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LETTER TO THE EDITOR

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

Department of Anesthesiology; Hôpital Maisonneuve-Rosemont; Université de Montréal; Montréal, Québec, Canada; francois.donati{at}umontreal.ca

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.

References

1. Agarwal A, Pandey R, Dhiraaj S, et al. The effect of epidural bupivacaine on induction and maintenance doses of propofol (evaluated by bispectral index) and maintenance doses of fentanyl and vecuronium. Anesth Analg 2004;99:1684–8.[Abstract/Free Full Text]
2. Matsuo S, Rao DB, Chaudry I, Foldes FF. Interaction of muscle relaxants and local anesthetics at the neuromuscular junction. Anesth Analg 1978;57:580–7.[Abstract]
3. Burm AG, Vermeulen NP, van Kleef JW, et al. Pharmacokinetics of lignocaine and bupivacaine in surgical patients following epidural administration: simultaneous investigation of absorption and disposition kinetics using stable isotopes. Clin Pharmacokinet 1987;13:191–203.[Web of Science][Medline]
4. Telivuo L, Katz RL. The effects of modern intravenous local analgesics on respiration during partial neuromuscular block in man. Anaesthesia 1970;25:30–5.[Web of Science][Medline]
5. Toft P, Kirkegaard NH, Severinsen I, Helbo-Hansen HS. Effect of epidurally administered bupivacaine on atracurium-induced neuromuscular blockade. Acta Anaesthesiol Scand 1990;34:649–52.[Web of Science][Medline]
6. Taivainen T, Meretoja OA, Rosenberg PH The effect of epidural bupivacaine on vecuronium-induced neuromuscular blockade in children. Acta Anaesthesiol Scand. 1994;38:453–6.[Web of Science][Medline]

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