A Comparison of Dexmedetomidine Versus Propofol for Use in Intravenous Sedation

April 28, 2020 updated by: Patrick Nolan, Montefiore Medical Center
Hypothesis: A combination of midazolam with dexmedetomidine for sedation during third molar surgery will provide 1) superior patient satisfaction, 2) superior operator satisfaction and 3) no significant hemodynamic or respiratory changes when compared to a sedation combination of midazolam, fentanyl and propofol for sedation during third molar surgery.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Intravenous sedation (IVS) is an integral aspect of the oral and maxillofacial surgeon's practice. For many minor oral surgical procedures, intravenous sedation is often necessary to manage patient anxiety and discomfort, while also facilitating a safe and efficient procedure in the outpatient setting. Ideally, sedative agents have anxiolytic, amnestic, and analgesic properties while maintaining cardiopulmonary stability. The medications used should allow for rapid onset of action, as well as a quick recovery, with minimal side effects.

Several pharmacologic agents are frequently used for conscious sedation in the oral surgery practice. These medications often include midazolam, fentanyl, ketamine and propofol, either alone or in conjunction with one another. While propofol and fentanyl have proved to be efficacious agents for use in intravenous sedation, they are not without associated side effects. Propofol has the potential to cause a quick progression from conscious sedation to general anesthesia, with the undesired effect of associated cardiovascular and respiratory depression. Decreased respiratory drive, hypotension, and dose-dependent bradycardia are often seen with opioid analgesics such as fentanyl.1,2 Ketamine can cause emergence delirium, increased salivation and pulmonary secretions, tachycardia, and post-operative nausea and vomiting (PONV).

Midazolam is a benzodiazepine that is an attractive agent for intravenous sedation due to its sedative, amnestic, and hypnotic properties. In addition, it is associated with very minimal cardiovascular and respiratory changes. However, midazolam lacks significant analgesic effects, and therefore is routinely used in conjunction with additional agents when used for procedural sedation. Though several studies have explored the use of midazolam as a sole anesthetic, very high doses are required for deep sedation. This can lead to dose-dependent respiratory depression, prolonged emergence and longer recovery time.

Dexmedetomidine (Precedex, Hospira, Inc., Lake Forest, IL) is a highly selective alpha2-adrenergic agonist that possesses hypnotic, sedative, anxiolytic, and analgesic properties. It is currently approved for use as a sedative agent in ICU patients, and has been proven a safe and effective agent for use during procedural sedation. In the central nervous system, the primary site of action of dexmedetomidine is the locus ceruleus, resulting in a level of sedation similar to natural sleep, associated with fast and easy arousal. It demonstrates relative hemodynamic stability with little effect on respiratory depression. Unlike propofol and fentanyl, dexmedetomidine's lack of adverse effects on respiration makes it an attractive agent for use during intravenous sedation in the oral and maxillofacial surgery practice.

Several studies involving dexmedetomidine exist in the oral and maxillofacial surgery literature. Dexmedetomidine has been compared as a substitute for midazolam, as well as propofol, in conscious sedation by several authors. For third molar surgery, dexmedetomidine was noted to preserve the respiratory rate and oxygen saturation throughout operation and recovery periods. Fan et al also found no significant differences in respiratory rate when comparing the two agents for conscious sedation. In comparison to midazolam, Ryu et al reported safe sedation without airway compromise and minimal effects on the respiratory system.

Dexmedetomidine also possesses sympatholytic properties, and is commonly associated with a dose-dependent decrease in both heart rate and blood pressure.4,9 Taniyama et al compared dexmedetomidine to propofol for intravenous sedation for minor oral surgical procedures. They found that dexmedetomidine lead to significant hemodynamic changes during the initial loading infusion. An initial increase in blood pressure was seen, followed by a significant decrease in both systolic and diastolic blood pressure, as well as heart rate. These variations are attributed to the fact that dexmedetomidine does not have selectivity for alpha-2A versus alpha-2B receptors. While alpha-2A receptors are found in the CNS and are therefore responsible for the analgesic and sedative effects of the drug, alpha-2B receptors are found in vascular smooth muscle and thereby mediate the hypertensive effects of high doses of dexmedetomidine. Because of this, initial loading doses of dexmedetomidine may be associated with a transient increase in blood pressure, followed by an overall reduction in blood pressure and heart rate from baseline. Hall et al reported that dexmedetomidine demonstrated a decrease in heart rate from baseline between 16 and 18%, and a decrease in blood pressure of 10 to 20%.15 However, in some studies, similar biphasic changes were not observed, possibly due to the use of a lower dosage of dexmedetomidine.

Aside from dose-dependent depression of the cardiovascular system, dexmedetomidine has been associated with minimal to no amnesic effects. One other possible disadvantage of dexmedetomidine as a sedative agent for in-office procedures is the increased postoperative recovery time. Peak sedative effects of the drug occur approximately 90-105 minutes after administration, continuing to as much as 180 minutes. This may necessitate post-operative observation periods of increased duration. Intravenously administered dexmedetomidine has a distribution half-life of 6 minutes and an elimination half-life of 2 hours. It undergoes biotransformation in the liver and is excreted primarily in the urine.

The purpose of this study is to measure the relative efficacy (sedation, analgesia, operating conditions, and patient satisfaction) and safety (hemodynamic and respiratory changes) of dexmedetomidine and midazolam compared to the traditional combination of midazolam, fentanyl, and propofol in office based intravenous sedation for extraction of third molars.

