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Successful pulpal anesthesia for symptomatic irreversible pulpitis
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ENDODONTICS
Successful pulpal anesthesia for symptomatic irreversible pulpitis Melissa Drum, DDS, MS; Al Reader, DDS, MS; John Nusstein, DDS, MS; Sara Fowler, DMD, MS
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o easy solution has been identified for successfully anesthetizing all patients with vital mandibular painful teeth diagnosed with symptomatic irreversible pulpitis. Patients with this painful clinical condition are more difficult to anesthetize for various reasons, all of which are not fully understood. Some of the reasons described in the research literature are altered resting potentials and decreased excitability thresholds of inflamed nerves, tetrodotoxin-resistant sodium channels (resistant to anesthetics), increased expression of sodium channels in irreversibly inflamed pulps, and apprehensive patients with lower pain thresholds.1-4 The reason most often cited but least likely to hold true is lowered pH of inflamed tissue. This theory hypothesizes that the lowered pH reduces the amount of the base form of the anesthetic available to penetrate the membrane thereby preventing anesthesia. This is not the best explanation for failure of anesthesia with the inferior alveolar nerve block (IANB) when the injection is not given at the primary site of inflammation. Likely, this is a more complicated neuronal process. Inflammation and bacterial insult can lead to sprouting of nerve fibers, increased expression of neuropeptides such as substance P and calcitonin gene-related peptide, and the release of inflammatory mediators such as prostaglandins E2, prostaglandins F2a, interleukins 1 and 6, and tumor necrosis factor.5 This can also lead to excitability of nociceptor isoforms (such as Nav 1.7, 1.8, 1.9). The clinical conditions may include neuronal plasticity, allodynia, hyperalgesia peripherally and centrally, and central sensitization.5 These factors may help explain why local anesthesia is not always effective when patients are in pain. Copyright ª 2017 American Dental Association. All rights reserved.
ABSTRACT Background and Overview. Profound pulpal anesthesia after a successful inferior alveolar nerve block can be difficult to achieve when the clinical condition is a pulpal diagnosis of symptomatic irreversible pulpitis. The authors reviewed the literature as it relates to the anesthesia necessary for endodontic therapy of patients with painful, vital, mandibular teeth diagnosed with symptomatic irreversible pulpitis. Conclusions. Supplemental anesthetic techniques and medications are available that can be used to improve pulpal anesthesia for patients with the clinical condition of symptomatic irreversible pulpitis. Practical Implications. The authors identified treatment recommendations for anesthesia in the case of symptomatic irreversible pulpitis based on a review of the available evidence. Key Words. Anesthesia; anesthetics; inferior alveolar nerve block; irreversible pulpitis; symptomatic irreversible pulpitis. JADA 2017:148(4):267-271 http://dx.doi.org/10.1016/j.adaj.2017.01.002
There is no miracle solution or nerve block injection technique that will guarantee effective pulpal anesthesia in patients with symptomatic irreversible pulpitis. For most patients, only the addition of supplemental techniques produces effective pain relief. Success rates of the IANB, when success is defined as no or mild pain on endodontic access, are 28% for the first molars, 25% for the second molars, and 39% for the premolars in patients with symptomatic irreversible pulpitis according to Fowler and colleagues.6 The success rates listed here and throughout the article assume a successful IANB (lip numbness) and are indicative of actual pulpal numbness (successful pulpal anesthesia). There is a difference in success rates between patients with asymptomatic and symptomatic irreversible pulpitis.
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As stated, dentists will find symptomatic patients are going to have a harder time achieving pulpal anesthesia.7,8 ANESTHETIC SOLUTIONS
Different volumes, anesthetic solutions, and concentrations have been studied to try to achieve higher success rates but to no avail. Mepivacaine (a 3% solution) was not found to increase the success rate of the IANB.9 However, it can be used in patients with contraindications to epinephrine-containing solutions. Parirokh and colleagues10 found that bupivacaine (0.5%) did not result in a higher success rate for the IANB in patients with symptomatic irreversible pulpitis. Because bupivacaine has a slower onset than other anesthetics,11 its indication would be at the end of an appointment as an additional IANB to promote prolonged anesthesia and pain control (only in the mandible) rather than as an initial IANB. Articaine (a 4% solution), although superior to lidocaine when given as a mandibular infiltration, has not been found to be superior to lidocaine when given as a block.12,13 Furthermore, the increased concentration with no added anesthetic benefit should preclude its use for an IANB. In a systemic review and meta-analysis, Kung and colleagues14 found that articaine was not superior to lidocaine for IANBs but was superior for supplemental infiltration in the mandible after an IANB. Another meta-analysis also confirmed the superiority of articaine over lidocaine for mandibular infiltration anesthesia.15 Therefore, articaine’s best use would be in mandibular infiltrations rather than nerve blocks. Articaine’s superiority for mandibular infiltrations has often been noted as being due to the increased concentration (4%). However, the percentage of solution is not necessarily the advantage of articaine in these injections. Nydegger and colleagues16 found that 4% articaine was statistically better than both 4% lidocaine and 4% prilocaine in mandibular buccal infiltrations. The 3-dimensional molecular structure may be what gives it the advantage. It is thought that the presence of the thiophene ring and an internal hydrogen bond (between amine nitrogen and ester carbonyl oxygen) causes the molecule to fold over on itself when entering the bone.17,18 Concentrations of epinephrine have also not proved to achieve higher success in IANBs in patients with symptomatic irreversible pulpitis. Aggarwal and colleagues19 found no difference between 2% lidocaine with 1:80,000 epinephrine when compared with 2% lidocaine with 1:200,000 epinephrine with success rates of 20% and 28%, respectively, in patients with symptomatic irreversible pulpitis. Some clinicians believe repeating the IANB after achieving lip numbness will result in more profound pulpal anesthesia. In patients with symptomatic irreversible pulpitis, repeating an IANB is only
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approximately 30% successful for pulpal anesthesia.20 Giving 2 cartridges can help decrease the chance of missing the block but because that is such a low incidence (6% or less) and does not increase the chance for pulpal anesthesia, it is not necessary.21 Sometimes, giving a second injection and getting success is actually due to giving the first injection the appropriate time to work since the onset of pulpal anesthesia after an IANB ranges from 5 to 19 minutes.22 In cases of slow onset, pulpal anesthesia can occur as late as 30 minutes postinjection.22 Using different block injection techniques has also not been shown to increase success of mandibular anesthesia. The success rate with the Gow-Gates technique (35%)23 was similar to the 24% to 35% success rates of the traditional IANBs in studies having patients with symptomatic irreversible pulpitis.24-28 Studies have also been done in asymptomatic patients and no difference in success was found between the Gow-Gates technique and the standard IANB technique.29 No difference does not necessarily mean the Gow-Gates is inferior. It means either technique can be used. Unfortunately, in patients with symptomatic irreversible pulpitis, a buccal infiltration of articaine may also not be reliable for pulpal anesthesia. Success rates for a buccal infiltration of articaine after an IANB in symptomatic irreversible pulpitis were only 42% for first molars, 48% for second molars, and 73% for premolars.6 This is not to be confused with the high success rates when articaine is used as an infiltration after an IANB in asymptomatic patients.15,30-32 Also, articaine, as an infiltration, may be a helpful addition to the other supplemental techniques, but it often does not provide pulpal anesthesia for symptomatic irreversible pulpitis. ANXIOLYTICS
The addition of anxiolytics has also been suggested to increase success of pulpal anesthesia. The theory is that because anxiety can reduce pain tolerance, a decrease in anxiety should lead to a decrease in pain. However, studies of patients diagnosed with symptomatic irreversible pulpitis when preoperative triazolam or alprazolam were given did not achieve increased success rates.33,34 Even when using conscious sedation, profound local anesthesia is still required. Payen and colleagues35 and Aissaoui and colleagues36 found that sedated, unconscious patients detect, experience, and respond to pain but they do not remember it. If unconscious patients can feel pain, consciously sedated patients will feel pain as well. This does not mean that dentists should not use antianxiety medications to help with anxiety but they should not be substituted as a pain medication or ABBREVIATION KEY. IANB: Inferior alveolar nerve block.
