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Surgical removal of impacted mandibular third molars is the most frequent surgical intervention in oral surgery. The most common reasons for removal of impacted third molars include recurrent pericoronitis, periodontal problems, un-restorable carious lesions on second or third mandibular molars, presence of cysts or tumors or to prevent future complications.(6) The surgical extraction of impacted mandibular third molars often causes swelling of facial soft tissues, trismus and pain. (9 ) These are attributed to the inflammation produced as a result of surgical trauma. Oral surgeons have been using corticosteroids to minimize these sequelae and have obtained satisfactory results. (15) In 1949, Hench and Kendal used corticosteroids as anti inflammatory agents for the treatment of rheumatoid arthritis. Their use in dental practice began in the early 1950s when Spies etal, Strean and Horton administered hydrocortisone to prevent inflammation in oral surgery. (23). Different corticosteroids with different efficacies, biological half lives and mineralocorticoid activities have been used since then (10). Steroids are known to exert their anti inflammatory activity by preventing the release of fatty acids from membrane phospholipids, thereby reducing formation of cyclooxygenase and lipooxygenase product which are important inducers of post operative inflammatory process leading to edema and pain.(1). The analgesic activity of glucocorticoids has been related to their

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Discussion anti-inflammatory action by inhibiting phospholipase A2 and thus inhibiting the formation of arachidonic acid (1). In order to reduce inflammation, corticosteroids must be administered at doses in excess of the physiological concentrations released under normal conditions. (4). Ideal glucocorticoids should possess only minimum mineralocorticoid action and provide therapeutic activity on the immediate postoperative period that is when the inflammatory reaction is most intense. (steroids in m3). Various synthetic formulations of steroids which undergo slower metabolism leading to prolonged plasma and tissue levels of the drugs are now being available(10). Dexamethasone and methylprednisolone are the most widely used corticosteroids in oral surgery primarily due to great anti-inflammatory actions and minimal mineralocorticoid effect. A pervasive argument for use of dexamethasone is prevention of a rebound swelling on second and third postoperative days. However Stephen etal (28) did not observe any rebound swelling in their study. Tarek etal(5) reported less pain and trismus with submucosal infiltration of 125mg methylprednisolone when compared to 4mg of submucosal dexamethasone infiltration. We have chosen methylprednisolone because it is fivefold more potent than hydrocortisone, has less mineralocorticoid action and a biological half life of 18-36 hours.(12). Methylprednisolone has been widely used in oral surgical procedures for its anti inflammatory actions in doses of 10mg, 40mg, 80mg and 125mg. Huffman etal( j.oral surg 1977) did not observe any statistically
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Discussion significant clinical differences between the administration of 40mg or 125mg intravenous methylprednisolone. Ustun etal (3) compared the efficacy of two intravenous doses of methylprednisolone. No significant benefit of 3mg/kg MP in comparison with1.5mg/kg was detected. Schultz-Mosgau etal (use of ibu ndmp) noted a decrease in selling of 56% and in pain perception of 67% after a perioperative application of 64mg methylprednisolone orally. J.M Mico etal (4) with 40mg intramuscular injection of methylprednisolone into the gluteal muscle, C.S.Holland (11) with 40mg preoperative intravenous methylprednisolone and Emin Essen etal (2) with 125mg intravenous preoperative administration of methylprednisolone reported a significant reduction of swelling, pain and trismus when compared to placebo. Milles etal (9) reported a significant reduction in swelling during first three days after mandibular third molar surgery using 16mg methylprednisolone orally, the evening before surgery and 20mg IV immediately prior to surgery. Various routes of administration (PO,IV,IM and Submucosal) of administration of steroids have been advocated. Graziani etal(15) reported that endoalveolar application of 4mg dexamethasone powder at the operation site offered an effective reduction of post operative sequelae. E.Vegasetal (23), Jasmine Kaur etal(29), and Loganathan etal(25) evaluated intra massetric injection of 40mg methylprednisolone and found that there was a significant action against inflammation. The intramuscular route of steroid application has also been shown to decrease sequelae in the immediate post interventional period (22). But there are several stringent reasons to avoid the intra muscular application of steroids. A slow onset of action highly dependent on the rate of blood flow
