Can a patient with a history of bleeding disorders, renal impairment, or gastrointestinal issues use Zynrelef (bupivacaine and meloxicam) and local anesthetic for postoperative pain management after total joint replacement?

Can Patients Use Zynrelef and Local Anesthetic for Total Joint Replacement?

Yes, Zynrelef (bupivacaine/meloxicam extended-release) can be safely used in combination with a single nerve block for total joint replacement, and this combination is both safe and effective for postoperative pain management, even in patients with comorbidities.

Primary Recommendation for Total Joint Replacement

The optimal analgesic regimen for total joint replacement should include:

• Paracetamol and NSAIDs/COX-2 inhibitors administered pre-operatively or intra-operatively and continued postoperatively 1
• Single-shot regional anesthesia (fascia iliaca block for hip, femoral nerve block for knee) or local infiltration analgesia 1
• Intravenous dexamethasone 8-10 mg intra-operatively for analgesic and anti-emetic effects 1
• Opioids reserved as rescue analgesics only 1

Zynrelef Specific Considerations

Zynrelef provides 72-hour sustained analgesia through its extended-release polymer technology that simultaneously releases bupivacaine and meloxicam at the surgical site 2, 3, 4. This formulation is FDA-approved for postoperative pain management and has demonstrated:

• Significant reduction in postoperative pain and opioid consumption compared to bupivacaine HCl and placebo in total knee arthroplasty 3, 4
• Enhanced pain control when used as the foundation of a scheduled non-opioid multimodal analgesia regimen 3
• Generally well-tolerated profile with lower incidence of opioid-related adverse events 3

Safety of Combining Zynrelef with Nerve Blocks

The combination of Zynrelef with a single unilateral or bilateral nerve block is safe and effective 5. A quality improvement study of 184 patients demonstrated:

• No symptoms of local anesthetic systemic toxicity (LAST) when combining single nerve blocks (using 20 mL of 0.375% bupivacaine or 0.5% ropivacaine) with Zynrelef 5
• 50% reduction in patients filling opioid prescriptions at discharge when using the combination 5
• Safe use in adductor canal blocks for total knee replacement 5

Critical Contraindications and Precautions

Bleeding Disorders

Meloxicam (the NSAID component of Zynrelef) is not recommended in patients with bleeding disorders as safety has not been established in these patients 6. This is a critical consideration given that:

• NSAIDs possess potential to induce gastrointestinal ulcerations and/or perforation 6
• One study showed increased intraoperative hemorrhage in NSAID treatment groups 6

Renal Impairment

Patients with renal dysfunction are at greatest risk for adverse events from NSAIDs 6. Key considerations include:

• NSAIDs may inhibit prostaglandins that maintain normal homeostatic renal function 6
• Patients who are dehydrated or on concomitant diuretic therapy require careful monitoring 6
• Perioperative parenteral fluids are recommended to decrease potential renal complications 6
• Concurrent administration of potentially nephrotoxic drugs should be carefully approached 6

Gastrointestinal Issues

Concomitant use of meloxicam with other anti-inflammatory drugs should be avoided 6. Specific precautions:

• Do not combine with other NSAIDs or corticosteroids due to increased risk of GI ulceration and perforation 6
• Consider appropriate washout times when switching from corticosteroid use 6
• Patients with pre-existing GI disease require careful risk-benefit assessment 6

Clinical Algorithm for Decision-Making

For patients WITHOUT contraindications:

1. Apply Zynrelef at surgical closure for 72-hour analgesia 2, 3
2. Consider adding a single nerve block (fascia iliaca for hip, adductor canal for knee) performed pre-operatively 5
3. Administer paracetamol and COX-2 inhibitors as baseline analgesia 1
4. Give intravenous dexamethasone 8-10 mg intra-operatively 1
5. Reserve opioids for breakthrough pain only 1

For patients WITH bleeding disorders:

• Avoid Zynrelef entirely due to meloxicam component 6
• Use alternative local infiltration with bupivacaine alone 1
• Rely on nerve blocks and paracetamol-based multimodal analgesia 1

For patients WITH significant renal impairment:

• Avoid or use extreme caution with Zynrelef 6
• Ensure adequate perioperative hydration with parenteral fluids 6
• Consider alternative regional techniques without systemic NSAID exposure 1
• Monitor renal function closely if proceeding 6

For patients WITH active GI disease or ulcers:

• Avoid Zynrelef due to NSAID-related GI perforation risk 6
• Use local anesthetic infiltration without meloxicam component 1
• Employ nerve blocks as primary regional technique 1

Common Pitfalls to Avoid

• Do not exceed safe local anesthetic doses when combining nerve blocks with Zynrelef—the study used single blocks with 20 mL of 0.375% bupivacaine, which is within safe limits 5
• Do not use multiple nerve blocks (e.g., femoral + sciatic) as this increases local anesthetic burden and complications without clear benefit over single blocks plus systemic analgesia 1
• Do not follow Zynrelef with additional NSAIDs or corticosteroids due to compounded GI and bleeding risks 6
• Do not use in patients on anticoagulation without careful assessment of bleeding risk 6
• Ensure proper patient selection—elderly patients with multiple comorbidities (hypertension, ischemic heart disease, renal dysfunction) require individualized risk assessment 1