- Email: [email protected]
Analgesic and Anti-Inflammatory Effects of Articaine and Perineural Dexamethasone for Mandibular Third Molar Surgery: A Randomized, Double-Blind Study
Journal Pre-proof Analgesic and anti-inflammatory effects of articaine and perineural dexamethasone for mandibular third molar surgery: A randomized, double-blind study Berkem Atalay, Phd, Asst. Prof. Dr., Abdullah Tolga Şitilci, MD, Asst. Prof. Dr., Özen Doğan Onur, PhD, Prof. Dr. PII:
S0278-2391(19)31252-2
DOI:
https://doi.org/10.1016/j.joms.2019.10.024
Reference:
YJOMS 58959
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 12 June 2019 Revised Date:
28 October 2019
Accepted Date: 28 October 2019
Please cite this article as: BA, Şitilci AT, Onur ÖD, Analgesic and anti-inflammatory effects of articaine and perineural dexamethasone for mandibular third molar surgery: A randomized, double-blind study, Journal of Oral and Maxillofacial Surgery (2019), doi: https://doi.org/10.1016/j.joms.2019.10.024. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons
Analgesic and anti-inflammatory effects of articaine and perineural dexamethasone for mandibular third molar surgery: A randomized, double-blind study
Berkem Atalay, Phd, Asst. Prof. Dr. ¥*, Abdullah Tolga Şitilci, MD, Asst. Prof. Dr.†, Özen Doğan Onur, PhD, Prof. Dr.†
¥Vocational School of Health Sciences, İstanbul University-Cerrahpaşa, İstanbul, Turkey †Department of Oral Surgery, Faculty of Dentistry, Istanbul University, İstanbul, Turkey
Short Title: Anti-inflammatory effects of perineural dexamethasone
*Corresponding author: Berkem Atalay, Asst. Prof. Dr.
Address: İstanbul University, Dis Hekimligi Fak. Ağız, Dis, Cene Cerrahisi Bölümü, Fatih, 34093, İstanbul, Turkey
E-mail: [email protected]
Telephone: +90 (542) 581 20 99
Fax: +90 (212) 414 25 64
Analgesic and anti-inflammatory effects of articaine and perineural dexamethasone for mandibular third molar surgery: A randomized, double-blind study Abstract Purpose: To investigate the effectiveness of articaine and perineural dexamethasone (DX) in reducing postoperative sequelae such as swelling and maximum mouth opening, which is harming the quality of life of patients after impacted mandibular third molar surgery (IMTM). Patients and Methods: The investigators implemented a randomized clinical trial composed of patients with the IMTM. The predictor variable was the treatment group. The subjects were randomly assigned to one of three groups: group A; administered 3.6-mL articaine mixed with 2-mL saline; group B; administered 3.6-mL articaine, 1-mL DX (4 mg/ml solution) with 1-mL saline; and group C; administered 3.6-mL articaine with 2-mL DX (8 mg/ml solution). The primary outcome variables were swelling (determined by anatomical facial landmarks), pain, and maximum mouth opening. Other variables were grouped as the duration of surgery, the number of analgesics taken in the postoperative period, hygiene, and petechia. Results: The sample was composed of 60 subjects (20 per treatment group), with a mean age of 25.18±5.22 and 53.3% female. Postoperative swelling was significantly reduced in groups B and C (P < 0.05). Maximum mouth opening was significantly increased in groups B and C. (P < 0.05). Conclusion: The results of this study suggest that combining DX with articaine improves the management of discomfort after IMTM surgery. The use of articaine via mandibular block in our study was not associated with neural damage. Keywords: swelling; dexamethasone; impacted mandibular third molar; pain; mouth opening.
1
Introduction Surgical removal of impacted mandibular third molars (IMTM) is the most common procedure performed in oral surgery.1 This procedure is usually associated with significant postoperative sequela. Pericoronitis, periodontal defects, second and third molar caries, resorption of second molar roots, odontogenic cysts, tumors, orthodontic problems, and neurogenic pain are associated with the mandibular third molar. Swelling, trismus, infection, bleeding, and paresthesia are the most common complications during and after the extraction of the third molar teeth. The damage to the second molar and bone fractures while surgery is among the less common complications.2,3 Numerous factors affect these complications, but the inflammatory process after surgical trauma remains a crucial factor. Clinical studies have heuristic approaches to reduce postoperative complications by using antibiotics, physiotherapy, corticosteroid treatment, antiseptic mouthwashes, and muscle relaxants. Corticosteroids are used in surgery to reduce transudation and edema of fluids.4 Supplemental
drugs,
such
as
morphine,
pethidine,
butorphanol,
clonidine,
dexamethasone (DX), and midazolam, have recently been added to local anesthetics to achieve faster, longer-lasting, and more intense anesthesia.5 However, morphine, pethidine, and butorphanol have side effects, such as severe sedation, and respiratory depression, and are psychomimetic.6 There is, therefore, a need to identify safer drug combinations that can increase the efficacy of anesthesia, increase pain, and edema control during the postoperative period, and reduce the loss of work hours. The purpose of this study was to compare different doses of DX administered along with a local anesthetic, articaine, in a single injection, for surgical extraction of IMTM’s, to evaluate the effectiveness of this combination for perineural inferior alveolar nerve (IAN) block. The investigators hypothesize that perineural injection of DX could reduce swelling and improve maximum mouth opening postoperatively. The specific aims of the study were to 2
measure differences in swelling, pain, trismus, maximum mouth opening for the three different treatment groups.
