Esketamine as an Adjuvant to Ropivacaine in Genicular Nerve and IPACK Blocks for Total Knee Arthroplasty: A Double-Blind Randomized Trial.

Summary

In a double-blind RCT of 367 TKA patients, perineural esketamine (0.2 mg/kg) added to 0.5% ropivacaine for genicular and IPACK blocks reduced 6-month CPSP to 4.9% versus 17.9% (ropivacaine) and 27.0% (control). Pain burden and early functional recovery improved without increased adverse events.

Key Findings

• Esketamine adjuvant reduced 6-month CPSP to 4.9% versus 17.9% (ropivacaine) and 27.0% (control).
• Overall pain burden (AUC) and early functional metrics (eg, TUG, walking distance, QoR-15) improved in the esketamine group.
• No increase in adverse events was reported with perineural esketamine.

Clinical Implications

Consider perineural esketamine (0.2 mg/kg) as an adjuvant to ropivacaine for genicular and IPACK blocks to mitigate CPSP risk and improve early recovery after TKA, with ongoing vigilance for neurotoxicity or local reactions.

Limitations

• Single-trial setting with journal not field-top; external validation needed
• Details on long-term safety of perineural esketamine remain limited

Future Directions

Replicate in multicenter settings, define optimal dose ranges and formulations, and assess durability beyond 6–12 months and in other orthopedic procedures.