Study Type

Interventional

Enrollment (Actual)

144

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 31 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subject must have 3-4 partial or full bony impacted third molars requiring surgical extraction
  • ASA Class I or II
  • English-speaking and Spanish-speaking subjects

Exclusion Criteria:

  • ASA Class III or higher
  • Patients taking alpha-2 agonists or benzodiazepines
  • Allergy or drug reaction to any of the drugs used in this study (benzodiazepines, opioids, propofol, alpha-2 agonists, NSAIDs, local anesthetic)
  • BMI greater than 30
  • History of or current substance abuse or alcoholism
  • History of mood-altering medications, tranquilizers, or antidepressants.
  • Pregnant females

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Propofol Group
Group of patients to be administered a standard Propofol, Midazolam, Fentanyl anesthesia combination.
Drug: Propofol, Midazolam, and Fentanyl
Administration of Propofol, Midazolam, and Fentanyl for sedation during third molar surgery.
Other Names:
  • Diprivan
Experimental: Dexmedetomidine Group
Group of patients to be administered the Dexmedetomidine and Midazolam anesthesia combination.
Drug: Dexmedetomidine and Midazolam
Administration of Dexmedetomidine and Midazolam for sedation during third molar surgery.
Other Names:
  • Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Respiratory Events Requiring Intervention
Time Frame: During surgery
To compare the groups regarding the number of respiratory events requiring intervention, described as: Chin lift/jaw thrust, Tongue thrust, Yankauer suctioning, Positive pressure oxygen administration, Placement of an oral or nasal airway.
During surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reaction to Administration of Local Anesthesia
Time Frame: During the first injection of local anesthesia during surgery

To compare the groups regarding movement of the patient during the first injection of local anesthesia during the IVS at time of injection measured using the Behavioral Pain Scale - Non-Intubated patients.

The minimum value is 3 and the maximum value is 12. Higher scores mean a worse outcome (i.e., more pain and movement on injection)
During the first injection of local anesthesia during surgery
Patient Satisfaction
Time Frame: 30 minutes following surgery

Visual Analog Scale was used to measure overall satisfaction with the IV sedation and memory of the procedure.

The minimum score is 0 (not satisfied at all) to a maximum score of 100 (completely satisfied).

A higher score is a better outcome.
30 minutes following surgery
Surgeon Satisfaction - Survey
Time Frame: 15 minutes following surgery

Surgeon satisfaction was measured by the surgeon grading the "Operating Conditions" scale.

The minimum value was 0 and the maximum was 3. 0=very poor, 1=poor, 2=fair, 3=good
15 minutes following surgery
Cooperation Scale
Time Frame: 15 minutes following surgery
Surgeon satisfaction is measured by the Cooperation Scale. Minimum score of 0 and maximum of 9. Higher indicates a worse outcome (i.e., discomfort and movement)
15 minutes following surgery
Hemodynamic Stability - Heart Rate
Time Frame: During the procedure, up to 40 minutes

To compare the differences in hemodynamic stability using a D/M combination compared to the MFP combination. (In this study, a deviation from baseline of both the blood pressure and heart rate by 20% or greater will be considered clinically significant)

a. Change in heart rate (change ≥ 20 BPM)
During the procedure, up to 40 minutes
Hemodynamic Stability - Blood Pressure
Time Frame: During the procedure, up to 40 minutes

To compare the differences in hemodynamic stability using a D/M combination compared to the MFP combination. (In this study, a deviation from baseline by 20% or greater will be considered clinically significant)

a. Change in blood pressure (NIBP) (change ≥ 20%) Blood pressure is presented as mean arterial pressure
During the procedure, up to 40 minutes
Respiratory Depression - Respiratory Rate
Time Frame: During the procedure, up to 40 minutes

To assess whether a D/M combination leads to a significant change in respiratory depression compared to the MFP combination.

a. Change in respiratory rate (change ≥ 20%)
During the procedure, up to 40 minutes
Respiratory Depression - Oxygen Saturation
Time Frame: During the procedure, up to 40 minutes

To assess whether a D/M combination leads to a significant change in respiratory depression compared to the MFP combination.

a. Change in arterial oxygen saturation (as measured by pulse oximeter) i. number of events of ≤92%
During the procedure, up to 40 minutes
Postoperative Recovery Time - Duration of Procedure
Time Frame: During the procedure, up to 40 minutes

To assess whether a D/M combination increases postoperative recovery time when compared the MFP combination.

a. Duration of procedure will be recorded
During the procedure, up to 40 minutes
Postoperative Recovery Time - Ambulation
Time Frame: After the procedure until ambulation, up to 20 minutes

To assess whether a D/M combination increases postoperative recovery time when compared the MFP combination.

a. Time to ambulation (to recovery room) will be recorded
After the procedure until ambulation, up to 20 minutes
Postoperative Recovery Time - Time to Discharge
Time Frame: After the procedure until discharge, up to 45 minutes

To assess whether a D/M combination increases postoperative recovery time when compared the MFP combination.

a. Time to discharge or "virtual discharge" (comparative statistic) - Aldrete score of ≥ 9 or pre-procedure score is met The minimum score is 0 and the maximum score is 10. A higher score indicates wakefulness, hemodynamically stable, and able to ambulate.

ii. All subjects are required to stay a minimum of 30 minutes after the end of the procedure. Therefore, at least two postoperative vital sign readings will be obtained. If the subject meets discharge criteria prior to 30 minutes, this time will be the "virtual discharge" time
After the procedure until discharge, up to 45 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Montefiore Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 20, 2018

Primary Completion (Actual)

August 23, 2019

Study Completion (Actual)

December 27, 2019

Study Registration Dates

First Submitted

June 28, 2017

First Submitted That Met QC Criteria

August 16, 2017

First Posted (Actual)

August 21, 2017

Study Record Updates

Last Update Posted (Actual)

May 13, 2020

Last Update Submitted That Met QC Criteria

April 28, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-6953

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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