Summary

An “orthococktail” containing morphine, ropivicaine, epinephrine and ketorolac proved effective in reducing inflammatory and degradative mediator production by osteoarthritic cartilage.

Abstract

Purpose

Multimodal perioperative analgesia is a hotbed topic. Immediate post-surgical intra-articular injections may be helpful to reduce narcotic requirements. However, the safety and efficacy of combination injections have not been thoroughly investigated. Our purpose was to investigate the in vitro chondrotoxicity and anti-inflammatory properties of a commonly used “orthococktail” containing morphine, ropivicaine, epinephrine, and ketorolac. Our hypothesis was that this injection would demonstrate minimal chondrotoxicity and favorable anti-inflammatory effects compared to saline control.

Methods

With IRB approval, tissue normally discarded after total knee arthroplasty was collected from five patients (mean age 68.6). Cartilage explants were created using a 6 mm dermal biopsy punch (n=12/patient) and each explant was split in half. The explant halves were cultured separately in 2mls of DMEM using 24-well culture plates. The orthococktail (containing morphine (2.5 mg), ropivacaine 0.5% (200 mg (40mL)), epinephrine (0.3 mg) and ketorolac (15 mg)) was created according to standard of practice by a pharmacist. One cartilage explant half was treated with 1ml of the orthococktail and the corresponding half was treated with 1 ml of normal saline as a control. Explants were cultured for 6 days. Media were collected on day 3 for biomarker analyses and refreshed, and explants were collected on day 6 for cell viability. Results were analyzed statistically.

Results

Chondrocyte viability was assessed using a live-cell-stain calcein AM viability assay. There was no significant difference in viable cell density between orthococktail-treated OA cartilage and controls (p=0.42). Media collected on day 3 were assessed for relevant biomarkers. Concentrations of PGE2 (p<0.001), MCP-1 (p<0.01), and MMP-7 (p<0.041) were significantly lower in orthococktail-treated cartilage explants compared to controls.

Conclusion

In this in vitro study of osteoarthritic knee cartilage, the “orthococktail” containing morphine, ropivicaine, epinephrine and ketorolac demonstrated no chondrotoxicity when compared to saline control. Further, the “orthococktail” reduced inflammatory (PGE2 and MCP-1) and degradative (MMP-7) mediator production by osteoarthritic articular cartilage. While in vivo study is necessary, these results suggest that the “orthococktail” is likely safe and effective for use as an intra-articular injection to reduce post-operative knee pain and inflammation.