Comparison of the Effect of Ketorolac and Betamethasone Injec8on on Post Complica8ons of Third Molar Surgery (A Clinical Trial) Vol 12 No 1 (2024) DOI 10.5195/d3000.2024.513 h#p://den*stry3000.pi#.edu Comparison of the Effect of Ketorolac and Betamethasone Injection on Post Complications of Third Molar Surgery (A Clinical Trial) Parnian Tarabosi1, Hamed Nazari2, Neda Omidpanah3 1General Dentist, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran 2Department of Oral and Maxillofacial Surgery, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran 3Department of Oral Medicine, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran Abstract BACKGROUND: The aim of this study was to evaluate the effect of preopera8ve ketorolac and betamethasone injec8ons on reducing postopera8ve complica8ons mandibular third molar surgery. MATERIALS AND METHODS: In this randomized clinical trial, 134 pa8ents at the age group of 18-40 years who required mandibular molars surgery were studied. Pa8ents were randomly divided into two groups. In A group, 1 mL of betamethasone LA was injected into the master muscle before surgery, and in the A group, 30 mg of ketorolac per 1 mL was injected before surgery. On the second and seventh days aSer surgery, pa8ents were evaluated for the variables of maximum mouth opening, pain, swelling, and general sa8sfac8on with the surgery through telephone calls on the second and seventh days. Independent t-test and Mann-Whitney test were used to evaluate the variables. RESULTS: The mean of pain intensity and the swelling variables in the betamethasone group were lower than the ketorolac group in second and seventh days (P<0.05). The mean of maximum mouth opening and the pa8ent sa8sfac8on variables in the betamethasone group were higher than the ketorolac group in second day (P<0.05). There was no sta8s8cally significant difference in the pa8ent sa8sfac8on and maximum mouth opening variables on the seventh day (P>0.05). CONCLUSION: This study concluded that betamethasone performed significantly beZer in reducing swelling, pain, maximum mouth opening limita8on, and general sa8sfac8on. KEYWORDS: Ketorolac; Injec8on; Masseter Muscle; Betamethasone LA; Third molar surgery Cita9on: Tarabosi, P. et al. (2024) Comparison of the Effect of Ketorolac and Betamethasone Injec9on on Post Complica9ons of Third Molar Surgery (A Clinical Trial) Den9stry 3000. 1:a001 doi:10.5195/d3000.2024.513 Received: May 27, 2023 Accepted: July 14, 2023 Published: April 24, 2024 Copyright: ©2024 Tarabosi, P. et al. This is an open access ar9cle licensed under a Crea9ve Commons AXribu9on Work 4.0 United States License. Email: n.omidpanah20000@gmail.com Introduction Impacted mandibular third molar surgery is one of the most common interventions and that is a traumatic process in the field of oral and maxillofacial surgery, which has many complications such as pain, swelling, and trismus .These phenomena are caused by excessive inflammatory processes [1,2]. Pain is an unpleasant sensory experience that is connected to real or potential tissue damage and is originated from inflammatory mediators such as bradykinin, histamine, and prostaglandin. Prostaglandins and leukotrienes play a role in the inflammatory process and pain production. These substances are produced from arachidonic acid, which is caused by http://dentistry3000.pitt.edu/ Comparison of the Effect of Ketorolac and Betamethasone Injec8on on Post Complica8ons of Third Molar Surgery (A Clinical Trial) Vol 12 No 1 (2024) DOI 10.5195/d3000.2024.513 h#p://den*stry3000.pi#.edu the cell membrane destruction and damage due to surgery [3,4]. Edema or swelling is the body's expected physiological response to injury, which is due to the accumulation of