Recent Advances In Local Anesthesia PDF

CHAPTER 20 45 Recent Advances in Local Anesthesia 377 1,800,000 40 1,600,000 Hillerup paper 35 1,400,000 30 1,200,000 25 1,000,000 20 800,000 EU report 15 600,000 10 09 Use 20 20 07 08 20 20 20 20 20 20 20 20 06 - 05 0 04 200,000 03 5 02 400,000 01 10 Adve...

CHAPTER 20 45 Recent Advances in Local Anesthesia 377 1,800,000 40 1,600,000 Hillerup paper 35 1,400,000 30 1,200,000 25 1,000,000 20 800,000 EU report 15 600,000 10 09 Use 20 20 07 08 20 20 20 20 20 20 20 20 06 - 05 0 04 200,000 03 5 02 400,000 01 10 Adverse reactions The number of suspected adverse reactions reported to the Danish Medicines Agency for articaine. The chart shows which year a reported adverse reaction began. It also shows the use of articaine in dental practices in mL. • Fig. 20.9 Articaine use and reports of paresthesia (Denmark). TABLE Lingual Nerve Involvement in Reported 20.9 Cases of Paresthesia Authors Country Year Lingual Nerve Involvement (%) Haas and Lennon43 Canada 1995 70.6 Hillerup and Jensen44 Denmark 2006 77.0 Garisto et al.45 United States 2010 92.7 Kingon et al.46 Australia 2011 80.0 to 1946 involve the maxilla).70 Considering the mandible, paresthesia has rarely been reported following alternative nerve blocks, such as the Gow-Gates mandibular nerve block.70 Articaine has been used increasingly in medicine, primarily dermatology, plastic and reconstructive surgery, ophthalmology, and orthopedic surgery. There are no reported cases of paresthesia following the nondental use of articaine.21-22,71 Is it possible for a drug be so specifically neurotoxic that it only damages nerves in the oral cavity, specifically in the mandible and more specifically the lingual nerve? Possible, yes, but highly improbable.␣ The Lingual Nerve following dental treatment.68,69 Informed consent, specifically with discussion of the risk of paresthesia, is required before these procedures. Given that most dental treatment is nonsurgical (e.g., restorative, periodontal), the primary risk of paresthesia would involve local anesthetic administration. In a MEDLINE search for reported cases of paresthesia in dentistry dating to 1946, more than 95% of all cases occurred in the mandible.70 The overwhelming proportion involve the lingual nerve. Table 20.9 shows lingual nerve involvement in four published articles. We have been told that 4% articaine appears to be more neurotoxic than other local anesthetics, and that its administration by IANB should be avoided.43-48,53 The following needs to be considered: if 4% articaine is more neurotoxic than other local anesthetics, then how do we explain that paresthesia is rarely reported in the maxilla when half of all dental treatment involves maxillary teeth (less than 5% of all cases in the dental literature dating The lingual nerve appears to be involved in reports of dentally related paresthesia in a disproportionate percentage of cases (see Table 20.9). Pogrel has studied paresthesia, with publications dating from the early 1990s.51,52 In a 2000 article (before the introduction of articaine in the United States), Pogrel and Thamby51 estimated the risk of permanent nerve damage following IANB at 1 in 26,762 injections. They stated that “it is reasonable to suggest that during a career, each dentist may encounter at least one patient with an inferior alveolar nerve block resulting in permanent nerve involvement. The mechanisms are unknown and there is no known prevention or treatment.”51 In the course of a 20- to 30-year dental career, it is estimated that more than 30,000 IANBs will be administered.52 Why is it that the lingual nerve is primarily involved in cases of paresthesia? Considering that when one is administering the IANB the vast majority of local anesthetic volume is deposited close to the inferior alveolar nerve (e.g., 1.3 to 1.5 mL), not the lingual nerve (e.g., 0.2 to 0.3 mL), if 378 PART IV Complications, Legal Considerations, Questions, and the Future TABLE Risk of Paresthesia From Local Anesthetic 20.10 Drugs55,56 2007 2012 Result Lidocaine 0.64 0.5 <1.0, less than expected Articaine 1.19 0.97 ∼1.0, expected Mepivacaine NA 2.2 >1.5, higher than expected Prilocaine 4.96 3.25 >3.0, higher than expected The ratio derived from the percentage of reported cases of paresthesia divided the percent market share of the drug. • Fig. 20.10 Fascicles within a nerve. (From McGill Physiology Virtual Laboratory. http://www.medicine.mcgill.ca/physio/vlab/.) paresthesia