What are the treatment options for severe knee pain?

Treatment Algorithm for Severe Knee Pain

For severe knee pain, initiate acetaminophen up to 4,000 mg/day as first-line therapy, combined with non-pharmacological interventions including exercise and weight loss if overweight; if inadequate response after full-dose trial, escalate to oral NSAIDs (ibuprofen 1,200-3,200 mg/day) or consider intra-articular corticosteroid injection, particularly if effusion is present. 1, 2

First-Line Treatment Approach

Pharmacological Management:

• Start with acetaminophen (paracetamol) at full dosage up to 4,000 mg/day, which remains the preferred initial oral analgesic due to its favorable safety profile despite somewhat lower efficacy compared to NSAIDs 1, 3
• Counsel patients to avoid other acetaminophen-containing products to prevent exceeding maximum daily dose 1
• A full-dose trial must be completed before deeming acetaminophen ineffective 1
• Evidence demonstrates acetaminophen and ibuprofen are comparably effective even when knee pain is severe, contrary to the assumption that more severe pain requires anti-inflammatory therapy 4

Mandatory Non-Pharmacological Interventions (concurrent with medications):

• Exercise programs, particularly quadriceps strengthening exercises, provide additional benefit beyond analgesics alone 3, 5
• Weight reduction if BMI is elevated 2, 1
• Patient education and self-management programs 3, 5
• Physical therapy 3

Second-Line Treatment (If Acetaminophen Fails)

Oral NSAIDs:

• Ibuprofen 1,200-3,200 mg daily (400-800 mg three to four times daily) is strongly recommended as second-line therapy 1, 6
• Start with 1,200 mg daily; patients may show better response up to 3,200 mg daily, though the physician must weigh increased clinical benefit against potential increased risk 6
• Administer with meals or milk if gastrointestinal complaints occur 6
• For patients ≥75 years old, topical NSAIDs are strongly preferred over oral NSAIDs due to superior safety profile 1
• For patients with GI risk factors requiring oral NSAIDs, use COX-2 selective inhibitor or nonselective NSAID with proton-pump inhibitor 1

Alternative Second-Line Options:

• Topical NSAIDs, particularly for elderly patients 1, 2
• Tramadol for patients who cannot use acetaminophen or NSAIDs 1

Acute Exacerbations with Effusion

Intra-articular corticosteroid injection is the treatment of choice for acute exacerbation of severe knee pain, especially when accompanied by effusion, providing significant pain relief within 1-2 weeks with benefits lasting 1-24 weeks. 7, 3, 2

• This intervention is more effective when effusion is present 7
• Can be used as alternative to oral medications or in combination 1, 7

Third-Line Options (Refractory Cases)

Before Surgical Referral:

• Hyaluronic acid injections may be considered, though effect size is relatively small and suitable patients are not well-defined 3, 7
• Genicular artery embolization (GAE) may be considered as a third-line option before proceeding to total knee replacement, though not mentioned in established guidelines 2
• Radiofrequency (conventional and cooled) ablation of genicular nerves has shown effectiveness 8

Surgical Consideration

Total knee replacement is the final option for refractory pain and disability with radiological deterioration after exhausting all appropriate conservative measures. 2, 7

Critical Safety Considerations

NSAID Precautions:

• Monitor for cardiovascular thrombotic events (chest pain, shortness of breath, weakness, slurring of speech) 6
• Watch for GI complications including ulceration and bleeding, which can occur without warning symptoms 6
• Monitor hemoglobin/hematocrit on long-term therapy; studies show decreased hemoglobin ≥1 gram in 17-22% of patients on ibuprofen 1,600-2,400 mg daily 6
• Check liver function tests; borderline elevations occur in up to 15% of patients, with notable ALT/AST elevations in approximately 1% 6
• Avoid in patients with aspirin-sensitive asthma due to risk of severe bronchospasm 6

Treatments NOT Recommended

• Glucosamine and chondroitin sulfate are conditionally not recommended due to lack of efficacy evidence 1
• Topical capsaicin is conditionally not recommended 1

Common Pitfall to Avoid

The most significant error is initiating NSAIDs as first-line therapy based on pain severity alone. Research demonstrates that even severe knee pain responds comparably to acetaminophen versus ibuprofen, and the assumption that greater pain intensity predicts better response to anti-inflammatory doses is not supported by evidence 4. Always trial full-dose acetaminophen first unless acute effusion is present, which specifically indicates corticosteroid injection 7.