Advances in Human Biology

: 2020  |  Volume : 10  |  Issue : 3  |  Page : 188--192

Efficacy of preemptive oral doses of acetaminophen and celecoxib for post-operative pain management after open-flap debridement: A randomised controlled study

Santosh Kumar1, Pratik Kamlesh Sanghavi2, Parth Narendra Patel3, Palak Hitesh Sonvane4, Para Rakesh Dave5, Vani Udaybhai Gor6, Irfan Mohammed7,  
1 Department of Periodontology and Implantology, Karnavati School of Dentistry, Gandhinagar, Gujarat, India
2 Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada
3 Department of Periodontology and Implantology, Goenka Research Institute of Dental Sciences, Gandhinagar, Gujarat, India
4 Department of Healthcare Leadership, Trinity Western University, Langley Township, Canada
5 Department of Paediatric and Preventive Dentistry, College of Dental Sciences and Hospital, Bhavnagar, Gujarat, India
6 Department of Paediatric and Preventive Dentistry, Narsinhbhai Patel Dental College and Hospital, Visnagar, Gujarat, India
7 Department of Forensic Dentistry, Federal University of Pelotas, Pelotas, Brazil

Correspondence Address:
Santosh Kumar
Karnavati University, A/907, Uvarsad, Gandhinagar - 382 422, Gujarat


Background: Open-flap debridement therapy often leads to frequent pain postoperatively. It has been reported that open-flap debridement causes pain in 79% of patients. The preemptive approach focuses on preventing post-operative analgesic flare and blocking the occurrence of hyperalgesic states. This study aimed to compare the preemptive analgesia of oral celecoxib with oral acetaminophen after surgical open-flap debridement. Materials and Methods: A randomised, double-blinded, placebo-controlled research was conducted to study the patients presenting with an open-flap debridement under local anaesthesia. A total of forty patients were randomised to receive open-flap debridement, and either celecoxib or acetaminophen was prescribed. Visual analogue scale (VAS) pain score was noted every 2, 4, 6, 8, 10 12 and 20 h post-surgery. Consumption of analgesics was also recorded postoperatively. Results: The average age and weight of the patients in the celecoxib group were 35.85 ± 8.32 and 54.75 ± 8.90 kg, respectively. The average age and weight of the patients in the acetaminophen group were 36.8 ± 8.71 and 53.15 ± 9.90 kg, respectively. The mean VAS pain score at 4 h was 2.6 ± 1.14 and 4.9 ± 1.20 for celecoxib and acetaminophen groups, respectively. The mean post-operative analgesic drug consumption in the celecoxib group was 0.60 ± 0.87 and 1.30 ± 0.80 in the acetaminophen group. Conclusion: Celecoxib shows a significant preemptive analgesic effect, thereby reducing the use of post-surgical analgesics after open-flap debridement. Hence, pre-surgical single dose of celecoxib can be used to minimise the post-operative analgesic use.

How to cite this article:
Kumar S, Sanghavi PK, Patel PN, Sonvane PH, Dave PR, Gor VU, Mohammed I. Efficacy of preemptive oral doses of acetaminophen and celecoxib for post-operative pain management after open-flap debridement: A randomised controlled study.Adv Hum Biol 2020;10:188-192

How to cite this URL:
Kumar S, Sanghavi PK, Patel PN, Sonvane PH, Dave PR, Gor VU, Mohammed I. Efficacy of preemptive oral doses of acetaminophen and celecoxib for post-operative pain management after open-flap debridement: A randomised controlled study. Adv Hum Biol [serial online] 2020 [cited 2021 May 13 ];10:188-192
Available from:

Full Text


Periodontal therapy often leads to frequent pain. The most common pain-causing procedure is scaling and root planing.[1] Ninety per cent of patients complain of some degree of pain within 6.1 h.[1],[2] It has been reported that open-flap debridement causes pain in 79% of patients[3] and 93% after flap surgery with osseous resection.[3] The post-operative pain is often influenced by procedure, age, location, duration and anxiety level.[2],[3] Inadequate pre-operative and post-operative pain management may lead to decreased quality of life post-surgery. Inflammatory mediators such as leucotrienes, prostaglandins and platelet-activating factors are predominantly released after operation-induced surgery, which causes dilatation of vessels and increased permeability, causing oedema of the tissue.[4] Therefore, post-operative analgesics are required for treating post-operative pain after open-flap debridement.[5]

