A Comparison of Dexmedetomidine Versus Propofol for Use in Intravenous Sedation

Anesthesia Clinical Trial

Official title:

A Comparison of Dexmedetomidine Versus Propofol for Use in Intravenous Sedation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03255824
• Other study ID #: 2016-6953
• Status: Completed
• Phase: Phase 4
• Start date: March 20, 2018
• Est. completion date: December 27, 2019

Study information

• Verified date: April 2020
• Source: Montefiore Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: December 27, 2019
• Est. primary completion date: August 23, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Anesthesia

Intervention

Drug:
• Dexmedetomidine and Midazolam
Administration of Dexmedetomidine and Midazolam for sedation during third molar surgery.
• Propofol, Midazolam, and Fentanyl
Administration of Propofol, Midazolam, and Fentanyl for sedation during third molar surgery.

Locations

Country	Name	City	State
United States	Montefiore Medical Center	Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
Montefiore Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (19)

Barone CP, Pablo CS, Barone GW. Postanesthetic care in the critical care unit. Crit Care Nurse. 2004 Feb;24(1):38-45. Review. — View Citation

Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs. 2000 Feb;59(2):263-8; discussion 269-70. — View Citation

Chanques G, Payen JF, Mercier G, de Lattre S, Viel E, Jung B, Cissé M, Lefrant JY, Jaber S. Assessing pain in non-intubated critically ill patients unable to self report: an adaptation of the Behavioral Pain Scale. Intensive Care Med. 2009 Dec;35(12):2060-7. doi: 10.1007/s00134-009-1590-5. — View Citation

Cheung CW, Ng KF, Liu J, Yuen MY, Ho MH, Irwin MG. Analgesic and sedative effects of intranasal dexmedetomidine in third molar surgery under local anaesthesia. Br J Anaesth. 2011 Sep;107(3):430-7. doi: 10.1093/bja/aer164. Epub 2011 Jun 16. — View Citation

Cheung CW, Ying CL, Chiu WK, Wong GT, Ng KF, Irwin MG. A comparison of dexmedetomidine and midazolam for sedation in third molar surgery. Anaesthesia. 2007 Nov;62(11):1132-8. — View Citation

Eberl S, Preckel B, Bergman JJ, Hollmann MW. Safety and effectiveness using dexmedetomidine versus propofol TCI sedation during oesophagus interventions: a randomized trial. BMC Gastroenterol. 2013 Dec 30;13:176. doi: 10.1186/1471-230X-13-176. — View Citation

Fan TW, Ti LK, Islam I. Comparison of dexmedetomidine and midazolam for conscious sedation in dental surgery monitored by bispectral index. Br J Oral Maxillofac Surg. 2013 Jul;51(5):428-33. doi: 10.1016/j.bjoms.2012.08.013. Epub 2012 Oct 8. — View Citation

Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg. 2000 Mar;90(3):699-705. — View Citation

Jaakola ML. Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery. J Clin Anesth. 1994 May-Jun;6(3):204-11. — View Citation

Jun NH, Shim JK, Choi YS, An SH, Kwak YL. Effect of ketamine pretreatment for anaesthesia in patients undergoing percutaneous transluminal balloon angioplasty with continuous remifentanil infusion. Korean J Anesthesiol. 2011 Oct;61(4):308-14. doi: 10.4097/kjae.2011.61.4.308. Epub 2011 Oct 22. — View Citation

Makary L, Vornik V, Finn R, Lenkovsky F, McClelland AL, Thurmon J, Robertson B. Prolonged recovery associated with dexmedetomidine when used as a sole sedative agent in office-based oral and maxillofacial surgery procedures. J Oral Maxillofac Surg. 2010 Feb;68(2):386-91. doi: 10.1016/j.joms.2009.09.107. — View Citation

Nooh N, Sheta SA, Abdullah WA, Abdelhalim AA. Intranasal atomized dexmedetomidine for sedation during third molar extraction. Int J Oral Maxillofac Surg. 2013 Jul;42(7):857-62. doi: 10.1016/j.ijom.2013.02.003. Epub 2013 Mar 14. — View Citation

Parworth LP, Frost DE, Zuniga JR, Bennett T. Propofol and fentanyl compared with midazolam and fentanyl during third molar surgery. J Oral Maxillofac Surg. 1998 Apr;56(4):447-53; discussion 453-4. Erratum in: J Oral Maxillofac Surg. 1999 Feb;57(2):219. — View Citation

Roback MG, Wathen JE, Bajaj L, Bothner JP. Adverse events associated with procedural sedation and analgesia in a pediatric emergency department: a comparison of common parenteral drugs. Acad Emerg Med. 2005 Jun;12(6):508-13. — View Citation

Roback MG, Wathen JE, MacKenzie T, Bajaj L. A randomized, controlled trial of i.v. versus i.m. ketamine for sedation of pediatric patients receiving emergency department orthopedic procedures. Ann Emerg Med. 2006 Nov;48(5):605-12. Epub 2006 Aug 14. — View Citation

Ryu DS, Lee DW, Choi SC, Oh IH. Sedation Protocol Using Dexmedetomidine for Third Molar Extraction. J Oral Maxillofac Surg. 2016 May;74(5):926.e1-7. doi: 10.1016/j.joms.2015.12.021. Epub 2016 Jan 7. — View Citation

Smiley MK, Prior SR. Dexmedetomidine sedation with and without midazolam for third molar surgery. Anesth Prog. 2014 Spring;61(1):3-10. doi: 10.2344/0003-3006-61.1.3. — View Citation

Taniyama K, Oda H, Okawa K, Himeno K, Shikanai K, Shibutani T. Psychosedation with dexmedetomidine hydrochloride during minor oral surgery. Anesth Prog. 2009 Autumn;56(3):75-80. doi: 10.2344/0003-3006-56.3.75. — View Citation

Ustün Y, Gündüz M, Erdogan O, Benlidayi ME. Dexmedetomidine versus midazolam in outpatient third molar surgery. J Oral Maxillofac Surg. 2006 Sep;64(9):1353-8. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Respiratory Events Requiring Intervention	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	Reaction to Administration of Local Anesthesia	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
Secondary	Patient Satisfaction	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
Secondary	Surgeon Satisfaction - Survey	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
Secondary	Cooperation Scale	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
Secondary	Hemodynamic Stability - Heart Rate	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
Secondary	Hemodynamic Stability - Blood Pressure	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
Secondary	Respiratory Depression - Respiratory Rate	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
Secondary	Respiratory Depression - Oxygen Saturation	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
Secondary	Postoperative Recovery Time - Duration of Procedure	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
Secondary	Postoperative Recovery Time - Ambulation	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
Secondary	Postoperative Recovery Time - Time to Discharge	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