A Comparison of Dexmedetomidine Versus Propofol for Use in Intravenous Sedation

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.

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