SPECIALTY UPDATE
anesthetic. Also, even though pain may not be recalled, it is not known what physiological and biochemical effects may occur with the stimulation of pain, especially considering what we know about neuronal plasticity. Just because the pain is not remembered, it doesn’t mean there is no effect. BUFFERING
Buffering has also been highly promoted to increase the success of anesthesia. Two commercially available dental anesthetic buffering systems are sold in the United States. Onset (Onpharma) buffers local anesthetic solutions within the dental anesthetic cartridge using a dispensing system that includes a mixing pen, Onpharma Cartridge Connector, and Onset Sodium Bicarbonate Additive Solution. The other system is Anutra (Anutra Medical), which consists of a dispenser and multiple-dose vials of lidocaine and bicarbonate in a cassette that is drawn into a disposable syringe. The theory is that a higher pH will increase the anesthetic success rate. Research has shown that 2% or 4% buffered lidocaine formulations with epinephrine did not result in an increase in the success rate or decrease injection pain over nonbuffered lidocaine formulations with epinephrine in patients with symptomatic irreversible pulpitis.37,38 The reasoning behind the negative findings is that the body has the ability to intrinsically buffer so that it maintains tissues at physiological pH. Wennberg and colleagues39 suggested that the pH conversion buffering process could occur within several minutes. Punnia-Moorthy40 reported freshly prepared 2% lignocaine with epinephrine with a pH of 5.25 being converted to a pH of 7.17 within 3 minutes after an intradermal injection. PREEMPTIVE MEDICATIONS
Preemptive medications have been hypothesized to help reduce the levels of prostaglandins and other inflammatory mediators and thus improve anesthetic success by reducing the prostaglandin sensitization of peripheral nociceptors. Studies in which patients received preoperative ibuprofen, a combination of ibuprofen with acetaminophen, acetaminophen with hydrocodone, or ketorolac for the clinical condition of symptomatic irreversible pulpitis have failed to detect significant improvements in pulpal anesthesia success rates or they detected success rates too low to provide treatment without supplemental anesthesia.25-27,41-44 Although not useful for intra-appointment anesthesia, steroids may be useful in controlling pain in untreated irreversible pulpitis.45-47 Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals) has also been studied to help control pain in untreated symptomatic irreversible pulpitis (with the intention that evidence of pain control and anesthesia could lead to the use of Exparel postoperatively). Exparel combines bupivacaine with DepoFoam (Pacira
Pharmaceuticals) and consists of microscopic, spherical, lipid-based chambers. On injection, approximately 3% is free bupivacaine and the rest of the drug is released from the liposome over time (by erosion and lipid membrane reorganization). Administration of Exparel (theoretically providing local anesthesia for up to 72 hours) as an infiltration (it is not US Food and Drug Administration approved for nerve blocks) did not reduce pain to manageable clinical levels in patients with untreated, symptomatic irreversible pulpitis.48 It is unknown whether the concentration released will be effective even if it is studied as a nerve block in the future (after US Food and Drug Administration approval as a nerve block). OTHER SUPPLEMENTAL TECHNIQUES AND MEDICATIONS
Although there is ongoing research to develop a simple solution to anesthesia problems, none is available. The following supplemental techniques and medications are those that research supports to help with pulpal anesthesia in symptomatic irreversible pulpitis. The most predictable way to achieve pulpal anesthesia in a clinical scenario of irreversible pulpitis is the supplemental intraosseous injection, using the Stabident (Fairfax Dental) or X-tip system (Dentsply), of 1 cartridge of 2% lidocaine with 1:100,000 epinephrine after a successful (lip numbness) IANB. This injection is reported to be successful approximately 90% of the time in mandibular posterior teeth.49 Using volumes less than a full cartridge will decrease the success rate.50,51 Mepivacaine plain (3% Carbocaine, 3% Polocaine) can also be used for those patients who have medical contraindications or would react poorly to the increase in heart rate associated with an intraosseous injection of lidocaine, although 2 cartridges may be necessary to achieve the same success rate as 1 cartridge of lidocaine (80% 1 cartridge versus 98% 2 cartridges).52 Similar to the results when evaluating an IANB, articaine does not show a superior effect when used as an intraosseous injection.53 Supplemental intraligamentary periodontal ligament injections can also be used. Success rates for the intraligamentary injection for patients with irreversible pulpitis are in the range of 63% to 74%.54-57 Reinjection improves success rates to levels of 92% to 96%.55-57 This injection is relatively easy to give and no special equipment is required. Because of the need to reinject and the short duration of anesthesia due to the smaller volume of solution injected, intraosseous injections can provide more predictable anesthesia. Intraseptal injections, which are the deposition of anesthetic solution directly into the interdental septum without an intraosseous device, have also been studied but the supplemental injection has a low success rate (29%) in patients with symptomatic irreversible pulpitis.58
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In approximately 5% to 10% of patients with irreversible pulpitis, supplemental injections do not produce pulpal anesthesia. Therefore, intrapulpal anesthesia is indicated and will likely be successful if given under back pressure.59 The disadvantage is that the injection is painful and should only be used after all other supplemental techniques have been attempted. Nitrous oxide is the most commonly used inhalation anesthetic in dentistry and has an impressive safety record. Nitrous oxide has a potential benefit because of its combination of both antianxiety and analgesic effects. As mentioned, antianxiety medications alone did not show increased success rates. It is thought that nitrous oxide causes an analgesic effect by the release of endogenous opiate peptides with activation of opioid receptors and inhibition of N-methyl-D-aspartate glutamate receptors. Administration of 30% to 50% nitrous oxide resulted in a statistically significant increase in the success of the IANB in patients with irreversible pulpitis.28 The increased success rates allow nitrous oxide to be a good adjunct in this clinical scenario. However, the success rates are not high enough to work without supplemental anesthesia. CONCLUSION
No single drug, solution, or technique will allow dentists to comfortably treat every patient with symptomatic irreversible pulpitis. However, there are some supplemental techniques and adjuncts that can be used to increase the success rates of pulpal anesthesia that will benefit both dentists and their patients. n Dr. Drum is an associate professor and the advanced program director, Division of Endodontics, The Ohio State University, 3059B Postle Hall, 305 W. 12th Ave., Columbus, OH 43210, e-mail [email protected]. Address correspondence to Dr. Drum. Dr. Reader is a professor, Division of Endodontics, The Ohio State University, Columbus, OH. Dr. Nusstein is a professor and the chair, Division of Endodontics, The Ohio State University, Columbus, OH. Dr. Fowler is an assistant professor and the predoctoral program director, Division of Endodontics, The Ohio State University, Columbus, OH. Disclosure. None of the authors reported any disclosures. Endodontics is published in collaboration with the American Association of Endodontists. 1. Modaresi J, Dianat O, Soluti A. Effect of pulp inflammation on nerve impulse quality with or without anesthesia. J Endod. 2008;34(4):438-441. 2. Wallace JA, Michanowicz AE, Mundell RD, Wilson EG. A pilot study of the clinical problem of regionally anesthetizing the pulp of an acutely inflamed mandibular molar. Oral Surg Oral Med Oral Pathol. 1985;59(5): 517-521. 3. Roy M, Narahashi T. Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons. J Neurosci. 1992;12(6):2104-2111. 4. Sorensen H, Skidmore L, Rzasa R, Kleier S, Levinson S, Hendry M. Comparison of pulpal sodium channel density in normal teeth to diseased teeth with severe spontaneous pain [abstract]. J Endod. 2004;30(4):287. 5. Hargreaves KM, Goodis HE, Tay F, eds. Seltzer and Bender’s Dental Pulp. 2nd ed. Hanover Park, IL: Quintessence; 2012.
