Premedication to Enhance the Efficacy of Dental Anesthesia

Premedication to enhance the efficacy of dental anesthesia

Premedication is used in several clinical situations. Antibiotic premedication is used for at-risk patients to prevent systemic infection with oral organisms that gain entry into the bloodstream during dental treatment. In recent years the use of such premedication has been greatly reduced due to a review of the evidence supporting the use of antibiotic premedication.1American Dental Association. Antibiotic prophylaxis prior to dental procedures. Available at: https://www.ada.org/en/member-center/oral-health-topics/antibiotic-prophylaxis. Reduction of patient anxiety prior to dental treatment is another indication for premedication.2Newton T, Asimakopoulou K, Daly B, Scambler S, Scott S. The management of dental anxiety: time for a sense of proportion? Br Dent J 2012;213(6):271-4. A third indication is to enhance pain control and the efficacy of local anesthesia (LA), including the success rates, depth and duration of anesthesia. This last indication has been the subject of recent reports in the literature. Most of these reports have evaluated the efficacy of premedication prior to inferior alveolar nerve blocks (IANB) associated with endodontic therapy for irreversible pulpitis.

Success rates for IANB

Success rates of up to 90% are reported for IANB in association with restorative procedures.3Jena 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):171-4. However, success rates are lower in patients with irreversible pulpitis, particularly when it is symptomatic.4Pulikkotil SJ, Nagendrababu V, Veettil SK, Jinatongthai P, Setzer FC. Effect of oral premedication on the anaesthetic efficacy of inferior alveolar nerve block in patients with irreversible pulpitis: A systematic review and network meta-analysis of randomized controlled trials. Int Endod J 2018;51(9):989-1004.^,5Argueta-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:e39-43.^,6Aggarwal V, Singla M, Subbiya A, Vivekanandhan P, Sharma V, Sharma R, Prakash V, Geethapriya N. Effect of preoperative pain on inferior alveolar nerve block. Anesthesia Progress 2015;62:135–9. Reported success rates for IANB in patients with symptomatic irreversible pulpitis range from 15% to 57%, and between 32% and 71% of these patients experience moderate to severe pain after an IANB.7Fullmer 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. In a systematic review of 72 studies, LA following IANB was inadequate in 60% of patients with symptomatic irreversible pulpitis.8Pak JG, White SN. Pain prevalence and severity before, during, and after root canal treatment: A systematic review. J Endod 2011;37:429-38.

Low success rates for IANB are proposed to be due to anatomical variances (e.g., lingual or buccal accessory innervation), inflammatory changes in the pulp including an increased level of prostaglandins, and decreased tissue pH.5Argueta-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:e39-43.^,9Ghoddusi J, Zarrabi MH, Daneshvar F, Naghavi N. Efficacy of IANB (RR) and Gow-Gates techniques in mandibular molars with symptomatic irreversible pulpitis: A prospective randomized double blind clinical study. Iran Endod J 2018;13(2):143-8.^,10Rood JP. Some anatomical and physiological causes of failure to achieve mandibular analgesia. Br J Oral Surg 1977;15(1):75-82. Other proposed factors include fear and anxiety, and the concentration and amount of local anesthetic administered.11Sivaramakrishnan G, Sridharan K. Oral ketorolac with inferior alveolar nerve block for irreversible pulpitis: A systematic review and meta-analysis. The Open Dent J 2018;12:340-6.^,12Dou L, Vanschaayk MM, Zhang Y, Fu X, Ji P, Yang D. The prevalence of dental anxiety and its association with pain and other variables among adult patients with irreversible pulpitis. BMC Oral Health 2018;18(1):101. Methods used to increase IANB success rates include supplemental lingual and buccal infiltration, intraosseous and periodontal ligament injections, and the Gow-Gates technique (GG) for mandibular LA.5Argueta-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:e39-43.^,8Pak JG, White SN. Pain prevalence and severity before, during, and after root canal treatment: A systematic review. J Endod 2011;37:429-38.^,10Rood JP. Some anatomical and physiological causes of failure to achieve mandibular analgesia. Br J Oral Surg 1977;15(1):75-82.^,13Gow-Gates GA. Mandibular conduction anesthesia: a new technique using extraoral landmarks. Oral Surg Oral Med Oral Pathol 1973;36(3):321-8. (Table 1) However, conflicting results have been reported for supplemental LA, with some studies reporting increased success rates while others did not.8Pak JG, White SN. Pain prevalence and severity before, during, and after root canal treatment: A systematic review. J Endod 2011;37:429-38.^,10Rood JP. Some anatomical and physiological causes of failure to achieve mandibular analgesia. Br J Oral Surg 1977;15(1):75-82.^,14Matthews 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;35:343–6.. In addition, in a recent randomized, double-blind clinical trial, success rates were 42.5% and 50%, respectively, for LA administered using the GG and IANB, with no statistically significant differences between the techniques.10Rood JP. Some anatomical and physiological causes of failure to achieve mandibular analgesia. Br J Oral Surg 1977;15(1):75-82. The use of premedication has been proposed as an alternative method of increasing IANB success rates.

