Which is better for pain management, ketorolac (Non-Steroidal Anti-Inflammatory Drug (NSAID)) or diclofenac (NSAID)?

Ketorolac and Diclofenac: Comparative Effectiveness for Pain Management

Primary Recommendation

For acute pain management, ketorolac and diclofenac demonstrate equivalent analgesic efficacy and safety profiles, but ketorolac may offer superior pain relief with less gastrointestinal irritation in certain contexts, while diclofenac carries higher cardiovascular risk and should be avoided in patients with cardiovascular disease or risk factors. 1, 2, 3

Evidence-Based Comparison

Analgesic Efficacy

• Postoperative pain: Both agents provide equivalent pain relief after major surgery, with no significant differences in efficacy 1
• Acute low back pain: Ketorolac (10 mg every 8 hours) resulted in 80% of patients achieving mild or no pain by day 5, compared to 62% with ibuprofen and 71% with diclofenac, though functional disability improvements were similar across all three NSAIDs 3
• Cancer pain: Both ketorolac 10 mg three times daily and diclofenac 50 mg three times daily showed comparable analgesic efficacy in advanced cancer patients, with ketorolac allowing patients to delay escalation to stronger opioids longer than diclofenac 4, 5
• Injectable formulations: Low-dose IV diclofenac (18.75-37.5 mg) and IV ketorolac (30 mg) both provided significant pain reduction compared to placebo after abdominal/pelvic surgery, with no clinically meaningful differences between them 2

Safety Profile Comparison

Gastrointestinal Effects

• Ketorolac causes significantly less stomach irritation than other NSAIDs: only 5% of ketorolac patients reported stomach irritation versus 26% with ibuprofen in acute low back pain treatment 3
• Both agents carry risks of gastrointestinal bleeding, ulceration, and perforation, but no significant differences were found in serious GI bleeding rates (0.04% overall) after major surgery 1
• Gastric disturbances with ketorolac occurred primarily when given after prior diclofenac treatment, suggesting a sequence effect 4

Cardiovascular Risk

• Diclofenac carries substantially higher cardiovascular risk with a relative risk of 1.63 for vascular events versus placebo, making it one of the highest-risk traditional NSAIDs 6, 7
• Diclofenac should be avoided entirely in patients with prior cardiovascular events or multiple cardiovascular risk factors 6, 7
• The FDA mandates black box warnings for diclofenac regarding cardiovascular thrombotic events, myocardial infarction, and stroke 7

Renal and Bleeding Risk

• No differences in acute renal failure rates (0.09% overall) or surgical site bleeding (1.04% overall) between ketorolac and diclofenac after major surgery 1
• Postoperative anticoagulants increased surgical site bleeding risk equally with ketorolac (odds ratio 2.65) and comparator NSAIDs including diclofenac (odds ratio 3.58) 1

Mortality

• Death rates were equivalent and extremely low (0.17%) with both agents in postoperative settings 1

Duration of Treatment Limitations

• Ketorolac must be limited to maximum 5 days due to cumulative risks of gastrointestinal toxicity, renal injury, and bleeding 8
• Recommended parenteral ketorolac dosing is 15-30 mg IV per dose, with 5-day maximum duration 8
• Diclofenac can be used for longer durations but cardiovascular risk increases with duration of use, particularly in the first 6 months and with higher dosages 6

Additional Tolerability Considerations

• Diclofenac caused sleepiness four times more frequently than ketorolac in cancer pain patients (p < 0.05) 5
• Both agents showed acceptable adverse event profiles overall, with treatment-related adverse events occurring in approximately 20% of patients 2

Clinical Decision Algorithm

Choose Ketorolac When:

• Short-term pain control (≤5 days) is needed for acute pain 8
• Patient has cardiovascular disease or risk factors (diclofenac contraindicated) 6, 7
• Gastrointestinal tolerability is a concern 3
• Postoperative pain management is required 1, 2

Choose Diclofenac When:

• Longer duration of treatment (>5 days) is anticipated 8
• Patient has no cardiovascular risk factors 6, 7
• Topical formulation is preferred for localized pain (superior safety profile with lower systemic absorption) 6

Avoid Both When:

• Patient is critically ill (NSAIDs not recommended as opioid adjuvants due to serious bleeding and renal injury concerns) 8
• Patient has chronic kidney disease stage III or higher 6
• Patient is taking anticoagulants or corticosteroids (significantly increased bleeding risk) 6

Critical Safety Principles

• Always use the lowest effective dose for the shortest duration possible to minimize adverse effects 6, 7
• Never combine multiple NSAIDs concurrently, as this increases risk without additional therapeutic benefit 6
• Add proton pump inhibitor co-therapy for elderly patients (≥75 years) or those with GI risk factors requiring NSAIDs 6, 7
• Monitor blood pressure, renal function, and watch for signs of gastrointestinal bleeding in all patients receiving either agent 6, 7

Common Pitfalls to Avoid

• Exceeding 5-day duration with ketorolac 8
• Prescribing diclofenac to patients with cardiovascular disease 6, 7
• Failing to consider topical diclofenac as a safer alternative for localized pain 6
• Using NSAIDs routinely as adjuvants to opioids in critically ill patients 8