Age-dependent bupivacaine-induced muscle toxicity during continuous peripheral nerve block in rats.
BACKGROUND
Regional blocks improve postoperative analgesia and postoperative rehabilitation in children and adult patients. Continuous peripheral nerve blocks have been proposed as safe and effective techniques for postoperative pain relief and chronic pain therapy, particularly in small children. Few clinical reports have described myotoxicity induced by bupivacaine in these young patients, in contrast with a larger number of observations in adults. Here, the authors addressed this issue by a comparative evaluation of bupivacaine-induced myotoxicity in young versus adult rats.


METHODS
Femoral nerve block catheters were inserted in male Wistar rats. Young (3-week-old) and adult (12-week-old) rats were randomly assigned to received seven injections (1 ml/kg) of 0.25% bupivacaine (n = 6 per experiment) or isotonic saline (n = 6 per experiment) at 8-h intervals. Rats were killed 8 h after the last injection. Psoas muscle adjacent to the femoral nerve was quickly dissected. Oxygen consumption rates were measured in saponin-skinned fibers, mitochondrial adenosine triphosphate synthesis rates were determined by bioluminescence, and citrate synthase activity was determined by spectrophotometry. Muscle ultrastructural damage was also examined and scored as normal, focal disruption, moderate disruption, or extreme disruption of the sarcomeres.


RESULTS
Bupivacaine caused a reduction of mitochondrial adenosine triphosphate synthesis rate, a decrease of citrate synthase activity, and muscle ultrastructural damages. Young rats treated with bupivacaine showed more severe alterations of mitochondrial bioenergetics and muscle ultrastructure.


CONCLUSIONS
These findings demonstrate that bupivacaine-induced myotoxicity can be explained by mitochondrial bioenergetics alterations, which are more severe in young rats.
Nouette-Gaulain
Karine
K
Laboratoire de physiopathologie mitochondriale, Université Victor Segalen Bordeaux 2, Bordeaux, France. karine.nouette-gaulain@u-bordeaux2.fr
Dadure
Christophe
C
Morau
Didier
D
Pertuiset
Claire
C
Galbes
Olivier
O
Hayot
Maurice
M
Mercier
Jacques
J
Sztark
François
F
Rossignol
Rodrigue
R
Capdevila
Xavier
X
D000367:Age Factors; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009407:Nerve Block / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
D000779:Anesthetics, Local; D002045:Bupivacaine