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6. Fowler S, Drum M, Reader A, Beck M. Anesthetic success of an inferior alveolar nerve block and supplemental articaine buccal infiltration for molars and premolars in patients with symptomatic irreversible pulpitis. J Endod. 2016;42(3):390-392. 7. Argueta-Figueroa L, Arzate-Sosa G, Mendieta-Zeron H. Anesthetic efficacy of articaine for inferior alveolar nerve blocks in patients with symptomatic versus asymptomatic irreversible pulpitis. Gen Dent. 2012; 60(1):e39-e43. 8. Fragouli E, Panopoulos P, Georgopoulou M. Efficacy of inferior alveolar nerve block using 1.7 mL of 4% articaine with 1:100,000 epinephrine in reversible and irreversible pulpitis. ENDO. 2011;5(4): 285-291. 9. Lammers E, Nusstein J, Reader A, Drum M, Beck M, Fowler S. Does the combination of 3% mepivacaine plus 2% lidocaine with epinephrine improve anesthesia and reduce the pain of anesthetic injection for the inferior alveolar nerve block? A prospective, randomized, double-blind study. J Endod. 2014;40(9):1287-1292. 10. Parirokh M, Yosefi MH, Nakhaee N, Abbott PV, Manochehrifar H. The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain. Restor Dent Endod. 2015;40(2):155-160. 11. Fernandez C, Reader A, Beck M, Nusstein J. A prospective, randomized, double-blind comparison of bupivacaine and lidocaine for inferior alveolar nerve blocks. J Endod. 2005;31(7):499-503. 12. Claffey E, Reader A, Nusstein J, Beck M, Weaver J. Anesthetic efficacy of articaine for inferior alveolar nerve blocks in patients with irreversible pulpitis. J Endod. 2004;30(8):568-571. 13. Tortamano IP, Siviero M, Costa CG, Buscariolo IA, Armonia PL. A comparison of the anesthetic efficacy of articaine and lidocaine in patients with irreversible pulpitis. J Endod. 2009;35(2):165-168. 14. Kung J, McDonagh M, Sedgley CM. Does articaine provide an advantage over lidocaine in patients with symptomatic irreversible pulpitis? A systematic review and meta-analysis. J Endod. 2015;41(11): 1784-1794. 15. Brandt RG, Anderson PF, McDonald NJ, Sohn W, Peters MC. The pulpal anesthetic efficacy of articaine versus lidocaine in dentistry: a metaanalysis. JADA. 2011;142(5):493-504. 16. Nydegger B, Nusstein J, Reader A, Drum M, Beck M. Anesthetic comparisons of 4% concentrations of articaine, lidocaine, and prilocaine as primary buccal infiltrations of the mandibular first molar: a prospective randomized, double-blind study. J Endod. 2014;40(12): 1912-1916. 17. Skjevik AA, Haug BE, Lygre H, Teigen K. Intramolecular hydrogen bonding in articaine can be related to superior bone tissue penetration: a molecular dynamics study. Biophys Chem. 2011;154(1):18-25. 18. Kuhn B, Mohr P, Stahl M. Intramolecular hydrogen bonding in medicinal chemistry. J Med Chem. 2010;53(6):2601-2611. 19. Aggarwal V, Singla M, Miglani S, Kohli S. Comparison of the anaesthetic efficacy of epinephrine concentrations (1:80 000 and 1:200 000) in 2% lidocaine for inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a randomized, double-blind clinical trial. Int Endod J. 2014;47(4):373-379. 20. Fowler S, Reader A. Is a volume of 3.6 mL better than 1.8 mL for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? J Endod. 2013;39(8):970-972. 21. Fowler S, Reader A, Beck M. Incidence of missed inferior alveolar nerve blocks in vital asymptomatic subjects and in patients with symptomatic irreversible pulpitis. J Endod. 2015;41(5):637-639. 22. Reader A, Nusstein J, Drum M. Successful Local Anesthesia for Restorative Dentistry and Endodontics. Hanover Park, IL: Quintessence; 2011. 23. Click V, Drum M, Reader A, Nusstein J, Beck M. Evaluation of the Gow-Gates and Vazirani-Akinosi techniques in patients with symptomatic irreversible pulpitis: a prospective randomized study. J Endod. 2015;41(1): 16-21. 24. Matthews R, Drum M, Reader A, Nusstein J, Beck M. Articaine for supplemental buccal mandibular infiltration anesthesia in patients with irreversible pulpitis when the inferior alveolar nerve block fails. J Endod. 2009;35(3):343-346. 25. Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients with irreversible pulpitis. J Endod. 2010;36(3):379-382.