Patients and Methods Study Design To address the research purpose, it is designed a randomized clinical trial. The study sample was composed of all patients for IMTM extraction applied to our clinic from March 1, 2019, to March 31, 2019, were included, if they signed informed consent, were ASA Class I, more than 18 years old but less than 35 years old, were Class II Position B,7 required mandibular third molar tooth surgery, and had no acute inflammation, excessive caries, pain, and pathology around the third molar teeth. Patients were excluded if they were pregnant; had diabetes mellitus, systemic endocrine disorders, hypertension, kidney diseases, osteoporosis, psychiatric disorders, blood clotting disorders, infection around the related tooth, cataracts, or an allergy to any of the drugs or materials to be used; were menstruating, lactating, in early menopause, or obese; had used antibiotics in the previous 2 weeks or non-steroidal antiinflammatory drugs during the last week; could not cooperate or refused participation were excluded from this study. Additionally, any patient requiring more than one anesthetic, who did not experience numbness in the lip corner 15 minutes after administering anesthetic, in whom surgical procedures exceeded 30 minutes, or with local complications, such as root fracture, mandibular fracture, temporomandibular joint dislocation during extraction, were excluded from the analysis. The study was approved by the İstanbul University, Faculty of Dentistry, Clinical Research Ethics Board (Approval Number 2018/82). Predictor/Outcome Variables The predictor variable is the treatment group. The subjects were randomly assigned to 3
one of three groups: group A; administered 3.6-mL articaine mixed with 2-mL saline; group B; administered 3.6-mL articaine, 1-ml DX (4 mg/mL solution) with 1-mL saline; and group C; administered 3.6-mL articaine with 2-ml DX (8 mg/mL solution). Swelling is the primary outcome variable. Before the operation and on the third day after the surgery, the distance between the mouth commissure to the tragus, and between the tragus to the soft pogonion was measured, using a paper ruler, to evaluate the swelling. The secondary outcome variable was the maximum mouth opening. Additionally, the distance between the maxillary and mandibular incisal borders of the central teeth were measured with a compass and recorded in millimeters (mm) to evaluate trismus. All measurement values were recorded in mm. Sex, age, and duration of operation are the third category of variables related to the outcome. Duration of operation time recorded from the start of the incision to the last suture. All the IMTM were Class II Position B, so the variables were eliminated due to radiographic classification, type of impaction, and level of difficulty. Drugs were prepared and coded by a person who was blinded to the patients. The injector codes were written in the patients’ follow-up files. The surgeon and surgical assistants were blinded to the meaning of the codes until the end of the study. All patients were anesthetized and operated on by a 10-year experienced surgeon throughout the study, and the same doctor removed the sutures after seven days and examined each patient postoperatively. Sex, age, injector codes, pre- and postoperative mouth opening, postoperative swelling, and duration of operation were recorded. The administration time of anesthesia, and operation start and end times, were recorded. Surgical Technique Preoperatively extraoral antisepsis with 2% chlorhexidine gluconate and intraoral 4
antisepsis with 15 mL of 0.12% chlorhexidine gluconate were applied to all patients. Anesthesia was performed with a mixture of 4% articaine hydrochloride with epinephrine (1:200,000) and either saline or DX. More specifically, in group A, 3.6 mL or articaine was mixed with 2 mL saline; in group B, 3.6 mL of articaine, 1 mL of DX (4 mg/ml solution), and 1 mL of saline was mixed; and in group C, a mixture of 3.6 mL articaine and 2 mL DX (8 mg/mL solution) was used. These mixtures were injected for the regional anesthetic block of the IAN, lingual nerve, and in the buccal area near the IMTM targeted for extraction. All patients underwent the same surgical technique and started with a linear incision on the alveolus with a scalpel number 15, starting from the buccal region second molar tooth; an oblique incision of 1 cm was made. When necessary, osteotomy was performed with a drill and irrigation with a saline solution using high-speed rotary instruments. After the extraction, the irregular bone margins were flattened and sutured with 3-0 silk in all operations. Patients were recommended to use ice compress at 10-minute intervals after the operation for the first 24 hours postoperatively and were given the same analgesics. The patients could record their pain start time, the time when the first pain relief was required, the time at which this medication was taken, the amount of analgesic consumed in the first 24 hours after surgery, and the amount of analgesic consumed in the second 24 hours after the onset of pain. One week after the operation, patients were recalled for removing sutures and healing control, after which observation was terminated. Statistical Analysis All data are presented using descriptive statistics, including mean and standard deviation. Nonparametric tests, including Spearman’s rho, Kruskal–Wallis, Mann–Whitney U, and Wilcoxon’s signed-ranks tests were used to analyze intergroup and intragroup differences. Statistical significance was set at P < 0.05. Statistical analyses were performed using IBM SPSS Statistics 21.0 program. 5
Results Seventy-two patients assessed for eligibility and randomization. 8 patients did not meet inclusion criteria, and four patients declined to participate (Figure 1). Eventually, 60 patients were enrolled and randomly allocated to three groups (20 patients for each group), which received different anesthetic drug combinations (Table 1). The baseline characteristics of patients in all groups are shown in Table 2. In this study, postoperative infection and complications caused by DX injection were not observed. There was no significant difference between the groups in terms of duration of surgery. However, the addition of DX significantly reduced postoperative swelling after surgical removal of the IMTM (P > 0.05). There was a significant increase in swelling postoperatively as compared with preoperatively in group A (P < 0.05). The differences between pre- and postoperative traguscommissure and tragus-pogonion measurements were statistically significantly smaller in group B than in group A (P < 0.05). In addition, there was a statistically significant difference between pre- and postoperative maximum mouth opening measurements when groups A and B were compared (P < 0.05). There was a statistically significant difference between pre- and postoperative measurements for groups A, B, and C. The differences between pre- and postoperative traguscommissure and tragus-pogonion measurements were statistically significantly smaller in group C than in group A (P < 0.05). Furthermore, there was a statistically significant difference between group A and group C in terms of the preoperative vs. postoperative maximum postoperative mouth opening measurement values (Figure 2) (P < 0.05). The differences between the pre- and postoperative tragus-commissure and traguspogonion measurements were not statistically significantly different between groups B and C (Figures 3a, 3b, 3d, and 3e) (P > 0.05). However, the difference between pre- and 6
postoperative maximum mouth opening was statistically significantly different between groups B and C. Group C had higher maximum mouth opening measurement values (Figures 3c and 3f) (P < 0.05). There was no significant difference among groups of A, B, and C in terms of the analgesics taken and the duration of surgery. The average duration of surgery was 22.23 minutes (Table 3) (P > 0.05). Postoperative tragus-commissure, tragus-pogonion, and maximum mouth opening data were not correlated with swelling, pain, petechiae, and bleeding in all groups.
