|Year : 2019 | Volume
| Issue : 1 | Page : 3-9
Comparison between acetaminophen, ibuprofen, and ketorolac as an efficient single-dose preoperative medication for control of pain associated with initial aligning archwire: A double-blind randomized control trial
Nimish Arun Wajekar1, Murlidhar Radhakrishnan Sastri2, Neha Naresh Vazirani3, Snehal Satish Pathak1
1 PG Student, Department of Orthodontics and Dentofacial Orthopedics, S. M. B. T. Dental College and Hospital, Ahmendnagar, Maharashtra, India
2 Prof, Department of Orthodontics and Dentofacial Orthopedics, S. M. B. T. Dental College and Hospital, Ahmendnagar, Maharashtra, India
3 DDS Student, School of Dentistry, University of Michigan, Ann Arbor, Michigan, United States
|Date of Submission||17-Feb-2018|
|Date of Acceptance||15-Nov-2018|
|Date of Web Publication||04-Feb-2019|
Dr. Nimish Arun Wajekar
Department of Orthodontics and Dentofacial Orthopedics, S. M. B. T. Dental College and Hospital, Nashik Pune Highway, Ghulewadi, Sangamner, Ahmednagar - 422 608, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Pain regulation is an issue of utmost importance for an orthodontist and a patient that undergoes orthodontic treatment. This is mainly because there is no set standard for controlling pain during orthodontic treatment. Objectives: The aim of the present study is to compare the efficacy of commonly prescribed drugs, acetaminophen, ibuprofen, and ketorolac on relieving orthodontic pain. Materials and Methods: A sample of 80 orthodontic patients scheduled to undergo fixed orthodontic treatment were selected and allocated (block randomized) into four experimental groups of 20 patients each, of which Group 1 was prescribed acetaminophen (500 mg), while Groups 2–4 were prescribed ibuprofen (400 mg), ketorolac (10 mg), and placebo (lactose capsule), respectively. All the prescriptions were given as a single-dose preoperatively. Each patient was thereafter asked to note the degree of pain perceived at specific intervals of time with reference to a questionnaire and a 100-mm visual analog scale. Statistical Analysis: Data comparison was done by applying the analysis of variance test to compare each group for every experimental parameter. To further elucidate the individual comparisons between each time point, the Tukey's test was used as post hoc analysis. Results: There were significant relationships between the four drug groups for each parameter, namely chewing, biting, occluding on anterior teeth together, and occluding on posterior teeth together (P < 0.05). Conclusion: The present study concluded that, when compared with the placebo group, the use of (nonsteroidal anti-inflammatory drugs) ketorolac, ibuprofen, and acetaminophen preoperatively reduced the pain perceived at 2 hours and 6 hours after archwire placement. However, the results were much significant for the ketorolac group as compared with the ibuprofen and acetaminophen groups. Trial Registration: Clinical Trials Registry-India CTRI/2017/03/007995.
Keywords: Analgesic, nonsteroidal anti-inflammatory drugs, pain control
|How to cite this article:|
Wajekar NA, Sastri MR, Vazirani NN, Pathak SS. Comparison between acetaminophen, ibuprofen, and ketorolac as an efficient single-dose preoperative medication for control of pain associated with initial aligning archwire: A double-blind randomized control trial. J Indian Orthod Soc 2019;53:3-9
|How to cite this URL:|
Wajekar NA, Sastri MR, Vazirani NN, Pathak SS. Comparison between acetaminophen, ibuprofen, and ketorolac as an efficient single-dose preoperative medication for control of pain associated with initial aligning archwire: A double-blind randomized control trial. J Indian Orthod Soc [serial online] 2019 [cited 2019 Jun 17];53:3-9. Available from: http://www.jios.in/text.asp?2019/53/1/3/251541
| Introduction|| |
One of the most common questions which seem to be foremost in almost every patient's mind as they pursue their orthodontic treatment is: “Are the braces going to hurt?” The answer is yes, braces will make the teeth sore. The experience of pain and discomfort during the tenure of orthodontic treatment is common; however, it differs from person to person. Orthodontic treatment methods such as separation, placement of archwires, activation of fixed or removable appliances, and debonding cause a certain degree of pain to the patient. Hence, pain and discomfort may be the sole reason that keeps the patient from seeking orthodontic treatment.