Oral premedication agents prior to IANB

Agents studied as oral premedication prior to IANB include non-steroidal anti-inflammatory drugs (NSAIDs), steroids, acetaminophen (paracetamol), opioids, combination analgesics and anxiolytics. NSAIDs block cyclooxygenase-1 (COX-1) and COX-2 enzymes. This ultimately inhibits the release of prostaglandins as part of the inflammatory process, resulting in reduced pain due to reduced nociception.7Fullmer 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.^,15Dubin AE, Patapoutian A. Nociceptors: the sensors of the pain pathway. J Clin Invest 2010;120(11):3760-72. Decreases in prostaglandin levels in the dental pulp have been observed following use of NSAIDs.7Fullmer 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. The steroid dexamethasone also blocks COX pathways, as well as the lipoxygenase pathway, thereby reducing the levels of both prostaglandins and leukotrienes involved in the inflammatory process.7Fullmer 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. Acetaminophen has both antipyretic and analgesic properties.16Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF. The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacol 2013;21(3):201-32. It is now believed that acetaminophen inhibits the cyclooxygenase pathways, and that it is selective for COX-2. Tramadol is a synthetic narcotic that inhibits norepinephrine and serotonin uptake, reducing pain transmission, and also acts as an opioid agonist.17Beakley BD, Kaye AM, Kaye AD. Tramadol, pharmacology, side effects, and serotonin syndrome: A review. Pain Physician 2015;18:395-400.

Efficacy of Oral Premedication

A recent systematic review of 19 randomized controlled trials with more than 1600 participants examined the efficacy of oral premedication agents prior to IANB and nonsurgical endodontic therapy for the treatment of irreversible pulpitis.5Argueta-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:e39-43. In comparison to placebo, 0.5 mg dexamethasone resulted in a more than three-fold increase in IANB success rates (RR 3.29). In addition, a more than two-fold increase in IANB success rates was found for 400 mg ibuprofen/500 mg acetaminophen, 20 mg piroxicam, 10 mg ketorolac and Tramadol (RR 2.42, 2.40, 2.34 and 2.28, respectively). Significantly greater increases in IANB success rates were found for dexamethasone and NSAIDS compared to piroxicam and ketorolac. No statistically significant differences in efficacy were found between dexamethasone and NSAIDs. (Figure 1) Ibuprofen at ≥400 mg also improved IANB success rates.5Argueta-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:e39-43.

