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ORIGINAL ARTICLE
Year : 2019  |  Volume : 22  |  Issue : 6  |  Page : 796-800

Comparative analgesic efficacy and tolerability of celecoxib and tramadol on postoperative pain after mandibular third molar extraction: A double blind randomized controlled trial


1 Department of Dental and Maxillofacial Surgery, Federal Teaching Hospital Ido-Ekiti P.M.B 201 Ido Ekiti; Faculty of Clinical Sciences, College of Medical and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria
2 Department of Oral and Maxillofacial Surgery, University of Nigeria, Ituku-Ozalla, Enugu, Nigeria
3 Department Oral and Maxillofacial Surgery, Obafemi Awolowo University, Ile-Ife, Nigeria

Date of Acceptance18-Feb-2019
Date of Web Publication12-Jun-2019

Correspondence Address:
Dr. A O Akinbade
Department of Dental and Maxillofacial Surgery, Federal Teaching Hospital, Ido-Ekiti; Department of Dentistry, Faculty of Clinical Sciences, College of Medical and Health Sciences, Afe Babalola University, Ado-Ekiti
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_544_18

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   Abstract 


Background: The choice of an efficacious and well-tolerated analgesic for the control of postoperative pain after third molar surgical extraction remains a challenge. Aim: The aim of this study was to compare analgesic efficacy and tolerability of celecoxib and tramadol following mandibular third molar extraction. Materials and Methods: This was a prospective randomized, double blind controlled trial. Ninety patients were randomly assigned equally to either celecoxib or tramadol. Appropriate doses of the assigned drugs were administered orally immediately after the surgical extraction and patients recorded the pain intensity felt before the extraction, immediately after extraction, at 4 h, 8 h, 16 h, 24 h, and 48 h after the extraction using the visual analogue scale (VAS). Adverse effects of the medications were also recorded. Results: Four of the patients dropped out of the study. Fifty five percent of patients in tramadol group experienced adverse effects but none in celecoxib group. The median VAS score of the celecoxib group was lower than tramadol group throughout the postoperative period and there was statistically significant difference in the median VAS score between the two groups 4 hours after drug administration (P = 0.001). Conclusion: In our study, celecoxib was more efficacious and better tolerated than tramadol for the management of pain after surgical extraction of mandibular third molar.

Keywords: Celecoxib, postoperative pain, third molar surgery, tramadol


How to cite this article:
Akinbade A O, Ndukwe K C, Owotade F J. Comparative analgesic efficacy and tolerability of celecoxib and tramadol on postoperative pain after mandibular third molar extraction: A double blind randomized controlled trial. Niger J Clin Pract 2019;22:796-800

How to cite this URL:
Akinbade A O, Ndukwe K C, Owotade F J. Comparative analgesic efficacy and tolerability of celecoxib and tramadol on postoperative pain after mandibular third molar extraction: A double blind randomized controlled trial. Niger J Clin Pract [serial online] 2019 [cited 2019 Jun 26];22:796-800. Available from: http://www.njcponline.com/text.asp?2019/22/6/796/260039




   Introduction Top


Postoperative pain is the major cause of morbidity after surgical extraction of mandibular third molar, which can be so distressing if inadequately managed. It can lead to significant deterioration in the oral health-related quality of life and consequently disrupt patients' socioeconomic activities.[1],[2] Management of this pain is still generally far from being satisfactory despite the development of new standards for pain management and pharmacological advances.[3]

Celecoxib, a sulfa nonsteroidal anti-inflammatory drug (NSAID) chemically designated as 4-[5-(4-methylphenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzene sulfonamide, is a selective cyclooxygenase (COX) enzyme inhibitor. It only inhibits COX-2 enzyme unlike the traditional NSAIDs (t-NSAIDs) and in the process inhibits the production of prostaglandins that are responsible for pain. It is a newer drug which was found to be effective in controlling acute pain such as other NSAIDs, but does not produce most of their adverse effects.[4],[5]

Tramadol hydrochloride, (1RS, 2RS)-2-[(dimethyl amino)-methyl]-1-(3-methoxyphenyl)-cyclohexanol hydrochloride, on the other hand, is a centrally active synthetic opioid, which has been reported to be efficacious in controlling moderate to severe pain following third molar surgery.[6] It is a racemic mixture of two pharmacologically active enatiomeres, each of which contributes independently to its anti-nociceptive action. Because it does not markedly affect respiration and does not impair gastrointestinal functions, it has been suggested to be a useful alternative for patients who are intolerant to the effects of NSAIDs and other opioids.[7]

There are studies in the literature that examined the effects of the two drugs following third molar surgery.[8],[9],[10] However, we are not aware of any that compared the efficacy of oral celecoxib and tramadol over a sufficient postoperative period following surgical extraction of mandibular third molars. The aim of this study, therefore, was to compare analgesic efficacy of celecoxib and tramadol as well as their tolerability among the subjects who were administered the drugs over a period of 48 h.


