A Comparison of Dexmedetomidine Versus Propofol for Use in Intravenous Sedation
Condition: Anesthesia
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Dexmedetomidine and Midazolam; Propofol, Midazolam, and Fentanyl
Intervention type(s): Drug; Drug
Intervention description(s): Administration of Dexmedetomidine and Midazolam for sedation during third molar surgery.; Administration of Propofol, Midazolam, and Fentanyl for sedation during third molar surgery.
Other intervention name(s): Precedex; Diprivan
Intervention MeSH terms: Midazolam; Fentanyl; Dexmedetomidine; Propofol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Other
Keywords: Oral Surgery; Third Molars; Intravenous Sedation; Dexmedetomidine