In another systematic review with 7 studies, 600 mg and 800 mg ibuprofen, 75 mg indomethacin, 50 mg diclofenac potassium and 8 mg lornoxicam increased the success rate of IANB by 52%, 94%, 240% and 280%, respectively, compared to placebo.18Li C, Yang X, Ma X, Li L, Shi Z. Preoperative oral nonsteroidal anti-inflammatory 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):209-19. The success rate of IANB following premedication with NSAIDs increased almost two-fold for patients with symptomatic irreversible pulpitis in a third review with 9 randomized controlled studies.19Shirvani A, Shamszadeh S, Eghbal MJ, Marvasti LA, Asgary S. Effect of preoperative oral analgesics on pulpal anesthesia in patients with irreversible pulpitis: A systematic review and meta-analysis. Clin Oral Investig 2017; 21(1):43-52. Further, in a systematic review including 4 studies, oral premedication with ketorolac increased the success rate of IANB by 87% compared to placebo.11Sivaramakrishnan G, Sridharan K. Oral ketorolac with inferior alveolar nerve block for irreversible pulpitis: A systematic review and meta-analysis. The Open Dent J 2018;12:340-6. In contrast, premedication with ketorolac, as well as ibuprofen at doses of ≤400 mg,100 mg aceclofenac, 55 mg naproxen, acetaminophen/hydrocodone, alprazolam (a benzodiazepine) and ibuprofen/acetaminophen, were found in other studies to be ineffective.5Argueta-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:e39-43.^,18Li C, Yang X, Ma X, Li L, Shi Z. Preoperative oral nonsteroidal anti-inflammatory 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):209-19.^,20Nagendrababu V, Pulikkotil SJ, Veettil SK, Teerawattanapong N, Setzer FC. Effect of nonsteroidal anti-inflammatory drug as an oral premedication on the anesthetic success of inferior alveolar nerve block in treatment of irreversible pulpitis: A systematic review with meta-analysis and trial sequential analysis. J Endod 2018;44(6):914-22.e2.

However, individual studies have reported increase in success rates for IANB following premedication with analgesic agents that were not found to be effective in systematic reviews. In one randomized, double-blind study, IANB success rates following premedication with 4 mg dexamethasone, 400 mg ibuprofen and placebo were 80.8%, 73.1% and 38.5%, respectively, with no statistically significant difference between dexamethasone and ibuprofen.21Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with irreversible pulpitis: a prospective, randomized, controlled double-blind study. Bull Tokyo Dent Coll 2017;58(4):231-6. In contrast, only dexamethasone increased IANB success rates in a study comparing a placebo with 400 mg ibuprofen or 0.5 mg dexamethasone.22Shahi S, Mokhtari H, Rahimi S, Yavari HR, Narimani S, Abdolrahimi M, Nezafati S. Effect of premedication with ibuprofen and dexamethasone on success rate of inferior alveolar nerve block for teeth with asymptomatic irreversible pulpitis: a randomized clinical trial. J Endod 2013;39(2):160-2. In addition, oral premedication with ketorolac or 600 mg ibuprofen at higher doses did not result in statistically significant increases in success rates for IANB in a prospective, double-blind randomized study.23Aggarwal 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):375-8. IANB success rates increased by 144% and 94% with premedication using 400 mg ibuprofen and 75 mg indomethacin, respectively, in another randomized study, with no statistically significant difference between groups.24Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, Abbott PV. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod 2010;36:1450-4. Further, in a randomized, double-blind study, IANB success rates were 92%, 88% and 60% for 600 mg ibuprofen, 7.5 mg meloxicam and placebo, respectively.25Lamba S, Swamy UKP, Kaushik M, Reddy PY, Kumar P. Effect of premedication with ibuprofen and meloxicam on the efficacy of inferior alveolar nerve block in irreversible pulpitis. J Med Sci Clin Res 2018;6(5):290-5. No statistically significant differences were found for ibuprofen and meloxicam (p>0.05). In other studies, neither 800 mg of ibuprofen, 800 mg ibuprofen/1000 mg acetaminophen or 1000 mg acetaminophen/10 mg hydrocodone increased the success rate of IANB.8Pak JG, White SN. Pain prevalence and severity before, during, and after root canal treatment: A systematic review. J Endod 2011;37:429-38.^,26Oleson 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):379-82.27Simpson M, Drum M, Nusstein J, Reader A, Beck M. Effect of preoperative ibuprofen/acetaminophen on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod 2011;37(5):593–7.