fluids at the injury site. Accumulation of fluids and extensive inflammation in the masticatory muscles after surgery can lead to mouth opening restriction or trismus [5,6]. Third molar extraction can reduce the life quality in patients who experience pain and swelling up to 3 times [7]. It seems that factors such as age, sex, medical history, oral contraceptives, pericoronitis, inappropriate oral hygiene, smoking, type of impaction, the third molar relationship with inferior alveolar nerve, surgical time, surgical technique, surgeon's experience, using Postoperative antibiotics, local antiseptics, intraoral drugs, anesthetic techniques [8], individual physiological inflammatory response, tissue trauma degree and bone manipulation [9] effect on the third molar extraction post complications. Different medical treatment methods have been proposed to control the impacted third molar surgery post complications- which are caused by inflammation- to reduce the complications by inhibiting the inflammatory pathway, including non-steroidal anti-inflammatory drugs and corticosteroids [4,10]. Corticosteroids inhibit the phospholipase A2 enzyme, which plays a role in the inflammatory pathway and the conversion of cell membrane phospholipids into arachidonic acid. This inhibitory effect reduces the release of arachidonic acid and ultimately leads to a reduction in inflammatory mediators (bradykinin, prostaglandin, etc.) production [4]. Long-acting betamethasone is a combination of short-acting (betamethasone diphosphate) and long-acting (betamethasone acetate), two forms of corticosteroids, and its acting duration is more than 36 hours, and its anti-inflammatory power is 25 times of body's natural cortisol , and it is similar to the dexamethasone power [11,12]. Using corticosteroids in dentistry in low doses and for a short period does not cause significant side effects [4,13]. NSAIDs inhibit the inflammatory mediators’ productions by inhibiting cyclooxygenases 1 and 2. Ketorolac from the NSAID category has a moderate to strong analgesic effect and has been useful for acute and chronic pain and it has anti- inflammatory effects and has shown a good analgesic effect on tooth extraction [14]. Ketorolac is more potent among different anti-inflammatory drugs under similar experimental conditions [15]. Intramuscular Corticosteroid injection is very effective for reducing pain, and while it is injected into the masseter muscle, there is no need for additional anesthesia injection to the patient and it is easily available for the dentist [16-18]. Grossi et al. showed that injection in the anesthetized area of the mouth is comfortable for the patient and the surgeon, While the injection in the gluteal muscle requires special facilities and equipment [19]. In addition, a study by Selvaraj et al. showed that there is no statistically significant difference between methylprednisolone injection into the masseter muscle and gluteal muscle injection in terms of pain after impacted third molar surgery [20]. Skjelbred et al. showed in their study that betamethasone can be effective in reducing pain after mandibular third molar surgery [21]. RAO et al. have shown in their study that ketorolac provides better analgesia than acetaminophen in tooth extraction [14]. Ketorolac has a similar effect to morphine [22] and is even better than opioids in pain relief [23]. In a study, Majid et al. showed that the use of corticosteroids can be useful in improving the complications and quality of life after mandibular third molar surgery [6]. More studies are necessary to compare the effect of corticosteroids with NSAIDs on the wisdom teeth surgery post complications . The purpose of this study is to compare the effect of