Comparison of Therapeutic Effects of 8 mg Dexamethasone Intramuscular Administered Pre-operatively vs. Post Operatively after the Surgical Extraction of Impacted Mandibular Third Molars

Objective of this study was aimed to compare the therapeutic effects of 8 mg dexamethasone intramuscular administered pre-operatively vs post-operatively after the surgical extraction of impacted mandibular third molars, in Al-Qurayyat, Saudi Arabia, population. One hundred and fifty patients who visited the Department of Oral and Maxillofacial Surgery of Gurayat specialized dental center, Al-Qurayyat, Saudi Arabia, were included in the study. The study was conducted from February 2018 to August 2018. 150 patients constituted the study and were randomly divided into two groups. Group A received 8 mg dexamethasone (intramuscular) 1hr pre-operatively. Group B received 8 mg dexamethasone (intramuscular) immediately after the surgery. According to the gender there were 81(54%) males and 69 (46%) females, in both the groups combined. Males to females’ ratio was 1.17: 1 in this study. Post-operative 1st and 3rd day follow-up showed that there was a significant difference between the two groups in terms of swelling and mouth opening (P=0.000). Overall, Group A showed much better results as far as the post-operative swelling and mouth opening was concerned. There was no statistical difference in the scores when the post-operative pain was evaluated on 1st, 3rd and 7th day (P=0.679, P=0.755, P=0.202). The depth, angulation and the position of the tooth did not affect the study in terms of significance (P=0.626, P=0.874, P=1.000). It was concluded that preoperative administration of single dose of dexamethasone intramuscularly was more effective than the postoperative period, in reducing the swelling and trismus.


Journal of Dental and Craniofacial Research
ISSN 2576-392X mandibular third molar.
6. All patients who agree to participate in the study.
Exclusion criteria 1.Patient with history of allergy to dexamethasone.
3.Simple or non-surgical extraction. 4.Any surgery extending more than 45 min of time period.
Demographic details and the written informed consent were entered on a Performa and signed by patients.
All patients were subjected to clinical and radiographic examination, by single examiner (periapical x-ray, Orthopantomogram OPG). The patients were randomly distributed into two groups using the computer based software "Epicalc200". Each group constituted of 75 patients. Both researcher and the patients were blind at the time of randomization. Patients in Group A received 8 mg dexamethasone (intramuscular) 1 hr pre-operatively. Patients in Group B received 8 mg dexamethasone (intramuscular) immediately after surgery.

Surgical technique
All the surgeries were performed by the same maxillofacial surgeon. Patients were advised to rinse their mouth by 0.12% Chlorhexidine mouthwash. Local anaesthesia, 2% Lidocaine (1: 100000 epinephrine) was administered to all the patients. Three sided mucoperiosteal flap was reflected, bone guttering was done under sterile saline irrigation and if required the tooth was sectioned into multiple pieces. Once the tooth was delivered from the socket, the socket was irrigated with 0.12% Chlorhexidine and normal saline wash. The walls of the socket were smoothed and flap was repositioned and sutured by 3/0 or 4/0 black silk. The patients were given the routine post-operative home care instruction. The sutures were removed at 7th day follow up. The duration of the surgery ranged from 30-45 minutes, starting from incision until the last suture was placed.