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26. Simpson M, Drum M, Nusstein J, Reader A, Beck M. Effect of combination of preoperative ibuprofen/acetaminophen on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2011;37(5):593-597. 27. Fullmer S, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative acetaminophen/hydrocodone on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double-blind, placebo-controlled study. J Endod. 2014;40(1):1-5. 28. Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565-569. 29. Goldberg S, Reader A, Drum M, Nusstein J, Beck M. Comparison of the anesthetic efficacy of the conventional inferior alveolar, Gow-Gates, and Vazirani-Akinosi techniques. J Endod. 2008;34(11):1306-1311. 30. Robertson D, Nusstein J, Reader A, Beck M, McCartney M. The anesthetic efficacy of articaine in buccal infiltration of mandibular posterior teeth. JADA. 2007;138(8):1104-1112. 31. Haase A, Reader A, Nusstein J, Beck M, Drum M. Comparing anesthetic efficacy of articaine versus lidocaine as a supplemental buccal infiltration of the mandibular first molar after an inferior alveolar nerve block. JADA. 2008;139(9):1228-1235. 32. Kanaa MD, Whitworth JM, Corbett IP, Meechan JG. Articaine buccal infiltration enhances the effectiveness of lidocaine inferior alveolar nerve block. Int Endod J. 2009;42(3):238-246. 33. Lindemann M, Reader A, Nusstein J, Drum M, Beck M. Effect of sublingual triazolam on the success of inferior alveolar nerve block in patients with irreversible pulpitis. J Endod. 2008;34(10):1167-1170. 34. Khademi AA, Saatchi M, Minaiyan M, Rostamizadeh N, Sharafi F. Effect of preoperative alprazolam on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2012;38(10): 1337-1339. 35. Payen JF, Bru O, Bosson JL, et al. Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med. 2001; 29(12):2258-2263. 36. Aissaoui Y, Zeggwagh AA, Zekraoui A, Abidi K, Abougal R. Validation of a behavioral pain scale in critically ill, sedated, and mechanically ventilated patients. Anesth Analg. 2005;101(5):1470-1476. 37. Schellenberg J, Drum M, Reader A, Nusstein J, Fowler S, Beck M. Effect of buffered 4% lidocaine on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double-blind study. J Endod. 2015;41(6):791-796. 38. Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate-buffered lidocaine on the success of the inferior alveolar nerve block for teeth with symptomatic irreversible pulpitis: a prospective, randomized double-blind study. J Endod. 2015; 41(1):33-35. 39. Wennberg E, Haljamäe H, Edwall G, Dhuner KG. Effects of commercial (pH approximately 3.5) and freshly prepared (pH approximately 6.5) lidocaine-adrenaline solutions on tissue pH. Acta Anaesthesiol Scand. 1982;26(5):524-527. 40. Punnia-Moorthy A. Buffering capacity of normal and inflamed tissues following the injection of local anaesthetic solutions. Br J Anaesth. 1988;61(2):154-159. 41. Ianiro SR, Jeansonne BG, McNeal SF, Eleazer PD. The effect of preoperative acetaminophen or a combination of acetaminophen and ibuprofen on the success of the inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2007;33(1):11-14.
42. Jena A, Shashirekha G. Effect of preoperative medications on the efficacy of inferior alveolar nerve block in patients with irreversible pulpitis: a placebo-controlled clinical study. J Conserv Dent. 2013;16(2):171-174. 43. Aggarwal V, Singla M, Kabi D. Comparative evaluation of effect of preoperative oral medication of ibuprofen and ketorolac on anesthetic efficacy of inferior alveolar nerve block with lidocaine in patients with irreversible pulpitis: a prospective, double-blind, randomized clinical trial. J Endod. 2010;36(3):375-378. 44. Li C, Yang X, Ma X, Li L, Shi Z. Preoperative oral nonsteroidal antiinflammatory drugs for the success of the inferior alveolar nerve block in irreversible pulpitis treatment: a systematic review and meta-analysis based on randomized controlled trials. Quintessence Int. 2012;43(3):209-219. 45. Gallatin E, Reader A, Nist R, Beck M. Pain reduction in untreated irreversible pulpitis using an intraosseous injection of Depo-Medrol. J Endod. 2000;26(11):633-638. 46. Bane K, Charpentier E, Bronnec F, et al. Randomized clinical trial of intraosseous methylprednisolone injection for acute pulpitis pain. J Endod. 2016;42(1):2-7. 47. Aminoshariae A, Kulild JC, Donaldson M, Hersh EV. Evidence-based recommendations for analgesic efficacy to treat pain of endodontic origin: a systematic review of randomized controlled trials. JADA. 2016;147(10): 826-839. 48. Bultema K, Fowler S, Drum M, Reader A, Nusstein J, Beck M. Pain reduction in untreated symptomatic irreversible pulpitis using liposomal bupivacaine (Exparel): a prospective, randomized, double-blind trial. J Endod. 2016;42(12):1707-1712. 49. Nusstein J, Reader A, Nist R, Beck M, Meyers WJ. Anesthetic efficacy of the supplemental intraosseous injection of 2% lidocaine with 1:100,000 epinephrine in irreversible pulpitis. J Endod. 1998;24(7):487-491. 50. Parente SA, Anderson RW, Herman WW, Kimbrough WF, Weller RN. Anesthetic efficacy of the supplemental intraosseous injection for teeth with irreversible pulpitis. J Endod. 1998;24(12):826-828. 51. Kanaa MD, Whitworth JM, Meechan JG. A prospective randomized trial of different supplementary local anesthetic techniques after failure of inferior alveolar nerve block in patients with irreversible pulpitis in mandibular teeth. J Endod. 2012;38(4):421-425. 52. Reisman D, Reader A, Nist R, Beck M, Weaver J. Anesthetic efficacy of the supplemental intraosseous injection of 3% mepivacaine in irreversible pulpitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997; 84(6):676-682. 53. Bigby J, Reader A, Nusstein J, Beck M, Weaver J. Articaine for supplemental intraosseous anesthesia in patients with irreversible pulpitis. J Endod. 2006;32(11):1044-1047. 54. Malamed SF. The periodontal ligament (PDL) injection: an alternative to inferior alveolar nerve block. Oral Surg Oral Med Oral Pathol. 1982; 53(2):117-121. 55. Smith GN, Walton RE, Abbott BJ. Clinical evaluation of periodontal ligament anesthesia using a pressure syringe. JADA. 1983;107(6):953-956. 56. Walton RE, Abbott BJ. Periodontal ligament injection: a clinical evaluation. JADA. 1981;103(4):571-575. 57. Cohen HP, Cha BY, Spangberg LS. Endodontic anesthesia in mandibular molars: a clinical study. J Endod. 1993;19(7):370-373. 58. Webster S Jr, Drum M, Reader A, Fowler S, Nusstein J, Beck M. How effective is supplemental intraseptal anesthesia in patients with symptomatic irreversible pulpitis? J Endod. 2016;42(10):1453-1457. 59. VanGheluwe J, Walton R. Intrapulpal injection: factors related to effectiveness. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997; 83(1):38-40.
