Vol. 116 No.1 July 2013 Evaluation of postoperative discomfort following third molar surgery using submucosal dexamethasone e a randomized observer blind prospective study Riaz Warraich, MD, DDS,a Muhammad Faisal, DDS,b Madiha Rana, MSc, PhD,c Anjum Shaheen, DDS, PhD,d Nils-Claudius Gellrich, MD, DDS,e and Majeed Rana, MD, DDSf King Edward University, Lahore, Pakistan; and Hannover Medical School, Hannover, Germany Background. Surgical removal of impacted lower third molar is still the most frequent procedure done by Oral and Maxillofacial surgeons and is often associated with pain, swelling and trismus. These postoperative sequelae can cause distress to the patient as a result of tissue trauma and affect the patient’s quality of life after surgery. Use of antiseptic mouthwashes, drains, muscle relaxants, cryotherapy, antibiotics, corticosteroids and physiotherapy seems to decrease postoperative discomfort. Among them corticosteroids are well-known adjuncts to surgery for suppressing tissue mediators of inflammation, thereby reducing transudation of fluids and lessening edema. The rationale of this study is to determine the effectiveness of submucosal injection of dexamethasone in reducing postoperative discomfort after third molar surgery. Patients and Methods. 100 patients requiring surgical removal of third molar under local anesthesia were randomly divided into 2 groups, group I receiving 4 mg dexamethasone as submucosal injection and the control group II received no steroid administration. Facial swelling was quantified by anatomical facial landmarks. Furthermore, pain and patient satisfaction, as well as neurological score and the degree of mouth opening were observed from each patient. Results. Patients receiving dexamethasone showed significant reduction in pain, swelling, trismus, a tendency to less neurological complaints and improved quality of life compared with the control group. Conclusions. Submucosal injection of dexamethasone is more efficient to manage postoperative discomfort after removal of third molars compared to no steroid administration. (Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116:16-22) The surgical extraction of lower third molars is the most frequent intervention in oral surgery.1 This procedure is often associated with significant postoperative sequelae that may have both a biological and social impact.2,3 This is because molars show a high incidence of impaction and are often associated to highly diverse disorders such as pericoronitis, periodontal defects in the distal aspect of the second molar, caries of the third molar or second molar, pressure resorption of second molar, different types of cysts and odontogenic tumors and neurogenic pain, provoking or aggravating orthodontic problems and obstruction of placement of a complete or partial denture.4 The surgical procedure which usually involves incision, flap reflection and bone removal to expose the impacted tooth is associated a Professor and Head, Department of Oral and Maxillofacial Surgery, King Edward University. b Assistant Professor, Department of Oral and Maxillofacial Surgery, King Edward University. c Assistant Professor, Department of Craniomaxillofacial Surgery, Hannover Medical School. d Assistant Professor, Department of Oral and Maxillofacial Surgery, King Edward University. e Professor and Head, Department of Craniomaxillofacial Surgery, Hannover Medical School. f Consultant, Department of Craniomaxillofacial Surgery, Hannover Medical School. Received for publication Nov 9, 2012; accepted for publication Dec 14, 2012. Ó 2013 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2012.12.007 16 with postoperative pain, swelling and trismus. The adverse effects of wisdom tooth surgery on the quality of life has been reported to show a threefold increase in patients who experience pain, swelling or trismus alone or in combinations; compared to those who were asymptomatic.5 Many clinical studies investigate treatments to reduce postoperative complications by using antiseptic mouthwashes, use of drains, flap design, antibiotics, corticosteroid treatment, muscle relaxant and physiotherapy.6 Among them corticosteroids are well-known adjuncts to surgery for suppressing tissue mediators of inflammation, thereby reducing transudation of fluids and lessening edema.7 As a routine protocol, antibiotics and NSAIDs (non-steroidal anti inflammatory drugs) have been prescribed pre- and postoperatively. The introduction of NSAIDs has significantly altered the management of Statement of Clinical Relevance This study provides modern treatment strategies and effectiveness of submucosal injection of dexamethasone on swelling, pain, trismus, neurological complaints and patient satisfaction after third molar surgery. This study provides a basis for the routine administration of preoperative submucosal dexamethasone in a subtherapeutic dose to reduce the intensity of post surgical sequelae such as pain, swelling and trismus. OOOO Volume 116, Number 1 postoperative pain in dentistry and medicine. By administering the NSAIDs prior to pain onset, drug absorption would have begun and therapeutic blood level will be present at the time of pain onset. Secondly, the presence of cyclooxygenase inhibitor may limit the production of prostaglandins and prostacyclins associated with pain and edema.8 Corticosteroids (Dexamethasone, Prednisolone) dramatically reduce the manifestations of inflammation including redness, swelling, heat and tenderness that are commonly present at the inflammatory site. The effect of dexamethasone on the