Authors: Babul A et al.
Cureus. 17(11): e98017, November 28, 2025. DOI: 10.7759/cureus.98017
Summary:
This randomized, double-blind, placebo-controlled, dose-ranging trial examined the analgesic efficacy and safety of intravenous (IV) ketoprofen, tramadol, and morphine in acute postoperative dental pain. The study enrolled 185 patients experiencing moderate-to-severe pain following surgical extraction of bony impacted mandibular third molars—a standard model for evaluating acute analgesics.
Participants were randomized to IV ketoprofen 50 mg, ketoprofen 100 mg, tramadol 100 mg, tramadol 150 mg, morphine 4 mg, or placebo, administered over two minutes at the first onset of qualifying pain. Pain relief was assessed for eight hours, with the primary endpoint being total pain relief over four hours (TOTPAR 0–4). Secondary outcomes included summed pain intensity difference (SPID), peak pain relief, time to meaningful relief, need for rescue analgesia, and patient global evaluation.
IV ketoprofen—both 50 mg and 100 mg—demonstrated the strongest and most consistent analgesic effect across nearly all measures. Both ketoprofen doses significantly outperformed tramadol (100 mg and 150 mg), morphine 4 mg, and placebo. IV tramadol at both doses was more effective than morphine and placebo but consistently less effective than ketoprofen.
Strikingly, IV morphine 4 mg showed no significant benefit over placebo in any analgesic endpoint, raising concerns about assay sensitivity in postoperative dental pain studies and whether this low morphine dose is sufficient to demonstrate expected opioid analgesic effects in this model.
Safety profiles differed markedly. Adverse event rates were similar between placebo and both ketoprofen doses, indicating excellent tolerability. In contrast, both tramadol and morphine were associated with higher rates of adverse effects. Importantly, two subjects in the tramadol 150 mg arm (9%) experienced seizures shortly after administration—despite lacking known seizure risk factors—leading to premature discontinuation of this dosing arm. No severe adverse events were reported with ketoprofen.
Overall, IV ketoprofen provided the most effective and safest analgesia in this trial, outperforming tramadol and demonstrating clear superiority over low-dose morphine. The findings reinforce ketoprofen’s value as a non-opioid analgesic with rapid, reliable postoperative benefit. They also highlight safety concerns with higher-dose tramadol and the possibility that IV morphine 4 mg is ineffective for acute dental pain in this assay.
What You Should Know
• IV ketoprofen (50 mg and 100 mg) was consistently the most effective analgesic across all outcomes.
• Both tramadol doses also surpassed morphine and placebo but were inferior to ketoprofen.
• IV morphine 4 mg performed no better than placebo—suggesting poor assay sensitivity or underdosing for this model.
• Seizures occurred in 9% of patients receiving tramadol 150 mg, highlighting a real safety concern for higher doses.
• Ketoprofen had an adverse event rate comparable to placebo, showing excellent tolerability.
• The trial supports non-opioid analgesics as safe, effective first-line treatment in acute postoperative dental pain.
Key Points
• Ketoprofen delivered the best overall pain control with minimal side effects.
• Tramadol worked but was less effective and associated with greater adverse events—including seizures at higher dose.
• Morphine at 4 mg IV was ineffective for this pain model.
• Non-opioid IV analgesics may be preferable to opioids in postoperative dental surgery due to safety and efficacy advantages.
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