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ENDODONTICS
Successful pulpal anesthesia for symptomatic irreversible pulpitis Melissa Drum, DDS, MS; Al Reader, DDS, MS; John Nusstein, DDS, MS; Sara Fowler, DMD, MS
N
o easy solution has been identified for successfully anesthetizing all patients with vital mandibular painful teeth diagnosed with symptomatic irreversible pulpitis. Patients with this painful clinical condition are more difficult to anesthetize for various reasons, all of which are not fully understood. Some of the reasons described in the research literature are altered resting potentials and decreased excitability thresholds of inflamed nerves, tetrodotoxin-resistant sodium channels (resistant to anesthetics), increased expression of sodium channels in irreversibly inflamed pulps, and apprehensive patients with lower pain thresholds.1-4 The reason most often cited but least likely to hold true is lowered pH of inflamed tissue. This theory hypothesizes that the lowered pH reduces the amount of the base form of the anesthetic available to penetrate the membrane thereby preventing anesthesia. This is not the best explanation for failure of anesthesia with the inferior alveolar nerve block (IANB) when the injection is not given at the primary site of inflammation. Likely, this is a more complicated neuronal process. Inflammation and bacterial insult can lead to sprouting of nerve fibers, increased expression of neuropeptides such as substance P and calcitonin gene-related peptide, and the release of inflammatory mediators such as prostaglandins E2, prostaglandins F2a, interleukins 1 and 6, and tumor necrosis factor.5 This can also lead to excitability of nociceptor isoforms (such as Nav 1.7, 1.8, 1.9). The clinical conditions may include neuronal plasticity, allodynia, hyperalgesia peripherally and centrally, and central sensitization.5 These factors may help explain why local anesthesia is not always effective when patients are in pain. Copyright ª 2017 American Dental Association. All rights reserved.
ABSTRACT Background and Overview. Profound pulpal anesthesia after a successful inferior alveolar nerve block can be difficult to achieve when the clinical condition is a pulpal diagnosis of symptomatic irreversible pulpitis. The authors reviewed the literature as it relates to the anesthesia necessary for endodontic therapy of patients with painful, vital, mandibular teeth diagnosed with symptomatic irreversible pulpitis. Conclusions. Supplemental anesthetic techniques and medications are available that can be used to improve pulpal anesthesia for patients with the clinical condition of symptomatic irreversible pulpitis. Practical Implications. The authors identified treatment recommendations for anesthesia in the case of symptomatic irreversible pulpitis based on a review of the available evidence. Key Words. Anesthesia; anesthetics; inferior alveolar nerve block; irreversible pulpitis; symptomatic irreversible pulpitis. JADA 2017:148(4):267-271 http://dx.doi.org/10.1016/j.adaj.2017.01.002
There is no miracle solution or nerve block injection technique that will guarantee effective pulpal anesthesia in patients with symptomatic irreversible pulpitis. For most patients, only the addition of supplemental techniques produces effective pain relief. Success rates of the IANB, when success is defined as no or mild pain on endodontic access, are 28% for the first molars, 25% for the second molars, and 39% for the premolars in patients with symptomatic irreversible pulpitis according to Fowler and colleagues.6 The success rates listed here and throughout the article assume a successful IANB (lip numbness) and are indicative of actual pulpal numbness (successful pulpal anesthesia). There is a difference in success rates between patients with asymptomatic and symptomatic irreversible pulpitis.
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As stated, dentists will find symptomatic patients are going to have a harder time achieving pulpal anesthesia.7,8 ANESTHETIC SOLUTIONS
Different volumes, anesthetic solutions, and concentrations have been studied to try to achieve higher success rates but to no avail. Mepivacaine (a 3% solution) was not found to increase the success rate of the IANB.9 However, it can be used in patients with contraindications to epinephrine-containing solutions. Parirokh and colleagues10 found that bupivacaine (0.5%) did not result in a higher success rate for the IANB in patients with symptomatic irreversible pulpitis. Because bupivacaine has a slower onset than other anesthetics,11 its indication would be at the end of an appointment as an additional IANB to promote prolonged anesthesia and pain control (only in the mandible) rather than as an initial IANB. Articaine (a 4% solution), although superior to lidocaine when given as a mandibular infiltration, has not been found to be superior to lidocaine when given as a block.12,13 Furthermore, the increased concentration with no added anesthetic benefit should preclude its use for an IANB. In a systemic review and meta-analysis, Kung and colleagues14 found that articaine was not superior to lidocaine for IANBs but was superior for supplemental infiltration in the mandible after an IANB. Another meta-analysis also confirmed the superiority of articaine over lidocaine for mandibular infiltration anesthesia.15 Therefore, articaine’s best use would be in mandibular infiltrations rather than nerve blocks. Articaine’s superiority for mandibular infiltrations has often been noted as being due to the increased concentration (4%). However, the percentage of solution is not necessarily the advantage of articaine in these injections. Nydegger and colleagues16 found that 4% articaine was statistically better than both 4% lidocaine and 4% prilocaine in mandibular buccal infiltrations. The 3-dimensional molecular structure may be what gives it the advantage. It is thought that the presence of the thiophene ring and an internal hydrogen bond (between amine nitrogen and ester carbonyl oxygen) causes the molecule to fold over on itself when entering the bone.17,18 Concentrations of epinephrine have also not proved to achieve higher success in IANBs in patients with symptomatic irreversible pulpitis. Aggarwal and colleagues19 found no difference between 2% lidocaine with 1:80,000 epinephrine when compared with 2% lidocaine with 1:200,000 epinephrine with success rates of 20% and 28%, respectively, in patients with symptomatic irreversible pulpitis. Some clinicians believe repeating the IANB after achieving lip numbness will result in more profound pulpal anesthesia. In patients with symptomatic irreversible pulpitis, repeating an IANB is only
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approximately 30% successful for pulpal anesthesia.20 Giving 2 cartridges can help decrease the chance of missing the block but because that is such a low incidence (6% or less) and does not increase the chance for pulpal anesthesia, it is not necessary.21 Sometimes, giving a second injection and getting success is actually due to giving the first injection the appropriate time to work since the onset of pulpal anesthesia after an IANB ranges from 5 to 19 minutes.22 In cases of slow onset, pulpal anesthesia can occur as late as 30 minutes postinjection.22 Using different block injection techniques has also not been shown to increase success of mandibular anesthesia. The success rate with the Gow-Gates technique (35%)23 was similar to the 24% to 35% success rates of the traditional IANBs in studies having patients with symptomatic irreversible pulpitis.24-28 Studies have also been done in asymptomatic patients and no difference in success was found between the Gow-Gates technique and the standard IANB technique.29 No difference does not necessarily mean the Gow-Gates is inferior. It means either technique can be used. Unfortunately, in patients with symptomatic irreversible pulpitis, a buccal infiltration of articaine may also not be reliable for pulpal anesthesia. Success rates for a buccal infiltration of articaine after an IANB in symptomatic irreversible pulpitis were only 42% for first molars, 48% for second molars, and 73% for premolars.6 This is not to be confused with the high success rates when articaine is used as an infiltration after an IANB in asymptomatic patients.15,30-32 Also, articaine, as an infiltration, may be a helpful addition to the other supplemental techniques, but it often does not provide pulpal anesthesia for symptomatic irreversible pulpitis. ANXIOLYTICS
The addition of anxiolytics has also been suggested to increase success of pulpal anesthesia. The theory is that because anxiety can reduce pain tolerance, a decrease in anxiety should lead to a decrease in pain. However, studies of patients diagnosed with symptomatic irreversible pulpitis when preoperative triazolam or alprazolam were given did not achieve increased success rates.33,34 Even when using conscious sedation, profound local anesthesia is still required. Payen and colleagues35 and Aissaoui and colleagues36 found that sedated, unconscious patients detect, experience, and respond to pain but they do not remember it. If unconscious patients can feel pain, consciously sedated patients will feel pain as well. This does not mean that dentists should not use antianxiety medications to help with anxiety but they should not be substituted as a pain medication or ABBREVIATION KEY. IANB: Inferior alveolar nerve block.
