Effect of pretreatment with ketorolac tromethamine on operative pain during periodontal surgery: A case-control study

Abstract

Background:

The efficacy of a nonsteroidal anti-inflammatory agent, ketorolac tromethamine, was evaluated in pain control after periodontal surgery. This type of agent acts peripherally by inhibiting the release of prostaglandins and minimizing the local inflammatory response. Thus, there may be an advantage in pretreatment administration of ketorolac tromethamine, 10 mg, compared with placebo on operative pain during periodontal surgery.

Materials and Methods:

Two groups of 40 outpatients from the Department of Periodontology, Darshan Dental College and Hospital, Udaipur, were selected for this study. Patients who were to undergo periodontal surgery were randomly given either one group 10 mg ketorolac immediately before surgery or the other group placebo tablets at least 30 minutes before administration of local anesthesia (LA). All procedures were performed under LA, and the total volume of anesthetic used was recorded. The duration of surgery from the time of incision to the placement of the last suture was recorded. At the completion of the surgery, patients were supplied with printed record forms and were asked to rate their subjective operative pain intensity using a visual analog scale.

Statistical analysis:

The data were analyzed using the student t test.

Results:

Results indicated that preoperative treatment with ketorolac significantly reduced initial pain intensity of operative pain as compared with placebo. No adverse reactions related to preoperative medication were observed.

Conclusions:

The results of this study showed that 10-mg ketorolac administered immediately before periodontal surgery was effective for alleviating the operative painful sequelae.

INTRODUCTION

Pain after periodontal surgical procedures is a common occurrence. The perception of pain is highly subjective and therefore varies considerably among individuals. Many factors may influence pain intensity, such as the nature, duration, and extent of the surgery, and psychological aspects, such as stress and anxiety.[1] Postoperative pain has been reported to peak in the first 24 hours after periodontal surgery. The intensity of this pain is related to the surgical procedure itself.[2]

Operative pain during oral surgical procedures is matter of considerable consequence to most patients and clinical strategies aimed to reduce its incidence and severity are greatly appreciated. Factors contributing to the occurrence of operative dental pain are complex; many are related to the inflammatory process that is initiated by surgical trauma.[3] Injury to tissue during surgical procedure results in the release of chemical mediators of inflammation. Some of these mediators evoke pain (histamine, acetylcoline, and bradykinin), and others cause hyperalgesia, which is characterized by decreased pain threshold and increased sensitivity to supra threshold stimuli. The prostaglandins have been demonstrated to act, at least in part, by the latter mechanism[4] [Figure 1].

Figure 1.

Action of prostaglandins

Nonsteroidal anti-inflammatory analgesics drugs (NSAIDs) have become an accepted part of pain control in dental treatment. They inhibit the formation and release of prostaglandins. Although NSAIDs have been shown to be particularly effective in suppressing operative dental pain, their use does not prevent the initial pain and discomfort that occur when local anesthesia (LA) wears off.[5] It is proposed that when NSAIDs are given preoperatively, absorption and distribution of the medication may occur before the initiation of the tissue trauma, the ensuing synthesis of prostaglandins, and the subsequent inflammatory response. Prevention of the inflammatory response may in turn decrease the sequelae of tissue trauma, especially the associated pain experience.[6] Common findings include delays in the onset of pain after completion of the surgical procedure, decreased levels of pain intensity, delayed peak pain intensity, and, finally, decrease in the number and relative strength of postoperative analgesics needed.

Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug with an analgesic potency comparable with morphine, but without the opiate receptor-associated side effects.[7] The beneficial effects of ketorolac are probably due to its ability to block prostaglandin synthesis by preventing the conversion of arachidonic acid to the endoperoxides. Animal studies demonstrated that the analgesic activity of ketorolac results principally from a peripheral action.[8] Previous studies have shown that the oral formulation in 10 and 20 mg postoperative doses in an oral surgery model provided the same analgesia as 400 mg ibuprofen, and significantly better analgesia than acetaminophen and acetaminophen codeine combinations.[9]

The purpose of the present study was to evaluate the analgesic effect of preoperative administration of ketorolac tromethamine 10 mg, compared with placebo on operative pain during periodontal surgery.

MATERIALS AND METHODS

This was a randomized, single-dose, double-blind placebo-controlled clinical trial of parallel design. The study included 40 patients from the department of Periodontology at Darshan Dental College and Hospital, Udaipur, who were scheduled for full mouth flap surgery. In each patient, two quadrants were considered, one quadrant was given ketorolac before the surgery and the other quadrant was given placebo before the surgery. All patients gave verbal informed consent to participate in the study before anesthesia and surgery.

Patients excluded were those under 18 years of age, pregnant patients, nursing mothers, those who were hypersensitive or allergic to NSAIDs, those receiving treatment with systemic corticosteroids or anticoagulants, and those patients suffering from active peptic ulceration, gastrointestinal hemorrhage, liver or kidney disease, hemopoietic disorders, or any other significant medical problem.