Studies till now suggest that pain percentage experienced by orthodontic patient population is approximately 95%. A survey conducted by Tayer and Burek demonstrated that adult patients undergoing orthodontic treatment stated discomfort as the most discouraging aspect of orthodontia.
Most favored method for the management of pain caused due to orthodontic treatment still remains to be the use of nonsteroidal anti-inflammatory drugs (NSAIDs), in spite of developing various techniques such as low-level laser therapy to periodontal tissue, transcutaneous electrical nerve stimulation,, and vibratory stimulation of periodontal ligament.,
Despite their widespread use in orthodontia even today, there is still no universal evidence-based recommendation for the use of analgesics. Both acetaminophen and ibuprofen are commonly used by the clinicians for the relief of orthodontic pain.
People who endure from a toothache or orthodontic-related pain have a common tendency to self-medicate, and overdose with readily available over the counter analgesics instead of seeking professional dental attention. This necessitates the development of evidence-based guidelines for the prescription of the correct dosage of the most effective drugs available and also raises awareness among the health-care professionals regarding the importance of early remedial treatment.
The consumption of preemptive analgesics is rapidly gaining widespread attention in both medical and dental literature. Steen Law et al. and Bernhardt et al. have found that preoperative analgesic consumption of ibuprofen, 1 hour before orthodontic procedure decreases the perceived pain levels from 2 hours after bonding until night time, whereas Polat et al., Young et al., Kohli and Kohli, and Zarif Najafi et al. found that naproxen sodium, valdecoxib therapy, piroxicam, and meloxicam, respectively were as effective as or more efficient than ibuprofen in controlling the post separator pain or pain after initial archwire placement.
The efficacy of acetaminophen, ibuprofen, and ketorolac which belong to different classes of drugs has not yet been studied in the orthodontic literature, and hence, the purpose of the present study was to compare the efficacy of commonly prescribed drugs acetaminophen, ibuprofen, and ketorolac for relieving orthodontic pain.
| Materials and Methods|| |
A total of 150 patients who needed fixed orthodontic therapy were screened for this prospective, double-blind randomized clinical trial from the Department of Orthodontics and Dentofacial Orthopedics of SMBT Dental College and Hospital, Sangamner, Maharashtra. Informed consent was taken from all patients. This study was approved by the SMBT Institutional Ethical Committee and is also registered with Clinical Trials Registry-India with Reg. no. CTRI/2017/03/007995. Of 150 patients, 44 did not meet the inclusion criteria, and six declined to participate in the study.
Following was the selection criteria:
- Orthodontic patients scheduled for fixed orthodontic treatment
- Age >16 years.
- Presence of systemic disease
- Contraindication to use of NSAID
- Currently using any antibiotics or analgesics
- If any prophylactic antibiotic coverage is required
- If any teeth have been extracted at least 2 weeks before bonding.
Taking into account for potential patient dropouts during the study, 150 patients were screened, and 100 patients were recruited in this study. The sample size was determined to be 80 using a power analysis based on variances of similar studies reported previously. The total sample of 100 was categorized using block randomization. Block randomization was used based on the age as the categorizing factor. This was chosen to minimize the variability among different age categories. The four drugs were randomly administered among patients in each age category. Out of 100, 16 patients were lost to follow-up, as they failed to return the questionnaire. Now, 84 patients remaining, 4 were not analyzed as 3 did not complete the questionnaire correctly, and 1 took an additional analgesic to control the pain [Figure 1]. Double blinding was done in which both the patient and the laboratory assistant (who randomly distributed drugs) were unaware about which drug was consumed and distributed. All drugs were covered by identical silver foil so that neither the patients nor the investigators knew about the control and experimental group. The bracket slot size and archwire combination were standardized. Mclaughlin, Bennett, Trevisi (MBT) 0.022” slot and 0.016” NiTi (G & H Orthodontics) initial aligning wire were used for patients with mild-to-moderate crowding. All patients were prescribed with a single preoperative dose, 1 hour before the initial archwire placement. Each patient was thereafter asked to note the degree of pain perceived at specific intervals of time (2 hours, 6 hours, 12 hours, 24 hours; 2 and 3 days, and 7th day), during each of the following activities, that is, chewing, biting, occluding posterior teeth together, and occluding anterior teeth together, with reference to a questionnaire, and a 100-mm visual analog scale (VAS).