This preemptive approach focuses on preventing post-operative analgesic flare and blocking the occurrence of hyperalgesic states. Preemptive analgesia techniques are directed to control central sensitisation. The basic principles of therapeutic intervention include the following: (1) distinguishing between analgesic conditions that abolish all physiological pain and those that reject only abnormal hypersensitivity, (2) precisely targeting the orientation or preservation of central sensitisation by particular treatments and (3) averting or plummeting post-operative pain with approaches intended to inhibit the onset of central sensitisation during surgery.[6] The way to achieve pre-operative analgesia is by administrating local anaesthetic injections or drugs before surgery.[7],[8]

Acetaminophen is considered a non-opioid analgesic and antipyretic agent used to treat pain and fever. It is a well-tolerated and effective analgesic used for pain management. The exact mechanism of action is still unclear, but it is categorised along with non-steroidal anti-inflammatory drugs (NSAIDs) as it inhibits the cyclooxygenase (COX) pathways.[9] It works through the central process, including pathways that affect the production of prostaglandins, serotonin, opioids, cannabinoids and nitric oxide.[10] To the present date, acetaminophen has been prescribed for preemptive analgesia; however, unintentional overdoses due to its full availability resulted in liver injury and even acute liver failure.[11]

Celecoxib is chemically known as 4-(5-[4-methyl phenyl]-3-[trifluoromethyl]-1H-pyrazol-1-yl) benzenesulfonamide and is a diaryl-substituted pyrazole. Celecoxib inhibits COX-2 (COX-2) which is responsible for prostaglandin synthesis, which is an essential part of inflammation and pain pathway.[12] It also significantly reduces gastrointestinal toxicity, shows no effect on platelet aggregation and exhibits anti-inflammatory and analgesic effects by reducing prostaglandin formation.[13] Various studies have reported that celecoxib is effective in post-operative pain reduction by pre-operative management.[7],[14],[15],[16]

The aim of this study is to compare the efficacy of pre-operative administration of celecoxib and acetaminophen on post-operative pain relief after open-flap debridement.

 Materials and Methods

This was a randomised, controlled, double-blind study performed in accordance with the guidelines of Good Clinical Practiced and the Declaration of Helsinki. This study was approved by the ethical committee of the concerned institution (KSD/20/19/221).

Forty systemically healthy male patients were included in this study. Cochran formulae were used in this study to calculate the ideal sample size. All the patients aged between 20 and 50 years in age and scheduled to undergo open-flap debridement in the mandibular posterior region (without vertical defects) were selected for this study. All the patients were informed about the details of the research, and a written consent form was obtained before the study commenced. Patients who had any conditions that contraindicated the dose of COX-2 and NSAIDs inhibitors; were pregnant and lactating; had kidney, liver and cardiovascular diseases; had bleeding ulcers in the digestive tract; were mentally unstable and who had vertical bone defects were excluded from the study. Patients were included in the study if they were at least 18 years of age, were indicated for an open-flap debridement in the mandibular posterior region, were non-allergic to any drugs and had not taken any anti-inflammatory or analgesic drug for 5 days prior to surgery.

All the patients were randomly divided into two groups by the use of the coin toss method. Group A consisted of patients who consumed 200 mg of oral celecoxib, whereas Group B patients consumed 500 mg of oral acetaminophen. The patient and the surgeon were not informed about the type of drug consumed. Surgery was performed 40 min post-drug administration. A single periodontist performed all the open-flap surgeries to minimise the interoperator bias. All the operations were performed by using the same local anaesthesia technique (inferior alveolar nerve block) and the same drug (2% lidocaine). Local infiltration was achieved using a 4% articaine with 1:100,000 epinephrine (Septocaine, Septodont, USA). Both groups were treated with the same surgical procedure to reduce surgery-related bias.

In short, buccal and lingual crevicular incision was given, and the flaps were raised. Root debridement was performed, and tissue tags on the mucoperiosteal flap were removed. Irrigation was achieved with the betadine solution, and the flaps were sutured back with the interrupted suturing technique. An 11-point visual analogue scale (VAS) was formulated to analyze the intensity of pain. Post-operative pain was recorded every 2 h till 12 h and then at 24th h post-surgery on the VAS scale (2, 4, 6, 8, 10, 12 and 24 h), and the time to the first analgesic was taken after surgery was completed.

Statistical analysis

The entire data were analysed using SPSS software (SPSS, v. 7 for Windows, IBM, Chicago, IL, USA). An independent t-test was performed to determine any significant differences among the groups. The parametric outcomes were expressed as mean ± standard deviation.