Assessment of the patients Swelling
Facial measurements were taken in 3 planes using modified measuring tape method described by Ustun, Gabka, Matsumara, Schultze-Mosgau and co-authors [17][18][19]. The three facial planes (cm) were: M1: Distance from the tragus of the ear to the corner of the mouth.
M2: Distance from the tragus of the ear to the pogonion.
M3: Distance from lateral canthus of the eye to the angle of the mandible.
The sum of all these measurements were considered as the base line of that side, and the mean was extracted from them. The measuring was done pre-operatively, on the 1 st , 3 rd and 7 th days post operatively.
effects of the surgery. Corticosteroids have proven to be the most effective [6][7][8]. Corticosteroids are natural steroid hormones that are produced in the adrenal cortex of vertebrates. They are 21 carbon compounds having a cyclopentano perhydrophenanthrene (steroid) nucleus. They were discovered by Dr. William C. Kendall, who later on, together with Drs. Phillip S. Hench and Tadeus Reichstein, won a Nobel Prize for Physiology or Medicine. It was first used to reduce the inflammatory process of rheumatoid arthritis [9]. Due to least adverse effects on leukocyte chemotaxis, which is important in inflammation and healing, dexamethasone and methylprednisolone have been extensively used in various oral surgical procedure [10].
Glucocorticoids such as dexamethasone and methylprednisolone exert their anti-inflammatory reaction by binding to specific receptor within the cell. The result of the receptor-steroid complex is the regulation of the synthesis of inflammatory autacoids and immune-related cytokines [11,12].
There is adequate evidence suggesting that the excess of the glucocorticoids can lead to euphoria and psychosis, whereas deficiency results in lethargy, apathy and depression [12].
Dexamethasone has proven itself to be one of the most effective anti-inflammatory agents and this has been a prime reason for its use following the minor and the major surgical procedures in the field of oral and maxillofacial surgery across the globe since 3-4 decades [13].
A single large dose of glucocorticoid or a short course of the therapy (1-7 days), in the absence of local or systemic contraindications, is every likely to be harmless [14].
There is no clear consensus regarding the dose, timing, route and duration of administration of dexamethasone [15,16]. In this randomize clinical trial we compared the effects of intramuscular dexamethasone injection Prior to and after the extraction of impacted lower third molars.

Materials and Methods
The One hundred and fifty healthy patients requiring surgical removal of the mandibular impacted third molar under local anaesthesia constituted the study group. All the patients reported to the outpatient clinic, Oral and Maxillofacial Surgery Department, Gurayat Dental Centre, Saudi Arabia. The duration of study was 6 months, including the follow up, starting from February 2018 to August 2018.
Complete study protocol was explained to the patients who fulfilled the inclusion criteria.
2. Patients indicated for surgical extraction of impacted lower third molar/molars.
3. Age of the patient, 18 years or older.

Journal of Dental and Craniofacial Research ISSN 2576-392X
scores when the post-operative pain was evaluated on 1 st , 3 rd and 7 th day (P=0.679, P=0.755, P=0.202).
The depth, angulation and the position of the tooth did not affect the study in terms of significance (P=0.626, P=0.874, P=1.000) (Tables 1-8).

Discussion
A surgical insult in the oral cavity leads to tissue injury characterized by increased osmotic pressure in capillaries (Starling law). It states that the fluid movement due to filtration across the wall of a capillary is dependent on the balance between the hydrostatic pressure gradient and the oncotic pressure gradient across the capillary. It presents itself as hyperaemia, vasodilatation, increased capillary permeability with liquid accumulation in the interstitial space and cellular migration [22,23].
The post-operative tissue response in 3rd molar extractions is highly unpredictable. Gender, weight, duration of surgery, degree and depth of impacted tooth, surgical methods used, density of bone, skill of the operator, angulation and size of the tooth, a proximity of the tooth to the vital structures, amount of the tooth developed and association with a pathological lesion affect the post-operative swelling, pain, trismus, compromised oral intake of fluids and diet, aesthetic deformity, fracture of the angle of the mandible and infection [24,25].
Corticosteroids have been used since long by many surgeons to decrease the post-operative sequelae in 3rd molar surgeries. According to the literature review conducted by Francesco and co-authors [26] analysis of the scientific publications in the last 20 years revealed that there were no definite protocols relative to different molecules or regimens, time and route of administration of corticosteroids in preventing the post-operative adverse effects in 3rd molar surgeries. Dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate, methylprednisolone, methylprednisolone acetate and methylprednisolone sodium succinate have been extensively studied in the last 5 to 6 decades and their therapeutic effects, in the 3 rd molar surgery, have been documented. It is a proven fact that Long-acting steroids give better results than short-acting ones and intramuscular and intravenous routes of administration have almost same effects [27,28].
There are various factors which influence the post-operative outcomes in an impacted third molar surgery. Factors like age, gender, duration of surgery, angulation and depth of impacted tooth and operator skill commonly affect the significance of the study. In our study they were statistically insignificant and did not affect the comparative analysis between the two groups.
A study conducted by Hashem M revealed that pre-operative administration of dexamethasone is more effective than the postoperative period [29]. Post-operative edema on 2 nd , 5 th and 7 th day was evaluated for both groups and showed significant results on all the occasions. For Group B (post-operative group) P-value was 0.003, 0.003 and 0.038 respectively showing that on all the occasions there was statistical increase in the swelling and edema in Group B. Our study showed almost similar results as there was significant difference on the 1st and 3rd day follow-up after

Pain
Visual analog scale was used to analyzed the intensity of the pain (0-10) 1 st , 3 rd and 7 th days post-surgery (Figure 1) [21].

