Introduction

Pain is one of the most frequent and significant post-operative complications associated with third molar surgery. Several analgesics including non-steroidal antiinflammatory drugs (NSAIDs) and opioids have been used to manage the post-operative pain. Ketorolac, an NSAID has been used in pain management following third molar surgeries, but the evidence suggests that preoperative administration may not be sufficient to manage post-operative pain. A combination of analgesics may provide greater analgesia in such cases, thus; ketorolac in combination with opioid analgesic such as tramadol/acetaminophen may be an effective strategy. Till date, no trial has compared the efficacy of ketorolac alone vs. ketorolac in combination with tramadol/acetaminophen to control pain intensity after third molar surgery.

Aim

To compare the efficacy of ketorolac alone vs. its combination with tramadol/acet­aminophen for pain control after mandibular third molar surgery

Patient Profile

• Patients with indication of treatment for bilateral third-molar removal, with an extraction de­gree of difficulty from mild to moderate and at least 1/3 of the root formed as per the radiologic evaluation (n=52).

Methods

Study Design

• A randomized, triple-blind cross-over trial

Treatment Strategy

• Patients were divided into 2 groups:
  • Group K+T+A (1 tablet of Ketorolac 10 mg plus and 1 capsule of Tramadol 37.5 mg/acetaminophen 325 mg)
  • Group K (1 tablet of Ketorolac 10 mg plus and 1 placebo capsule)
• The treatment was initiated 1 hour before the surgery and was repeated 4 times per day, for 48 h.
• Antibiotic prophylaxis with oral pre-admin­istration of amoxicillin 1 g or clindamycin 600 mg (in patients allergic to amoxicillin), was initiated 1 h prior to surgery.

Outcomes

• Difference in post-operative pain in study groups assessed as:
  • Pain intensity (VAS 100 mm, for 48 h)
  • Use of rescue medications
  • Overall assessment      
  • Adverse effects

Results

• Mean age of the study population was 20.8 years and majority of them were women (77%). Pain intensity differed significantly at different times in the study population (p < 0.05).
• The pain intensity increased post-surgery and peaked at 3 hours in both the study groups. The pain intensity started to reduce in following hours though few patients experienced pain 48 hours post-surgery.
• The pain intensity differed significantly between the groups only at the time interval of 9 hours, with lower level of pain intensity for group K+T+A vs. group K (p = 0.005).

• The mean difference of pain intensity in the different assessment periods varied from approximately 4 to 7 units on a 0 to 100 VAS scale.
• Patients in group K had a significantly higher requirement for analgesics (19% vs. 9.6%; p < 0.001). On the contrary, patients in group K+T+A had a significantly higher requirement for antiemetic (0% vs. 30.8%; p < 0.0001).
• Overall assessment did not differ significantly between the study groups.
• The incidence of adverse effects, particularly; dizziness, nausea and vomiting was higher in Group K+T+A (Table 2).

* Loss of appetite (n = 1), Drowsiness (n = 7)*

**Drowsiness (n = 2)

Conclusions

• Both ketorolac and the combination of ketorolac plus tramadol/acet­aminophen showed good control of pain following the third molar surgery.
• Although the combination group showed lower pain at 9 hours, the difference was small and not clinically relevant.
• The combination was more expensive and caused more adverse events.

Med Oral Patol Oral Cir Bucal. 2019;24(1):e96-e102.