Plasma Bupivacaine Concentrations Are Too Low to Explain Reduced Vecuronium Requirement with an Epidural

To the Editor: Agarwal et al. (1) concluded that epidural anesthesia decreases the hypnotic, opioid, and muscle relaxant requirement during a general anesthetic with or without bupivacaine injected epidurally. Surprisingly, the dose of vecuronium was almost 50% less in the epidural group, 0.023 mg · kg−1 · h−1 versus 0.042 in the control group. In both groups, incremental doses were administered at 10% twitch recovery at the adductor pollicis. The authors explained this finding by bupivacaine having “a direct effect on presynaptic, postsynaptic, and muscle membrane, which may result in enhancement of neuromuscular block.” However, the local anesthetic doses given were much too small to produce potentiation of blockade. In the rat hemidiaphragm preparation, it took 25 μg/mL lidocaine to halve the 50% blocking dose for pancuronium (2). In patients receiving 400 mg epidural lidocaine, peak plasma concentrations were 2.65 μg/mL (3), or one order of magnitude less. After 0.75 mg/kg bupivacaine, or 50 mg in the average adult, injected IV in the presence of nondepolarizing blockade, a decrease of only 6.5% in twitch height was found (4). Agarwal et al. (1) administered much less, 6 mg/h, and it was administered in the epidural space. In a clinical study involving substantially larger epidural doses (up to 150 mg), duration of action of a loading dose of atracurium was increased mildly from 40 to 46 min, with no change in the duration of subsequent doses (5). In children, the 50% blocking dose of vecuronium (ED50) was decreased marginally from 33.8 to 28.4 μg/kg if epidural bupivacaine was given, with no change in recovery (6). Thus, the major reduction in muscle relaxant requirements observed by Agarwal et al. (1) with an epidural anesthetic is in sharp contrast with earlier clinical findings and cannot be explained by the blocking effect of bupivacaine at the neuromuscular junction. François Donati, PhD, MD, FRCPC Louis-Philippe Fortier, MSc, MD, FRCPC Department of Anesthesiology Hôpital Maisonneuve-Rosemont Université de Montréal Montréal, Québec, Canada [email protected]

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