Pre-emptive 8 mg dexamethasone and 120 mg etoricoxib for pain prevention after periodontal surgery: A randomised controlled clinical trial.

Several anti-inflammatory drugs have been used to reduce pain and discomfort after periodontal surgeries. This study evaluates the efficacy of using etoricoxib and dexamethasone for pain prevention after open-flap debridement surgery. In this study, 60 patients who were undergoing open flap debridment surgery were randomly assigned to receive a single dose preoperative medication 1 hour prior to surgery. The patients were divided into three groups. In Group 1, 20 patients were given placebo drug orally. In Group 2, 20 patients were given 8 mg Dexamethasone orally and in Group 3, 20 patients were given 120 mg Etoricoxib orally. Patients were instructed to complete a pain diary hourly for the first 8 hours after each surgery and three times a day on the following 3 days. The four point verbal rating scale (VRS 4) and Numerical rate scale were used to assess discomfort. Post-operative Assessment of Pain and Discomfort showed that persistent discomfort and pain were found to be more in the placebo group compared to dexamethasone and etoricoxib group. The adoption of a preemptive medication protocol using either etoricoxib or dexamethasone may be considered effective for pain and discomfort prevention after open-flap debridement surgeries.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

“Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.” Pain after periodontal therapy is a common occurrence. Scaling and root planning (SRP) is one of the most common procedures in periodontal practice and may promote pain of significant duration and magnitude.[1] Many times, periodontal surgery also generates pain and discomfort with greater intensity than that occasioned by SRP alone.[23] Therefore, patients who are candidates for surgery may be treated with effective protocols. Preemptive analgesia is a protocol that aims to reduce pre and postoperative pain and discomfort. Some trials[45] suggested that preoperative administration of different anti-inflammatory drugs reduced postoperative pain intensity and the need for supplementary analgesics.

Etoricoxib is a cyclooxygenase-2 (COX-2), a selective inhibitor, nonsteroidal anti-inflammatory drug (NSAID) that has been used to prevent and control acute pain after different surgical procedures. COX-2 is an enzyme substantially induced in the presence of tissue injury or surgical trauma. It leads to the production of prostaglandins, prostacyclin's, and thromboxane's, which are important mediators in promoting pain and swelling. Dexamethasone is a steroidal anti-inflammatory drug that induces annexing, a protein that, among other actions, is capable of inhibiting phospholipaseA2 (i.e., the enzyme responsible for the induction of arachidonic acid).[6] The arachidonic acid cascade initiation culminates in the expression of prostaglandins, prostacyclin's, thromboxane's, and leukotrienes, which are related to pain. Thus, the aim of the present study was to evaluate the efficacy of 120 mg etoricoxib or 8 mg dexamethasone as a single– the dose preemptive medication on pain prevention after open flap debridement surgery.

MATERIALS AND METHODS

A total of 60 patients were selected from the OPD, Department of Periodontics, and M. S. Ramaiah Dental College and Hospital Bangalore. The study was approved by the ethical committee of M. S. Ramaiah Dental College, Bangalore. The ages of the patient included in the study were between 18 and 56 years. A written informed consent was taken from the patients. The patients with moderate or severe periodontitis who were scheduled for open-flap debridement surgery were included in the study. Patients allergic to any of the formulations used in the study, patients using analgesics and anti-inflammatory drugs, patients with history of systemic disease – diabetes mellitus, hypertension or gastric ulcer, pregnant or lactating females and patients who were at risk for infective endocarditis were excluded from the study. Patient who was undergoing flap surgery were randomly assigned to receive a single dose preoperative medication 1 h prior to surgery. The patients were divided into three groups. In Group 1, 20 patients were given placebo drug orally. In Group 2, 20 patients were given 8 mg dexamethasone orally and in Group 3, 20 patients were given 120 mg etoricoxib orally. Patients were instructed to complete a pain diary hourly for the first 8 h after each surgery and 3 times a day on the following 3 days. For ethical reasons, all participants were given rescue medicine (650 mg acetaminophen) and were instructed to take it as needed. Patients were instructed that they can take the painkiller whenever considerable pain is felt, according to their judgment and to wait at least 6 h between intakes and write in the pain diary each time the medication was used. The four point verbal rating scale (VRS-4) and numerical rate scale were used to assess discomfort. VRS was assessed only on the 1st day and numerical rating scale (NRS) was assessed on 3 consecutive days. Statistical analysis was performed using Spearman correlation coefficient, which was used to assess correlation between NRS and VRS-4. Chi-square test was also used. For these tests, the significance level was set at 0.05 and data analysis was carried out using Statistical Package for Social Science (SPSS, version 10.5, SPSS, Chicago, IL, USA) package.