Discussion The purpose of the study is to investigate the effect of perineural injection of DX with articaine on analgesia and postoperative swelling related to third molar surgery. The hypothesize was a perineural injection of DX could reduce swelling and improve maximum mouth opening postoperatively. The specific aims of the study were to identify swelling, pain, trismus, maximum mouth opening. It is demonstrated that combining DX with articaine improved the management of postoperative discomfort after the removal of IMTM’s. Articaine can be safely used for IAN blocks. Paresthesia incidents are associated with mandibular blocks, and primarily affecting the lingual nerve. The frequency of direct needle trauma to the nerve during the inferior alveolar block is 7.7%. The injection has the risk of causing more neural damage than the anesthetic solution itself.8 There were no adverse neurologic effects attributed to using articaine to block the IAN in this study. Trismus, limits maximum mouth opening, is as a sequela to postoperative swelling within the mastication muscles. Individually, the medial pterygoid muscles and the masseter muscles can compress nerves and produce mild to severe pain. Adequate anti-inflammatory treatment should be provided preoperatively and postoperatively to control postoperative 7
inflammation and associated symptoms.9 Filho et al. reported that the limitation of maximum mouth opening by using 8 mg DX decreased by 9.3% and increased to 11.74% in 48 hours postoperatively.10 Nair et al. reported that the differences in the amount of trismus were not significant between the control group and DX group at days 2 or 7.11 In our study, limitation of maximum mouth opening was observed less with the DX groups compared to control group. The use of steroids with many systemic diseases is contraindicated. Some of those are hypertension, active or latent peptic ulcer, diabetes mellitus, Cushing's syndrome, osteoporosis, acute or chronic infections, and hepatic problems. Prolonged steroid use may delay recovery and increase vulnerability to infection, but these steroid-related effects are not common in oral surgery.12 In our study utilizing single-dose DX for extractions, there were no post-operative infections that can be attributed to the single-dose usage of steroids. Although systemic steroids can induce infection, our study suggests that perineural injections in patients with no history of an active infection do not show an increased rate of infection with single dose steroid injections. Majid and Mahmood reported that 4 mg DX significantly reduced pain in all DX groups compared with the control group.13 In some studies, the total number of analgesic tablets consumed in DX groups were found to be significantly lower.12-16 Unlike previous studies, Nair et al. showed that there was no significant difference in pain reduction between a group receiving a submucosal injection of DX during the operation and the control group.11 Grossi et al. concluded that DX injected intraorally during the operation was not significantly different from the total number of analgesic tablets consumed postoperatively compared with the control group.16 In this study, the pain was evaluated objectively by recording the number of analgesic tablets taken within the first and second 24 hours after surgery. Total analgesic consumption 8
in the first 24 hours was 4.7 and 3.8 in the second 24 hours. There was no significant difference in pain control, and the analgesics consumed in groups A, B, and C. These results are similar to previous studies.16-18 Our data indicate that DX administration with anesthetics responds better in terms of swelling than in group A, in which no DX was administered, and there is no statistically significant difference between groups B and C. This latest finding supports the study by Graziani et al. in which they evaluated the dose-dependent effects of DX powder on swelling in dentoalveolar applications.12 Skjelbred and Lokken report that DX reduces postoperative facial swelling after surgical removal of mandibular third molar teeth by reducing the release of prostaglandins, lymphokines, bradykinin, and serotonin from the injured tissue.14 In this study, the swelling and maximum mouth opening values were evaluated by using a tape-measuring method and compass, respectively. The results obtained for maximum mouth opening agree with those of previous studies.19,20 In this study, with the use of DX, maximum mouth opening was significantly improved in groups B and C, as compared with group A. This study was limited that the exclusion criteria were comprehensive because we chose to study young and healthy individuals to improve the accuracy of the results. General health problems may increase with advanced age, and with menopausal osteoporosis in women, bone flexibility decreases, which increases the risk of complications and prolong the operation time. Another limitation was the small sample size. This study also showed no significant difference in duration of surgery between groups A, B, and C, as the same surgeon performed all operations. To the best of our knowledge, no previous prospective study has used DX, administered perineural with an anesthetic in a single injection, to determine the ideal dose to reduce the postoperative sequela after IMTM surgery. Perineural injection of anesthetic with a single dose of 4 mg DX is effective in reducing swelling after third molar extraction surgery. DX (4 mg) can reduce postoperative swelling 9
and improve maximum mouth opening after surgical removal of IMTM’s, but does not affect pain after such surgery.
Declaration of patient consent The authors document that they received consent forms from all patients. In the forms, patients permitted clinical information and images to be reported in the journal. Patients were informed that their names and initials would not be published, and their identities would be hidden.