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Discussion at the site of administration, an increased risk of adrenal suppression (3) and local complications like necrosis, hematoma and abscess formation are the adverse reactions of intramuscular injection(28). Carmen etal (8) observed a reduction of inflammation with 4mg oral methylprednisolone when compared to its local injection. Ibrahim.S etal (1) found reduction of swelling and pain with oral administration of 10mg MP when compared to its local injection. Though oral dosing is possibly the most comfortable option for the patient, it does not seem to be as effective as parenteral administration. (effect of mp on m3) Due to the attainment of the instant plasma drug concentration, the intravenous application is frequently considered to be most effective route of administration. (2). Sayed etal investigated the pharmacokinetics of intravenous methylprednisolone sodium succinate and oral methylprednisolone and reported that the bioavailability of drug is incomplete following oral administration.(18). Emin etal (2) observed a significant decrease of edema, trismus and facial pain in patients receiving pre interventional administration of 125mg MP intravenously. Studies have shown that parenteral administration of the steroid pre operatively and immediately after surgery obtained good results. (10). So in our study we administered intravenous methylprednisolone both preoperatively and after 6 hours postoperatively to ensure adequate concentration of the plasma levels of the drug during the post operative period. A few investigators have put forward that MP in combination NSAIDS would offer improved relief of symptoms. M.Cemil etal(22) reported a greater
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Discussion relief of pain of symptoms with a combination of 25mg intra muscular prednisolone and diclofenc potassium. O.A.Olstad (12) suggested that MP in combination with paracetamol may hasten the onset of analgesia. Methylprednisolone offered superior anti-inflammatory actions but its combination with flurbiprofen or ibuprofen provide greater initial analgesia(14,15). Edin Selvimovic etal (30) reported an enhanced impact on reduction of post operative pain and swelling by combined therapy of MP and meloxicam. Marc Leon etal (7) reported only a transient improvement of analgesia by using a combination of paracetamol and MP when compared to ketoprofen. In our study, 50mg diclofenac sodium was given in common to all patients in both steroid and placebo groups. Various methods have been used to measure facial swelling /edema. In our study, facial swelling was determined by a modification of tape measuring method of Gabka and Matsumara (16). Obviously, this method is not as accurate as computed tomography(CT) or magnetic resonance imaging (MRI) for making precise measurement of facial soft tissue volume. However, it is a non invasive, simple, cost effective and time saving method which provides numeric data for determination of tissue contour changes. Milles etal (9) reported that swelling may increase on the third day after surgery. So we recalled the patient on the second post operative day to record the intensity of swelling pain and trismus In our study, the steroid group showed a significant (p< 0.05) reduction of swelling when compared to placebo on 2nd post operative day while the difference was insignificant (p > 0.05) on 7th post operative day. By the 7th post operative day the facial measurements have returned to the pre operative measurements in both the groups suggesting that
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Discussion post operative dose of the steroid was effective in limiting the rebound swelling that would occur within the first 48-72 hours. Trismus was maximum in both the groups on second post operative day but the steroid group showed a significantly (< 0.05) greater amount of mouth opening when compared to placebo group. From preoperative day to 2nd post operative day, pain scores were significantly higher in placebo when compare to steroid group. However all the parameters returned to the preoperative scores by 7th post operative day in both the groups. The steroid group did not show any significant reduction in WBC count post operatively, indicating that short term steroid dose as administered in our study would not result in steroid induced leucopoenia Thus our study concluded that pre and post operative administration of intravenous methylprednisolone obtained only a transient (5%) reduction of post operative complications after mandibular third molar surgery when compared to the placebo suggesting the necessity for further studies with different dosage schedules to arrive at significant conclusions. .

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