SPECIALTY UPDATE
anesthetic. Also, even though pain may not be recalled, it is not known what physiological and biochemical effects may occur with the stimulation of pain, especially considering what we know about neuronal plasticity. Just because the pain is not remembered, it doesn’t mean there is no effect. BUFFERING
Buffering has also been highly promoted to increase the success of anesthesia. Two commercially available dental anesthetic buffering systems are sold in the United States. Onset (Onpharma) buffers local anesthetic solutions within the dental anesthetic cartridge using a dispensing system that includes a mixing pen, Onpharma Cartridge Connector, and Onset Sodium Bicarbonate Additive Solution. The other system is Anutra (Anutra Medical), which consists of a dispenser and multiple-dose vials of lidocaine and bicarbonate in a cassette that is drawn into a disposable syringe. The theory is that a higher pH will increase the anesthetic success rate. Research has shown that 2% or 4% buffered lidocaine formulations with epinephrine did not result in an increase in the success rate or decrease injection pain over nonbuffered lidocaine formulations with epinephrine in patients with symptomatic irreversible pulpitis.37,38 The reasoning behind the negative findings is that the body has the ability to intrinsically buffer so that it maintains tissues at physiological pH. Wennberg and colleagues39 suggested that the pH conversion buffering process could occur within several minutes. Punnia-Moorthy40 reported freshly prepared 2% lignocaine with epinephrine with a pH of 5.25 being converted to a pH of 7.17 within 3 minutes after an intradermal injection. PREEMPTIVE MEDICATIONS
Preemptive medications have been hypothesized to help reduce the levels of prostaglandins and other inflammatory mediators and thus improve anesthetic success by reducing the prostaglandin sensitization of peripheral nociceptors. Studies in which patients received preoperative ibuprofen, a combination of ibuprofen with acetaminophen, acetaminophen with hydrocodone, or ketorolac for the clinical condition of symptomatic irreversible pulpitis have failed to detect significant improvements in pulpal anesthesia success rates or they detected success rates too low to provide treatment without supplemental anesthesia.25-27,41-44 Although not useful for intra-appointment anesthesia, steroids may be useful in controlling pain in untreated irreversible pulpitis.45-47 Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals) has also been studied to help control pain in untreated symptomatic irreversible pulpitis (with the intention that evidence of pain control and anesthesia could lead to the use of Exparel postoperatively). Exparel combines bupivacaine with DepoFoam (Pacira
Pharmaceuticals) and consists of microscopic, spherical, lipid-based chambers. On injection, approximately 3% is free bupivacaine and the rest of the drug is released from the liposome over time (by erosion and lipid membrane reorganization). Administration of Exparel (theoretically providing local anesthesia for up to 72 hours) as an infiltration (it is not US Food and Drug Administration approved for nerve blocks) did not reduce pain to manageable clinical levels in patients with untreated, symptomatic irreversible pulpitis.48 It is unknown whether the concentration released will be effective even if it is studied as a nerve block in the future (after US Food and Drug Administration approval as a nerve block). OTHER SUPPLEMENTAL TECHNIQUES AND MEDICATIONS
Although there is ongoing research to develop a simple solution to anesthesia problems, none is available. The following supplemental techniques and medications are those that research supports to help with pulpal anesthesia in symptomatic irreversible pulpitis. The most predictable way to achieve pulpal anesthesia in a clinical scenario of irreversible pulpitis is the supplemental intraosseous injection, using the Stabident (Fairfax Dental) or X-tip system (Dentsply), of 1 cartridge of 2% lidocaine with 1:100,000 epinephrine after a successful (lip numbness) IANB. This injection is reported to be successful approximately 90% of the time in mandibular posterior teeth.49 Using volumes less than a full cartridge will decrease the success rate.50,51 Mepivacaine plain (3% Carbocaine, 3% Polocaine) can also be used for those patients who have medical contraindications or would react poorly to the increase in heart rate associated with an intraosseous injection of lidocaine, although 2 cartridges may be necessary to achieve the same success rate as 1 cartridge of lidocaine (80% 1 cartridge versus 98% 2 cartridges).52 Similar to the results when evaluating an IANB, articaine does not show a superior effect when used as an intraosseous injection.53 Supplemental intraligamentary periodontal ligament injections can also be used. Success rates for the intraligamentary injection for patients with irreversible pulpitis are in the range of 63% to 74%.54-57 Reinjection improves success rates to levels of 92% to 96%.55-57 This injection is relatively easy to give and no special equipment is required. Because of the need to reinject and the short duration of anesthesia due to the smaller volume of solution injected, intraosseous injections can provide more predictable anesthesia. Intraseptal injections, which are the deposition of anesthetic solution directly into the interdental septum without an intraosseous device, have also been studied but the supplemental injection has a low success rate (29%) in patients with symptomatic irreversible pulpitis.58
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In approximately 5% to 10% of patients with irreversible pulpitis, supplemental injections do not produce pulpal anesthesia. Therefore, intrapulpal anesthesia is indicated and will likely be successful if given under back pressure.59 The disadvantage is that the injection is painful and should only be used after all other supplemental techniques have been attempted. Nitrous oxide is the most commonly used inhalation anesthetic in dentistry and has an impressive safety record. Nitrous oxide has a potential benefit because of its combination of both antianxiety and analgesic effects. As mentioned, antianxiety medications alone did not show increased success rates. It is thought that nitrous oxide causes an analgesic effect by the release of endogenous opiate peptides with activation of opioid receptors and inhibition of N-methyl-D-aspartate glutamate receptors. Administration of 30% to 50% nitrous oxide resulted in a statistically significant increase in the success of the IANB in patients with irreversible pulpitis.28 The increased success rates allow nitrous oxide to be a good adjunct in this clinical scenario. However, the success rates are not high enough to work without supplemental anesthesia. CONCLUSION
No single drug, solution, or technique will allow dentists to comfortably treat every patient with symptomatic irreversible pulpitis. However, there are some supplemental techniques and adjuncts that can be used to increase the success rates of pulpal anesthesia that will benefit both dentists and their patients. n Dr. Drum is an associate professor and the advanced program director, Division of Endodontics, The Ohio State University, 3059B Postle Hall, 305 W. 12th Ave., Columbus, OH 43210, e-mail [email protected]. Address correspondence to Dr. Drum. Dr. Reader is a professor, Division of Endodontics, The Ohio State University, Columbus, OH. Dr. Nusstein is a professor and the chair, Division of Endodontics, The Ohio State University, Columbus, OH. Dr. Fowler is an assistant professor and the predoctoral program director, Division of Endodontics, The Ohio State University, Columbus, OH. Disclosure. None of the authors reported any disclosures. Endodontics is published in collaboration with the American Association of Endodontists. 1. Modaresi J, Dianat O, Soluti A. Effect of pulp inflammation on nerve impulse quality with or without anesthesia. J Endod. 2008;34(4):438-441. 2. Wallace JA, Michanowicz AE, Mundell RD, Wilson EG. A pilot study of the clinical problem of regionally anesthetizing the pulp of an acutely inflamed mandibular molar. Oral Surg Oral Med Oral Pathol. 1985;59(5): 517-521. 3. Roy M, Narahashi T. Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons. J Neurosci. 1992;12(6):2104-2111. 4. Sorensen H, Skidmore L, Rzasa R, Kleier S, Levinson S, Hendry M. Comparison of pulpal sodium channel density in normal teeth to diseased teeth with severe spontaneous pain [abstract]. J Endod. 2004;30(4):287. 5. Hargreaves KM, Goodis HE, Tay F, eds. Seltzer and Bender’s Dental Pulp. 2nd ed. Hanover Park, IL: Quintessence; 2012.
