title: Single-dose local anesthetics exhibit a type-, dose-, and time-dependent chondrotoxic effect on chondrocytes and cartilage: a systematic review of the current literature.
abstract: OBJECTIVE
  Many studies have shown that local anesthetics may impede chondrocyte metabolism. However, the influence of a single-dose local anesthetics is controversial. The aim of this metaanalysis was to review the literature for studies investigating the cytotoxic effects of single-dose local anesthetics on chondrocytes and cartilage.
  
  
  METHODS
  A comprehensive literature search was performed using established search engines (Medline, Embase) to identify studies, investigating the influence of single-dose local anesthetics on cartilage. The systematic analysis included the influence on histology, cell viability, morphology, and matrix production depending upon dose, exposure time, and type of local anesthetics.
  
  
  RESULTS
  Twelve studies with four different local anesthetics were included in this metaanalysis. Bupivacaine and lidocaine were found to be more chondrotoxic than mepivacaine and ropivacaine. The amount of dead cells increased in a substance-, dose-, and time-dependent process. Osteoarthritic cartilage seems to be more vulnerable compared to intact cartilage. The toxic effects occur first in the superficial cartilage layers and include damage to membrane integrity, mitochondrial DNA, and nuclear changes. There is no study that could show a significant chondrotoxic effect with low concentrations of bupivacaine (0.0625%), ropivacaine (0.1 and 0.2%), and mepivacaine (0.5%).
  
  
  CONCLUSIONS
  The cytotoxicity of local anesthetics on chondrocytes is dependent on dose, time, and type of local anesthetics. Single-dose intra-articular administration of local anesthetics impede chondrocyte metabolism and should be performed only with low concentrations for selected diagnostic purposes and painful joints. The use of lidocaine should be avoided.
  
  
  METHODS
  II.
authors.affiliation: Center for Orthopaedic Surgery, Atrium Holzkirchen, Münchner Str. 56a, 83607, Holzkirchen, Germany. prof.kreuz@mvz-atrium.de.
authors.forename: Peter Cornelius
authors.identifier: http://orcid.org/0000-0003-2647-1647
authors.initials: PC
authors.lastname: Kreuz
authors.affiliation: SportClinic Zurich, Witelliker Str. 40, 8032, Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Steinwachs
authors.affiliation: Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Angele
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects*; D002356:Cartilage / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans
chemical_list: D000779:Anesthetics, Local
keywords: Cartilage; Chondrocytes; Chondrotoxicity; Cytotoxicity; Local anesthetics