were a local anesthetic neurotoxic phenomenon, we would expect the inferior alveolar nerve to be affected much more often than the lingual nerve. The fact that the lingual nerve is stretched when the patient opens the mouth for an IANB probably prevents the lingual nerve from “getting out of the way” of the needle. The resulting injury is more likely than not to be a result of mechanical trauma to the lingual nerve from the metal needle. Stated in another way: “the lingual nerve is in the way.” In 2003 Pogrel et al.72 attempted to explain why lingual nerve damage was commonly seen as more profound. At the level at which the IANB is administered, the inferior alveolar nerve had five to seven fascicles, whereas the lingual nerve in that area usually had around three, but in one-third of the cases was actually unifascicular in the area where the IANB was given (Fig. 20.10). If a nerve with many fascicles (e.g., inferior alveolar nerve) is damaged, only a small portion of the sensory distribution would be affected. When a nerve with one to three fascicles (e.g., lingual nerve) is damaged, the resulting area of sensory involvement will be considerably larger. It is this author’s opinion that if paresthesia involves the distribution of the lingual nerve—and especially when an “electric shock” (e.g., “zap”) is experienced during injection, the likely cause is mechanical trauma secondary to contact of the metal needle with the nerve. If paresthesia involves the distribution of the inferior alveolar nerve (e.g., chin, lip, mucous membrane), then possible causes include (1) neurotoxicity of the local anesthetic, (2) mechanical contact of the needle to the inferior alveolar nerve, (3) edema, and (4) hemorrhage.␣ Local Anesthetics Are Neurotoxins All local anesthetics are neurotoxic.54 If all local anesthetics were equally neurotoxic, then the percentage of reported cases of paresthesia for that drug should approximate its market share. The resulting fraction ideally should be 1.0 (Table 20.10). In 2007 Pogrel55 reported on 52 patients with paresthesia. Lidocaine produced the greatest number (20) and percentage (35%) of cases of paresthesia. However, with a market share of 54% at that time, the ratio was 0.64, lower than expected (Table 20.10). Prilocaine, on the other hand, with a 6% market share was involved in 29.8% (17) of the cases of paresthesia (ratio of 4.96). Articaine, with a market share of 25%, was also involved in 29.8% (17) of the cases, for a ratio of 1.19. Pogrel concluded55: “Therefore, using our previous assumption that approximately half of all local anesthetic used is for inferior alveolar nerve blocks, then on the figures we have generated from our clinic we do not see a disproportionate nerve involvement from articaine.” In a 2012 update reporting on a subsequent 38 patients with paresthesia evaluated in his clinic between 2006 and 2011, Pogrel56 stated that “articaine is still causing permanent inferior alveolar and lingual nerve damage (36%) which is proportionate to its market share (37%) .... The number of cases caused by lidocaine, on the other hand, appears to be only around 50% of its market share. Prilocaine however by causing 26% of all cases seen since 2005 with a market share of only 8% is somewhat disproportionate to its market share” (see Table 20.10).␣ Is Articaine a More Effective Local Anesthetic and Does It Have a Greater Risk of Paresthesia? Meta-analyses comparing articaine with lidocaine have concluded “that articaine as compared with lignocaine provides a higher rate of anaesthetic success, with comparable safety to lignocaine when used as infiltration or blocks for routine dental treatments” and “this meta-analysis thus supports a recommendation for 4% articaine (1:100,000 epinephrine) in routine dental practice over and above 2% lidocaine (1:100,000 epinephrine).”73,74 A 2012 article reporting on a histologic analysis of the neurotoxicity of lidocaine, articaine, and epinephrine on the mental nerve in rats, concluded that “articaine is not toxic to the nervous structure and (that) further studies are necessary to explain the possible relation between articaine injection and paresthesia.”75 CHAPTER 20 In a 2013 laboratory study, human neuroblastoma cells were exposed to various concentrations of articaine, lidocaine, and prilocaine to determine neurotoxicity at six different drug concentrations.76 The results of this in vitro study revealed that 