betamethasone long acting (LA ) or ketorolac injection on the masseter muscle immediately after mandibular block anesthesia injection, on pain, http://dentistry3000.pitt.edu/ Comparison of the Effect of Ketorolac and Betamethasone Injec8on on Post Complica8ons of Third Molar Surgery (A Clinical Trial) Vol 12 No 1 (2024) DOI 10.5195/d3000.2024.513 h#p://den*stry3000.pi#.edu swelling, overall patient satisfaction, and maximum mouth opening after mandibular impacted third molar surgery. Material and Methods Ethics approval of the study This randomized, single blind, clinical trial study included 134 patients, Aged 18-40 years with impacted lower third molar. The study methods were approved by the Ethics Committee of Kermanshah University of Medical Sciences with the rigestery ID of IR.KUMS.REC.1400.801 . Witnessed written consent was obtained from of all participants before enrolment in the study. .This study was registered at WWW.IRCT.IR with IRCT Registration Code: IRCT20191127045516N6. The inclusion criteria were: Age of 18 -40 years, healthy medical assessment ( ASA I or II), diagnosis of bony impacted mandibular third molars requiring surgery with panoramic radiography , free of pericoronitis or infection at the time of operation. Exclusion criteria included: concurrent lactating or pregnancy, systemic disease, allergy to the drugs , history of smoking or drinking alcohol, impaction according to Pell & Gregory [24] and Winter [25] classifications with severe complexity and those who use the antibiotic and anti-inflammatory medication in the one week before surgery and surgery lasting more than 1 hour. Participants, study design, and setting According to Paiva-Oliveira J, et al [15] the sample size was calculated using a standard deviation and mean of s1=1.29 , X!!!!1 = 1.05 for Dexamethasone group and s2=2.24, 𝑋!! = 2.35 for Ketorolac Tromethamine group, With considering 𝛼 = 0.05 (power) 1- β=90%, minimum sample size in each group was 62 persons. The sample volume was calculated with the following formula: Total of 134 patient using a Sequentially Numbered, Opaque Sealed Envelopes (SNOSE) divided into two groups (A, B) with a 1:1 allocation ratio. Each patient allocated to the groups was based on systematic random numbering; letter “A” was allocated to the first group, letter “B” was allocated to the second group . Group “A” received 6 mg/1ml ampoule betamethasone LA (Alborz Iran Company) in masseter muscle and the group B received 30 mg/ml of ketorolac (Alborz Iran Company) into the masseter muscle immediately after anesthesia. Neither the surgeons nor the participants were blinded to use of the receiving drugs .Postoperative amoxicillin 500 mg , metronidazole 250 and acetaminophen 325mg were prescribed for All patients in the study. The operations were performed by one surgeon in private office. Two surgeries in both sides were carried out in each patient with a minimum interval of 15 days. Using a solution of 2% lidocaine with 1:2 00,000 adrenaline (persocaine-E ; Darou Pakhsh, Tehran, Iran). inferior alveolar nerve block and long buccal nerve block were carried out. Standard impacted third molar surgery were carried out with bone removal and irrigation with sodium chloride 0.9%. Sutures were performed with 3.0 silk (Braided silk; Supa, Tehran, Iran). A gauze pack was held in the surgical site for 30 -45 minutes. The effect of the surgery on Postoperative pain, swelling, general patient satisfaction and maximum mouth opening were measured on days 2 and 7 after operation by telephonic interview. Postoperative pain scores were estimated using a visual analog scale(VAS), 10 mm in length, ranging from 0 for “no pain” to 10 for “the worse unbearable pain” [1,15]. http://dentistry3000.pitt.edu/ Comparison of the Effect of Ketorolac and Betamethasone Injec8on on Post Complica8ons of Third Molar Surgery (A Clinical Trial) Vol 12 No 1 (2024) DOI 10.5195/d3000.2024.513 h#p://den*stry3000.pi#.edu Swelling scores was assessed by asking the patient to rate it on a visual analog scale of 0 to 5 [1,26- 28] .General patient satisfaction of the surgery was recorded from 0 to 10 by telephonic interview at 2 and 7 days after surgery [1]. The patients were asked to score their satisfaction from 0 to 10, where 0 represents no satisfaction and 10 representing complete satisfaction of the surgery. Patients measured maximum distance inter upper central and lower central incisal with ruler for 2 and 7 days after operation [15,29]. Before enrollment the study, these variables were explained to all patients by leaflet and how to report them to the operator, who called them through a phone at 2 and 7 days after operation. Statistical analysis Data analysis was carried out using SPSS version 18 Statistical software (SPSS, Inc, Chicago, IL). Subject demographic data were analyzed by Chi-Square or Independent Samples T-Test, as appropriate. To compare the paired results among groups and across time were used Mann Whitney test and Wilcoxon, respectively. P value of less than 0.05 was considered significant. Results 134 participants of both genders, between 18 and 39 years (mean 25.03±5.47 years) with impacted lower third molars were present in this study. 57of the participants (42.5%) were male and the rest (77 individuals (57.5 %)) were female. 68 of which (50.7%) were allocated to the group A (betamethasone) and 66 individuals (49.3) to the group B (ketorolac). There were no statistically significant differences in the distribution of the mean age (P=0.788) and gender (P=0.979) between the two groups. There wasn't a significant difference in Difficulty level of impacted teeth between the two groups (Table 1). The betamethasone group had significantly less pain and swelling scores on the second and seventh days after the surgery compared with the ketorolac group (p<0.001) (Table 2). General patient satisfaction and maximum mouth opening on the second day were significantly higher in the betamethasone group than the ketorolac group. However, no significant difference was showed between the groups on 7th day (Table 2). Pain and swelling scores on the seventh day after the surgery were lower than the second day after surgery in both groups (p < 0.0001). General patient satisfaction and maximum mouth opening on the seventh day after the surgery were higher than the second day after surgery in both groups (p < 0.0001) (Table 2). Medication group P-value Betamethasone Ketorolac Sex Male 29(42.6%) 28(42.4) 0.979† Female 39(57.4%) 38(57.6) Difficulty level of impacted teeth Minimally difficult 27(39.7%) 26(39.4%) 0.971† Moderate 41(60.3%) 40(60.6%) Age 25.16±5.83 24.89±5.11 0.778‡ Mean±standard deviation and percentage (%) are presented for parametric and categorical data, respectively. †Chi-Square test was used. ‡Independent Samples T-Test was used. Table 1: Demographic and Difficulty level of impacted teeth data http://dentistry3000.pitt.edu/ Comparison of the Effect of Ketorolac and Betamethasone Injec8on on Post Complica8ons of Third Molar Surgery (A Clinical Trial) Vol 12 No 1 (2024) DOI 10.5195/d3000.2024.513 h#p://den*stry3000.pi#.edu Discussion The main findings of this study were that there was a statistically significant difference in variables of pain intensity and swelling on the second and seventh day between the two study groups, as the average of these variables was lower in the betamethasone group than in the ketorolac group, and there was a statistically significant difference in the maximum mouth opening rate variable. There was a difference in the patient's maximum mouth opening on the second day between the two study groups, as the mean of this variable in the betamethasone group was higher than in the ketorolac group. Also, the average of the maximum mouth opening on the second day in both groups was less than 35 mm. This study shows that betamethasone performed significantly better in reducing swelling, pain, and maximum mouth opening and general satisfaction. Moghadasi et al [30]., Messer et al. [31] , and Mahmoud et al.