Statistical analysis
Data was analyzed by using SPSS 21.0. Quantitative variables were presented as means and standard deviations. Qualitative variables were presented as frequencies and percentages. The results of the two groups were compared using t-test and chisquare test. The level of significant was set at P<0.05.

Results
150 healthy patients were included in the study and results were analyzed. These patients were divided into 2 groups. Group A; 75 patients received intra-muscular 8 mg dexamethasone 1 hour pre-operatively and Group B; 75 patients received intra-muscular 8 mg dexamethasone immediate post-operatively. The patients were randomly divided into two groups. According to the gender there were 81(54%) males and 69 (46%) females, in both the groups combined. Males to female's ratio was 1.17: 1 in this study.
Post-operative 1 st and 3 rd day follow-up showed that there was a significant difference between the two groups in terms of swelling and mouth opening (P=0.000). Overall, Group A showed much better results as far as the post-operative swelling and mouth opening was concerned. There was no statistical difference in the Three facial planes according to the Schultze-Mosgau [19].     surgery (p-value= 0.000 and 0.000 respectively) but insignificant findings on 7th day (p-value= 0.386). Further in their study, for trismus, only after 7 days, group B showed statistically significant higher mean% reduction in maximum interincisal opening value than group A (p-value= 0.021). This contradicts with our study in which group B showed statistically significant higher mean% reduction in maximum interincisal opening value on 1 st and 3 rd days and insignificant values on 7 th day (p-value= 0.000, 0.000, 0.285 respectively). There are multiple studies which are consistent with the findings of our study. Laureano Filho compared the efficacy of different doses of dexamethasone given 1 h pre-operatively [30]. They found a significant reduction of post-operative complications with the use of 8 mg of dexamethasone.
Majid 16 presented reports on the effects of dexamethasone in 2011. In one of the reports, he compared the effect of submucosal and intramuscular injection of 4 mg dexamethasone after third molar surgery in his subjects. Both routes produced significantly less swelling and pain than control. Deo and Shetty studied the efficacy of single injection of a higher dose (8 mg) of dexamethasone given pre-operatively in the third molar surgery [31]. They found that dexamethasone proved significantly effective in reducing swelling and trismus on the second day post-operative. Majid and Mahmood compared the effect of giving post-operative dexamethasone using various routes of administration, namely intramuscular injection, intravenous injection, oral tablets, submucosal injection and endo-alveolar application [32]. Their study revealed no significant differences   among groups on any follow-up days in terms of swelling, pain and trismus in the subjects. They stated that "to control the swelling, the best results were obtained via the intravenous route, followed by the intramuscular, submucosal, oral and endoalveolar routes in a descending order".

Journal of Dental and Craniofacial Research ISSN 2576-392X
Warraich found dexamethasone was significantly beneficial in reducing pain and trismus [19]. Their patients were also satisfied as they suffered fewer complications post-operatively. In summary, dexamethasone has proven to be an effective agent for reducing pain, swelling and trismus to a certain degree, irrespective of the route and the timing of administration. Variations in the results may be because of differences in surgical methods, differences in individual response to treatment and differences in the methodology used.
Further studies should be carried out to evaluate the effect of various corticosteroids in difficult and lengthy surgeries. These surgeries might advocate the use of the steroids for longer durations. There effects might also differ due to the tissue response to extensive surgical trauma. Variables, like presence of infection, weight of the patient, associated pathological conditions, systemically compromised patients; extractions requiring general anesthesia, etc. should also be studied to evaluate the effect of the steroids.

Conclusion
It was concluded from the study that superior post-operative therapeutic effects are achieved by pre-emptive administration of 8 mg intramuscular injection of dexamethasone as compared to post-surgical administration in impacted third molar surgeries. Post-operative swelling and trismus were significantly reduced in the early post-surgical period. Pain on the other hand showed no significant reduction in the intensity in either of the groups.