Research hypothesis

The research hypothesis stated that the patients in either group required a similar amount of analgesic for pain control after the open-flap debridement.


All the data were obtained from the forty patients selected for this study. These forty patients were randomly divided into two groups. No unwanted complications were observed in this study. Only male patients were included in this study to keep the pain sensitivity to a similar level.[17] The average age and weight of the patients in the celecoxib group were 35.85 ± 8.32 and 54.75 ± 8.90 kg, respectively. Whereas the average age and weight of the patients in the acetaminophen group were 36.8 ± 8.71 and 53.15 ± 9.90 kg, respectively. The average duration of the surgery was 35.4 ± 2.77 in the celecoxib group and 35.05 ± 2.87 in the acetaminophen group. No statistical difference was found with regard to age, weight and duration of surgery among the groups [Table 1].{Table 1}

Visual analogue scale score analysis

The mean VAS score at 2 h was 2.2 ± 0.60, which increased to 2.6 ± 1.14 at 4 h and then continued decreasing till 24 h to 0.2 ± 0.61. This value was lower than that of the acetaminophen group. There was a statistical difference in the VAS score from 4 to 12 h in between both the groups [Table 2] and [Graph 1]. The mean value of all the VAS score and P value are mentioned in [Table 2].{Table 2}[INLINE:1]

Analgesic dose

A preemptive dose of celecoxib significantly reduced the dose of analgesic significantly. In Group A, only eight patients took the rescue drug, whereas 16 patients consumed in Group B. During the study period, the mean drug consumption of the celecoxib group and acetaminophen group was 0.60 ± 0.87 and 1.30 ± 0.80, respectively (P < 0.05). The difference between the non-consumers of rescue drugs among both the groups was 65%. There was a statistically significant difference between both the groups who took the rescue drugs [P < 0.05 [Table 3].{Table 3}


Celecoxib has various indications, both non-Food and Drug Administration (FDA) and FDA approved. The FDA has approved this drug for the management of acute pain. It is a relatively safe drug, and its safety has been established through various studies.[18],[19] Celecoxib has dose-dependent comparable efficacy to Non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of arthritis pain. It is also reported to have good tolerability, very similar to NSAIDs when combined with proton pump inhibitors.[20] It has analgesic and anti-inflammatory effects. Celecoxib also provides antipyretic potential by inhibiting the enzyme COX-2, leading to an impaired biosynthesis of prostanoids. COX-2 inhibitors can cross the blood–brain barrier and can easily reach to cerebrospinal fluid and plasma, influencing central nervous system nociception.[21] In a dental surgery model, preemptive treatment with celecoxib suppressed prostaglandin E2 in local tissues at 80–240 min from the end of surgery.[22]

Celecoxib offers adequate preemptive analgesia for patients undergoing hip surgery and periodontal surgery. A study by Liu and Wang[7] proved that the preemptive dose of 400 mg celecoxib was better and more effective than the post-operative dosage. However, knowledge regarding the preemptive analgesic dose of 200 mg celecoxib in the extraction of impacted tooth was minimal. Another study by Xie et al. reported that celecoxib exhibits a significant preemptive analgesic effect, hence reducing the use of post-operative analgesics after the removal of impacted tooth.[23]

Open-flap debridement is one of the forms of periodontal surgeries. This surgery can be affected by the method of treatment, instrument type, incision, tissue laceration and more extended pain period. These factors often lead to stressful treatment. To reduce this post-operative pain, patients are often advised analgesic drug. These NSAIDs often lead to a high frequency of upper gastrointestinal bleeding and perforation of ulcers. Unfortunately, all the newer NSAIDs also appear to be similar in propensity to cause a mucosal ulcer. Hence, we need to devise a treatment protocol that requires less consumption of analgesics.

