At therapeutic concentration bupivacaine causes neuromuscular blockade and enhances rocuronium-induced blockade

Partially paralyzed patients may be placed in the risk of pharyngeal dysfunction. Bupivacaine acts as acetylcholine receptor ion channel blocker and may synergistically interact with rocuronium to augment NM blockade. Thus, this study aims to elucidate whether or not, at a therapeutic concentration, bupivacaine by itself may cause NM blockade and reduce an effective concentration of rocuronium.

Twenty-two left phrenic nerve-hemidiaphragms (Male SD rats, 150-250 g) were hung in Krebs solution. Three consecutive ST, 0.1 Hz and one TT, 50 Hz for 1.9 s were obtained before drug application and at each new drug concentration. A concentration of bupivacaine in Krebs solution (n = 5) was cumulatively increased by way of 0.01, 0.1, 1, (1, 2, 3, 4, 5, 6, 7) × 10 µM. In a Krebs solution, pre-treated with bupivacaine 0 (n = 5), 0.1 (n = 5), 1.0 (n = 5), 10 (n = 2) µM, and then concentrations of rocuronium were cumulatively increased by way of 1, 3, 5, 7, 9, 12, 14, 16, 18, 20 µM. EC for each experiment were determined by a probit. The EC(50)'s of rocuronium were compared using a Student's t-test with Bonferroni's correction. Differences were considered significant when P < 0.05.

The potency of bupivacaine for normalized TF was 11.4 (± 1.1) µM. Below 30 µM of bupivacaine, the single twitch potentiation sustained despite the development of tetanic fade and partial inhibition of PTT. Bupivacaine significantly facilitated the NM blockade induced by rocuronium.

Clinicians should be aware that bupivacaine by itself at its therapeutic concentration inhibit NM conduction and enhances rocuronium-induced muscle relaxation.