Patients were randomized under double blind conditions to receive either one 10 mg tablet of ketorolac tromethamine, 30 minutes before administration of LA, or one matching placebo tablet. The packaging and appearance of the two medication regimes were identical, so that the administering clinician was unaware of this selection [Figure 2]. All procedures were performed under LA, and the total volume of anesthetic used was recorded. Surgical procedure comprised of mucoperiosteal flap elevation, and root debridement was to be achieved. The duration of surgery from the time of incision to the placement of the last suture was recorded. At the completion of the surgery, the patients were supplied with printed record forms and were asked to rate their subjective postoperative pain intensity using a visual analog scale (VAS). Table 1 (placebo group) and Table 2 (ketorol group) show the amount of LA given (ml), number of times LA was given, time taken (min), and VAS score taken during surgery.

Figure 2.

Packaging of 2 medications (placebo and ketorol)

Table 1.

Placebo group

Table 2.

Ketorol group

Visual analogue scales commonly consist of a vertical or horizontal line, 10 cm in length, with words that convey “no pain” at one end and “worst pain” at the opposite end. It modified with using numerical rating scales and Wong-Baker Faces Pain Rating Scale. The patient was asked to place a mark on the line that corresponds to the intensity of the pain he or she is experiencing [Figure 3].

Figure 3.

Wong-baker faces pain rating scale

RESULTS

Surgical factors that could have influenced the subjects’ analgesic responses to study medication included duration of surgery, amount of LA administered, and number of times LA was given. In Table 3, group comparison and significance are taken. The data were analyzed using the student t test in this study. So, in placebo group, it was noticed that amount of LA given was more and also was the frequency. The effect of LA was prolonged in the ketorol group. Intensity of pain felt by the patient was less in ketorol group as compared with the placebo group. VAS scores as recorded immediately after the completion of surgery were similar in both groups; mean pain scores for ketorolac group were lower than those for placebo group during the overall observation period.

Table 3.

Comparison between placebo and ketorol group

However, differences were statistically significant. Comparison of sum of pain intensity showed significantly greater pain levels in the placebo than in the ketorolac group. Results indicated that preoperative treatment with ketorolac significantly reduced initial pain intensity of operative pain as compared with placebo. Neither the ketorolac nor the placebo-treated patients reported any adverse reactions related to preoperative medication.

DISCUSSION

The present study demonstrated that ketorolac treatment immediately before periodontal surgery significantly reduced operative pain as compared with placebo. Patients receiving the preoperative dose of ketorolac had a significant increase in the amount of time between the presurgical drug administration and the need for postoperative analgesics. The rational for prophylactic NSAIDs administration is that the presence of the drug in the tissues at the time of surgery results in blocking of both synthesis and direct effects of prostaglandins, and thereby limits operative pain and other components of surgically induced inflammation. Studies on clinical efficacy of NSAID premedication, however, seem to suggest that surgical pain control is strictly related to many factors, such as patient selection, nature of medication, and drug regimen.[6] Furthermore, although NSAIDs may produce adequate analgesia and anti-inflammatory effects, the unwanted side effects may limit their practicality.

Oral ketorolac is completely absorbed, with a mean peak plasma concentration occurring at an average of 44 minutes after a single 10-mg dose.[10] Ketorolac is strongly (99%) protein bound, with the degree of binding apparently independent of the plasma concentration of the drug.[7] Plasma half-life is 4 to 6 hours in the normal adult, and analgesia may be maintained for 6 to 8 hours.[11] Although preoperative ketorolac treatment significantly reduced pain intensity on the day of surgery, delayed pain levels were not affected by presurgical treatment.[12] It is possible to admit that this pain model may have masked the delayed analgesic efficacy of preoperatively administered ketorolac.

Alternative explanation may involve the mechanism implicated in the development of inflammation and pain. The biochemical interactions of short-lived inflammatory mediators released after injury results in a positive feedback loop continually refueling the inflammatory process. This explains the prolonged time of inflammation and related pain response, which far exceed the initial stimulation of the surgical procedure, and potentially surpass the analgesic activity of NSAID premedication.[5] Gastrointestinal intolerance and adverse CNS manifestations are among the most common side effects seen in NSAID therapy. A major concern when taking any NSAID is the subsequent effect on platelet aggregation.[10] In the present study, low dosage and single-dose administration has observed no adverse side effects.

CONCLUSION

The results of this single-dose, parallel-group, and double-blind placebo-controlled study showed that 10-mg ketorolac administered immediately before periodontal surgery was effective for better response by the patient during the procedure. However, ketorolac premedication neither affect delayed pain levels, nor postoperative analgesic consumption. No disadvantages related to this method of administration were noted.