[16] reported a significant reduction in pain, swelling, and trismus by administering dexamethasone intramuscularly, which was according to the results of our study. In the clinical trial study by Jose Marques et al. ,[29] a dose of 12 mg long-acting betamethasone was administered submucosally after Items Medication group Betamethasone Ketorolac P value Mean ±SD Mean±SD Pain Vas day 2nd 2.75± 2.43 4.37±3.04 0.001† Pain Vas day 7th 0.44±1.04 1.50±2.06 <0.001† <0.001‡ <0.001‡ Swelling Vas day 2nd 2.16±1.50 3.36±1.39 <0.001† Swelling Vas day7th 0.29±0.52 0.67±0.93 0.005† <0.001‡ <0.001‡ General patient satisfaction day 2nd 8.91 ±1.05 8.20±2.01 .012† General patient satisfaction day 7th 9. 43±0.97 9.09±1.77 .178† <0.001‡ <0.001‡ maximum mouth opening day 2nd 29.12±7.72 25.94±8.73 .027† maximum mouth opening day 7th 38.37±5.05 38.85 ±8.73 .698† <0.001‡ <0.001‡ Table 2: P values in comparing the pain, swelling, general pa8ent sa8sfac8on scores between each 3 groups †Independent Samples T-Test was used ‡Paired T-Test was used http://dentistry3000.pitt.edu/ Comparison of the Effect of Ketorolac and Betamethasone Injec8on on Post Complica8ons of Third Molar Surgery (A Clinical Trial) Vol 12 No 1 (2024) DOI 10.5195/d3000.2024.513 h#p://den*stry3000.pi#.edu surgery, and no significant difference was observed between the two study groups in terms of postoperative pain, facial swelling, and trismus, which was contrary to the results of our study. The clinical trial study by Bertossi et al. [32] showed that the use of a 4 mg submucosal injection of betamethasone after surgery leads to a reduction in edema, trismus, and pain in the patients undergoing extraction of impacted third molar which was according to the results of our study. In a clinical trial study, Chopra et al.[33] showed that ibuprofen is more effective than betamethasone in reducing pain and swelling, which was contrary to the results of our study. In Paiva-Oliveira [15] clinical trial study in 2016, compared 10 mg of oral ketorolac (1 hour before third molar surgery and then every 8 hours for two days) with 8 mg of oral dexamethasone (1 capsule 1 hour before Third molar surgery) and concluded that there was no statistically significant difference between the two groups in terms of pain and edema variables. However, for mouth opening limitation, 24 hours and 7 days after surgery, the dexamethasone group had less limitation in mouth opening, and it behaved better than Ketorolac for this variable in these periods, which was contrary to the results of our study. In Martin's 2021 [34] clinical trial study, 8 mg single dose of oral dexamethasone was compared with 20 mg single dose of sublingual ketorolac tromethamine 1 hour before surgery. Compared to ketorolac tromethamine, dexamethasone showed a significant reduction in pain level up to 72 hours, in swelling, and trismus up to 72 hours and 7 days later, and the clinical performance of dexamethasone in controlling pain, swelling, and trismus following mandibular third molar removal was superior to ketorolac tromethamine. It seems that the superiority of dexamethasone compared to ketorolac in this study is related to the characteristics of its