inflammatory process is the result of a number of actions including the redistribution of leukocytes to other body compartments, thereby lowering their blood concentrations. Also involved is the inhibition phospholipase A2 (due to steroid mediated elevation of lipocortin) which blocks the release of arachidonic acid, the precursor of prostaglandins and leukotrienes from membrane bound phospholipids.9 Clinical trials in Oral Surgery have also supported the hypothesis that preemptive NSAIDs and Corticosteroids are effective in delaying and preventing many postoperative sequelae.5 Topographical considerations make it difficult to quantify facial volume of swelling. However, different methods of measuring facial swelling have been proposed, e.g., verbal response scales (VRS), mechanical methods (cephalostat, calipers, registration of reference points or landmarks), ultrasound, photographic techniques, computer tomography (CT), magnetic resonance imaging (MRI) and optical face scanning with mirror construction.10-15 The aim of this study was to evaluate the effectiveness of submucosal injection of dexamethasone on swelling, pain, trismus, neurological complaints and patient satisfaction after third molar surgery. MATERIALS AND METHODS The study was approved by the local ethics committee at the Nishtar Institute of Dentistry (NID/01-2008). At the beginning of the study, written informed consent was obtained from each patient. Patients 100 healthy male and female patients (M ¼ 26.9, SD ¼ 4.45 years) attending the Oral and Maxillofacial Surgery requiring surgical removal of upper third molars and bilateral impacted lower third under local anesthesia were included. Only patients, who required an osteotomy of the lower mandible wisdom teeth, were included in the study. They were divided randomly into 2 treatment groups. The observer did not know about the kind of therapy applied at the time of the patient examinations. ORIGINAL ARTICLE Warraich et al. 17 Fig. 1. This figure shows an orthopantomogramm (OPT) of a patient, who fulfills the criteria by Pell & Gregory level B and C. Surgical procedure The surgical procedure took place using local anesthesia. Surgical procedure involved adequate elevation and reflection of adequate buccal mucoperiosteal flap under local anesthesia (2% lidocaine hydrochloride with 1:100,000 adrenaline), buccal and distal guttering to facilitate delivery of the third molar and then meticulous irrigation of the surgical site with normal saline (0.9%). Flap was repositioned and sutured. Only in group I, patients were given injection of dexamethasone (Decadron 4 mg/mL; Merck Sharp & Dhome of Pakistan, Ltd.) in submucosa before the start of the surgical procedure (in the mucogingival junction on the buccal aspect of molars and loose submucosa distal to the third molar). A single experienced surgeon has performed the surgical procedure. Study including criteria and protocols Only patients with a Pell & Gregory level B and C were included in this study (Figure 1). Patients who needed a simple extraction of wisdom teeth of the mandible were not included in this study. Clinical significant medical history was taken to exclude participants on the basis of known hypersensitivity, allergies or idiosyncratic reaction to any study medications, hepatic or renal disease, blood dyscrasias, heart disease, gastric ulcer, cushing syndrome or adrenocortical insufficiency, pregnancy and lactation, recent anti-inflammatory treatment or chronic use of medications that would obscure assessment of anti-inflammatory response, infected third molar with associated swelling. All patients were examined and scanned on fixed dates using standardized methods and techniques. Thus every patient received the same postoperative analgetic (1st day: ibuprofen 600 mg 3 times per day, 2nd day: ibuprofen 600 mg 2 times per day, 3rd day: ibuprofen 600 mg 1 time per day, 4th day: ibuprofen 600 mg 1 time per day) and no antibiotic prophylaxis therapy. During the study the following parameters were assessed: swelling, pain, neurological complaints, patient satisfaction and mouth opening. ORAL AND MAXILLOFACIAL SURGERY 18 Warraich et al. OOOO July 2013 Fig. 2. Consort flow diagram illustrate that at the time of presentation 166 patients were assessed for eligibility to be included in the study. Out of these 106 patients were randomly allocated in two groups. Six patients were not available for follow-up. Consort flow diagram At the time of presentation 166 patients were assessed for eligibility to be included in the study. Out of these 36% of the patients (n ¼ 60) were not included in the study as 24% patients (n ¼ 41) did not meet the inclusion criteria while 11% (n ¼ 19) did not want to participate in the study. A total of 106 patients were randomly allocated in 2 groups with 53 patients allocated in each group for intervention. In submucosal dexamethasone group 100% patients (n ¼ 53) received the selected intervention. In the No dexamethasone group 100% patients (n ¼ 53) received the selected intervention. Among the 53 patients who received submucosal injection of dexamethasone 3.7% (n ¼ 2) were lost to follow-up as these patients come from far areas and could not travel due to economic or personal reasons. While the 53 patients who did not receive dexamethasone 1.8% (n ¼ 1) were lost to follow-up. The 50 patients who received dexamethasone in group I were available for follow-up, 1 of them had their data lost during the data analysis procedure. So the total number of patients who were analyzed for submucosal dexamethasone was 50. The 