2% lidocaine had a lower neurotoxicity profile than 4% prilocaine and that 4% articaine had a lower neurotoxicity profile than 2% lidocaine. In vitro studies are accurate, sensitive, and reproducible because they are conducted in a controlled environment. However, in vitro studies do not consider other factors, such as (1) local pharmacokinetics (concentration in tissues, local diffusion, absorption), (2) potential influence of other drugs on local pharmacokinetics (e.g., epinephrine), (3) systemic behavior of the drug after absorption (distribution, elimination, metabolism), and (4) all other variables, such as differences between patients. In 2018 Albalawi et al.77 tested the neurotoxicity of lidocaine and articaine in SH-SY5Y cells. They reported that “articaine did not produce a prolonged block of neuronal responsiveness or an increased toxicity as compared with lidocaine in SH-SY5Y cells. The corollary that articaine does not produce a prolonged loss of responsiveness or cell death as compared with lidocaine under these reductionist conditions is perhaps the most relevant conclusion.”␣ So, What Should You Do? Doctors must always consider the benefit to be gained from use of a procedure or drug versus the risk involved in the use of the procedure or drug. Only when, in the opinion of the treating doctor, the benefit to be gained by the patient clearly outweighs the risk should the procedure be undertaken or the drug administered. All reports claiming an increased risk of paresthesia with articaine are anecdotal, consisting of case reports. No scientific evidence has demonstrated an increased risk of paresthesia following the administration of articaine compared with other local anesthetics. In a discussion of current controversies in dentistry, Christenson78 stated: “There have been allegations of more patients having lingering paresthesia and anesthesia when articaine is used for mandibular block than lidocaine. Studies have not shown this to be true. Also, the observations of practitioners show about the same quantities of paresthesia with articaine versus lidocaine. The controversy is unfounded.” The choices for IANB include (1) continuing with the use of 4% articaine with epinephrine 1:100,000 or 1:200,000 or (2) if you are unconvinced or still concerned, use of either 2% lidocaine with epinephrine 1:100,000 or 2% mepivacaine with levonordefrin 1:20,000 (United States) or epinephrine 1:100,000 (Canada) for IANB, followed immediately by a buccal infiltration of 0.6 to 0.9 mL of articaine (preferably buffered) at the apex of each tooth to be treated. The administration of 4% prilocaine with epinephrine appears to be associated with a considerably greater risk of TABLE 20.11 Recent Advances in Local Anesthesia 379 Comparison of Plain Local Anesthetic Versus Vasoconstrictor-Containing Local Anesthetic Plain Local Anesthetic Local Anesthetic + Vasoconstrictor Onset of pulpal anesthesia Somewhat faster Slower Duration of pulpal anesthesia Shorter Longer Depth of pulpal anesthesia Not as profound More profound Peak blood level Higher Lower paresthesia to the lingual and/or inferior alveolar nerves when administered by IANB. Its use for IANB is not recommended by this author.␣ Conclusions Articaine hydrochloride has become a very popular local anesthetic in dentistry. It provides the same depth and duration of pulpal and soft tissue anesthesia as the other intermediate-acting dental local anesthetics—lidocaine, mepivacaine, and prilocaine. Because the elimination halflife of articaine is considerably shorter than that of other amide local anesthetics, it is the preferred drug in special patient populations, including children, pregnant women, and nursing mothers. Because of the greater lipid solubility of articaine, the buccal infiltration of articaine in the adult mandible has a clinically significant rate of success in providing pulpal anesthesia compared with other amide local anesthetics. Several meta-analyses have concluded that articaine is a preferred dental local anesthetic. Regarding paresthesia, there is no scientific basis for stating that articaine is more neurotoxic than other commonly used dental local anesthetics.