   Materials and Methods Top


The design of this study was a double blind randomized controlled trial. After the approval of the Ethical Committee, a total of 90 adult patients with impacted mandibular third molars were recruited into the study. Eligibility criteria included patients aged between 18 and 45 years with at least one impacted mandibular third molar indicated for surgical extraction. Exclusion criteria included patients with compromised cardiac function, hematological abnormalities, metabolic disorders, central nervous system disorder, impaired renal or hepatic function or depressed respiratory functions, history of allergy or hypersensitivity to celecoxib and tramadol. Patients with peptic ulcer disease, pregnant and breastfeeding women, patients with history suggestive of psychological or physical dependence on opioids as well as those who had history of use of analgesics 24 h prior to the extraction were also excluded.

A pilot study which recruited 18 subjects who were randomized into two groups was carried out. The pilot study assisted in calibrating both the researcher and the independent observer for appropriate data collection and dispensing of the drugs. The experience gained during the pilot study assisted in evolving adequate logistics, which ensured patients adherence to the research protocol while at the same time maintaining the blinding.

Randomization

The appropriate doses of each of the two medications---celecoxib capsules (Heinrich Mack Nachf. GmbH and Co.KG, a subsidiary of Pfizer group, Illertissen, Germany) and tramadol tablets (PT DEXA MEDICA Palembang-Indonesia) were dispensed and kept in non-transparent sealed envelopes as follows: Caps celecoxib 400 mg start, then 200 mg 12 hourly and tabs tramadol 100 mg 8 hourly.

There were 45 of such envelopes for each study groups. There was no inscription of name or symbol on the tablets and capsules or anything that could reveal the identity of any of the drugs. This assisted in ensuring the blinding of the patients to the drugs.

Each medication was labeled with a medication code number according to the randomization sequence that has been generated before the commencement of the study. These drugs were kept in custody of the independent observer who also dispensed the drug to the patients. The surgeon (researcher) was blinded to the particular medication each patient was given throughout the study as all matters pertaining to the drugs were handled by the independent observer.

Surgical procedure

After adequate preoperative clinical and radiographic assessment of patients, extractions were done on out-patient basis by a single operator (the investigator) using 2% lignocaine hydrochloride (with 1:100,000 adrenaline) as the local anesthetic agent. A three-sided mucoperiosteal flap was raised and buccodistal guttering of bone was done with a rose-head surgical bur. The bone was copiously irrigated with normal saline while drilling. The tooth was delivered with appropriate elevators with or without tooth sectioning as necessitated by the type of impaction. Lingual tissues were gently retracted and protected throughout the procedure. Sharp bone edges were smoothened and sutures were placed to close the wound. Hemostasis was achieved and postoperative instructions were given to the patient. The same antibiotic regimen was prescribed to the patients which were Caps Amoxicillin 500 mg 8 hourly and tabs metronidazole 400 mg 8 hourly for 5 days.

Drug administration

Patients were made to wait for postoperative monitoring in the recovery room where the medications were dispensed in sealed non-transparent envelopes and the first dose of the enclosed oral medication was administered immediately after extraction by the independent observer. Patients were also commenced on the prescribed antibiotics which were dispensed in the hospital pharmacy. They were adequately educated on how to take the remaining drugs at home and were also given a telephone number of the independent observer which they called in case of any complaints related to the medications. Patients were instructed not to take any medications other than the ones already prescribed. Each patient was provided the course of the assigned analgesic free of charge for a 48 h period.

Postoperative pain assessment

Before the extraction, patients were given a VAS, which comprised a horizontal line 100 mm in length with word descriptors at each end point 0 at the left end representing “no pain” and point 100 at the right end representing “worst pain imaginable.” They were then properly educated on how to record their pain intensity on the VAS by placing a vertical mark with a pen across the horizontal line of the VAS at the point they felt represented the pain they felt at intervals. Patients were then asked to record the pain intensity felt before the extraction, immediately after extraction thereafter, serially at 4 h, 8 h, 16 h, 24 h, and 48 h after the extraction using the VAS. Patients were also asked to record any side effect or complication of the medication they felt and report to the independent observer administering the drug. Each patient was reviewed with their pain records 24 h after the surgery, and subsequently at suture removal on the seventh postoperative day when they submitted their VAS recordings if there was no means of collecting it before then.