52 patients who received no dexamethasone in group II were available for follow-up, 2 of them had their data lost during the data analysis procedure. So the total number of patients who were analyzed for no dexamethasone was 50 (Figure 2). Sample size Sample size of 100 cases (50 cases in each group) with 95% confidence level, 80% power of study and taking magnitude of postoperative pain, i.e., 0.5 þ 0.51 and 1.3 þ 0.62 and magnitude of facial swelling, i.e., 31 þ 1.58 and 32.04 þ 1.5 in group I and group II undergoing third molar surgery. Randomization Randomization was done using a computer based software “EpiCalc2000” (Brixton Health). The software was used to generate serial numbers 1-100 into 2 groups randomly and those patients who fulfilled the inclusion criteria were allocated serial numbers according to date and sequence of admission to hospital. The person responsible for conducting the measurements at the time of assessment of variables was blindfolded regarding the type of procedure that was conducted. Measurement of facial width (swelling) A measuring tape was used to measure facial width and swelling in one dimension only due to nonavailability OOOO Volume 116, Number 1 of 3D optical scanner. This method seems to be a useful alternative for assessing facial swelling. A measuring tape was used to measure facial width and swelling in 1 dimension only. The tip of the tragus of the right and left ears with the gonium in between were used as “reference landmarks”. The operator has repeated the procedure three times on each patient and the average of the measurements has been taken in centimeters and recorded. The measurements were carried out just before the surgery and on postoperative day 2 as swelling are not observed immediately after surgery but rather begin gradually peaking 2 days after the extraction. Postoperative pain analysis Postoperative pain analysis was conducted with the help of a visual analog scale (VAS) on a daily base from 2nd to 10th day, where the patients should rate their pain on a score from 0 to 10, with 0 describing a situation without pain and 10 denoting a maximum intensity of pain. Measurement of mouth opening Trismus was calculated with interincisal mouth opening and was measured with a caliper. The result was quoted in millimeters and observed at 5 days: before surgery (T0), directly after surgery (T1), on the 2nd (T2), the 10th (T3) and the 28th (T4) postoperative day. Neurological analysis The neurological analysis was performed bilaterally. It was used to be able to evaluate nerve dysfunctions. The skin of the infraorbital, mental region, upper and lower lip were checked using a cotton test for touch sensation, a pinprick test using a needle for sharp pain and a blunt instrument for testing pressure. Additionally, a two point discrimination test was executed on these regions. The same procedure was accomplished for the lower lip and the mental nerve skin region. The results were recorded on a score that ranges between 0 and 13, with 13 being the worst neurological score. The neurological score was assessed at 3 points in time: before surgery (T0), on the 2nd (T1) and the 28th (T2) postoperative day. Patients satisfactory Each patient was asked to complete a questionnaire on the 10th postoperative day. The question was how they evaluated satisfaction and convenience of the applied postoperative cooling therapy on a subjective base. The grading scale ranged from 1 to 4, where 1 stands for very satisfied and 4 for not satisfied. ORIGINAL ARTICLE Warraich et al. 19 Table I. Baseline characteristics of patients Decadron Gender female e no./total no. (%) Age (y) SD BMI (kg/m2) SD Surgical procedure duration (min) SD 15/5027 Conventional P value 13/5025 26.90 4.42 27.04 4.53 22.6 3.8 22.9 3.6 69.2 18.8 66.3 17 .65 .87 .26 .69 Statistical analysis Regarding the statistical analysis, all data is expressed as mean values 1 SEM. For repeating measures a one-way analysis of variance (ANOVA) with post hoc Bonferroni’s test for multiple comparisons of means was applied. Since the observed parameters consist above all of dichotomous variables, a c2-test and a Wilcoxon-test were conducted to detect differences between group I and group II. To check for statistical significance of quantitative variables the Student t-test was used, denoting a P value of <.05 as significant. The statistical analysis was conducted using SPSS for Windows version 14.0 (SPSS Inc., Chicago, IL, USA). RESULTS Baseline characteristics A total of 100 patients requiring surgical removal of unilateral or bilateral impacted lower third molar teeth under local anesthesia were selected in this study. Patients were randomly allocated in 2 groups with 1 group (case group) which were treated with dexamethasone and the second group called control group which were not given dexamethasone injection. The clinical and demographic characteristics of patients in both groups are shown in Table I. Both groups showed no statistical significances regarding gender, age, body mass index (BMI) and surgery duration. Postoperative swelling Figure 3 demonstrates the differences in facial swelling between groups observed over time. Mean facial swelling was significantly increased after surgery in both groups (within subject effect; P ¼ .0005) while on the 2nd postoperative day, mean facial swelling score was significantly less in those patients who were treated with dexamethasone than control (P ¼ .02). Postoperative pain Postoperative pain intensity between groups. The median pain score from 2nd to 10th day was significantly