Efficacy of Nitrous Oxide Premedication or Sublingual Premedication

Nitrous oxide functions as an anxiolytic and an analgesic. The effect of 30% to 50% nitrous oxide for conscious sedation given 5 minutes prior to administration of IANB and 20 minutes prior to treatment was examined in one study.28Stanley 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):565-9. Nitrous oxide sedation resulted in an IANB success rate of 50% compared to 28% for placebo (room air/oxygen mix). The efficacy of intranasal ketorolac (31.5 mg), together with nitrous oxide/oxygen inhalation 10 minutes prior to IANB administration, was also compared to placebo in a randomized double-blind study with more than 100 patients with symptomatic irreversible pulpitis. No statistically significant increase in the success rate of IANB was found for intranasal ketorolac.29Stentz D, Drum M, Reader A, Nusstein J, Fowler S, Beck M. Effect of a combination of intranasal ketorolac and nitrous oxide on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: A prospective, randomized, double-blind study. J Endod 2018; 44(1):9-13. In another study, no statistically significant differences were found in IANB success rates for sublingual administration of 0.25 mg triazolam for conscious sedation compared to placebo.30Lindemann 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):1167-70.

Other Considerations

Contraindications, potential side effects, adverse events and differences in the rate of metabolism must be considered when considering premedication for specific patients. In addition, while potential side effects are generally less likely with single-dose premedication rather than with the use of medications for chronic pain, they can occur. Before selecting premedication, the patient’s full medical history must be known, and the full prescribing information consulted. Further considerations include ease of use and level of convenience for the patient, any requirement for additional equipment (e.g., apparatus required for nitrous oxide), training/certification and licensing, and other regulations.

Conclusions

Clinically, the need for more effective LA following IANB, particularly for patients with symptomatic irreversible pulpitis, is generally acknowledged. Premedication using analgesic agents, or a combination of agents, can increase the success rate of IANB. However, head-to-head comparisons among the many proposed oral premedication protocols have been lacking, and studies vary in protocol and the doses used. Results of a recent systematic review, however, now provide a head-to-head comparison of oral premedication agents. It was concluded that dexamethasone, NSAIDs and Tramadol are effective in increasing the success rate of IANB in patients with symptomatic irreversible pulpitis. In all situations, selection of an agent must be patient-specific, and based on health status, contraindications, potential side effects and other considerations. Further, additional high-quality, randomized controlled trials have been recommended to confirm the relative efficacy of premedication agents.4Pulikkotil SJ, Nagendrababu V, Veettil SK, Jinatongthai P, Setzer FC. Effect of oral premedication on the anaesthetic efficacy of inferior alveolar nerve block in patients with irreversible pulpitis: A systematic review and network meta-analysis of randomized controlled trials. Int Endod J 2018;51(9):989-1004.^,18Li C, Yang X, Ma X, Li L, Shi Z. Preoperative oral nonsteroidal anti-inflammatory 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):209-19.

