• Thomas Stueber, Jan Karsten, Carsten Stoetzer, and Andreas Leffler.
• From the Department of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany *Both Thomas Stueber and Jan Karsten contributed equally to this work.
• Eur J Anaesthesiol. 2014 Nov 1;31(11):640-5.

BackgroundIntra-articular injection of local anaesthetics, opioids and corticosteroids is frequently used to obtain perioperative analgesia following joint surgery. Although local anaesthetics were shown to induce chondrotoxicity, the safety profile regarding chondrotoxicity of other injected drugs is less clear.ObjectiveOur objective was to investigate cytotoxicity of drugs used for intra-articular analgesia.DesignAn experimental in-vitro study.SettingHannover Medical School, science laboratory, 2013.MaterialHuman cartilage cell line T/C 28-a2.InterventionIncubation of cells with different concentrations of bupivacaine, s-ketamine, morphine and dexamethasone for 1 h.Main Outcome MeasuresFraction of Annexin V positive and Annexin V and propidium iodide double positive cells after 1 h of incubation with tested drug measured by flow cytometry.ResultsBoth morphine (0.1 to 10 μmol l) and dexamethasone (10 to 1000 μmol/l) failed to induce cytotoxicity after 1 h of exposure. The previously reported chondrotoxicity of bupivacaine (10 to 500 μmol l or 2.8 to 140 μg ml) was confirmed by a concentration-dependent increased staining with Annexin V and propidium iodide. Exposure to S-ketamine (10 to 500 μmol l) induced a significant late apoptotic and necrotic cell fraction at 10 μmol l or 2.4 μg ml. Concentrations of 100 and 500 μmol l induced a significant increase in early apoptotic cells.ConclusionMorphine and dexamethasone showed no cytotoxic effects in our study and might thus be better alternatives to the clinically frequently applied bupivacaine. S-ketamine induced an intensive dose-dependent cytotoxic effect and should probably be avoided for intra-articular injection.

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