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6. Fowler S, Drum M, Reader A, Beck M. Anesthetic success of an inferior alveolar nerve block and supplemental articaine buccal infiltration for molars and premolars in patients with symptomatic irreversible pulpitis. J Endod. 2016;42(3):390-392. 7. Argueta-Figueroa L, Arzate-Sosa G, Mendieta-Zeron H. Anesthetic efficacy of articaine for inferior alveolar nerve blocks in patients with symptomatic versus asymptomatic irreversible pulpitis. Gen Dent. 2012; 60(1):e39-e43. 8. Fragouli E, Panopoulos P, Georgopoulou M. Efficacy of inferior alveolar nerve block using 1.7 mL of 4% articaine with 1:100,000 epinephrine in reversible and irreversible pulpitis. ENDO. 2011;5(4): 285-291. 9. Lammers E, Nusstein J, Reader A, Drum M, Beck M, Fowler S. Does the combination of 3% mepivacaine plus 2% lidocaine with epinephrine improve anesthesia and reduce the pain of anesthetic injection for the inferior alveolar nerve block? A prospective, randomized, double-blind study. J Endod. 2014;40(9):1287-1292. 10. Parirokh M, Yosefi MH, Nakhaee N, Abbott PV, Manochehrifar H. The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain. Restor Dent Endod. 2015;40(2):155-160. 11. Fernandez C, Reader A, Beck M, Nusstein J. A prospective, randomized, double-blind comparison of bupivacaine and lidocaine for inferior alveolar nerve blocks. J Endod. 2005;31(7):499-503. 12. Claffey E, Reader A, Nusstein J, Beck M, Weaver J. Anesthetic efficacy of articaine for inferior alveolar nerve blocks in patients with irreversible pulpitis. J Endod. 2004;30(8):568-571. 13. Tortamano IP, Siviero M, Costa CG, Buscariolo IA, Armonia PL. A comparison of the anesthetic efficacy of articaine and lidocaine in patients with irreversible pulpitis. J Endod. 2009;35(2):165-168. 14. Kung J, McDonagh M, Sedgley CM. Does articaine provide an advantage over lidocaine in patients with symptomatic irreversible pulpitis? A systematic review and meta-analysis. J Endod. 2015;41(11): 1784-1794. 15. Brandt RG, Anderson PF, McDonald NJ, Sohn W, Peters MC. The pulpal anesthetic efficacy of articaine versus lidocaine in dentistry: a metaanalysis. JADA. 2011;142(5):493-504. 16. Nydegger B, Nusstein J, Reader A, Drum M, Beck M. Anesthetic comparisons of 4% concentrations of articaine, lidocaine, and prilocaine as primary buccal infiltrations of the mandibular first molar: a prospective randomized, double-blind study. J Endod. 2014;40(12): 1912-1916. 17. Skjevik AA, Haug BE, Lygre H, Teigen K. Intramolecular hydrogen bonding in articaine can be related to superior bone tissue penetration: a molecular dynamics study. Biophys Chem. 2011;154(1):18-25. 18. Kuhn B, Mohr P, Stahl M. Intramolecular hydrogen bonding in medicinal chemistry. J Med Chem. 2010;53(6):2601-2611. 19. Aggarwal V, Singla M, Miglani S, Kohli S. Comparison of the anaesthetic efficacy of epinephrine concentrations (1:80 000 and 1:200 000) in 2% lidocaine for inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a randomized, double-blind clinical trial. Int Endod J. 2014;47(4):373-379. 20. Fowler S, Reader A. Is a volume of 3.6 mL better than 1.8 mL for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis? J Endod. 2013;39(8):970-972. 21. Fowler S, Reader A, Beck M. Incidence of missed inferior alveolar nerve blocks in vital asymptomatic subjects and in patients with symptomatic irreversible pulpitis. J Endod. 2015;41(5):637-639. 22. Reader A, Nusstein J, Drum M. Successful Local Anesthesia for Restorative Dentistry and Endodontics. Hanover Park, IL: Quintessence; 2011. 23. Click V, Drum M, Reader A, Nusstein J, Beck M. Evaluation of the Gow-Gates and Vazirani-Akinosi techniques in patients with symptomatic irreversible pulpitis: a prospective randomized study. J Endod. 2015;41(1): 16-21. 24. Matthews R, Drum M, Reader A, Nusstein J, Beck M. Articaine for supplemental buccal mandibular infiltration anesthesia in patients with irreversible pulpitis when the inferior alveolar nerve block fails. J Endod. 2009;35(3):343-346. 25. Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients with irreversible pulpitis. J Endod. 2010;36(3):379-382.
