The long term myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blocks.
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.
Zink
Wolfgang
W
Departments of *Anesthesiology and †Vascular Surgery, University of Heidelberg, Heidelberg; and ‡Department of Neuropathology, University of Mainz, Mainz, Germany.
Bohl
Jürgen R E
JRE
Hacke
Nicola
N
Sinner
Barbara
B
Martin
Eike
E
Graf
Bernhard M
BM
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
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D002045:Bupivacaine