title: Differential cytotoxic properties of drugs used for intra-articular injection on human chondrocytes: an experimental in-vitro study.
abstract: BACKGROUND
  Intra-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.
  
  
  OBJECTIVE
  Our objective was to investigate cytotoxicity of drugs used for intra-articular analgesia.
  
  
  METHODS
  An experimental in-vitro study.
  
  
  METHODS
  Hannover Medical School, science laboratory, 2013.
  
  
  METHODS
  Human cartilage cell line T/C 28-a2.
  
  
  METHODS
  Incubation of cells with different concentrations of bupivacaine, s-ketamine, morphine and dexamethasone for 1 h.
  
  
  METHODS
  Fraction 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.
  
  
  RESULTS
  Both 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.
  
  
  CONCLUSIONS
  Morphine 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.
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stueber
authors.forename: Jan
authors.initials: J
authors.lastname: Karsten
authors.forename: Carsten
authors.initials: C
authors.lastname: Stoetzer
authors.forename: Andreas
authors.initials: A
authors.lastname: Leffler
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019902:Chondrocytes / Q000187:drug effects* / Q000473:pathology; D003907:Dexamethasone / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007270:Injections, Intra-Articular; D007649:Ketamine / Q000008:administration & dosage / Q000633:toxicity*; D009020:Morphine / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000779:Anesthetics, Local; D007649:Ketamine; D009020:Morphine; D003907:Dexamethasone; D002045:Bupivacaine