Analgesic and Anti-Inflammatory
Effects of Articaine and Perineural
Dexamethasone for Mandibular Third
Molar Surgery: A Randomized,
Double-Blind Study
Berkem Atalay, PhD,
*
Abdullah Tolga S
¸itilci, MD,
y
and €
Ozen Dogan Onur, PhD
z
Purpose: We aimed to investigate the effectiveness of articaine and perineural dexamethasone (DX) in reducing postoperative sequelae such as swelling and maximum mouth opening that are harming the qual-ity of life of patients after impacted mandibular third molar (IMTM) surgery.
Patients and Methods: We implemented a randomized clinical trial composed of patients undergoing IMTM extraction. The predictor variable was the treatment group. The patients were randomly assigned to 1 of 3 groups: Group A was administered 3.6 mL of articaine mixed with 2 mL of saline solution; group B, 3.6 mL of articaine and 1 mL of DX (4-mg/mL solution) with 1 mL of saline solution; and group C, 3.6 mL of articaine with 2 mL of DX (8-mg/mL solution). The primary outcome variables were swelling (determined by anatomic facial landmarks), pain, and maximum mouth opening. Other variables comprised the dura-tion of surgery, number of analgesics taken in the postoperative period, hygiene, and petechiae.
Results: The sample was composed of 60 patients (20 per treatment group), with a mean age of 25.18 5.22 years; 53.3% were women. Postoperative swelling was significantly reduced in groups B and C (P < .05). Maximum mouth opening was significantly increased in groups B and C (P < .05).
Conclusions: The results of this study suggest that combining DX with articaine improves the manage-ment of discomfort after IMTM surgery. The use of articaine via a mandibular block was not associated with neural damage in our study.
Ó 2019 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 78:507-514, 2020
Surgical removal of impacted mandibular third molars (IMTMs) is the most common procedure performed via oral surgery.1This procedure is usually associated with substantial postoperative sequelae. 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 extraction of the third molar teeth. Damage to the second molar and bone fractures during surgery are among the less common complications.2,3Numerous factors affect these complications, but the
*Assistant Professor, Vocational School of Health Sciences, _Istanbul University-Cerrahpas¸a, Istanbul, Turkey.
yAssistant Professor, Department of Oral Surgery, Faculty of Dentistry, Istanbul University, Istanbul, Turkey.
zProfessor, Department of Oral Surgery, Faculty of Dentistry, Istanbul University, Istanbul, Turkey.
Conflict of Interest Disclosures: None of the authors have any relevant financial relationship(s) with a commercial interest.
Address correspondence and reprint requests to Dr Atalay: _Istanbul University, Dis Hekimligi Fak Agız, Dis, Cene Cerrahisi
B€ol€um€u, Fatih, 34093 _Istanbul, Turkey; e-mail: berkematalay@ gmail.com
Received June 12 2019 Accepted October 28 2019
Ó 2019 American Association of Oral and Maxillofacial Surgeons 0278-2391/19/31252-2
https://doi.org/10.1016/j.joms.2019.10.024
inflammatory process after surgical trauma remains a crucial factor. Clinical studies have described heuristic approaches to reduce postoperative complications us-ing antibiotics, physiotherapy, corticosteroid treat-ment, antiseptic mouthwash, and muscle relaxants. Corticosteroids are used in surgery to reduce fluid tran-sudation and edema.4
Supplemental drugs such as morphine, pethidine, butorphanol, clonidine, dexamethasone (DX), and midazolam have recently been added to local anes-thetics to achieve faster, longer-lasting, more intense anesthesia.5 However, morphine, pethidine, and bu-torphanol have side effects such as severe sedation and respiratory depression and are psychotomimetic.6There is, therefore, a need to iden-tify safer drug combinations that can increase the effi-cacy of anesthesia, decrease pain, and control edema during the postoperative period, as well as reduce the loss of work hours.
The purpose of this study was to compare different doses of DX administered along with a local anes-thetic, articaine, in a single injection, for surgical extraction of IMTMs, to evaluate the effectiveness of this combination as a perineural inferior alveolar nerve (IAN) block. We hypothesized that perineural injec-tion of DX could reduce swelling and improve maximum mouth opening postoperatively. The spe-cific aim of the study was to measure differences in swelling, pain, trismus, and maximum mouth opening for 3 different treatment groups.