␣ Phentolamine Mesylate: The Local Anesthesia “Off” Switch All currently used injectable local anesthetics are vasodilators. Three local anesthetics formulations without a vasoconstrictor are available for use in dental cartridges worldwide: 2% lidocaine HCl (not available in dental cartridges in North America); 3% mepivacaine HCl; and 4% prilocaine HCl. These drugs provide—compared with their formulations containing a vasoconstrictor—a short duration of not as profound anesthesia (see Table 4.17). Additionally, vasodilators increase blood flow in the area in which the drug was deposited as arterioles and capillaries dilate, leading to (1) a more “bloody” surgical field and (2) higher blood levels of the local anesthetic (see Table 20.11). 380 PART IV Complications, Legal Considerations, Questions, and the Future A vasoconstrictor (e.g., epinephrine) is added to the local anesthetic to (1) increase the depth and duration of pulpal and soft tissue anesthesia, (2) provide a “cleaner” surgical field, and (3) decrease the blood level of the local anesthetic drug, thereby increasing its safety (decreasing the risk of overdose caused by overadministration of the local anesthetic) (see Table 20.11). For dental procedures on teeth (e.g., restorations, endodontic procedures, extractions, implants) pulpal anesthesia is necessary until such time as the procedure is completed. Soft tissue anesthesia, although necessary for some procedures (e.g., scaling and root planing, periodontal surgery, exodontia) is always of considerably longer duration than pulpal anesthesia. When one is preparing teeth for placement of restorations—the most common procedure in dentistry79—pulpal anesthesia is a necessity for the duration of the preparation (e.g., cutting) of the tooth. Once this is complete, there is no longer a need for continued anesthesia of the tissues, either hard or soft. However, the need for effective intraoperative pain control normally mandates the use of a local anesthetic containing a vasoconstrictor such as epinephrine or levonordefrin, which has become a routine part of dentistry.80,81 Patients are commonly discharged from the dental office with residual numbness of their lips and tongue, typically persisting for an additional 3 to 5 hours.82 Residual soft tissue anesthesia is a possible inconvenience or embarrassment to the patient, who is unable to function normally for many hours after leaving the dental appointment. In a survey of patients receiving intraoral local anesthetic, Rafique et al.83 reported that there were several aspects of the post–local anesthetic experience that were disliked by patients, including three major areas: functional, sensory, and perceptual. Functionally, patients disliked their diminished ability to speak (lisping), to smile (asymmetric), and to drink (liquid runs from the mouth), and the inability to control drooling while still numb. Sensorially, the lack of sensation was described as quite discomfiting, while the perception that their body was distorted (e.g., swollen lips) was equally unpleasant. For many patients these sequelae become a significant detriment to their quality of life, making it difficult for them to return to their usual activities for hours after treatment. When the dental appointment concludes at a time approaching the time for a meal, either lunch or dinner, patients must consider whether to eat while numb or postpone their dining until the residual soft tissue anesthesia resolves. Although not normally a significant problem, residual soft tissue anesthesia may occasionally lead to self-inflicted soft tissue injury in any patient. Self-inflicted soft tissue injury—most commonly of the lip or tongue—is more likely to be noted in younger children and in mentally disabled adult and pediatric patients.84 A study of pediatric patients by College et al.85 revealed that a significant percentage of IANBs were associated with inadvertent biting of the lips. By age group, the frequency of trauma to the lips was 18% for younger than 4 years, 16% for 4 to 7 years, 13% for 8 to 11 years, and 7% for TABLE Incidence of Self-Inflicted Soft Tissue Injury 20.12 in Pediatric Populations85 Age (Years) Percentage With Self-Inflicted Soft Tissue Injury <4 18 4–7 16 8–11 13 ≥12 7 OH N N CH3SO3H N H H3C • Fig. 20.11 Phentolamine mesylate. 