Efficacy of anti-inflammatory drugs in third molar surgery: a randomized clinical trial


This was a double-blind randomized clinical trial to assess the effect of different pharmacological regimens on the level of prostaglandin E2 (PGE2) in urine and saliva, and to correlate the findings to the clinical course after removal of impacted lower third molars. Eighty patients were randomly divided into four groups: group 1 received placebo; group 2 received preoperative ibuprofen, which was continued for a week; group 3 received intraoperative dexamethasone; and group 4 received preoperative ibuprofen, which was continued for a week, in addition to intraoperative dexamethasone. Saliva and urine samples were taken at scheduled intervals. Patients receiving ibuprofen fared significantly better in most parameters. A single dose of dexamethasone alone had a potent but transient beneficial effect when compared to the results with ibuprofen, which showed significant improvement in both subjective and objective parameters. Use of a single dose of intravenous steroids perioperatively helped reduce untoward sequelae, although to a lesser degree and for a shorter duration than continuous ibuprofen. Combining ibuprofen with perioperative dexamethasone added some benefit in some of the measured parameters, but without a statistically significant advantage over using ibuprofen only.

Third molar surgery remains the mainstay of most oral and maxillofacial surgery practices. Pain, swelling, and transient loss of normal jaw function are usually associated with the removal of impacted third molar teeth. Management of these postoperative symptoms is frequently based on pharmacological manipulation of local and systemic mediators of pain and inflammation.

Unfortunately, the parameters for manipulation of these pathways with specificity in third molar surgery have not yet been defined. Currently, the use of anti-inflammatory drugs varies among practitioners based on a variety of factors, including personal experience and preference, information derived from pharmaceutical salespeople, or anecdotal information. If a specific marker of pain and inflammation, such as prostaglandins, could be quantitatively manipulated by preoperative and postoperative drug therapy, an improved clinical result with minimization of the usual postoperative symptomatology may result.

Prostaglandin E2 (PGE2) is a measurable marker of post-traumatic pain, fever, and inflammation, and has been isolated in many body systems, including saliva in the oral cavity. Decreasing local and systemic prostaglandin levels with the use of drugs is a well known method for reducing clinical inflammation. Some previous studies have evaluated the effects of a non-steroidal anti-inflammatory drug (NSAID) on tissue prostaglandin levels in gingival crevicular fluid. Roszkowski et al. reported that the administration of the NSAID effectively decreased prostaglandin release at extraction socket sites. PGE2 is known to cause hyperalgesia in psychophysical studies and also to evoke sensitization in electrophysiological studies. Thus, a comparative difference in preoperative and postoperative PGE2 levels serves as a useful tool in gauging quantitatively the efficacy of the administration of pharmacological agents, and a corresponding reduction of pain and inflammation.

The objectives of this prospective study were to: (1) evaluate PGE2 concentrations in urine and saliva after mandibular third molar surgery; (2) correlate PGE2 concentrations with subjective and objective clinical symptomatology after mandibular third molar surgery; and (3) compare the efficacy of three commonly used pharmacological regimens to a control group in manipulating PGE2 levels in patients undergoing impacted mandibular third molar removal. To the best of our knowledge, there is no published literature that relates salivary and urinary PGE2 levels to detailed objective and subjective evaluation of clinical symptoms over a 7-day postoperative period after mandibular third molar surgery. Our hypothesis was that there would be no statistically significant differences between the placebo group and the other three groups relative to the parameters examined.

Patients and methods

This prospective study included 80 ASA I patients (American Society of Anesthesiology classification, normal healthy) with bilateral full-bony mandibular third molar impactions. Institutional review board approval was obtained prior to commencement of the study. The patient population was randomly and consecutively selected from an outpatient oral and maxillofacial surgery clinic. Care was taken to maintain that the trial was in compliance with the current CONSORT (Consolidated Standards Of Reporting Trials) statement guidelines. Other criteria for inclusion into the study included: (1) age between 18 and 30 years; (2) no systemic disease (ASA I status); (3) taking no medications; (4) no allergies to any of the study drugs; and (5) absence of local or systemic infection. All patients underwent an initial preoperative screening consult with a single oral and maxillofacial surgery resident and a faculty member. All patients enrolled in the study completed the study without any postoperative complications.

All 80 patients underwent surgical removal of only bilateral full-bony impacted mandibular third molars under intravenous ambulatory general anaesthesia. All extractions were performed by one surgeon and required full-thickness mucoperiosteal flaps and bone removal (performed under irrigation) using an air driven rotary instrument. A uniform local anaesthetic technique was used which included bilateral inferior alveolar, lingual, and long buccal nerve blocks using 2% lidocaine with 1:100,000 epinephrine. Intravenous anaesthesia was provided by the same board-certified oral and maxillofacial surgery faculty member for all cases and included a combination of midazolam, fentanyl, and methohexital.

Patients were randomly divided into four groups using a random number generated by a computer (20 patients per group). The allocation sequence was concealed from the surgeon and anaesthesiologist. An independent pharmacist dispensed either active or placebo medications according to a computer generated randomization list. The four groups were as follows: group 1 received immediate preoperative placebo tablet, intraoperative normal saline (2 ml intravenous (i.v.)), and a postoperative placebo tablet every 6 h for a week; group 2 received immediate preoperative ibuprofen 600 mg, which was continued every 6 h postoperatively for a week, in addition to intraoperative normal saline (2 ml i.v.); group 3 received immediate preoperative placebo tablet, intraoperative dexamethasone (8 mg i.v.), and a placebo postoperative tablet every 6 h for a week; group 4 received immediate preoperative ibuprofen 600 mg, which was continued every 6 h postoperatively for a week, in addition to intraoperative dexamethasone (8 mg i.v.). All groups received 30 mg codeine tablets every 4 h as needed for postoperative pain management ( Table 1 ).

Table 1
Preoperative (oral), intraoperative (intravenous), and postoperative (oral) medication regimens.
Group Preoperative p.o. drug Intraoperative i.v. drug Postoperative p.o. drug
Group 1 Placebo tablet 2 ml of 0.9% saline Placebo qid × 7 days
Group 2 Ibuprofen 600 mg 2 ml of 0.9% saline Ibuprofen 600 mg qid × 7 days
Group 3 Placebo tablet 8 mg of dexamethasone Placebo qid × 7 days
Group 4 Ibuprofen 600 mg 8 mg of dexamethasone Ibuprofen 600 mg qid × 7 days

i.v., intravenous; p.o., by mouth; qid, four times a day.
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Jan 24, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Efficacy of anti-inflammatory drugs in third molar surgery: a randomized clinical trial
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