Patients and Methods
STUDY DESIGN
To address the research purpose, we designed a ran-domized clinical trial. The study sample was composed of all patients undergoing IMTM extraction performed in our clinic from March 1 to 31, 2019, who met the following criteria: Patients signed informed consent forms; had an American Society of Anesthesiologists class of I; were older than 17 years but younger than 35 years; had class II molars in position B7; required mandibular third molar surgery; and had no acute inflammation, excessive caries, pain, and pathology around the third molars. Patients were excluded if they were pregnant; had diabetes mellitus, systemic endocrine disorders, hypertension, kidney diseases, osteoporosis, psychiatric disorders, blood clotting dis-orders, infection around the third molars, 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 nonsteroidal anti-inflammatory drugs during the last week; or could not cooperate with or refused to participate in this study. In addition, any patient requiring more than 1 anesthetic, who did not
experience numbness in the lip corner 15 minutes after administration of anesthesia, in whom surgical procedures exceeded 30 minutes, or who had local complications during extraction, such as root fracture, mandibular fracture, or temporomandibular joint dislo-cation, were excluded from the analysis.
The study was approved by the Clinical Research Ethics Board of the _Istanbul University Faculty of Dentistry (approval No. 2018/82). Consent forms were received from all patients.
PREDICTOR AND OUTCOME VARIABLES
The predictor variable was the treatment group. The patients were randomly assigned to 1 of 3 groups: Group A was administered 3.6 mL of articaine mixed with 2 mL of saline solution; group B, 3.6 mL of arti-caine and 1 mL of DX (4-mg/mL solution) with 1 mL of saline solution; and group C, 3.6 mL of articaine with 2 mL of DX (8-mg/mL solution).
Swelling was the primary outcome variable. Before the operation and on the third day after surgery, the distance between the mouth commissure and the tragus, as well as the distance between the tragus and the soft pogonion, was measured, using a paper ruler, to evaluate swelling. The secondary outcome variable was maximum mouth opening. In addition, the distance between the maxillary and mandibular incisal borders of the central teeth was measured with a compass to evaluate trismus. All measurements were recorded in millimeters.
Gender, age, and duration of operation were the third category of variables related to the outcome. The duration of operation time was recorded from the start of the incision to the last suture. All the IMTMs were class II in position B, so variables result-ing from radiographic classification, type of impaction, and level of difficulty were eliminated.
Drugs were prepared and coded by a person who was blinded to the patients’ data. The injector codes were written in the patients’ follow-up files. The sur-geon and surgical assistants were blinded to the mean-ing of the codes until the end of the study. Throughout the study, all patients were anesthetized and operated on by a surgeon with 10 years’ experience; the same doctor removed the sutures after 7 days and examined each patient postoperatively.
Gender, age, injector code, preoperative and post-operative mouth opening, postpost-operative swelling, and duration of operation were recorded. In addition, the administration time of anesthesia and the opera-tion start and end times were recorded.
SURGICAL TECHNIQUE
Preoperatively, extraoral antisepsis with 2% chlorhex-idine gluconate and intraoral antisepsis with 15 mL of
0.12% chlorhexidine gluconate were applied to all pa-tients. Anesthesia was performed with a mixture of 4% articaine hydrochloride with epinephrine (1:200,000) and either saline solution or DX. Specifically, in group A, 3.6 mL of articaine was mixed with 2 mL of saline so-lution; in group B, 3.6 mL of articaine and 1 mL of DX (4-mg/mL solution) was mixed with 1 mL of saline solu-tion; and in group C, a mixture of 3.6 mL of articaine and 2 mL of DX (8-mg/mL solution) was used. These mixtures were injected for the regional anesthetic block of the IAN and lingual nerve and in the buccal area near the IMTM targeted for extraction.
All patients underwent the same surgical technique. Initially, a linear incision was made on the alveolus with a No. 15 scalpel, starting from the second molar in the buccal region; an oblique incision measuring
1 cm was made. When necessary, osteotomy was per-formed with a drill and irrigation with saline solution us-ing high-speed rotary instruments. After extraction, the irregular bone margins were flattened and sutured with No. 3-0 silk during all operations. Use of an ice compress at 10-minute intervals after the operation was recom-mended for the first 24 hours postoperatively, and pa-tients were given the same analgesics. Papa-tients were instructed to record their pain start time, the time when pain relief was first required, the time when the 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, pa-tients were recalled for removal of sutures and healing control, after which observation was terminated.
FIGURE 1. CONSORT (Consolidated Standards of Reporting Trials) flowchart of patient participation. Atalay, S¸itilci, and Onur. Anti-Inflammatory Effects of Perineural Dexamethasone. J Oral Maxillofac Surg 2020.