12 years or older (Table 20.12). This can be explained by the fact that the younger patient will test (by biting) their unnumb lip—which hurts—and then test the still-numb side—which does not hurt. Where the adult would normally not proceed beyond this point, the younger child may “play” with this “feeling” and continue to bite ever harder, not realizing the damage being inflicted. Mentally handicapped adults are just as likely to incur self-inflicted soft tissue injury. This author was surprised to learn from dentists who treat geriatric patients that another group—the geriatric patient with dementia—presents a risk of soft tissue injury following local anesthetic injection equal to or greater than that of children and mentally challenged adults. So, can the numbness produced by local anesthetics be made to resolve more quickly? The injection of a vasodilating drug into the area of prior local anesthetic administration should accomplish this goal by hastening the redistribution of local anesthetic from the nerve into the cardiovascular system, thereby decreasing the duration of residual soft tissue anesthesia. Phentolamine Mesylate Phentolamine mesylate is an α-adrenergic receptor antagonist approved by the FDA in 1952 (Fig. 20.11). Approved uses of phentolamine include diagnosis of pheochromocytoma and treatment of hypertension in pheochromocytoma,86,87 prevention of tissue necrosis after norepinephrine extravasation, 88,89 and reversal of soft tissue anesthesia.86 Phentolamine has also been used to treat hypertensive crisis associated with monoamine oxidase inhibitor therapy86,89 and in combination with papaverine to treat erectile dysfunction.86,90, 91 Phentolamine is a short-acting, competitive antagonist at peripheral α-adrenergic receptors. It antagonizes both α1 and α2 receptors, thus blocking the actions of the circulating catecholamines epinephrine and norepinephrine. CHAPTER 20 Phentolamine also stimulates β-adrenergic receptors in the heart and lungs. The clinical effects of phentolamine include peripheral vasodilation and tachycardia. Vasodilation is a result of both direct relaxation of vascular smooth muscle and α blockade. The drug produces positive inotropic and chronotropic effects, leading to an increase in cardiac output. In smaller doses the positive inotropic effect can predominate and raise blood pressure; in larger doses, peripheral vasodilation can mask the inotropic effect and lower blood pressure. These actions make phentolamine useful in treating hypertension caused by increased circulating levels of epinephrine and norepinephrine, as occurs in pheochromocytoma.86 For prevention or treatment of dermal necrosis or sloughing following extravasation of catecholamines (e.g., epinephrine, norepinephrine), 5 to 10 mg of phentolamine (diluted with 10 to 15 mL of normal saline) is injected into the affected area within 12 hours of extravasation. Visible hyperemia and increased tissue warmth at the site are signs of effective treatment.86,92 For the treatment of hypertensive emergency related to any catecholamine excess, such as interactions between monoamine oxidase inhibitors and sympathomimetic amines, phentolamine is administered intravenously as a bolus in a dose of 5 to 15 mg.86,93 Pregnancy and Lactation As presently used in medicine, phentolamine is categorized by the FDA as a pregnancy category C drug and as “safety unknown” for nursing mothers.39,40 (Pregnancy category C—animal studies show adverse fetal effect(s) but no controlled human studies or no animal or human studies; weigh possible fetal risk versus maternal benefit. Lactation category “safety unknown”—inadequate literature available to assess risk; caution advised.) Phentolamine is available as a 5 mg/mL solution for parenteral administration.␣ Clinical Trials: Adults and Adolescents In May 2008 the FDA approved phentolamine mesylate (OraVerse) for dental use to reverse anesthesia following dental injections. Marketed in 1.7-mL dental cartridges, the formulation contains 0.4 mg of phentolamine mesylate (0.235 mg/mL).94 The dental formulation of phentolamine is approximately 1/20 the concentration of that used in medicine. In phase 3 randomized, controlled, double-blind clinical trials, patients received a vasoconstrictor-containing local anesthetic on one side of their mouths before a restorative or periodontal maintenance procedure. The primary end point was the elapsed time to the return of normal lip sensation as measured by patient-reported responses to lip palpation. Secondary end points included the patients’ perception of altered function, sensation, and appearance, and functional deficits in smiling, speaking, drinking, and drooling, as assessed by both the patient and an observer blinded to the treatment.95-98 Patients were randomized to receive one of four local anesthetics: 2% lidocaine