Our study results show that celecoxib was far superior to acetaminophen in reducing post-operative analgesics. There was a 65% decrease in the analgesic drug dose when celecoxib was administered preoperatively. The mean VAS score of the patients who consumed celecoxib was significantly lower than that of the patients who consumed acetaminophen. Our results pointed at decent post-operative pain management with celecoxib. Similar to our results, various studies have shown that the use of oral celecoxib pre-surgery can reduce post-operative pain. An article by Pilatti et al.[24] showed that preemptive 200 mg of celecoxib and similar post-operative dose could effectively reduce pain after open-flap debridement. Xie et al. reported that 400 mg of celecoxib administered prior to surgery helped to reduce the post-operative pain after third molar surgery.[23] Al-Sukhun et al. in their study published about the higher analgesic effect of celecoxib, to reduce acute post-operative pain following surgery when compared with the traditional NSAID, ibuprofen.[14] Viswanath et al. conducted a randomised, single-blinded clinical study on 58 patients undergoing surgical extractions. This study compared two interventions: 800 mg of intravenous (IV) ibuprofen and 1000 mg of IV acetaminophen. They concluded that preemptive analgesia with IV ibuprofen is more effective than IV acetaminophen in reducing post-operative pain and opioid use for third molar surgery.[25] The whole of the above researches show that celecoxib might be more effective than acetaminophen in relieving the post-operative pain.

In this study, we have noted that celecoxib, when compared to acetaminophen, was more effective at 4, 6, 8, 10 and 12 h post-surgery. This can be attributed to the pharmacokinetics of celecoxib. Celecoxib reaches its peak plasma drug concentration at 2.3 h, and its apparent volume distribution is 6.3 l/kg with a half-life of 7.1 h. On the other hand, acetaminophen is a safe analgesic that reaches its peak plasma drug concentration at 0.73 h, and its apparent volume distribution is 1.3 l/kg with a half-life of 2.51 h.[26] The high volume distribution and high self-life of celecoxib indicate that the drug is well circulated in the tissues and its clearance rate is slow. This pharmacokinetics of the celecoxib leads to a prolonged therapeutic effect.

Our data suggest that the total analgesic consumed within 24 h post-surgery in the celecoxib group was 65% less than that in the acetaminophen group. Kang et al. in their study on 82 cognitively intact elderly patients about to undergo bipolar hemiarthroplasty after a hip fracture, suggested the use of celecoxib to provide additional pain relief until the 4th post-operative day. This improves patient satisfaction at discharge and reduces total narcotic consumption for post-operative pain management.[27] Similarly, Ulm et al. suggested that the use of oral celecoxib before hysterectomy minimised the consumption of opioids in the early stages. Akinbade et al.[28] in their study compared celecoxib with tramadol and found that celecoxib was more efficient and well tolerated than tramadol for managing the pain after surgical extraction of the mandibular third molar. Similarly, Cillo et al.[29] have also shown that the use of celecoxib pre-surgery in maxillomandibular advancement leads to decreased consumption of narcotic pills.

Our study similarly indicated that the celecoxib group had a longer active period when compared to acetaminophen. Data presented that 60% of patients in the celecoxib group did not consume any analgesic, whereas only 20% of patients did not consume analgesic in the acetaminophen group. This outcome may be related to a higher apparent volume distribution and higher self-life of celecoxib when compared to that of acetaminophen.