Data collection

A questionnaire was used for the collection of information on each patient. The VAS scores were determined by measuring in millimeters from the left hand end of the VAS to the point that patient marks. The indication for surgery, type of impaction, duration of surgery, history of previous extraction, presence and severity of preoperative pain, adverse effect of the analgesic given were also part of the data documented.

Data analysis

SPSS for Windows was used for data entry and analysis. Mann--Whitney U test was used to test statistical significance/difference for non-normally distributed data. Statistical analysis was done using intention-to-treat analysis and statistical significance was inferred at P < 0.05.


   Results Top


The present study recruited a total of 90 patients who comprised of 31 males (34.44%) and 59 females (65.56%). They were randomized into two groups of 45 each.

Group A received tramadol tablets. Three patients in this group failed to return the VAS form, hence, their outcome variables were not available for analysis. Out of the remaining 42 patients, eight of them discontinued their medications at different points before 48 h observation period because of unbearable adverse effects of the drug (19% discontinuation rate).

Group B received celecoxib. Only one of them discontinued the medication 24 h after the extraction (2% discontinuation rate) because the patient was no longer feeling pain.

The median VAS score of the patients in celecoxib group was lower than those of tramadol group at every point of postoperative pain assessment [Table 1] and [Figure 1] and there was statistically significant difference in the median VAS scores at 4 h after the extraction when the two groups were compared (P = 0.001).
Table 1: Comparison of pain intensity and other variables between the groups

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Figure 1: Pain intensity (median VAS) of tramadol and celecoxib groups

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None of the patients in the celecoxib group reported any adverse effect of their medications, but 25 (55.56%) out of the 42 patients in the tramadol group reported adverse effects of the drugs which were described as drowsiness, vomiting, nausea, dizziness, and others. It was also noted that 16 (80%) of the patients that experienced these adverse effects were females [Table 2].
Table 2: Adverse effects profile

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   Discussion Top


The need to achieve a pain-free postoperative period after third molar surgery and the choice of efficacious analgesic remain a challenge. This is especially so for patients presenting with symptoms suggestive of peptic ulcer disease for whom the effectiveness and safety of analgesics must be considered before making a choice. Patients with dyspeptic symptoms form a significantly large proportion of population globally,[11] and especially in Nigeria where a prevalence as high as 45% was noted in a study.[12] Administration of the traditional non-selective NSAIDs that are readily available and affordable is contraindicated in this category of patients.[13]

Studies have suggested that tramadol and celecoxib are useful options for this group of patients based on their pharmacological properties.[9],[14],[15] However, we are not aware of any randomized controlled study that compared these two drugs after third molar surgery over a period of up to 48 h postoperatively.

In this study, patients in the celecoxib group experienced greater pain control and tolerated the medication better throughout the postoperative period compared with tramadol group. This is similar to the finding of O'Donnell et al.[16] in which celecoxib was far more effective and better tolerated than tramadol for the treatment of low back pain. Zamiri et al.[10] also reported that pre-emptive administration of Celecoxib produced better pain relief than tramadol after intra-alveolar extraction of lower third molars. For effective treatment of acute pain such as postoperative pain after third molar surgery, a loading dose of celecoxib 400 mg is recommended.[9],[17] This should be followed by 200 mg 12 hourly afterwards as administered in this study.[17] The advantages of celecoxib over the traditional NSAIDs includes: Less risk of gastrointestinal ulceration, lack of effect on platelet function, and generally long duration of action with twice daily administration, which promotes good compliance.[18],[19],[20]

Patients in our study took multiple doses of the analgesics in order to assess the performance and tolerability of the drugs for at least 48 h. The effectiveness of a drug can be compromised if it has poor tolerability because compliance with the medication can be affected. The clinical benefits of opioids like tramadol are generally limited by their tolerability which was reported to cause up to 31% discontinuation rate.[21],[22] Drowsiness, vomiting, and nausea were the commonest adverse effects of tramadol in this study. This is similar to the findings of other studies.[15],[16],[23] Collins et al.[15] reported up to 39% drop out rate of patients in their study taking tramadol (100 mg four times daily) because of adverse effects predominantly nausea, vomiting, dizziness, and drowsiness.

The reason why most of the adverse effects reported in this study were felt by the females is an important finding which can be a subject for further research.