with epinephrine 1:100,000; 2% Recent Advances in Local Anesthesia 381 mepivacaine with levonordefrin 1:20,000; 4% articaine with epinephrine 1:100,000; or 4% prilocaine with epinephrine 1:200,000. At the conclusion of the procedure, the patient received either phentolamine mesylate or a control injection. Both patients and all investigators were blinded to the treatment assigned. The study drug was administered at the same site, and in the case of phentolamine mesylate, the same number of cartridges (one or two) as for the previous local anesthetic injection(s). The control was a sham injection in which the plastic needle cap attached to the dental syringe containing an empty cartridge was pushed against, but did not penetrate, the intraoral soft tissue at the site of the previous local anesthetic injection. After receiving phentolamine mesylate or the sham injection, all patients were observed for 5 hours to collect efficacy and safety data, and were then monitored for up to 48 hours. The 5-hour observation and testing period was a primary determinant in the lower age limit (4 years) for patients. It was felt (correctly, it turned out) that younger patients would be unable to cooperate fully with the assessments required over the 5-hour period of observation. All patients were trained in assessing the numbness of their lips. Those in the mandibular protocol group were also trained to tap their tongues. The procedure involved a light tapping of these soft tissues with their index or middle finger. Assessments were made every 5 minutes. The functional assessment battery included measurements of smiling, speaking, and drooling, and drinking 3 ounces of water at various time points during the study.97,98 Each functional assessment was rated as normal or abnormal by a research assistant and the patient.␣ Efficacy of Phentolamine Mesylate: Adolescents and Adults In the maxillary trial, the median time to recovery of normal sensation in the upper lip was 50 minutes for phentolamine mesylate patients and 132.5 minutes for control patients, a reduction in upper lip anesthesia of 82.5 minutes (P < .0001).95 In the mandibular trial, the median time to recovery of normal sensation in the lower lip was 70 minutes for phentolamine mesylate patients and 155 minutes for control patients, a reduction in lower lip anesthesia of 85 minutes (P < .0001).95 Within 30 minutes of phentolamine mesylate administration, 26.7% of maxillary patients reported return of normal lip sensation as compared with 1.7% in the control group. At 1 hour, 59.2% had normal upper lip sensation versus 11.7% for sham patients. At 90 minutes the proportions were 75% and 25%, respectively. Upper lip anesthesia persisting beyond 2 hours occurred in 54.2% of sham patients versus 11.6% of phentolamine mesylate patients.95 In the mandible, within 30 minutes of phentolamine mesylate administration, 17.2% of patients reported normal lower lip sensation as compared with 0.8% in the control group. At 1 hour, 41% had normal lower lip sensation versus 7.4% for sham patients. At 90 minutes the proportions were 70.5% and 13.1%, respectively. Lower 382 PART IV Complications, Legal Considerations, Questions, and the Future lip anesthesia persisting beyond 2 hours occurred in 70.5% of sham patients versus 18.9% of phentolamine mesylate patients.95 The median time to return of normal sensation to the tongue was 60 minutes for phentolamine mesylate patients and 125 minutes for sham patients, a statistically significant (P < .0001) difference of 65 minutes.95␣ TABLE 20.13 Indications for Local Anesthesia Reversal Conservative dental treatment Nonsurgical periodontal treatment (e.g., scaling and root planing) Pediatric dentistry Safety of Phentolamine Mesylate: Adolescents and Adults Medically compromised patients (e.g., type 1 diabetic patients) The overall frequency and the nature of adverse events reported in both the maxillary study and the mandibular study appeared similar in nature and frequency. None of the adverse events in either study was serious or rated severe, and no patient discontinued participation in the study because of an adverse event.94,95␣ Geriatric patients Safety and Efficacy of Phentolamine Mesylate: Children In a phase 2, double-blinded, randomized, multicenter (N = 11), controlled study, pediatric patients between the ages of 4 and 11 years received 2% lidocaine with epinephrine 1:100,000 and either phentolamine mesylate or sham