LETTERS TO THE EDITOR: Letters & Announcements
To the Editor:
Ohmura et al. (1) report that after IV infusion in rats different serum concentrations of bupivacaine, levobupivacaine, and ropivacaine were achieved at the start of dysrhythmias, whereas nearly identical serum concentrations of the three were measured at the time of asystole. This suggests there are probably different sites of anesthetic action underlying the two clinical end points. Local anesthetics interfere with a wide range of cellular activities and the clinical phenotype of local anesthetic cardiac toxicity is correspondingly complex (e.g., various arrhythmias, conduction abnormalities, contractile dysfunction).
Notably, the anesthetic concentrations found by Ohmura et al. (1) at the time of cardiovascular collapse were more than 100-fold more than those reported to block sodium ion channels (2), but were the same order of magnitude (0.1 mM) as inhibits mitochondrial transport of fatty acids, the heart’s preferred fuel in aerobic metabolism (3). Furthermore, their findings support a bupivacaine site of action leading to the end point of asystole that is neutral with respect to chirality. Sztark et al. (4) showed adverse effects on mitochondrial respiration at the same concentration for both isomers of bupivacaine.
I believe the findings of Ohmura et al. (1) support the potential relevance of a mitochondrial mechanism in severe local anesthetic-induced cardiac toxicity.
Guy Weinberg, MD
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. Clarkson CW, Hondeghem LM. Mechanism for bupivacaine depression of cardiac conduction: fast block of sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology 1985; 62: 396–405.
3. Weinberg GL, Palmer JW, VadeBoncouer TR, et al. Bupivacaine inhibits acylcarnitine exchange in cardiac mitochondria. Anesthesiology 2000; 92: 523–8.
4. Sztark F, Nouette-Gaulain K, Malgat M, et al. Absence of stereospecific effects of bupivacaine isomers on heart mitochondrial bioenergetics. Anesthesiology 2000; 93: 456–62.