From analgesia to myopathy: When local anesthetics impair the mitochondrion.
The expanding utilization of local anesthesia and analgesia revealed the occurrence of myopathies induced by local anesthetics. Such iatrogenic effect encouraged anesthesiologists to study the toxicity of local anesthetics and to reevaluate their protocols in order to reduce muscle pain and dysfunction. Studies performed in rats and human cells showed that bupivacaine induces muscle histological damages with sarcomers disruption along with structural alteration of mitochondria, the powerplant of the cell. Bupivacaine-induced myopathies (BIM) are underestimated as patients are not examined by the anesthesiologist after the surgery. Biochemical analyses indicate that BIM could be explained both by the alteration of mitochondrial energetics with consecutive oxidative stress and mitophagy, and the modification of sarcoplasmic reticulum activity with perturbations of calcium homeostasis. BIM is time-dependent, local anesthetic concentration-dependent, enhanced by preexisting metabolism alteration or young age, and could be prevented in part by antioxidant agents and rhEPO. These observations suggest that adapted changes in postoperative analgesia protocols, including the adjustment of LA concentration and volume, a more precise delivery of the drug and an adapted duration of analgesia, may prevent myopathies consecutive to local anesthesia.
Nouette-Gaulain
Karine
K
MRGM - Maladies Rares: Génétique et Métabolisme, Université Victor Segalen Bordeaux 2, F-33076 Bordeaux, France. karine.nouette-gaulain@u-bordeaux2.fr
Jose
Caroline
C
Capdevila
Xavier
X
Rossignol
Rodrigue
R
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D000772:Anesthesia, Local / Q000009:adverse effects; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000009:adverse effects; D002118:Calcium / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007049:Iatrogenic Disease / Q000517:prevention & control; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D017240:Mitochondrial Myopathies / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D010149:Postoperative Pain / Q000517:prevention & control; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure
D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D002118:Calcium; D002045:Bupivacaine