Celecoxib exhibits a statistically significant preemptive analgesic effect compared to acetaminophen. This results in minimal post-operative analgesic medication. The results suggested that a preemptive dose of celecoxib can be effectively used to reduce the analgesic consumption post-surgery in open-flap debridement.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Pihlstrom BL, Hargreaves KM, Bouwsma OJ, Myers WR, Goodale MB, Doyle MJ. Pain after periodontal scaling and root planing. J Am Dent Assoc 1939, 1999;130:801-7.
2Canakçi CF, Canakçi V. Pain experienced by patients undergoing different periodontal therapies. J Am Dent Assoc 1939, 2007;138:1563-73.
3Matthews DC, McCulloch CA. Evaluating patient perceptions as short-term outcomes of periodontal treatment: A comparison of surgical and non-surgical therapy. J Periodontol 1993;64:990-7.
4Bamgbose BO, Akinwande JA, Adeyemo WL, Ladeinde AL, Arotiba GT, Ogunlewe MO. Effects of co-administered dexamethasone and diclofenac potassium on pain, swelling and trismus following third molar surgery. Head Face Med 2005;1:11.
5Isiordia-Espinoza MA, Pozos-Guillén AJ, Martínez-Rider R, Herrera-Abarca JE, Pérez-Urizar J. Preemptive analgesic effectiveness of oral ketorolac plus local tramadol after impacted mandibular third molar surgery. Med Oral Patol Oral Cir Bucal 2011;16:e776-80.
6Woolf CJ, Chong MS. Preemptive analgesia--treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993;77:362-79.
7Liu X, Hu J, Gao L, Ji X, Zhai D, Song H, et al. Analgesic effect of preoperative dezocine-based local anesthesia in patients undergoing inguinal hernia repair. J Int Med Res 2018;46:4945-51.
8Rahimi M, Farsani DM, Naghibi K, Alikiaii B. Preemptive morphine suppository for postoperative pain relief after laparoscopic cholecystectomy. Adv Biomed Res 2016;5:57.
9Ghanem CI, Pérez MJ, Manautou JE, Mottino AD. Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity. Pharmacol Res 2016;109:119-31.
10Lachiewicz PF. The role of intravenous acetaminophen in multimodal pain protocols for perioperative orthopedic patients. Orthopedics 2013;36:15-9.
11Ramachandran A, Jaeschke H. Acetaminophen Hepatotoxicity. Semin Liver Dis 2019;39:221-34.
12McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, FitzGerald GA. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: The human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A 1999;96:272-7.
13Krasselt M, Baerwald C. Celecoxib for the treatment of musculoskeletal arthritis. Expert Opin Pharmacother 2019;20:1689-702.
14Al-Sukhun J, Al-Sukhun S, Penttilä H, Ashammakhi N, Al-Sukhun R. Preemptive analgesic effect of low doses of celecoxib is superior to low doses of traditional nonsteroidal anti-inflammatory drugs. J Craniofac Surg 2012;23:526-9.
15Khalili M, Modir H, Norouzi A, Mohammadbeigi A, Somesara SA. Premedication with oral gabapentin versus intravenous paracetamol for post-operative analgesia after tibial fracture surgery. Adv Hum Biol 2017;7:115.
16Aghajanloo M, Esmaeili F, Bathaei T, Piriaei A, Tavakoli E. Quality of life evaluation of patients undergoing lumbar surgery: A cross-sectional study in West of Iran. Adv Hum Biol 2019;9:147.
17Bartley EJ, Fillingim RB. Sex differences in pain: A brief review of clinical and experimental findings. Br J Anaesth 2013;111:52-8.
18Simon LS, Lanza FL, Lipsky PE, Hubbard RC, Talwalker S, Schwartz BD, et al. Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: Efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum 1998;41:1591-602.
19Emery P, Zeidler H, Kvien TK, Guslandi M, Naudin R, Stead H, et al. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison. Lancet 1999;354:2106-11.
20Chan FK, Lanas A, Scheiman J, Berger MF, Nguyen H, Goldstein JL. Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): A randomised trial. Lancet 2010;376:173-9.
21Buvanendran A, Kroin JS, Berger RA, Hallab NJ, Saha C, Negrescu C, et al. Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans. Anesthesiology 2006;104:403-10.
22Khan AA, Brahim JS, Rowan JS, Dionne RA.In vivo selectivity of a selective cyclooxygenase 2 inhibitor in the oral surgery model. Clin Pharmacol Ther 2002;72:44-9.
23Xie L, Yang RT, Lv K, Zhou HH, Li Z. Comparison of low pre-emptive oral doses of celecoxib versus acetaminophen for postoperative pain management after third molar surgery: A randomized controlled study. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg 2020;78:75, e1-75, e6.
24Pilatti GL, André dos Santos F, Bianchi A, Cavassim R, Tozetto CW. The use of celecoxib and dexamethasone for the prevention and control of postoperative pain after periodontal surgery. J Periodontol 2006;77:1809-14.
25Viswanath A, Oreadi D, Finkelman M, Klein G, Papageorge M. Does pre-emptive administration of intravenous ibuprofen (Caldolor) or intravenous acetaminophen (Ofirmev) reduce postoperative pain and subsequent narcotic consumption after third molar surgery? J Oral Maxillofac Surg 2019;77:262-70.
26Park SI, Park JY, Park MJ, Yim SV, Kim BH. Effects of ojeok-san on the pharmacokinetics of celecoxib at steady-state in healthy volunteers. Basic Clin Pharmacol Toxicol 2018;123:51-7.
27Kang H, Ha YC, Kim JY, Woo YC, Lee JS, Jang EC. Effectiveness of multimodal pain management after bipolar hemiarthroplasty for hip fracture: A randomized, controlled study. J Bone Joint Surg Am 2013;95:291-6.
28Akinbade AO, Ndukwe KC, Owotade FJ. 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.
29Cillo JE, Dattilo DJ. Pre-emptive analgesia with pregabalin and celecoxib decreases postsurgical pain following maxillomandibular advancement surgery: A randomized controlled clinical trial. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg 2014;72:1909-14.