Method of data analysis
Statistical Analysis System (SAS version 9.4, by SAS Institute, North Carolina State University) was used to perform statistical analysis. Data comparison was done by the application of specific statistical tests to evaluate the statistical significance of the results.
The data obtained was a continuous type. The normality of the data was checked by performing univariate analysis, and the data was found to be normal, hence, the parametric tests were used for analysis. Mean and standard deviation (SD) of pain levels for different drug groups were calculated.
One-way repeated measures analysis of variance (ANOVA) was performed as a parametric test for the comparison of different drug groups for each experimental parameter. The Tukey's test was used as a post hoc analysis to elucidate the individual comparisons between each time point.
| Results|| |
[Table 1] shows the descriptive statistics of the experimental groups. Results of ANOVA suggested that the mean ages of the four experimental groups were similar (P > 0.05).
Results of repeated measures ANOVA suggested the presence of significant relationships between the four drug groups for each parameter, i.e., chewing, biting, occluding on anterior teeth together, and occluding on posterior teeth together (P < 0.05). [Table 2] shows the mean pain values and SDs for chewing, biting, occluding on anterior teeth together and occluding on posterior teeth together in each of the four experimental groups.
|Table 2: Mean pain scores, standard deviation, and P value of the experimental groups|
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Differences in postoperative pain between experimental conditions
The one-way ANOVA test was carried out to compare the differences between the experimental groups at each time interval which showed significant differences between the drug groups up to 6-hours postoperatively. The Tukey HSD test analyzed the multiple comparisons between each time point.
For “pain on chewing,” results revealed significant differences between ketorolac, ibuprofen against placebo groups until 6-hours postoperatively. Pain levels differed in the groups administered acetaminophen and ibuprofen at 2 hours only. A comparison between the ibuprofen and ketorolac groups showed the difference in pain levels only at 6 hours. Significant differences were also observed between acetaminophen and ketorolac group at 2 and 6 hours intervals. No differences were noted between placebo and acetaminophen drug groups at any time interval postoperatively [Graph 1].
For “pain to biting,” results of all four drug groups were similar to pain on chewing, except that a significant difference between the pain levels was observed at both 2 and 6 hours intervals between acetaminophen and ibuprofen [Graph 2].
For “pain during anterior occlusion” [Graph 3], patients who were administered ketorolac and ibuprofen experienced significantly less pain than those who took placebo. With pain on anterior occlusion statistically significant difference between placebo and acetaminophen was noted at 6 hours time interval. Significant differences between acetaminophen and ketorolac were eminent at 2 and 6 hours time intervals. There was no statistical difference between pain levels for ibuprofen and acetaminophen drug groups during anterior occlusion.
“During posterior occlusion” [Graph 4], the pain levels were different for ketorolac, ibuprofen, and acetaminophen at 2 and 6 hours postoperatively. At these two time intervals, patients who took ketorolac, ibuprofen, and acetaminophen felt less pain than those who took placebo. Pain levels were highest in the group that was administered placebo as compared to other drug groups for 7 days' postoperatively.
| Discussion|| |
The ultimate aim of this study was to compare the efficacy of acetaminophen (analgesic-antipyretic with poor anti-inflammatory action), ibuprofen (propionic acid derivative), and ketorolac (pyrrolo-pyrrole derivatives) which belong to different classes of drugs; which are commonly prescribed drugs, and whose efficacy among each other has not yet been studied in the orthodontic literature.
