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Local Anesthetic Toxicity: Different Mechanisms for Different End Points

Ohmura, Shigeo, MD; Kawada, Masayuki, MD

doi: 10.1213/00000539-200202000-00062
LETTERS TO THE EDITOR: Letters & Announcements

Department of Anesthesiology and Intensive Care Medicine

Kanazawa University School of Medicine

Kanazawa, Japan

In Response:

We thank Dr. Weinberg for his interest in our recent publication (1) and appreciate the opportunity to respond to his comments. Dr. Weinberg and colleagues (2) proposed the inhibition of mitochondrial transport of fatty acid as a mechanism underlying the cardiovascular toxicity of local anesthetics. They calculated the half- inhibitory concentrations (IC50) for bupivacaine and ropivacaine as 0.26 mM and 0.65 mM, respectively. It seems that these IC50 values are still higher than the corresponding plasma concentrations of bupivacaine and ropivacaine at the onset of asystole reported in our paper (0.13 mM and 0.15 mM, respectively). However, care must be taken in interpreting our data because the plasma concentrations of local anesthetics at the onset of asystole are considerably affected by the rate of infusion (3). In addition, isoflurane, which has been reported to affect different mitochondrial functions (4), was used for basal anesthesia in our study.

We suppose that the cardiovascular toxicity induced by local anesthetics may be explained in part by the mitochondrial mechanism. However, the clinical relevance of the mechanism is yet to be determined.

Shigeo Ohmura, MD

Masayuki Kawada, MD

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1. Ohmura S, Kawada M, Ohta T, et al. Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats. Anesth Analg 2001; 93: 743–8.
2. Weinberg GL, Palmer JW, VadeBoncouer TR, et al. Bupivacaine inhibits acylcarnitine exchange in cardiac mitochondria. Anesthesiology 2000; 92: 523–8.
3. Dony P, Dewinde V, Vanderick B, et al. The comparative toxicity of ropivacaine and bupivacaine at equipotent doses in rats. Anesth Analg 2000; 91: 1489–92.
4. Cohen PJ. Effect of anesthetics on mitochondrial function. Anesthesiology 1973; 39: 153–64.
© 2002 International Anesthesia Research Society