broad anti- inflammatory effect mechanism and its long half-life. Therefore, it is a more accessible and more suitable option for preventive prescription in oral surgery. In a clinical trial study by Meta et al., [35] postoperative pain and swelling after dental implants were compared in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) versus NSAIDs and corticosteroids. This RCT did not show a difference between patients treated with ketorolac-betamethasone versus ketorolac alone in terms of postoperative pain and swelling, which was against the results of our study. These controversies among the results of the studies may be related to various factors, including drugs, dosage, administration method, administration time, and method of measuring postoperative complications including swelling and pain, and the follow-up period of patients after surgery. One of the limitations of this study is the measurement of swelling and maximum mouth by using a telephone report from the patients. It would be better to evaluate the intensity of pain on the first day after surgery, which is most intense in the first 6 hours after surgery. Conclusion Long-acting corticosteroids can be more effective in reducing swelling, pain, and maximum mouth opening, and in increasing general satisfaction than NSAIDs. Briefly, the present study shows that betamethasone has acted significantly better in reducing swelling, pain, limitation of maximum mouth opening, and general satisfaction. References 1. Comparison of the EffecGveness of Dexamethasone InjecGon into Two Different Sites in PrevenGng the PostoperaGve ComplicaGons aKer Mandibular Third Molar Surgery: A Randomized Clinical Trial. Shirani M, Hasanzade M, Moadabi A, ARar B. Br J Med Med Res 2016; 13(10), 1–11. hRp://dx.doi.org/10.9734/BJM MR/2016/23638. 2. Clinical postoperaGve findings aKer removal of impacted mandibular third molars: PredicGon of postoperaGve facial swelling and pain based on preoperaGve variables . Yuasa H, Sugiura M. Bri+sh Journal http://dentistry3000.pitt.edu/ Comparison of the Effect of Ketorolac and Betamethasone Injec8on on Post Complica8ons of Third Molar Surgery (A Clinical Trial) Vol 12 No 1 (2024) DOI 10.5195/d3000.2024.513 h#p://den*stry3000.pi#.edu of Oral and Maxillofacial Surgery 2004;42(3),209-14. hRps://doi.org/10.1016/j.bjoms. 2004.02.005. 3. Psychological aspects of pain. Gorczyca R, Filip R, Walczak E. Ann Agric Environ Med 2013, 20(1), 23–7. PMID: 25000837. 4. The use of corGcosteroids and nonsteroidal anGinflammatory medicaGon for the management of pain and inflammaGon aKer third molar surgery: A review of the literature. Kim K, Brar P, Jakubowski J, Kaltman S, Lopez E.. Oral Surg, Oral Med Oral Pathol Oral Radiol Endododed 2009,10(5), 630–40. hRps://doi.org/10.1016/j.tripleo .2008.11.005. 5. Pimenta L, Peterson LJ, Ellise E, Hupp JR TM. Contemporary Oral & Maxillofacial Surgery 4th EdiGon. Mosby, St. Louis Craniofacial and Dental Developmental Defects: Diagnosis and Management 2003. 113–124. 6. Submucosal dexamethasone injecGon improves quality of life measures aKer third molar surgery: A comparaGve study. Majid OW, Al-Mashhadani BA. J Oral Maxillofac Surg 2011,69(9),289–97. hRps://doi.org/10.1016/j.joms.2 011.01.037. 7. The impact of third molar symptoms, pain, and swelling on oral health-related quality of life. Slade GD, Foy SP, Shugars DA, Phillips C, White RP. J Oral Maxillofac Surg2004,62(9),1118- 1124. hRps://doi.org/10.1016/j.joms.2 003.11.014. 8. ComplicaGons of Third Molar Surgery. Bouloux GF, Steed MB, Perciaccante VJ. Oral and Maxillofac Surg Clin North Am 2007,19(1),117–28. hRps://doi.org/10.1016/j.coms. 2006.11.013 9. Beneficial effect of methylprednisolone aKer mandibular third molar surgery: A randomized, double-blind, placebo-controlled split-mouth trial. Acham S, Klampfl A, Truschnegg A, Kirmeier R, Sandner-Kiesling A, Jakse N. Clin Oral InvesGg, 2013,17(7)1693– 700. hRps://doi.org/10.1007/s00784- 012-0867-1. 