   Conclusion Top


In this study, the analgesic efficacy of celecoxib given at a dose of 400 mg start, then 200 mg 12 hourly was higher than that of tramadol at a dose of 100 mg 8 hourly all through the period of 48 h after surgical extraction of mandibular third molar. Celecoxib was also observed to be more tolerable than tramadol going by the adverse effect profile of the drugs as reported in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Leidholm R, Knutsson K, Lysell L, Rohlin M, Brickley M, Shepherd JP. The outcomes of mandibular third molar removal and non-removal: A study of patient preferences using a multiattribute method. Acta Odontol Scand 2000;58:293-8.  Back to cited text no. 1
    
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Liedholm R, Knutsson K, Norhund A. Economic aspect of mandibular third molar surgery. Acta Odontol Scand 2010;68:43-8.  Back to cited text no. 2
    
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Pozos-Guillen A, Martinez-Rider R, Aguirre-Banuelos P, Perez-Urizar J. Pre-emptive analgesic effect of tramadol after mandibular third molar extraction: A pilot study. J Oral Maxilllofac Surg 2007;65:1315-20.  Back to cited text no. 8
    
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Cheung R, Kowalski K. Analgesic efficacy of celecoxib in postoperative oral surgery pain: A single-dose, two centre, randomized, double blind, active and placebo-controlled study. Clin Ther 2007;29:44.  Back to cited text no. 9
    
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Zamiri B, Mousavideh K, Tajoddini M, Mohammadinezhad C, Aarabi AM. Comparison of ibuprofen, celecoxib and tramadol in relief of pain after extraction of mandibular third molar teeth. IRCMJ 2009;11:431-6.  Back to cited text no. 10
    
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Mahadeva S, Goh KL. Epidemiology of functional dyspepsia: A global perspective. World J Gastroenterol 2006;12:2661-6.  Back to cited text no. 11
    
12.
Tijani B, Umar A. Peptic ulcer disease and helicobacter pylori infection at Kano Nigeria. The Internet Journal of Gastroenterology 2008;8(1).  Back to cited text no. 12
    
13.
Ihezue CH, Oluwole FS, Onuminya JE, Okoronkwo MO. Dyspepsia among the highlanders of Nigeria. Afr J Med Sci 1996;25:23-9.  Back to cited text no. 13
    
14.
Hunt RH, Harper S, Watson DJ, Yu C, Quan H, Lee M, et al. The gastrointestinal safety of the COX-2 selective inhibitor etoricoxib assessed by both endoscopy and analysis of upper gastrointestinal events. Am J Gastroenterol 2003;98:1725-33.  Back to cited text no. 14
    
15.
Collins M, Young I, Sweeney P, Fenn GC, Stratford ME, Wilson A, et al. The effect of tramadol on dento-alveolar surgical pain. Br J Oral Maxillofac Surg 1997;35:54-8.  Back to cited text no. 15
    
16.
O'Donnel JB, Ekman EF, Spalding WM, Bhadra P, McCabe D, Berger MF. The effectiveness of a weak opioid medication versus a cyclo-oxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug in treating flare-up of chronic low-back pain, results from two randomized double-blind 6 week studies. J Int Med Res 2009;37:1789-802.  Back to cited text no. 16
    
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Celebrex (celecoxib capsules) [prescribing information]. Available from: http://www.pfizer.com/files/product/mg_celebrex.pdf. [Last accessed on 2012 Feb 01].  Back to cited text no. 17
    
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Moore PA, Hersh EV. Celecoxib and rofecoxib: The role of cox-2 inhibitors in dental practice. JADA 2001;132:451-6.  Back to cited text no. 18
    
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May N, Epstein J, Osborne B. Selective COX-2 inhibitors: A review of their therapeutic potential and safety in dentistry. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:399-405.  Back to cited text no. 19
    
20.
Bensen WG, Zhao SZ, Burke TA, Zabinski RA, Makuch RW, Maurath CJ, et al. Upper gastrointestinal tolerability of celecoxib a COX-2 specific inhibitor compared to naproxen and placebo. J Rheumatol 2000;27:1876-83.  Back to cited text no. 20
    
21.
Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E. Review: Opioids are more effective than placebo but not other analgesics for chronic noncancer pain. CMAJ 2006;174:1589-94.  Back to cited text no. 21
    
22.
Avouac J, Gossec L, Dougados M. Efficacy and safety of opioids for osteoarthritis: A meta-analysis of randomized controlled trials. Osteoarthritis Cartilage 2007;15:957-65.  Back to cited text no. 22
    
23.
Ong CK, Lirk P, Tan JMH, Sow BW. The analgesic effect of intravenous versus oral tramadol for preventing postoperative pain after third molar surgery. J Oral Maxillofac Surg 2005;63:1162-8.  Back to cited text no. 23
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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