STATISTICAL ANALYSIS
All data are presented using descriptive statistics, including means and standard deviations. Nonpara-metric tests, including the Spearman r, Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed rank tests were used to analyze intergroup and intragroup differences. Statistical significance was set at P < .05. Statistical analyses were performed using the IBM SPSS Statistics program (version 21.0; IBM, Ar-monk, NY).
Results
We assessed 72 patients for eligibility and randomi-zation. Of these patients, 8 did not meet the inclusion criteria and 4 declined to participate (Fig 1). Eventu-ally, 60 patients were enrolled and randomly allocated to 1 of 3 groups (20 patients in each group), which received different anesthetic drug combinations
(Table 1). The baseline characteristics of the patients
in all groups are shown inTable 2.
In this study, postoperative infections or complica-tions caused by DX injection were not observed. No significant difference was found between the groups in terms of duration of surgery. However, the addition of DX significantly reduced postoperative swelling af-ter surgical removal of the IMTM (P < .05).
A significant increase in swelling postoperatively compared with preoperatively was found in group A (P < .05). The differences between preoperative and postoperative tragus-commissure and tragus-pogonion measurements were statistically signifi-cantly smaller in group B than in group A (P < .05). In addition, a statistically significant difference was found between preoperative and postoperative maximum mouth opening measurements when groups A and B were compared (P < .05).
A statistically significant difference was noted be-tween preoperative and postoperative measurements for groups A, B, and C. The differences between preop-erative and postoppreop-erative tragus-commissure and tragus-pogonion measurements were statistically significantly smaller in group C than in group A (P < .05). Furthermore, a statistically significant differ-ence was found between groups A and C in terms of the preoperative versus postoperative maximum mouth opening measurements (P < .05) (Fig 2).
The differences between the preoperative and post-operative tragus-commissure and tragus-pogonion measurements were not statistically significantly different between groups B and C (P > .05) (Figs 3A, B, D, E). However, the difference between preopera-tive and postoperapreopera-tive maximum mouth opening was statistically significantly different between groups B and C; group C had higher maximum mouth opening measurements (P < .05) (Figs 3C, F).
No significant difference among groups A, B, and C was found in terms of the analgesics taken and the duration of surgery (P > .05). The average duration of surgery was 22.23 minutes (Table 3). Finally, postop-erative 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 this study was to investigate the ef-fect of perineural injection of DX with articaine on analgesia and postoperative swelling related to third molar surgery. The hypothesis was that a perineural in-jection of DX could reduce swelling and improve maximum mouth opening postoperatively. The spe-cific aim of the study was to identify swelling, pain, trismus, and maximum mouth opening. Our study showed that combining DX with articaine improved the management of postoperative discomfort after the removal of IMTMs.
Articaine can be safely used for IAN blocks. Pares-thesia incidents are associated with mandibular blocks and primarily affect the lingual nerve. The frequency of direct needle trauma to the nerve during an inferior alveolar block is 7.7%. The injection has the risk of causing more neural damage than the anesthetic solu-tion itself.8 We found no adverse neurologic effects attributed to using articaine to block the IAN in this study.
Trismus, which limits maximum mouth opening, is a sequela of postoperative swelling within the mastica-tion muscles. Individually, the medial pterygoid mus-cles and the masseter musmus-cles can compress nerves and produce mild to severe pain. Adequate anti-inflammatory treatment should be provided preopera-tively and postoperapreopera-tively to control postoperative inflammation and associated symptoms.9Filho et al10 reported that the limitation of maximum mouth open-ing decreased by 9.3% when usopen-ing 8 mg of DX and increased to 11.74% at 48 hours postoperatively. Nair
Table 1. STUDY GROUPS
Group Anesthetic Drug Combination A 120 mg of articaine + 2 mL of saline solution B 120 mg of articaine + 4 mg of dexamethasone + 1 mL of saline solution C 120 mg of articaine + 8 mg of dexamethasone
Atalay, S¸itilci, and Onur. Anti-Inflammatory Effects of Perineural Dexamethasone. J Oral Maxillofac Surg 2020.
et al11reported that the differences in the amount of trismus were not considerable between the control group and DX group at day 2 or 7. In our study, the lim-itation of maximum mouth opening observed was less in the DX groups than in the control group.
The use of steroids in patients with many systemic diseases is contraindicated, some of which are hyper-tension, active or latent peptic ulcers, diabetes melli-tus, Cushing syndrome, osteoporosis, acute or chronic infection, and hepatic problems. Prolonged steroid use may delay recovery and increase vulnera-bility to infection, but these steroid-related effects are not common in oral surgery.12In our study using single-dose DX for extractions, there were no postop-erative infections that could be attributed to the single-dose use of steroids. Although systemic steroids can induce infection, our study suggests that perineural in-jections in patients with no history of an active infec-tion do not show an increased rate of infecinfec-tion with single-dose steroid injections.