References 1. Contar C, De Oliveira P, Kanegusuku K, Berticelli R, Azevero-Alanis L, Machado M: Complications in third molar removal: a retrospective study of 588 patients. Med Oral Patol Oral Cir Bucal 15:74-78, 2010 2. Atalay B, Güler N, Cabbar F, Şençift K: Determination of incidence of complications and life quality after mandibular impacted third molar surgery. J Istanb Univ Fac Dent 48:3146, 2014 3. Grossi GB, Maiorana C, Garramone RA, et al.: Assessing postoperative discomfort after
third molar surgery: a prospective study. J Oral Maxillofac Surg 65:901-917, 2007 4. Klongnoi B, Kaewpradub P, Boonsiriseth K, et al.: Effect of single dose preoperative
intramuscular dexamethasone injection on lower impacted third molar surgery. Int J Oral Max Surg 41:376-379, 2012 5. Kanazi GE, Aouad MT, Jabbour-Khoury SI, et al.: Effect of low-dose dexmedetomidine or
clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand 50:222-227, 2006 6. Bazin JE, Massoni C, Bruelle P, et al.: The addition of opioids to local anaesthetics in
brachial plexus block: the comparative effects of morphine, buprenorphine and sufentanil. Anaesthesia 52:858-862, 1997 10
7. Pell GJ, Gregory GT: Impacted mandibular third molars: Classification and modified
techniques for removal. Dent Digest 39:330-338, 1933 8. Krafft TC, Hickel R: Clinical investigation into the incidence of direct damage to the lingual nerve caused by local anaesthesia. J Craniomaxillofac Surg 22:294-296, 1994 9. Klongnoi B, Kaewpradub P, Boonsiriseth K, Wongsirichat N: Effect of single dose preoperative intramuscular dexamethasone injection on lower impacted third molar surgery. Int J Oral Maxillofac Surg 41:376-379, 2012 10. Filho JRL, Maurette PE, Allais M, Cotinho M, Fernandes C: Clinical comparative study of the effectiveness of two dosages of Dexamethasone to control postoperative swelling, trismus and pain after the surgical extraction of mandibular impacted third molars. Med Oral Patol Oral Cir Bucal 13:129-132, 2008 11. Nair RB, Rahman NM, Ummar M, et al.: Effect of submucosal injection of
dexamethasone on postoperative discomfort after third molar surgery: a prospective study. J Contemp Dent Pract 14:401-404, 2013 12. Graziani F, D'Aiuto F, Arduino PG, et al.: Perioperative dexamethasone reduces post-
surgical sequelae of wisdom tooth removal. A split-mouth randomized double-masked clinical trial. Int J Oral Max Surg 35:241-246, 2006 13. Majid OW, Mahmood WK: Effect of submucosal and intramuscular dexamethasone on
postoperative sequelae after third molar surgery: comparative study. Br J Oral Maxillofac Surg 49:647-652, 2011 14. Skjelbred P, Lokken P: Post-operative pain and inflammatory reaction reduced by
injection of a corticosteroid. A controlled trial in bilateral oral surgery. Eur J Clin Pharmacol 21:391-396, 1982 15. Alexander RE, Throndson RR: A review of perioperative corticosteroid use in
dentoalveolar surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90:406-415, 11
2000 16. Grossi GB, Maiorana C, Garramone RA, et al.: Effect of submucosal injection of
dexamethasone on postoperative discomfort after third molar surgery: a prospective study. J Oral Maxillofac Surg 65:2218-2226, 2007 17. Majid OW: Submucosal dexamethasone injection improves quality of life measures after
third molar surgery: a comparative study. J Oral Maxillofac Surg 69:2289-2297, 2011 18. Laureano JR, Maurette PE, Allais M, et al.: Clinical comparative study of the
effectiveness of two dosages of Dexamethasone to control postoperative swelling, trismus and pain after the surgical extraction of mandibular impacted third molars. Med Oral Patol Oral Circ Buccal 13:129-132, 2008 19. Schmelzeisen R, Frolich JC: Prevention of postoperative swelling and pain by
dexamethasone after operative removal of impacted 3rd molar teeth. Eur J Clin Pharmacol 44:275-277, 1993 20. Messer EJ, Keller JJ: The use of intraoral dexamethasone after extraction of mandibular
third molars. Oral Surg Oral Med Oral Pathol 40:594-598, 1975
12
Figure Legends Figure 1. Consort flowchart of patient participation Figure 2. Preoperative and postoperative measurements for groups A, B, and C. Figure 3. a) Preoperative and postoperative differences for tragus-commisure in group B. b) Preoperative and postoperative differences for tragus-pogonion in group B. c) Preoperative and postoperative differences for maximum mouth opening in group B. d) Preoperative and postoperative differences for tragus-commisure in group C. e) Preoperative and postoperative differences for tragus-pogonion in group C. f) Preoperative and postoperative differences for maximum mouth opening in group C.
13
Table 1. Groups in the study. Groups A B C
Medicines Articaine 120 mg + 2 cc Saline Articaine 120 mg + Dexamethasone 4 mg + 1 cc Saline Articaine 120 mg + Dexamethasone 8 mg
Table 2. Baseline characteristics of patients. Sex
F M Age Hygiene
Preoperative Tragus-Commissure Preoperative Tragus-Pogonion Preoperative Maximum Mouth Opening *Kruskal Wallis Test
Group A 9 (45%) 11 (55%) 24.65 (5.56)
Group B 10 (50%) 10 (50%) 26.1 (5.34)
Group C 9 (45%) 11 (55%) 24.8 (4.89)
Test Statistics P-value 0.936* 0.132 0.802 0.670*
2.50 (0.68) 11.06 (1.496) 14.35 (1.601) 4.79 (0.525)
2.65 (0.587) 10.97 (1.617) 14.17 (1.828) 4.79 (0.521)
2.45 (0.686) 10.21 (2.895) 14.01 (1.526) 4.89 (0.490)
1.038
0.595*
1.121
0.571*
0.586
0.746*
0.500
0.779*
Table 3. Total analgesic intake after surgery in groups A, B, and C. a) Duration of surgery and number of analgesics consumed Duration of surgery (min) Number of analgesics consumed in the first 24hrs Number of analgesics consumed in the second 24hrs Valid N (listwise)
Minimum 5
Maximum 30
Mean 22.233
Std. Deviation 6.987
0
16
4.7321
3.887
0
10
3.85
3.36394
b) Number of analgesics consumed in the first 24hrs Frequency 2 or less 31 Between 3 and 5 4 Valid Between 6 and 8 16 More than 9 Total
9 60
Percent 51.7 6.7
Cumulative Percent 51.7 58.3
26.7 15 100
85 100
c) Number of analgesics consumed in the second 24hrs
Valid
2 or less Between 3 and 5 Between 6 and 8 More than 9 Total
Frequency 35 8 7 10 60
Percent 58.3 13.3 11.7 16.7 100
Cumulative Percent 58.3 71.7 83.3 100
S0278-2391(19)31252-2
DOI:
https://doi.org/10.1016/j.joms.2019.10.024
Reference:
YJOMS 58959
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 12 June 2019 Revised Date:
28 October 2019
Accepted Date: 28 October 2019
Please cite this article as: BA, Şitilci AT, Onur ÖD, Analgesic and anti-inflammatory effects of articaine and perineural dexamethasone for mandibular third molar surgery: A randomized, double-blind study, Journal of Oral and Maxillofacial Surgery (2019), doi: https://doi.org/10.1016/j.joms.2019.10.024. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons
Analgesic and anti-inflammatory effects of articaine and perineural dexamethasone for mandibular third molar surgery: A randomized, double-blind study
Berkem Atalay, Phd, Asst. Prof. Dr. ¥*, Abdullah Tolga Şitilci, MD, Asst. Prof. Dr.†, Özen Doğan Onur, PhD, Prof. Dr.†
¥Vocational School of Health Sciences, İstanbul University-Cerrahpaşa, İstanbul, Turkey †Department of Oral Surgery, Faculty of Dentistry, Istanbul University, İstanbul, Turkey
Short Title: Anti-inflammatory effects of perineural dexamethasone
*Corresponding author: Berkem Atalay, Asst. Prof. Dr.
