An Injectable Containing Morphine, Ropivacaine, Epinephrine, and Ketorolac Is Not Cytotoxic to Articular Cartilage Explants From Degenerative Knees

Published:December 21, 2021DOI:


      The purpose of this study was to determine the effects of a multidrug injectate containing morphine, ropivacaine, epinephrine, and ketorolac, commonly referred to as the “Orthococktail,” on cartilage tissue viability and metabolic responses using an established in vitro model.


      With institutional review board approval and informed patient consent, tissues normally discarded after total knee arthroplasty (TKA) were recovered. Full-thickness cartilage explants (n = 72, Outerbridge grade 1 to 3) were created and bisected. Paired explant halves were treated with either 1 mL Orthococktail or 1 mL of saline and cultured for 8 hours at 37°C, with 0.5 mL of the treatment being removed and replaced with tissue culture media every hour. Explants were cultured for 6 days, and media were changed and collected on days 3 and 6. After day 6, tissues were processed for cell viability, weighed, and processed for histologic grading. Outcome measures were compared for significant differences between treated and untreated samples.


      There were no significant differences in cartilage viability between control and Orthococktail-treated samples across a spectrum of cartilage pathologies. Orthococktail treatment consistently resulted in a significant decrease in the release of PGE2, MCP-1, MMP-7, and MMP-8 on day 3 of culture and PGE2, MMP-3, MMP-7, and MMP-8 on day 6 of culture, compared with saline controls.


      The results of the present study indicate that an Orthococktail injection composed of morphine, ropivacaine, epinephrine, and ketorolac is associated with a transient decrease in degradative and inflammatory mediators produced by more severely affected articular cartilage and may mitigate perioperative joint pain such that postoperative narcotic drug use could be reduced.

      Clinical Relevance

      The Orthococktail solution used in this study may be a safe intraoperative, intra-articular injection option for patients undergoing joint arthroplasty and other joint preservation surgical procedures.
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