Can both knees with osteoarthritis be injected on the same day using methylprednisolone acetate (Depo‑Medrol) and lidocaine?

Bilateral Knee Injections with Depo-Medrol and Lidocaine on the Same Day

Yes, both knees can be injected on the same day with methylprednisolone acetate (Depo-Medrol) plus lidocaine for osteoarthritis, but this practice carries a significant risk of adrenal suppression and requires careful patient selection and monitoring.

Evidence Supporting Same-Day Bilateral Injection

Guideline Support for Intraarticular Corticosteroids

• The American College of Rheumatology strongly recommends intraarticular glucocorticoid injections for knee osteoarthritis, particularly during acute pain exacerbations with effusion 1.
• The 2012 ACR guidelines conditionally recommend intraarticular corticosteroid injections as an initial pharmacologic option for knee OA 1.
• EULAR recommendations support intraarticular glucocorticoid therapy for knee osteoarthritis with appropriate patient information and shared decision-making 1.

Pharmacokinetic Evidence

• A 1981 study demonstrated that injecting 80 mg methylprednisolone as 40 mg into each knee produced consistently higher peak serum levels than a single 80 mg injection into one knee 2.
• Peak serum methylprednisolone levels occur between 2-12 hours following injection, with dose-dependent increases in systemic absorption 2.

Critical Safety Concerns with Bilateral Injection

Adrenal Suppression Risk

• 60% of patients developed secondary adrenal insufficiency (SAI) after simultaneous bilateral injection of 80 mg methylprednisolone acetate per knee (160 mg total dose) 3.
• SAI was most common at week 1 post-injection, but 10% of patients still had evidence of SAI at 8 weeks 3.
• Serum cortisol levels were substantially suppressed for up to 1 week at all dose levels studied 2.

Annual Frequency Limits

• EULAR guidelines recommend no more than 3-4 injections per joint per year, with a minimum 6-week interval between injections 4.
• This frequency limit applies to each individual joint, meaning bilateral injections count toward the annual limit for both knees simultaneously 4.

Practical Algorithm for Same-Day Bilateral Injection

Patient Selection Criteria

• Avoid in diabetic patients without glucose monitoring capability, as blood glucose levels rise significantly during days 1-3 post-injection 4.
• Avoid in patients with prosthetic joints unless performed after orthopedic consultation and infection screening (infection risk 0.6% or 1 per 625 injections) 4.
• Avoid within 3 months of planned knee replacement surgery due to increased prosthetic infection risk 4.

Dosing Considerations

• Consider 40 mg per knee (80 mg total) rather than 80 mg per knee to minimize adrenal suppression risk 2, 3.
• The combination of methylprednisolone acetate with 1% lidocaine shows significant chondrotoxicity in vitro; consider using 0.25% bupivacaine instead or lower lidocaine concentrations 5.

Monitoring Requirements

• Diabetic patients: Monitor glucose levels for 1-3 days post-injection 4.
• All patients receiving bilateral injection: Consider monitoring for symptoms of adrenal insufficiency (fatigue, weakness, hypotension) during the first 1-2 weeks 3.
• Document informed consent regarding adrenal suppression risk, particularly with bilateral high-dose injections 1.

Common Pitfalls to Avoid

• Do not use 80 mg per knee bilaterally (160 mg total) as this produces unacceptably high rates of adrenal suppression 3.
• Do not combine 1% lidocaine with methylprednisolone acetate due to demonstrated chondrotoxicity; use lower concentrations or alternative local anesthetics 5.
• Do not inject without informing patients about the 24-hour activity modification recommendation (avoid overuse but do not immobilize) 1.
• Do not exceed the 3-4 injections per joint per year limit even when bilateral injections are performed, as this counts toward both knees' annual limits 4.

Alternative Approach

If bilateral injection is deemed necessary, consider staggered injections (one knee followed by the contralateral knee 2-6 weeks later) to reduce systemic corticosteroid burden and adrenal suppression risk while still addressing bilateral symptoms 4, 3.