Address: İstanbul University, Dis Hekimligi Fak. Ağız, Dis, Cene Cerrahisi Bölümü, Fatih, 34093, İstanbul, Turkey
E-mail: [email protected]
Telephone: +90 (542) 581 20 99
Fax: +90 (212) 414 25 64
Analgesic and anti-inflammatory effects of articaine and perineural dexamethasone for mandibular third molar surgery: A randomized, double-blind study Abstract Purpose: To investigate the effectiveness of articaine and perineural dexamethasone (DX) in reducing postoperative sequelae such as swelling and maximum mouth opening, which is harming the quality of life of patients after impacted mandibular third molar surgery (IMTM). Patients and Methods: The investigators implemented a randomized clinical trial composed of patients with the IMTM. The predictor variable was the treatment group. The subjects were randomly assigned to one of three groups: group A; administered 3.6-mL articaine mixed with 2-mL saline; group B; administered 3.6-mL articaine, 1-mL DX (4 mg/ml solution) with 1-mL saline; and group C; administered 3.6-mL articaine with 2-mL DX (8 mg/ml solution). The primary outcome variables were swelling (determined by anatomical facial landmarks), pain, and maximum mouth opening. Other variables were grouped as the duration of surgery, the number of analgesics taken in the postoperative period, hygiene, and petechia. Results: The sample was composed of 60 subjects (20 per treatment group), with a mean age of 25.18±5.22 and 53.3% female. Postoperative swelling was significantly reduced in groups B and C (P < 0.05). Maximum mouth opening was significantly increased in groups B and C. (P < 0.05). Conclusion: The results of this study suggest that combining DX with articaine improves the management of discomfort after IMTM surgery. The use of articaine via mandibular block in our study was not associated with neural damage. Keywords: swelling; dexamethasone; impacted mandibular third molar; pain; mouth opening.
1
Introduction Surgical removal of impacted mandibular third molars (IMTM) is the most common procedure performed in oral surgery.1 This procedure is usually associated with significant postoperative sequela. Pericoronitis, periodontal defects, second and third molar caries, resorption of second molar roots, odontogenic cysts, tumors, orthodontic problems, and neurogenic pain are associated with the mandibular third molar. Swelling, trismus, infection, bleeding, and paresthesia are the most common complications during and after the extraction of the third molar teeth. The damage to the second molar and bone fractures while surgery is among the less common complications.2,3 Numerous factors affect these complications, but the inflammatory process after surgical trauma remains a crucial factor. Clinical studies have heuristic approaches to reduce postoperative complications by using antibiotics, physiotherapy, corticosteroid treatment, antiseptic mouthwashes, and muscle relaxants. Corticosteroids are used in surgery to reduce transudation and edema of fluids.4 Supplemental
drugs,
such
as
morphine,
pethidine,
butorphanol,
clonidine,
dexamethasone (DX), and midazolam, have recently been added to local anesthetics to achieve faster, longer-lasting, and more intense anesthesia.5 However, morphine, pethidine, and butorphanol have side effects, such as severe sedation, and respiratory depression, and are psychomimetic.6 There is, therefore, a need to identify safer drug combinations that can increase the efficacy of anesthesia, increase pain, and edema control during the postoperative period, and reduce the loss of work hours. The purpose of this study was to compare different doses of DX administered along with a local anesthetic, articaine, in a single injection, for surgical extraction of IMTM’s, to evaluate the effectiveness of this combination for perineural inferior alveolar nerve (IAN) block. The investigators hypothesize that perineural injection of DX could reduce swelling and improve maximum mouth opening postoperatively. The specific aims of the study were to 2
measure differences in swelling, pain, trismus, maximum mouth opening for the three different treatment groups.