Majid and Mahmood13 reported that 4 mg of DX importantly reduced pain in all DX groups compared with the control group. In some studies, the total
num-ber of analgesic tablets consumed in the DX groups was found to be considerably lower.12-16 Unlike previous studies, the study by Nair et al11 found no relevant difference in pain reduction between the group receiving a submucosal injection of DX during the operation and the control group. Grossi et al16 concluded that when DX was injected intraorally dur-ing the operation, the total number of analgesic tablets consumed postoperatively was not substantially different compared with the control group.
In our study, pain was evaluated objectively by recording the number of analgesic tablets taken within the first and second 24 hours after surgery. Total anal-gesic consumption was 4.7 analanal-gesics in the first 24 hours and 3.8 analgesics in the second 24 hours. There was no considerable difference in pain control and the number of analgesics consumed among groups A, B, and C. These results are similar to those of previous studies.10,16,17
Our data indicate that patients who underwent DX administration with anesthetics responded better in terms of swelling than patients in whom no DX was administered (group A), and there was no statistically
Table 2. BASELINE CHARACTERISTICS OF PATIENTS
Group A Group B Group C Test Statistic P Value
Gender, n (%) 0.132 .936* F 9 (45) 10 (50) 9 (45) M 11 (55) 10 (50) 11 (55) Age, yr 24.65 (5.56) 26.1 (5.34) 24.8 (4.89) 0.802 .670* Hygieney 2.50 (0.68) 2.65 (0.587) 2.45 (0.686) 1.038 .595* Preoperative tragus-commissure measurement, mm 11.06 (1.496) 10.97 (1.617) 10.21 (2.895) 1.121 .571* Preoperative tragus-pogonion measurement, mm 14.35 (1.601) 14.17 (1.828) 14.01 (1.526) 0.586 .746*
Preoperative maximum mouth opening, mm
4.79 (0.525) 4.79 (0.521) 4.89 (0.490) 0.500 .779*
Note: Data are presented as mean (standard deviation) unless otherwise indicated. Abbreviations: F, female; M, male.
* Kruskal-Wallis test.
y Hygiene was measured with a score of 1 for ‘‘bad,’’ 2 for ‘‘medium,’’ and 3 for ‘‘good.’’
Atalay, S¸itilci, and Onur. Anti-Inflammatory Effects of Perineural Dexamethasone. J Oral Maxillofac Surg 2020.
FIGURE 2. Preoperative and postoperative measurements in groups A, B, and C. Atalay, S¸itilci, and Onur. Anti-Inflammatory Effects of Perineural Dexamethasone. J Oral Maxillofac Surg 2020.
FIGURE 3. Preoperative (Preop) and postoperative (Postop) differences in tragus-commissure measurement (A), tragus-pogonion measurement (B), and maximum mouth opening (C) in group B and preoperative (Preop) and postoperative (Postop) differences in tragus-commissure mea-surement (D), tragus-pogonion meamea-surement (E), and maximum mouth opening (F) in group C.
relevant difference between groups B and C. This finding supports the results of the study by Graziani et al,12in which they evaluated the dose-dependent ef-fects of DX powder on swelling in dentoalveolar appli-cations. Skjelbred and Lokken14 reported that DX reduces postoperative facial swelling after surgical removal of mandibular third molar teeth by reducing the release of prostaglandins, lymphokines, bradyki-nin, and serotonin from the injured tissue.
In this study, the swelling and maximum mouth opening values were evaluated using a tape-measuring method and compass, respectively. The re-sults obtained for maximum mouth opening agree with those of previous studies.18,19 In our study, with the use of DX, maximum mouth opening was importantly improved in groups B and C as compared with group A.
This study was limited in 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 prolongs the operation time. Another limitation was the small sample size. Moreover, this study showed no substantial difference in the duration of surgery among groups A, B, and C as
the same surgeon performed all operations. To our knowledge, no previous prospective study has used DX administered in a perineural manner with an anes-thetic in a single injection to determine the ideal dose to reduce the postoperative sequelae after IMTM surgery.
Perineural injection of anesthesia with a single dose of 4 mg of DX is effective in reducing swelling after third molar extraction surgery. DX (4 mg) can reduce postoperative swelling and improve maximum mouth opening after surgical removal of IMTMs but does not affect pain after such surgery.
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