10. Randomized Controlled Trial to Evaluate the Efficacy of Oral Dexamethasone and Intramuscular Dexamethasone in Mandibular Third Molar Surgeries. Sabhlok S, Kenjale P, Mony D, Khatri I, Kumar P. J Clin Diagn Res 2015,9(11), ZC48-5 hRps://doi.org/10.7860%2FJCDR %2F2015%2F13930.6813. 11. Do CorGcosteroids SGll Have a Role in the Management of Third Molar Surgery? Advances in Therapy. Ngeow WC, Lim D. Springer Healthcare; 2016,33(7)1105–1139. hRps://doi.org/10.1007/s12325- 016-0357-y. 12. Betamethasone and methylprednisolone usage in lower third molar surgery : Review literature. Gozali P, KiaRavornchareon S, Wu M, Wongsirichat N, Suphangul S. M Dent J 2015,35(3),273–80. 13. CorGcosteroids reduce postoperaGve morbidity aKer third molar surgery: A systemaGc review and meta- analysis. Markiewicz MR,Brady MF, Ding EL , Dodson TB. J Oral Maxillofac Surg 2008,66(9), 1881-94. hRps://doi.org/10.1016/j.joms.2 008.04.022. 14. Analgesic Efficacy of Paracetamol Vs Ketorolac aKer Dental ExtracGons. Rao TD, Kumar MPS. Res J Pharm Technol. 2018,11(8),3375-9. hRp://dx.doi.org/10.5958/0974- 360X.2018.00621.2 15. Comparison of the anG- inflammatory effect of dexamethasone and ketorolac in the extracGons of third molars. Paiva-Oliveira J, Bastos P, Pontes E, Silva J, Delgado J, Oshiro-Filho N. Oral Maxillofac Surg 2016,20(2), 123-33. hRps://doi.org/10.1007/s10006- 015-0533-2. 16. Efficacy of sub-mucosal, intra- masseteric and intra-muscular routes of dexamethasone administraGon on post-operaGve complicaGons following impacted mandibular third molar surgeries, comparaGve clinical trial. Mahmoud N. Egyp+an Dental Journal 2019,65(1), 113–33. hRps://dx.doi.org/10.21608/edj. 2015.71254. 17. Comparison of Efficacy of Methylprednisolone InjecGon into Masseter Muscle Versus Gluteal Muscle for Surgical Removal of Impacted Lower Third Molar. Selvaraj L, Hanumantha Rao S, Lankupalli ASMaxillofac Oral Surge. 2014,13(4), 495–8. hRps://doi.org/10.1007/s12663- 013-0562-z. 18. Efficacy of methylprednisolone injected into the masseter muscle following the surgical extracGon of impacted lower third molars. Vegas-Bustamante E, Micó-Llorens J, Gargallo-Albiol J, Satorres-Nieto M, Berini-Aytés L, Gay-Escoda C. Int J Oral Maxillofac Surge2008,37(3),260– 3. hRps://doi.org/10.1016/j.ijom.2 007.07.018. 19. Effect of Submucosal InjecGon of Dexamethasone on http://dentistry3000.pitt.edu/ Comparison of the Effect of Ketorolac and Betamethasone Injec8on on Post Complica8ons of Third Molar Surgery (A Clinical Trial) Vol 12 No 1 (2024) DOI 10.5195/d3000.2024.513 h#p://den*stry3000.pi#.edu PostoperaGve Discomfort AKer Third Molar Surgery: A ProspecGve Study. Grossi GB, Maiorana C, Garramone RA, Borgonovo A, BereRa M, Farronato D, et al. J Oral Maxillofac Surg. 2007,65(11), 2218–26. hRps://doi.org/10.1016/j.joms.2 006.11.036. 20. Comparison of Efficacy of Methylprednisolone InjecGon into Masseter Muscle Versus Gluteal Muscle for Surgical Removal of Impacted Lower Third Molar. Selvaraj L, Hanumantha Rao S, Lankupalli AS. J MaxillofacOral Surg,2014,13(4), 495–8. hRps://doi.org/10.1007/s12663- 013-0562-z. 21. Post-operaGve pain and inflammatory reacGon reduced by injecGon of a corGcosteroid. A controlled trial in bilateral oral surgery. Skjelbred P, Loekken P, Løkken P. Eur J Clin Pharmacol ,1982,21(5), 391–6. hRps://doi.org/10.1007/BF0054 2325. 