Patients and Methods Study Design To address the research purpose, it is designed a randomized clinical trial. The study sample was composed of all patients for IMTM extraction applied to our clinic from March 1, 2019, to March 31, 2019, were included, if they signed informed consent, were ASA Class I, more than 18 years old but less than 35 years old, were Class II Position B,7 required mandibular third molar tooth surgery, and had no acute inflammation, excessive caries, pain, and pathology around the third molar teeth. Patients were excluded if they were pregnant; had diabetes mellitus, systemic endocrine disorders, hypertension, kidney diseases, osteoporosis, psychiatric disorders, blood clotting disorders, infection around the related tooth, cataracts, or an allergy to any of the drugs or materials to be used; were menstruating, lactating, in early menopause, or obese; had used antibiotics in the previous 2 weeks or non-steroidal antiinflammatory drugs during the last week; could not cooperate or refused participation were excluded from this study. Additionally, any patient requiring more than one anesthetic, who did not experience numbness in the lip corner 15 minutes after administering anesthetic, in whom surgical procedures exceeded 30 minutes, or with local complications, such as root fracture, mandibular fracture, temporomandibular joint dislocation during extraction, were excluded from the analysis. The study was approved by the İstanbul University, Faculty of Dentistry, Clinical Research Ethics Board (Approval Number 2018/82). Predictor/Outcome Variables The predictor variable is the treatment group. The subjects were randomly assigned to 3
one of three groups: group A; administered 3.6-mL articaine mixed with 2-mL saline; group B; administered 3.6-mL articaine, 1-ml DX (4 mg/mL solution) with 1-mL saline; and group C; administered 3.6-mL articaine with 2-ml DX (8 mg/mL solution). Swelling is the primary outcome variable. Before the operation and on the third day after the surgery, the distance between the mouth commissure to the tragus, and between the tragus to the soft pogonion was measured, using a paper ruler, to evaluate the swelling. The secondary outcome variable was the maximum mouth opening. Additionally, the distance between the maxillary and mandibular incisal borders of the central teeth were measured with a compass and recorded in millimeters (mm) to evaluate trismus. All measurement values were recorded in mm. Sex, age, and duration of operation are the third category of variables related to the outcome. Duration of operation time recorded from the start of the incision to the last suture. All the IMTM were Class II Position B, so the variables were eliminated due to radiographic classification, type of impaction, and level of difficulty. Drugs were prepared and coded by a person who was blinded to the patients. The injector codes were written in the patients’ follow-up files. The surgeon and surgical assistants were blinded to the meaning of the codes until the end of the study. All patients were anesthetized and operated on by a 10-year experienced surgeon throughout the study, and the same doctor removed the sutures after seven days and examined each patient postoperatively. Sex, age, injector codes, pre- and postoperative mouth opening, postoperative swelling, and duration of operation were recorded. The administration time of anesthesia, and operation start and end times, were recorded. Surgical Technique Preoperatively extraoral antisepsis with 2% chlorhexidine gluconate and intraoral 4
antisepsis with 15 mL of 0.12% chlorhexidine gluconate were applied to all patients. Anesthesia was performed with a mixture of 4% articaine hydrochloride with epinephrine (1:200,000) and either saline or DX. More specifically, in group A, 3.6 mL or articaine was mixed with 2 mL saline; in group B, 3.6 mL of articaine, 1 mL of DX (4 mg/ml solution), and 1 mL of saline was mixed; and in group C, a mixture of 3.6 mL articaine and 2 mL DX (8 mg/mL solution) was used. These mixtures were injected for the regional anesthetic block of the IAN, lingual nerve, and in the buccal area near the IMTM targeted for extraction. All patients underwent the same surgical technique and started with a linear incision on the alveolus with a scalpel number 15, starting from the buccal region second molar tooth; an oblique incision of 1 cm was made. When necessary, osteotomy was performed with a drill and irrigation with a saline solution using high-speed rotary instruments. After the extraction, the irregular bone margins were flattened and sutured with 3-0 silk in all operations. Patients were recommended to use ice compress at 10-minute intervals after the operation for the first 24 hours postoperatively and were given the same analgesics. The patients could record their pain start time, the time when the first pain relief was required, the time at which this medication was taken, the amount of analgesic consumed in the first 24 hours after surgery, and the amount of analgesic consumed in the second 24 hours after the onset of pain. One week after the operation, patients were recalled for removing sutures and healing control, after which observation was terminated. Statistical Analysis All data are presented using descriptive statistics, including mean and standard deviation. Nonparametric tests, including Spearman’s rho, Kruskal–Wallis, Mann–Whitney U, and Wilcoxon’s signed-ranks tests were used to analyze intergroup and intragroup differences. Statistical significance was set at P < 0.05. Statistical analyses were performed using IBM SPSS Statistics 21.0 program. 5
Results Seventy-two patients assessed for eligibility and randomization. 8 patients did not meet inclusion criteria, and four patients declined to participate (Figure 1). Eventually, 60 patients were enrolled and randomly allocated to three groups (20 patients for each group), which received different anesthetic drug combinations (Table 1). The baseline characteristics of patients in all groups are shown in Table 2. In this study, postoperative infection and complications caused by DX injection were not observed. There was no significant difference between the groups in terms of duration of surgery. However, the addition of DX significantly reduced postoperative swelling after surgical removal of the IMTM (P > 0.05). There was a significant increase in swelling postoperatively as compared with preoperatively in group A (P < 0.05). The differences between pre- and postoperative traguscommissure and tragus-pogonion measurements were statistically significantly smaller in group B than in group A (P < 0.05). In addition, there was a statistically significant difference between pre- and postoperative maximum mouth opening measurements when groups A and B were compared (P < 0.05). There was a statistically significant difference between pre- and postoperative measurements for groups A, B, and C. The differences between pre- and postoperative traguscommissure and tragus-pogonion measurements were statistically significantly smaller in group C than in group A (P < 0.05). Furthermore, there was a statistically significant difference between group A and group C in terms of the preoperative vs. postoperative maximum postoperative mouth opening measurement values (Figure 2) (P < 0.05). The differences between the pre- and postoperative tragus-commissure and traguspogonion measurements were not statistically significantly different between groups B and C (Figures 3a, 3b, 3d, and 3e) (P > 0.05). However, the difference between pre- and 6
postoperative maximum mouth opening was statistically significantly different between groups B and C. Group C had higher maximum mouth opening measurement values (Figures 3c and 3f) (P < 0.05). There was no significant difference among groups of A, B, and C in terms of the analgesics taken and the duration of surgery. The average duration of surgery was 22.23 minutes (Table 3) (P > 0.05). Postoperative tragus-commissure, tragus-pogonion, and maximum mouth opening data were not correlated with swelling, pain, petechiae, and bleeding in all groups.