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26. Simpson M, Drum M, Nusstein J, Reader A, Beck M. Effect of combination of preoperative ibuprofen/acetaminophen on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2011;37(5):593-597. 27. Fullmer S, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative acetaminophen/hydrocodone on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double-blind, placebo-controlled study. J Endod. 2014;40(1):1-5. 28. Stanley W, Drum M, Nusstein J, Reader A, Beck M. Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod. 2012;38(5):565-569. 29. Goldberg S, Reader A, Drum M, Nusstein J, Beck M. Comparison of the anesthetic efficacy of the conventional inferior alveolar, Gow-Gates, and Vazirani-Akinosi techniques. J Endod. 2008;34(11):1306-1311. 30. Robertson D, Nusstein J, Reader A, Beck M, McCartney M. The anesthetic efficacy of articaine in buccal infiltration of mandibular posterior teeth. JADA. 2007;138(8):1104-1112. 31. Haase A, Reader A, Nusstein J, Beck M, Drum M. Comparing anesthetic efficacy of articaine versus lidocaine as a supplemental buccal infiltration of the mandibular first molar after an inferior alveolar nerve block. JADA. 2008;139(9):1228-1235. 32. Kanaa MD, Whitworth JM, Corbett IP, Meechan JG. Articaine buccal infiltration enhances the effectiveness of lidocaine inferior alveolar nerve block. Int Endod J. 2009;42(3):238-246. 33. Lindemann M, Reader A, Nusstein J, Drum M, Beck M. Effect of sublingual triazolam on the success of inferior alveolar nerve block in patients with irreversible pulpitis. J Endod. 2008;34(10):1167-1170. 34. Khademi AA, Saatchi M, Minaiyan M, Rostamizadeh N, Sharafi F. Effect of preoperative alprazolam on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2012;38(10): 1337-1339. 35. Payen JF, Bru O, Bosson JL, et al. Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med. 2001; 29(12):2258-2263. 36. Aissaoui Y, Zeggwagh AA, Zekraoui A, Abidi K, Abougal R. Validation of a behavioral pain scale in critically ill, sedated, and mechanically ventilated patients. Anesth Analg. 2005;101(5):1470-1476. 37. Schellenberg J, Drum M, Reader A, Nusstein J, Fowler S, Beck M. Effect of buffered 4% lidocaine on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double-blind study. J Endod. 2015;41(6):791-796. 38. Saatchi M, Khademi A, Baghaei B, Noormohammadi H. Effect of sodium bicarbonate-buffered lidocaine on the success of the inferior alveolar nerve block for teeth with symptomatic irreversible pulpitis: a prospective, randomized double-blind study. J Endod. 2015; 41(1):33-35. 39. Wennberg E, Haljamäe H, Edwall G, Dhuner KG. Effects of commercial (pH approximately 3.5) and freshly prepared (pH approximately 6.5) lidocaine-adrenaline solutions on tissue pH. Acta Anaesthesiol Scand. 1982;26(5):524-527. 40. Punnia-Moorthy A. Buffering capacity of normal and inflamed tissues following the injection of local anaesthetic solutions. Br J Anaesth. 1988;61(2):154-159. 41. Ianiro SR, Jeansonne BG, McNeal SF, Eleazer PD. The effect of preoperative acetaminophen or a combination of acetaminophen and ibuprofen on the success of the inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod. 2007;33(1):11-14.
42. Jena A, Shashirekha G. Effect of preoperative medications on the efficacy of inferior alveolar nerve block in patients with irreversible pulpitis: a placebo-controlled clinical study. J Conserv Dent. 2013;16(2):171-174. 43. Aggarwal V, Singla M, Kabi D. Comparative evaluation of effect of preoperative oral medication of ibuprofen and ketorolac on anesthetic efficacy of inferior alveolar nerve block with lidocaine in patients with irreversible pulpitis: a prospective, double-blind, randomized clinical trial. J Endod. 2010;36(3):375-378. 44. Li C, Yang X, Ma X, Li L, Shi Z. Preoperative oral nonsteroidal antiinflammatory drugs for the success of the inferior alveolar nerve block in irreversible pulpitis treatment: a systematic review and meta-analysis based on randomized controlled trials. Quintessence Int. 2012;43(3):209-219. 45. Gallatin E, Reader A, Nist R, Beck M. Pain reduction in untreated irreversible pulpitis using an intraosseous injection of Depo-Medrol. J Endod. 2000;26(11):633-638. 46. Bane K, Charpentier E, Bronnec F, et al. Randomized clinical trial of intraosseous methylprednisolone injection for acute pulpitis pain. J Endod. 2016;42(1):2-7. 47. Aminoshariae A, Kulild JC, Donaldson M, Hersh EV. Evidence-based recommendations for analgesic efficacy to treat pain of endodontic origin: a systematic review of randomized controlled trials. JADA. 2016;147(10): 826-839. 48. Bultema K, Fowler S, Drum M, Reader A, Nusstein J, Beck M. Pain reduction in untreated symptomatic irreversible pulpitis using liposomal bupivacaine (Exparel): a prospective, randomized, double-blind trial. J Endod. 2016;42(12):1707-1712. 49. Nusstein J, Reader A, Nist R, Beck M, Meyers WJ. Anesthetic efficacy of the supplemental intraosseous injection of 2% lidocaine with 1:100,000 epinephrine in irreversible pulpitis. J Endod. 1998;24(7):487-491. 50. Parente SA, Anderson RW, Herman WW, Kimbrough WF, Weller RN. Anesthetic efficacy of the supplemental intraosseous injection for teeth with irreversible pulpitis. J Endod. 1998;24(12):826-828. 51. Kanaa MD, Whitworth JM, Meechan JG. A prospective randomized trial of different supplementary local anesthetic techniques after failure of inferior alveolar nerve block in patients with irreversible pulpitis in mandibular teeth. J Endod. 2012;38(4):421-425. 52. Reisman D, Reader A, Nist R, Beck M, Weaver J. Anesthetic efficacy of the supplemental intraosseous injection of 3% mepivacaine in irreversible pulpitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997; 84(6):676-682. 53. Bigby J, Reader A, Nusstein J, Beck M, Weaver J. Articaine for supplemental intraosseous anesthesia in patients with irreversible pulpitis. J Endod. 2006;32(11):1044-1047. 54. Malamed SF. The periodontal ligament (PDL) injection: an alternative to inferior alveolar nerve block. Oral Surg Oral Med Oral Pathol. 1982; 53(2):117-121. 55. Smith GN, Walton RE, Abbott BJ. Clinical evaluation of periodontal ligament anesthesia using a pressure syringe. JADA. 1983;107(6):953-956. 56. Walton RE, Abbott BJ. Periodontal ligament injection: a clinical evaluation. JADA. 1981;103(4):571-575. 57. Cohen HP, Cha BY, Spangberg LS. Endodontic anesthesia in mandibular molars: a clinical study. J Endod. 1993;19(7):370-373. 58. Webster S Jr, Drum M, Reader A, Fowler S, Nusstein J, Beck M. How effective is supplemental intraseptal anesthesia in patients with symptomatic irreversible pulpitis? J Endod. 2016;42(10):1453-1457. 59. VanGheluwe J, Walton R. Intrapulpal injection: factors related to effectiveness. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997; 83(1):38-40.
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