injection. One hundred fifty-two patients were enrolled and completed the study. There were 96 in the phentolamine mesylate group and 56 in the sham injection group. The median time to normal lip sensation was evaluated in patients aged 6 to 11 years who were trainable for lip palpation procedures (see earlier). The reduction in the median time to normal lip sensation for phentolamine mesylate patients (N = 60) was 60 minutes compared with 135 minutes in the control group (N = 43), representing a reduction of residual soft tissue anesthesia of 75 minutes (55.6%) for both maxillary and mandibular arches. Within 1 hour following administration of phentolamine mesylate, 61% of patients reported normal lip sensation, while only 21% of patients in the sham injection group reported normal lip sensation (P < .0001).96␣ Clinical Indications for Reversal of Local Anesthesia Reversal of local anesthesia should be a treatment option whenever prolonged soft tissue anesthesia presents a potential risk (soft tissue injury) or will negatively impact the patient’s lifestyle (e.g., inability to speak or eat) (Table 20.13). Froum et al.99 administered phentolamine mesylate following insertion of mandibular implants in an attempt to minimize the risk of postimplant paresthesia along the distribution of the inferior alveolar nerve. A situation that does not usually represent an indication for soft tissue anesthesia reversal includes postsurgical patients, where prolonged soft tissue anesthesia is desirable as a means of preventing breakthrough pain (see the discussion of postsurgical pain management in Chapter 16). Further, following local anesthetic administration via the periodontal ligament, intraseptal, or intraosseous injection, the localized area of soft tissue anesthesia associated Special needs patients Post mandibular implant patients Persons with a need to “return to normal” quickly: Business people Social gatherings Lunch or dinner engagements with these injections obviates the use of phentolamine mesylate.␣ Clinical Use of Phentolamine Mesylate in Dentistry Phentolamine mesylate is indicated for the reversal of soft tissue anesthesia (e.g., anesthesia of the lip and tongue) and the associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor. Phentolamine mesylate is not recommended for use in children younger than 3 years or weighing less than 15 kg (33 lb).94 The recommended dose of phentolamine mesylate is based on the number of cartridges of local anesthetic with vasoconstrictor administered. It is administered in an equal volume, up to a maximum of two cartridges. Phentolamine mesylate is administered at the same location(s) and by the same technique(s) (nerve block or infiltration) used earlier for the local anesthetic administration.94 Adverse reactions associated with the administration of phentolamine mesylate were discussed earlier (safety and adverse reaction discussion).94,95 Other potential complications are trismus and paresthesia, both of which are related to the act of injection rather than to the drug itself.␣ Conclusion Phentolamine mesylate enables the dentist or dental hygienist to significantly decrease the duration of residual soft tissue anesthesia in patients where such numbness may prove to be potentially injurious (children, geriatric, and special needs patients) or may have a negative influence on their quality of life (speaking, eating, negative body image). Although many patients might not be receptive to the concept of “making it go away faster,” the availability in a dental office gives each patient an option to be considered.␣ CHAPTER 20 TABLE 20.14 Expected Duration of Pulpal Anesthesia Local Anesthetic Formulation Approximate Expected Duration of Pulpal Anesthesia by Nerve Block (min) 3% mepivacaine 40 4% prilocaine 40–60 2% lidocaine with a vasoconstrictor 60 4% articaine with a vasoconstrictor 60 2% mepivacaine with a vasoconstrictor 60 4% prilocaine with a vasoconstrictor 60 0.5% bupivacaine with a vasoconstrictor 240–300 Buffering (Alkalinizing) of Local Anesthetics: The Local Anesthetic “On” Switch The dental profession depends on local anesthetics to provide patients with comfortable and pain-free treatment. Deposit a local anesthetic near to a nerve and it will provide anesthesia. Table 20.14 lists the local anesthetic formulations available with their expected onset of pulpal anesthesia. Despite the effectiveness of these drugs in providing pain control, there