lower in case than control (2 vs. 6,7; P < .0005) (Figure 4). ORAL AND MAXILLOFACIAL SURGERY 20 Warraich et al. Fig. 3. This figure demonstrates the amount of swelling in mm of both groups at different time points. At 2nd postoperative mean facial swelling score was significantly less in those patients who were treated with dexamethasone than control. OOOO July 2013 Fig. 5. Pre-operative mouth opening values did not differ significantly in both groups. On the 2nd postoperative day a significant reduction of mouth opening could be revealed in both groups. The reduction of mouth opening was significantly lower in the dexamethasone group compared to conventional group. Fig. 4. Pain was calculated in terms of a visual analog scale from subjective analysis ranging from 0 to 10. A significant increase of pain was reported in the control group compared to dexamethasone group during 2nd and 10th postoperative days. Fig. 6. The overall satisfaction was significantly lower of patients receiving no steroid therapy compared to patients receiving dexamethasone therapy by Decadron. Measurement of trismus Preoperative, there was no significant difference between the groups with regard to reduction in mouth opening whereas on the 2nd postoperative day the mean trismus scores were lower in control than case (29.36 mm vs. 32.8 mm; P ¼ .004) as presented in Figure 5. Patient satisfaction Regarding the patient’s satisfaction, which was assessed at 10th day after surgery, a statistically significant difference between group I and group II could be detected (dexamethasone: 1.8 0.2, control: 3.0 0.3, P ¼ .003) (Figure 6). Postoperative neurological score There were no statistical significant differences found between both groups concerning the neurological score 10 days after third molar extraction (df ¼ 2; Chisquare ¼ 7.714; P ¼ .021). DISCUSSION Corticosteroids such as dexamethasone and methylprednisolone have been used extensively in dentoalveolar surgery due to their nearly pure glucocorticoid effects, virtually no mineralocorticoid effects, and the least adverse effects on leukocyte chemotaxis.16,17 OOOO Volume 116, Number 1 Dexamethasone has a longer duration of action than methylprednisolone and is considered more potent.18 The submucosal injection of dexamethasone has been reported to have a significant effect on edema in 2 previous studies both of which reported a significant reduction in edema in the immediate postoperative period compared with controls, but only a limited effect on trismus and pain.16,17 In our study, submucosal injection of dexamethasone 4 mg preoperatively resulted in a significant decrease in edema on postoperative day 2 with results. As postoperative edema at the site of third molar surgery is related to the soft tissue trauma and bone cutting, application of steroids at the same very site results in reduced inflammation related events. Another possible advantage of using submucosal injection of dexamethasone at the site of surgery is its painless administration due to already achieved local anesthesia of the operative field. Acute postoperative pain following third molar extraction is predominantly a consequence of inflammation caused by tissue injury.19 Contrary to previous studies, our patients have experienced significantly less pain in submucosal group compared with controls. Graziani et al. did not state that which analgesic was prescribed and pain was only assessed subjectively on visual analog scale (VAS) without the number of analgesics taken postoperatively but in our study has definitely resulted in reduction in the number of analgesics tablets used after surgery in case group. This decrease in pain may be attributed to dexamethasone which might have increased patients’s reaction to pain by suppressing tissue bradykinin and b-endorphin levels.20 As known, bradykinin and kallidin are the 2 kinins that act independently as well as synergistically with products of the arachidonic acid cascade to produce both hyperalgesia as well as increased vascular permeability.21 Apart from the two principal variables of our study i.e., pain and swelling, trismus being one of the postoperative sequelae of third molar surgery has also been calculated. Graziani et al.20 has reported that endoalveolar application of dexamethasone has resulted in reduced trismus but its submucosal administration has not produced notable results. But, in our scenario, submucosal injection of dexamethasone has not resulted in significant decrease in trismus possibly because of its application at the site of injury. Steroids though do not have any direct influence on muscle contraction, decrease in trismus would be secondarily related to less degree of local inflammation. It has been shown that the healing process and the possible complaints after removal of third molars can be influenced by various factors such as surgeon experience, age and gender of the patient, necessity of tooth ORIGINAL ARTICLE Warraich et al. 21 sectioning or of bone removal.22-25 Another variable that can have an influence on the degree of facial swelling is the duration of operating time that again is related to surgical difficulties in extraction.26 Since operating time was not significant different in both groups this factor does not have any impact on the results. CONCLUSION Conclusion of this study provides a basis for the routine administration of preoperative submucosal dexamethasone in a subtherapeutic dose to reduce the intensity of post surgical sequelae such as pain, swelling and trismus. 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