Standardization regarding the conditions of experiment, or while selecting the sample was and were carried out to maximum, the bracket slot size and initial archwire used were same for all patients (3M Gemini MBT 0.022” slot and G and H 0.016 NiTi archwires).
As per the study conducted by Jones and Chan,, there is no relationship between pain experienced and initial crowding, and hence, the degree of initial crowding was not recorded in the present study.
It is well established that use of 100-mm, the VAS method to measure pain subjectively is reliable and suitable, having the test–retest reliability coefficient of (r = 0.71–0.94).
Peak levels of pain in all groups after initial archwire placement were observed at 24 hours, which is in agreement with results of other studies, while several studies differ in this opinion.
Severity and delayed onset of pain can be achieved with NSAIDs taken before oral surgical procedures has been found by Jackson et al. and Dionne and Cooper. NSAIDs have known to cause inhibition of prostaglandin synthesis in peripheral tissues and as a result, cause a probable anti-inflammatory effect preoperatively. However, if given preoperatively, the tissues absorb the drug before prostaglandin synthesis can occur, thus leading to a reduced anti-inflammatory response.
Similarly, NSAIDs have known to reduce periodontal bone loss. However, in these studies, the dosage of the anti-inflammatory drugs used was much higher than therapeutic doses. In contrast, lower doses are used for a short duration after orthodontic activation in clinical orthodontics. These lower doses are eliminated from the body before the commencement of orthodontic tooth movement in a healthy individual with no systemic compromise.
According to the results of the present study, the preoperative use of (NSAIDs) ketorolac, ibuprofen, and acetaminophen, when compared with the placebo group, decreased the perceived pain levels at 2 and 6 hours after archwire placement, but the results were much significant for the ketorolac group. This finding could be attributable to the absorption and high bioavailability of the drug as compared to others tested in this study, which results in the blockage of prostaglandins synthesis resulting in a reduction of the inflammatory response.
The disagreement of the present study with the findings of the aforementioned studies with respect to the analgesic effect of ibuprofen and acetaminophen is probably a consequence of the multifactorial nature of pain.
Peak levels of pain occurred at 24 hours after archwire adjustment, and the levels of pain thereafter started to decrease at 24 hours after archwire placement. The drugs did not have any effect on pain relief at 12 hours after archwire adjustment. It is thus beneficial to administer one postoperative dose in addition to a single preoperative dose for effective pain control.
However, one cannot make a final conclusion, before testing the efficacy of other longer acting and safer analgesics administered preemptive and postoperatively.
Increasing the number of doses or increasing the dosage of these medications will lead to an increased amount of drug in the patient's bloodstream that leads to a reduction in the peak pain that is perceived the day after initial archwire placement. Similarly, increasing the strength of these drugs to a longer acting NSAID would reduce the severity of pain perceived. Comparing the effectiveness of acetaminophen to a nonselective COX inhibitor, a preferential COX-2 inhibitor, and a selective COX-2 inhibitor is also an area that has not been explored so far. Thus, there is certainly a great scope for further research on the effectiveness of different drugs for orthodontic pain control.
| Conclusion|| |
- When compared with placebo (lactose capsule), ketorolac (10 mg), and ibuprofen (400 mg) administered 1 hour before archwire placement significantly reduced the severity of pain at 2 and 6 hours intervals at all the four parameters
- Pain levels were low with acetaminophen (500 mg) as compared to placebo (lactose capsule) and were only significant with occluding on anterior occlusion at 6 hours time interval and occluding on posterior occlusion at 2–6 hours intervals
- Peak levels of pain were observed at 24 hours interval after archwire placement, implying inefficacy of a single dose preoperative analgesic to relieve the pain; the use of an additional postoperative analgesic or a longer acting analgesic can be tested and administered.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]