RESULTS

All the patients in the study were allowed to take rescue pill if they felt pain. Maximum number of rescue pills were taken by placebo group (95%), followed by dexamethasone group (35%) and etoricoxib group (25%) (Graph 1). Postoperative assessment of pain and discomfort using VRS showed that persistent discomfort and pain were found to be more in the placebo group compared with dexamethasone and etoricoxib group. 45% of patients that had taken dexamethasone showed some transitory discomfort. 75% of the patients that had taken etoricoxib and 55% of patients that had taken dexamethasone showed no discomfort (Graph 2). On comparison of postoperative pain assessment using NRS on the 1st, 2nd and 3rd day, the etoricoxib group showed higher level of discomfort compared to the other two groups (Graph 3). This could have been due to the effect of rescue pill taken, which was found to be maximum in placebo followed by dexamethasone group.

DISCUSSION

Open-flap debridement surgery is an efficient therapeutic approach for patients who do not respond well to nonsurgical periodontal treatment. However, pain and discomfort are expected after this type of procedure.[37] Several medication protocols were proposed to minimize these effects.[8] The adoption of a pain model using open-flap debridement surgery was due to its frequent use in periodontal practice, the ease of recruiting patients and the possibility of a standardized surgical procedure. Preemptive analgesia is believed to promote improved clinical results for pain prevention than treatment initiated after surgery. Postoperative pain generally lasts for 24 h, with greater intensity at 6–8 h,[9] which justifies the evaluation of an 8-h period on the 1st day of surgery in this study. Waiting for pain initiation after surgery to medicate produces unnecessary discomfort and may reduce the efficacy of any posterior treatment. Etoricoxib is a novel NSAID that is highly selective for COX-2. It is rapidly absorbed, greater plasmatic levels are reached after 1-h and its elimination half-life is 25 h.[10] These data support the use of this medication in the proposed protocol, which promotes analgesic coverage for enough time.

Malmstrom et al.,[11] stated that 120 mg should be the minimum dose for the best analgesic action of this drug. The advantages of etoricoxib over traditional NSAIDs include less adverse reactions related to gastrointestinal problems, the absence of platelet-aggregation inhibition, long-action duration and elimination half-life and long-lasting pain relief. Furthermore, adverse effects related to the use of COX-2–selective drugs such as kidney or cardiovascular problems were only observed with chronic use.[12] Steroidal anti-inflammatory drugs may also be used for pain prevention. Dexamethasone (4 mg) was not an effective reducer of pain inflammatory markers after tissue injury in vivo or of pain prevention after open-flap debridement surgeries.[13] In contrast, Baxendale et al.,[14] observed significant pain prevention with the use of an 8-mg dose after multiple extractions of third molars. Although a significant amount of the administered glucocorticoid is eliminated from the blood before 24 h, some late anti-inflammatory effects may be observed for up to 3 days, which were the time period evaluated in this study.[15] The time needed for dexamethasone to reach a plasmatic-concentration peak varies from 1 to 2 h, and there were favorable results with its use 1 or 2 h before surgery.[141617] Adverse effects of glucocorticoids include immunosuppression, which is detected after 5 days of use and may take up to 9 months for the patient to recover.[16]

CONCLUSION

The adoption of a preemptive medication protocol using either etoricoxib or dexamethasone may be considered effective for pain and discomfort prevention after open-flap debridement surgeries. However, limitations of this study include the surgical approach adopted, and the number of patients enrolled. Open flap debridement surgeries are expected to generate less pain intensity than other surgical procedures, such as mucogingival surgery or bone-resective surgery.[7] Even the control group presented low pain-intensity values in the present study, which may mask the real influence of preemptive medication on pain prevention. Additional studies with a higher number of patients and using other modalities of periodontal surgery that are expected to cause more pain and swelling are necessary to evaluate the effectiveness of these preemptive anti-inflammatory protocols.