OraVerse (phentolamine mesylate) is a new agent in dentistry indicated for the reversal of soft tissue anesthesia and associated deficits resulting from intraoral anesthetic and vasoconstrictor application.1 OraVerse is currently sold in the United States and Germany with availability in Canada beginning Fall, 2014.
PHENTOLAMINE MESYLATE
Phentolamine mesylate (PM) is an alpha adrenergic blocker that competitively obstructs pre- and post- synaptic adrenergic receptors. The agent acts within the arterial and venous system to reduce total peripheral resistance, and lower venous return to the heart. While phentolamine mesylate (PM) is new to dentistry, its use in other aspects of health care goes back several decades. PM was originally produced for the treatment of hypertension and is occasionally used today as off-label treatment for hypertensive crises.2 The main medical indications for PM are treatment of dermal necrosis resulting from venous extravasation of norepinephrine or for diagnosis and treatment of patients with pheochromocytoma, a tumor that secretes excessive epinephrine and norepinephrine at the adrenal medulla.3-4 As it relates to dental application, PM is used to decrease the duration of soft tissue anesthesia after local anesthetic administration, by increasing the elimination of anesthetic from the localized area via a reduction in localized vascular resistance.4-5
RECOVERY FROM LIP AND TONGUE ANESTESIA
The administration of anesthetics has long been used to provide pain control during dentistry. One disadvantage with anesthetic administration during routine procedures is that soft tissue anesthesia can persist for three to five hours while the procedure itself usually lasts less than an hour.6 Some dental patients perceive this numbness, which leads to difficulty with speaking, eating, and drinking, as a temporary deficiency in quality of life.6-7 Residual sensations of numbness after leaving the dental office have also been shown to provoke anxiety and, in a small percentage of patients, lead to phobic tendencies.7-8
As previously described, PM’s primary effect is vasodilation which enhances redistribution of local anesthetic away from the injection site to decrease the time a patient is numb. This effect was evaluated in a series of clinical trials completed for Food and Drug Administration approval in the United States. In the phase 3 trials of adults and adolescents, commonly used anesthetics (lidocaine with epinephrine, articaine with epinephrine, mepivacaine with levonordefrin, and prilocaine with epinephrine) were administered as maxillary and mandibular injections followed by PM administration after completion of dental procedures.5 Instead of a placebo vehicle being used, a sham injection was administered to the patient while a visual barrier was applied.
As displayed in Figure 1, the median time to recovery of normal mandibular lip sensation was 70 minutes for subjects in the phentolamine group and 155 minutes for subjects in the sham group. In addition, those in the phentolamine group were more likely to have total sensation recovery in the early periods after injection (30-60 minutes). In Figure 2, the compared median time of return to normal lip sensation in the maxillary arch demonstrated an 83 minute reduction for subjects in the phentolamine group (50 minutes for the PM group versus 133 minutes for the sham injection group).
FIGURE 1. Comparison of median time to recovery of normal mandibular lip sensation between phentolamine mesylate and sham injections./201407040931540zzoqln55cbgkairfq31kolnl.jpg)
FIGURE 2. Comparison of median time to recovery of normal maxillary lip sensation between phentolamine mesylate and sham injections./201407040931551zzoqln55cbgkairfq31kolnl.jpg)
Additional analyses were completed during the trials using different assessment tools. Subjects completed a soft tissue anesthesia recovery (STAR) questionnaire, which measured the subject’s perception of altered function, sensation, and appearance. Median recovery times of the STAR questionnaire were earlier for the phentolamine group (90 minutes) compared to the group receiving the sham injection (150 minutes). A functional assessment battery (FAB) was also completed which included measurements of smiling, speaking, presence or absence of drooling, and the ability to drink three ounces of water. Recovery times measured with the FAB were significantly more rapid for the PM group (60 minutes) than the sham injection group (120 minutes).
CLINICAL APPLICATION, SAFTEY, AND BENEFIT
OraVerse contains 0.4 milligrams of PM in a standard 1.7 mL dental cartridge. The application of OraVerse is accomplished by administering a 1:1 ratio of the agent to local anesthetic cartridge at the local anesthetic injection site. The maximum dose is two cartridges and the agent is not recommended in patients under the age of six or weighing less than 33 lbs. A pivotal post marketing clinical trial in two to five-year-old subjects is currently being evaluated to establish safety and efficacy in this age group.4
FIGURE 3.Self-inflicted soft tissue lip injury./201407040931552zzoqln55cbgkairfq31kolnl.jpg)
Review of the adverse event reports for phentolamine mesylate used during dental procedures revealed no serious adverse events. The most frequently reported adverse events were injection site pain, headache, increased blood pressure and heart rate changes.1,4 All adverse events resolved in 48 hours. Measurements of standing blood pressures and pulse did not elicit any signs of postural hypotension. Lack of postural hypotension is considered an important finding since it has been reported as a common side effect with medical administration of alpha adrenergic blocking drugs.9 This is most likely due to the fact that the amount of PM used in OraVerse and the type of administration results in considerably lower systemic levels than that administered during medical intervention.
FIGURE 4. An additional figure has been attached of the OraVerse box and blister package for placement as warranted by the editor and staff./201407040931553zzoqln55cbgkairfq31kolnl.jpg)
One of the main clinical benefits proposed for OraVerse is a possible link to the reversal of soft tissue anesthesia and a decrease in self-inflicted soft tissue injuries.4,10 Self-inflicted soft tissue injuries are often observ
ed adverse events with local anesthesia administration, reported to occur 3-16% of the time following anesthetic injection.11-12 As demonstrated in Figure 3, soft tissue injuries related to dental local anesthesia can be troubling. In fact, there are reports of complete lip amputation following intraoral anesthetic administration.13-14 The results of a recent analysis suggest an improvement in complication occurrence with the administration of PM, especially as it relates to self-inflicted soft tissue trauma.11 The complication rate of the group administered PM was 2.6 percent while the group not administered PM had a complication rate of 6.1 percent.
CONCLUSION
OraVerse appears to be safe and effective in reducing soft tissue anesthesia in adults and children. It is possible that its use may also decrease the incidence of self-inflicted soft tissue injuries. The agent has a place in the dental profession and can be used to improve the patient experience. OH
Dr. Sean G. Boynes is a Dentist Anesthesiologist that received his D.M.D. from the University of Pittsburgh and completed a three-year residency in anesthesiology from the University of Pittsburgh Medical Center. He currently serves as Director of Dental Medicine at CareSouth Carolina in Society Hill, SC and as Expert Advisor to the DentaQuest Institute-Safety Net Solutions. Dr. Boynes has been recognized by many organizations and the National Health Service Corp recently featured him as one of the 40 top clinicians for their 40th Anniversary Celebration and the National Children’s Oral Health Foundation lists him as a Dentist of Distinction.
Oral Health welcomes this original article.
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