References

• 1.American Dental Association. Antibiotic prophylaxis prior to dental procedures. Available at: https://www.ada.org/en/member-center/oral-health-topics/antibiotic-prophylaxis.
• 2.Newton T, Asimakopoulou K, Daly B, Scambler S, Scott S. The management of dental anxiety: time for a sense of proportion? Br Dent J 2012;213(6):271-4.
• 3.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):171-4.
• 4.Pulikkotil SJ, Nagendrababu V, Veettil SK, Jinatongthai P, Setzer FC. Effect of oral premedication on the anaesthetic efficacy of inferior alveolar nerve block in patients with irreversible pulpitis: A systematic review and network meta-analysis of randomized controlled trials. Int Endod J 2018;51(9):989-1004.
• 5.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:e39-43.
• 6.Aggarwal V, Singla M, Subbiya A, Vivekanandhan P, Sharma V, Sharma R, Prakash V, Geethapriya N. Effect of preoperative pain on inferior alveolar nerve block. Anesthesia Progress 2015;62:135–9.
• 7.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.
• 8.Pak JG, White SN. Pain prevalence and severity before, during, and after root canal treatment: A systematic review. J Endod 2011;37:429-38.
• 9.Ghoddusi J, Zarrabi MH, Daneshvar F, Naghavi N. Efficacy of IANB (RR) and Gow-Gates techniques in mandibular molars with symptomatic irreversible pulpitis: A prospective randomized double blind clinical study. Iran Endod J 2018;13(2):143-8.
• 10.Rood JP. Some anatomical and physiological causes of failure to achieve mandibular analgesia. Br J Oral Surg 1977;15(1):75-82.
• 11.Sivaramakrishnan G, Sridharan K. Oral ketorolac with inferior alveolar nerve block for irreversible pulpitis: A systematic review and meta-analysis. The Open Dent J 2018;12:340-6.
• 12.Dou L, Vanschaayk MM, Zhang Y, Fu X, Ji P, Yang D. The prevalence of dental anxiety and its association with pain and other variables among adult patients with irreversible pulpitis. BMC Oral Health 2018;18(1):101.
• 13.Gow-Gates GA. Mandibular conduction anesthesia: a new technique using extraoral landmarks. Oral Surg Oral Med Oral Pathol 1973;36(3):321-8.
• 14.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;35:343–6.
• 15.Dubin AE, Patapoutian A. Nociceptors: the sensors of the pain pathway. J Clin Invest 2010;120(11):3760-72.
• 16.Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF. The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacol 2013;21(3):201-32.
• 17.Beakley BD, Kaye AM, Kaye AD. Tramadol, pharmacology, side effects, and serotonin syndrome: A review. Pain Physician 2015;18:395-400.
• 18.Li C, Yang X, Ma X, Li L, Shi Z. Preoperative oral nonsteroidal anti-inflammatory 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):209-19.
• 19.Shirvani A, Shamszadeh S, Eghbal MJ, Marvasti LA, Asgary S. Effect of preoperative oral analgesics on pulpal anesthesia in patients with irreversible pulpitis: A systematic review and meta-analysis. Clin Oral Investig 2017; 21(1):43-52.
• 20.Nagendrababu V, Pulikkotil SJ, Veettil SK, Teerawattanapong N, Setzer FC. Effect of nonsteroidal anti-inflammatory drug as an oral premedication on the anesthetic success of inferior alveolar nerve block in treatment of irreversible pulpitis: A systematic review with meta-analysis and trial sequential analysis. J Endod 2018;44(6):914-22.e2.
• 21.Bidar M, Mortazavi S, Forghani M, Akhlaghi S. Comparison of effect of oral premedication with ibuprofen or dexamethasone on anesthetic efficacy of inferior alveolar nerve block in patients with irreversible pulpitis: a prospective, randomized, controlled double-blind study. Bull Tokyo Dent Coll 2017;58(4):231-6.
• 22.Shahi S, Mokhtari H, Rahimi S, Yavari HR, Narimani S, Abdolrahimi M, Nezafati S. Effect of premedication with ibuprofen and dexamethasone on success rate of inferior alveolar nerve block for teeth with asymptomatic irreversible pulpitis: a randomized clinical trial. J Endod 2013;39(2):160-2.
• 23.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):375-8.
• 24.Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S, Abbott PV. The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis. J Endod 2010;36:1450-4.
• 25.Lamba S, Swamy UKP, Kaushik M, Reddy PY, Kumar P. Effect of premedication with ibuprofen and meloxicam on the efficacy of inferior alveolar nerve block in irreversible pulpitis. J Med Sci Clin Res 2018;6(5):290-5.
• 26.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):379-82.
• 27.Simpson M, Drum M, Nusstein J, Reader A, Beck M. Effect of preoperative ibuprofen/acetaminophen on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis. J Endod 2011;37(5):593–7.
• 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):565-9.
• 29.Stentz D, Drum M, Reader A, Nusstein J, Fowler S, Beck M. Effect of a combination of intranasal ketorolac and nitrous oxide on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: A prospective, randomized, double-blind study. J Endod 2018; 44(1):9-13.
• 30.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):1167-70.