remain a number of vexing “problems” that dentists must cope with, primarily associated with the acidity of the local anesthetic solution itself. These include: (1) pain during the actual administration (injection) of the anesthetic solution, (2) a slower than desired onset of profound (pulpal) anesthesia, and (3) less than optimal effectiveness when one is seeking to anesthetize infected teeth. Issue 1: Acidity Causes Pain During Injection of Local Anesthetics Fear of pain is the most common anxiety for dental patients.1 As effective as local anesthetics can be in preventing pain during treatment, patients fear the act of receiving the anesthetic as much as or more than they fear the dental procedure itself. The dental anesthetic injection also provokes more emergencies than actual dental treatment. Syncope (fainting) was the most common, accounting for 50.3% of all emergencies in a survey of 4307 dentists in North America.100 Asked for the location and timing of these emergencies, the respondents said that more than half (54.9%) occurred either during or immediately following local anesthetic administration.101,102 Recent Advances in Local Anesthesia 383 Some injection pain can be minimized or eliminated through use of drugs and techniques discussed in previous chapters including: injecting anesthetic slowly,103,104 using topical anesthetic, and stretching the tissue before needle penetration.105 Yet many patients still complain of a burning or stinging sensation as the first drops of anesthetic are injected. This “bee sting effect” is caused by the acidity of the anesthetic solution. On the pH scale, 7.0 is neutral, above 7.0 is basic, and below 7.0 is acidic. Human physiologic pH is 7.4. All injectable local anesthetics (plain drugs with no vasoconstrictor) are slightly acidic. The pH of a plain drug (e.g., 3% mepivacaine HCl, 4% prilocaine HCl) is approximately 6.4, which is closer to physiologic than local anesthetics containing a vasoconstrictor.106 Vasoconstrictors increase the depth and duration of anesthesia as well as the safety of the local anesthetic. Addition of epinephrine to local anesthetics increases pulpal anesthesia to approximately 60 minutes, with soft tissue anesthesia lasting between 3 and 5 hours or more. However, epinephrine is rapidly oxidized at near physiologic pH values, so the antioxidant sodium bisulfite (NaHSO3) is added to the solution.107 The addition of NaHSO3 lowers the pH of vasoconstrictorcontaining solutions to approximately 3.5. Clinical studies have shown pH values ranging between 2.86107 and 4.16.108 Alkalinizing (buffering) of local anesthetics has been practiced by the medical profession for more than 100 years.109 Medical professionals do not used sealed cartridges of local anesthetic solution. Rather, they use plastic syringes and multidose vials of local anesthetic. As the dental profession uses standardized sealed cartridges designed for use in dental syringes, until recently there was no practical means of buffering dental local anesthetics.␣ Issue 2: Low pH of Local Anesthetic Solutions Slows the Onset of Pulpal Anesthesia The amide anesthetics are generally stated to have an onset of between 3 and 5 minutes110-112; however, these figures represent the onset of soft tissue anesthesia. Pulpal, or surgical depth, anesthesia develops more slowly. Following completion of the local anesthetic injection, most dentists report that they wait between 10 and 15 minutes before returning to the treatment room. This is usually long enough for most patients to have achieved sufficient anesthesia for the dentist to start the procedure (the exception being missed blocks, which will require additional injections). As is known by all practicing dentists (clinical experience), and from the results of well-designed clinical trials, there exists a significant practical and clinical distinction between the onset of soft tissue anesthesia and the onset of pulpal anesthesia.105 Lai et al.112 found that at 4 minutes after IANB with 2% lidocaine with epinephrine 1:100,000, 70% of patients achieved soft tissue anesthesia (as determined with a sharp dental explorer), yet only 25% had pulpal anesthesia (determined with an EPT). At 6 minutes the proportions were 85% for soft tissue anesthesia and 40% for pulpal anesthesia. Kanaa et al.104 found that at 8 minutes following IANB with 2% lidocaine with epinephrine 1:80,000, 100% of patients had lingual anesthesia, 93% had