Discussion The purpose of the study is to investigate the effect of perineural injection of DX with articaine on analgesia and postoperative swelling related to third molar surgery. The hypothesize was a perineural injection of DX could reduce swelling and improve maximum mouth opening postoperatively. The specific aims of the study were to identify swelling, pain, trismus, maximum mouth opening. It is demonstrated that combining DX with articaine improved the management of postoperative discomfort after the removal of IMTM’s. Articaine can be safely used for IAN blocks. Paresthesia incidents are associated with mandibular blocks, and primarily affecting the lingual nerve. The frequency of direct needle trauma to the nerve during the inferior alveolar block is 7.7%. The injection has the risk of causing more neural damage than the anesthetic solution itself.8 There were no adverse neurologic effects attributed to using articaine to block the IAN in this study. Trismus, limits maximum mouth opening, is as a sequela to postoperative swelling within the mastication muscles. Individually, the medial pterygoid muscles and the masseter muscles can compress nerves and produce mild to severe pain. Adequate anti-inflammatory treatment should be provided preoperatively and postoperatively to control postoperative 7
inflammation and associated symptoms.9 Filho et al. reported that the limitation of maximum mouth opening by using 8 mg DX decreased by 9.3% and increased to 11.74% in 48 hours postoperatively.10 Nair et al. reported that the differences in the amount of trismus were not significant between the control group and DX group at days 2 or 7.11 In our study, limitation of maximum mouth opening was observed less with the DX groups compared to control group. The use of steroids with many systemic diseases is contraindicated. Some of those are hypertension, active or latent peptic ulcer, diabetes mellitus, Cushing's syndrome, osteoporosis, acute or chronic infections, and hepatic problems. Prolonged steroid use may delay recovery and increase vulnerability to infection, but these steroid-related effects are not common in oral surgery.12 In our study utilizing single-dose DX for extractions, there were no post-operative infections that can be attributed to the single-dose usage of steroids. Although systemic steroids can induce infection, our study suggests that perineural injections in patients with no history of an active infection do not show an increased rate of infection with single dose steroid injections. Majid and Mahmood reported that 4 mg DX significantly reduced pain in all DX groups compared with the control group.13 In some studies, the total number of analgesic tablets consumed in DX groups were found to be significantly lower.12-16 Unlike previous studies, Nair et al. showed that there was no significant difference in pain reduction between a group receiving a submucosal injection of DX during the operation and the control group.11 Grossi et al. concluded that DX injected intraorally during the operation was not significantly different from the total number of analgesic tablets consumed postoperatively compared with the control group.16 In this study, the pain was evaluated objectively by recording the number of analgesic tablets taken within the first and second 24 hours after surgery. Total analgesic consumption 8
in the first 24 hours was 4.7 and 3.8 in the second 24 hours. There was no significant difference in pain control, and the analgesics consumed in groups A, B, and C. These results are similar to previous studies.16-18 Our data indicate that DX administration with anesthetics responds better in terms of swelling than in group A, in which no DX was administered, and there is no statistically significant difference between groups B and C. This latest finding supports the study by Graziani et al. in which they evaluated the dose-dependent effects of DX powder on swelling in dentoalveolar applications.12 Skjelbred and Lokken report that DX reduces postoperative facial swelling after surgical removal of mandibular third molar teeth by reducing the release of prostaglandins, lymphokines, bradykinin, and serotonin from the injured tissue.14 In this study, the swelling and maximum mouth opening values were evaluated by using a tape-measuring method and compass, respectively. The results obtained for maximum mouth opening agree with those of previous studies.19,20 In this study, with the use of DX, maximum mouth opening was significantly improved in groups B and C, as compared with group A. This study was limited that the exclusion criteria were comprehensive because we chose to study young and healthy individuals to improve the accuracy of the results. General health problems may increase with advanced age, and with menopausal osteoporosis in women, bone flexibility decreases, which increases the risk of complications and prolong the operation time. Another limitation was the small sample size. This study also showed no significant difference in duration of surgery between groups A, B, and C, as the same surgeon performed all operations. To the best of our knowledge, no previous prospective study has used DX, administered perineural with an anesthetic in a single injection, to determine the ideal dose to reduce the postoperative sequela after IMTM surgery. Perineural injection of anesthetic with a single dose of 4 mg DX is effective in reducing swelling after third molar extraction surgery. DX (4 mg) can reduce postoperative swelling 9
and improve maximum mouth opening after surgical removal of IMTM’s, but does not affect pain after such surgery.
Declaration of patient consent The authors document that they received consent forms from all patients. In the forms, patients permitted clinical information and images to be reported in the journal. Patients were informed that their names and initials would not be published, and their identities would be hidden.
