients weighing 50-90 kg, size 3 for patients weighing 30-50 kg) was inserted using the standard technique by a single anaesthesiologist staff member with expertise in i-gel insertion and who entered the operating room immediately before i-gel insertion to blind him to the group assignment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EC50 of propofol required for successful i-gel insertion	The EC50 of propofol for successful i-gel insertion was determined by a modification of Dixon's up-and-down method. The response of each patient determined the effect-site propofol concentration for the next patient. If the response was deemed 'successful', the next target concentration of propofol was decreased by 0.5 µg mL-1. If the response was deemed a 'failure', the target concentration was increased by the same dose. The process was repeated until the sixth crossover point (success/failure) was obtained.	During i-gel insertion anticipated up to 1 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the total dose of propofol infused before i-gel insertion	The total amount of propofol infused before i-gel insertion was noted. The insertion time, defined as the time from picking up the i-gel until the initiation of mechanical ventilation.	During i-gel insertion time anticipated upto 1min
the presence/severity of airway trauma after i-gel insertion	After removing the i-gel, airway trauma (defined as any blood staining on the device) was recorded.	At the time point of removing the i-gel from patient's mouth

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Study Director: Hee Pyung Park, MD PhD, Professor; Principal Investigator: Young Cheol Kim, Md PhD, Professor

Publications and helpful links

General Publications

• Jang YE, Kim YC, Yoon HK, Jeon YT, Hwang JW, Kim E, Park HP. A randomized controlled trial of the effect of preoperative dexmedetomidine on the half maximal effective concentration of propofol for successful i-gel insertion without muscle relaxants. J Anesth. 2015 Jun;29(3):338-345. doi: 10.1007/s00540-014-1949-9. Epub 2014 Nov 14.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: March 24, 2014
• First Posted (Estimate): March 27, 2014

Study Record Updates

• Last Update Posted (Estimate): March 27, 2014
• Last Update Submitted That Met QC Criteria: March 24, 2014
• Last Verified: March 1, 2014

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; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Propofol; Dexmedetomidine
• Other Study ID Numbers: PreopDXM_PPF