Reversing Anesthesia

Recently, the search for a pharmacologic means of minimizing postoperative anesthesia has focused on phentolamine mesylate, which is a nonselective competitive adrenergic antagonist that has been demonstrated to reverse vasoconstriction in rats, cats, and dogs resulting from nerve-stimulated release of norepinephrine or locally applied norepinephrine or epinephrine.^11-13 Phentolamine antagonizes catecholamine-induced dysrhythmias in the heart¹⁴ and has been used clinically in the United States for the prevention of hypertensive episodes. There is a hypothesis that phentolamine accelerates the rate of recovery by accelerating the rate of redistribution of local anesthetic from the submucosa into the cardiovascular system.¹⁷Randomized, controlled phase 2 and phase 3 clinical trials evaluating the safety and efficacy of a proprietary formulation of phentolamine mesylate in both adults and children (aged 4 to 11 years) have been completed and a New Drug Application (NDA) was approved in May 2008 by the FDA for marketing under the name OraVerse (Novalar Pharmaceuticals, Inc, San Diego, CA).Briefly phentolamine mesylate accelerated the time to return of “normal lip sensation” relative to a “sham” injection by more than 80 minutes. These trials demonstrated no significant affect on pain (there was no return of pain after its administration nor was the injection of phentolamine mesylate itself painful (because it was injected into anesthetized tissues). The injection of phentolamine mesylate was not associated with any serious adverse events nor were there any adverse effects on vital signs or patient-reported pain. No clinically observable effects on the oral mucosa were noted. Clinical trials of phentolamine mesylate have compared the reversal action of the drug with articaine plus epinephrine, lidocaine plus epinephrine; mepivacaine plus levonordefrin; and prilocaine plus epinephrine. Similar results were obtained for each type of anesthetic solution.¹⁵ Phentolamine mesylate produces a localized vasodilation, increasing perfusion at the site of deposition, and likely leads to a more rapid redistribution of the local anesthetic from the injection site into capillaries and venules and away from the oral cavity.¹⁷ The results of clinical trials with phentolamine mesylate in anesthetized patients demonstrate that its administration after routine dental or periodontal maintenance procedures should yield a significant benefit.