References 1. Contar C, De Oliveira P, Kanegusuku K, Berticelli R, Azevero-Alanis L, Machado M: Complications in third molar removal: a retrospective study of 588 patients. Med Oral Patol Oral Cir Bucal 15:74-78, 2010 2. Atalay B, Güler N, Cabbar F, Şençift K: Determination of incidence of complications and life quality after mandibular impacted third molar surgery. J Istanb Univ Fac Dent 48:3146, 2014 3. Grossi GB, Maiorana C, Garramone RA, et al.: Assessing postoperative discomfort after
third molar surgery: a prospective study. J Oral Maxillofac Surg 65:901-917, 2007 4. Klongnoi B, Kaewpradub P, Boonsiriseth K, et al.: Effect of single dose preoperative
intramuscular dexamethasone injection on lower impacted third molar surgery. Int J Oral Max Surg 41:376-379, 2012 5. Kanazi GE, Aouad MT, Jabbour-Khoury SI, et al.: Effect of low-dose dexmedetomidine or
clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand 50:222-227, 2006 6. Bazin JE, Massoni C, Bruelle P, et al.: The addition of opioids to local anaesthetics in
brachial plexus block: the comparative effects of morphine, buprenorphine and sufentanil. Anaesthesia 52:858-862, 1997 10
7. Pell GJ, Gregory GT: Impacted mandibular third molars: Classification and modified
techniques for removal. Dent Digest 39:330-338, 1933 8. Krafft TC, Hickel R: Clinical investigation into the incidence of direct damage to the lingual nerve caused by local anaesthesia. J Craniomaxillofac Surg 22:294-296, 1994 9. Klongnoi B, Kaewpradub P, Boonsiriseth K, Wongsirichat N: Effect of single dose preoperative intramuscular dexamethasone injection on lower impacted third molar surgery. Int J Oral Maxillofac Surg 41:376-379, 2012 10. Filho JRL, Maurette PE, Allais M, Cotinho M, Fernandes C: Clinical comparative study of the effectiveness of two dosages of Dexamethasone to control postoperative swelling, trismus and pain after the surgical extraction of mandibular impacted third molars. Med Oral Patol Oral Cir Bucal 13:129-132, 2008 11. Nair RB, Rahman NM, Ummar M, et al.: Effect of submucosal injection of
dexamethasone on postoperative discomfort after third molar surgery: a prospective study. J Contemp Dent Pract 14:401-404, 2013 12. Graziani F, D'Aiuto F, Arduino PG, et al.: Perioperative dexamethasone reduces post-
surgical sequelae of wisdom tooth removal. A split-mouth randomized double-masked clinical trial. Int J Oral Max Surg 35:241-246, 2006 13. Majid OW, Mahmood WK: Effect of submucosal and intramuscular dexamethasone on
postoperative sequelae after third molar surgery: comparative study. Br J Oral Maxillofac Surg 49:647-652, 2011 14. Skjelbred P, Lokken P: Post-operative pain and inflammatory reaction reduced by
injection of a corticosteroid. A controlled trial in bilateral oral surgery. Eur J Clin Pharmacol 21:391-396, 1982 15. Alexander RE, Throndson RR: A review of perioperative corticosteroid use in
dentoalveolar surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90:406-415, 11
2000 16. Grossi GB, Maiorana C, Garramone RA, et al.: Effect of submucosal injection of
dexamethasone on postoperative discomfort after third molar surgery: a prospective study. J Oral Maxillofac Surg 65:2218-2226, 2007 17. Majid OW: Submucosal dexamethasone injection improves quality of life measures after
third molar surgery: a comparative study. J Oral Maxillofac Surg 69:2289-2297, 2011 18. Laureano JR, Maurette PE, Allais M, et al.: Clinical comparative study of the
effectiveness of two dosages of Dexamethasone to control postoperative swelling, trismus and pain after the surgical extraction of mandibular impacted third molars. Med Oral Patol Oral Circ Buccal 13:129-132, 2008 19. Schmelzeisen R, Frolich JC: Prevention of postoperative swelling and pain by
dexamethasone after operative removal of impacted 3rd molar teeth. Eur J Clin Pharmacol 44:275-277, 1993 20. Messer EJ, Keller JJ: The use of intraoral dexamethasone after extraction of mandibular
third molars. Oral Surg Oral Med Oral Pathol 40:594-598, 1975
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Figure Legends Figure 1. Consort flowchart of patient participation Figure 2. Preoperative and postoperative measurements for groups A, B, and C. Figure 3. a) Preoperative and postoperative differences for tragus-commisure in group B. b) Preoperative and postoperative differences for tragus-pogonion in group B. c) Preoperative and postoperative differences for maximum mouth opening in group B. d) Preoperative and postoperative differences for tragus-commisure in group C. e) Preoperative and postoperative differences for tragus-pogonion in group C. f) Preoperative and postoperative differences for maximum mouth opening in group C.
13
Table 1. Groups in the study. Groups A B C
Medicines Articaine 120 mg + 2 cc Saline Articaine 120 mg + Dexamethasone 4 mg + 1 cc Saline Articaine 120 mg + Dexamethasone 8 mg
Table 2. Baseline characteristics of patients. Sex
F M Age Hygiene
Preoperative Tragus-Commissure Preoperative Tragus-Pogonion Preoperative Maximum Mouth Opening *Kruskal Wallis Test
Group A 9 (45%) 11 (55%) 24.65 (5.56)
Group B 10 (50%) 10 (50%) 26.1 (5.34)
Group C 9 (45%) 11 (55%) 24.8 (4.89)
Test Statistics P-value 0.936* 0.132 0.802 0.670*
2.50 (0.68) 11.06 (1.496) 14.35 (1.601) 4.79 (0.525)
2.65 (0.587) 10.97 (1.617) 14.17 (1.828) 4.79 (0.521)
2.45 (0.686) 10.21 (2.895) 14.01 (1.526) 4.89 (0.490)
1.038
0.595*
1.121
0.571*
0.586
0.746*
0.500
0.779*
Table 3. Total analgesic intake after surgery in groups A, B, and C. a) Duration of surgery and number of analgesics consumed Duration of surgery (min) Number of analgesics consumed in the first 24hrs Number of analgesics consumed in the second 24hrs Valid N (listwise)
Minimum 5
Maximum 30
Mean 22.233
Std. Deviation 6.987
0
16
4.7321
3.887
0
10
3.85
3.36394
b) Number of analgesics consumed in the first 24hrs Frequency 2 or less 31 Between 3 and 5 4 Valid Between 6 and 8 16 More than 9 Total
9 60
Percent 51.7 6.7
Cumulative Percent 51.7 58.3
26.7 15 100
85 100
c) Number of analgesics consumed in the second 24hrs
Valid
2 or less Between 3 and 5 Between 6 and 8 More than 9 Total
Frequency 35 8 7 10 60
Percent 58.3 13.3 11.7 16.7 100
Cumulative Percent 58.3 71.7 83.3 100