22. Comparison of Intramuscular Ketorolac Tromethamine and Morphine Sulfate for Analgesia of Pain AKer Major SurgeryPharmacother.Yee JP, Koshiver JE, Allbon C, Brown CR. J Hum Pharmacol Drug Ther 1986,6(5), 253–61. hRps://doi.org/10.1002/j.1875- 9114.1986.tb03485.x. 23. ComparaGve EvaluaGon of Pre- EmpGve Analgesic Efficacy of Intramuscular Ketorolac Versus Tramadol Following Third Molar Surgery. Shah A V., Arun Kumar K V., Rai KK, Rajesh Kumar BP. J Maxillofac Oral Surg 2013,12(2), 197–202. hRps://doi.org/10.1007/s12663- 012-0420-4. 24. How well do clinicians esGmate third molar extracGon difficulty? Susarla SM, Dodson TB. J Oral Maxillofa Surg 2005,63(2), 191- 9. hRps://doi.org/10.1016/j.joms.2 004.05.220. 25. Winter GB: Principles of exodonGas as applied to the impacted third molar 1ed. St. Louis American medical books 1926. In Contemporary Oral and Maxillofacial Sugery. 2th ediGon. Edited by: Peterson LJ, Ellis E, Hupp JR, Tucker MR. Mosby, St Louis;1993:225-260. 26. Visual analogue scale assessment of postoperaGve swelling: A study of clinical inflammatory variables subsequent to third-molar surgery. Berge TI. Acta Odontol Scand 1988,2 6(4), 233–40. hRps://doi.org/10.3109/000163 58809004772. 27. The use of a visual analogue scale in observer assessment of postoperaGve swelling subsequent to third-molar surgery. Berge TI. Acta Odontol Scand1989,47(3),167–74. hRps://doi.org/10.3109/000163 58909007697. 28. Primary and secondary closure of the surgical wound aKer removal of impacted mandibular third molars: A comparaGve study. Pasqualini D, Cocero N, Castella A, Mela L, Bracco P. Int J Oral Maxillofac Surg 2005,34(1),52–7. hRps://doi.org/10.1016/j.ijom.2 004.01.023. 29. Effect of the local administraGon of betamethasone on pain, swelling and trismus aKer impacted lower third molar extracGon. A randomized, triple blinded, controlled trial. Marques J, Pié-Sánchez J, Figueiredo R, Valmaseda- Castellón E, Gay-Escoda C. Med Oral Patol Oral Cir Bucal 2014,19(1),e49-54. hRps://doi.org/10.4317/medora l.19280. 30. Effect of PreoperaGve Single Dose Dexamethasone InjecGon in Masseter Muscle on PostoperaGve Sequelae Following Lower Impacted Third Molar Surgery. Moghadasi M, Golestaneh A, Ghodosi A, Golestani SJ Isfahan Dent Sch 2021 Apr 10,17(1), 87–94 .hRps://doi.org/10.18502/ijds.v1 7i1.5919. 31. The use of intraoral dexamethasone aKer extracGon of mandibular third molars. Messer EJ, Keller JJ. Oral Surgery, Oral Med Oral Pathol1975,4(5),594–8. hRps://doi.org/10.1016/0030- 4220(75)90369-2. 32. EvaluaGon of pain, swelling and trismus aKer extracGon of impacted third molars relaGve to the use of betamethasone in submucusal infiltraGon. Bertossi D, Donadello D, Ricciardi G, Luciano U, Zox F, Nocini R, et al. J Biol Regul Homeost Agents 2019 20;33:9–17. PMID: 30966728. 33. A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serraGopepGdase, ibuprofen and betamethasone using the dental impacGon pain model. Chopra D, Rehan HS, Mehra P, Kakkar AK. Int J Oral Maxillofac Surg 2009,38(4),350–5. hRps://doi.org/10.1016/j.ijom.2 008.12.013. 34. Is dexamethasone superior to ketorolac in reducing pain, swelling and trismus following mandibular third molar removal? A split mouth triple- blind randomized clinical trial. MarGns-De-barros AV, Barros AMI, de Siqueira AKC, Lucena EE de S, de Souza PHS, Araújo FA da http://dentistry3000.pitt.edu/ Comparison of the Effect of Ketorolac and Betamethasone Injec8on on Post Complica8ons of Third Molar Surgery (A Clinical Trial) Vol 12 No 1 (2024) DOI 10.5195/d3000.2024.513 h#p://den*stry3000.pi#.edu C. Med Oral Patol Oral Cir Bucal 2021,26(2),141–50. hRps://doi.org/10.4317/medora l.24088. 35. Randomized Controlled Trial Comparing the Effects of 2 Analgesic Drug Protocols in PaGents who Received 5 Dental Implants. Meta IF, Bermolen M, MacChi R, Aguilar J. Implant Dent. 2017,26(3)3,412–6. 10.1097/ID.0000000000000544. http://dentistry3000.pitt.edu/