title: The long term myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blocks.
abstract: Compared with bupivacaine, acute myotoxicity of ropivacaine is less severe. Thus, in this study we compared the long term myotoxic effects of both drugs in a clinically relevant setting. Femoral nerve catheters were inserted in anesthetized pigs, and either 20 mL of bupivacaine (5 mg/mL) or ropivacaine (7.5 mg/mL) was injected. Subsequently, bupivacaine (2.5 mg/mL) and ropivacaine (3.75 mg/mL) were continuously infused (8 mL/h) over 6 h. Control animals were treated with corresponding volumes of normal saline. After 7 and 28 days, respectively, muscle samples were dissected at the former injection sites, and histological patterns of muscle damage were blindly scored (0 = no damage to 3 = marked lesions/myonecrosis) and compared. No morphological tissue changes were detected in control animals. In the observed period, both local anesthetics induced morphologically identical patterns of calcific myonecrosis, formation of scar tissue, and a marked rate of fiber regeneration. However, bupivacaine's effects were constantly more pronounced than those of ropivacaine. These data show that both drugs induce irreversible skeletal muscle damage in a clinically relevant model, and confirm the exceeding rate of myotoxicity of bupivacaine. However, the clinical impact of these long term myotoxic effects still has to be assessed.
  
  
  CONCLUSIONS
  In a period of 4 wk after peripheral nerve block, both long-acting local anesthetics, bupivacaine and ropivacaine, produced calcific myonecrosis suggestive of irreversible skeletal muscle damage. In comparison with ropivacaine, however, the extent of bupivacaine-induced muscle lesions was significantly larger.
authors.affiliation: Departments of *Anesthesiology and †Vascular Surgery, University of Heidelberg, Heidelberg; and ‡Department of Neuropathology, University of Mainz, Mainz, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Zink
authors.forename: Jürgen R E
authors.initials: JRE
authors.lastname: Bohl
authors.forename: Nicola
authors.initials: N
authors.lastname: Hacke
authors.forename: Barbara
authors.initials: B
authors.lastname: Sinner
authors.forename: Eike
authors.initials: E
authors.lastname: Martin
authors.forename: Bernhard M
authors.initials: BM
authors.lastname: Graf
mesh_terms: D000577:Amides / Q000633:toxicity*; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000633:toxicity*; D032342:Muscle Cells / Q000187:drug effects / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000473:pathology; D009336:Necrosis; D009407:Nerve Block; D010525:Peripheral Nerves; D000077212:Ropivacaine; D013552:Swine
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D002045:Bupivacaine