The effect of high concentration of magnesium with ropivacaine, gentamicin, rocuronium, and their combination on neuromuscular blockade

Background: Magnesium, ropivacaine, gentamicin, and rocuronium block neuromuscular (NM) transmission by different mechanisms. Therefore, concurrent administration of these agents may induce prolonged muscle paralysis via synergistic interaction. This study investigated the efficacy and safety of NM block caused by the administration of high concentrations of magnesium in combination with ropivacaine, gentamicin, and rocuronium.

Methods: Eighty-three left phrenic nerve-hemidiaphragms from male SD rats (150-250 g) were hung in Krebs solution. Three consecutive single twitch tension (ST, 0.1 Hz) and one tetanic tension (TT, 50 Hz for 1.9 s) were obtained before drug application and at each new drug concentration. The concentration of MgCl2 and MgSO4 in Krebs solution was increased until an 80 to 90% reduction in ST was reached. To test the effects of combinations of NM agents, a Krebs solution was premixed with MgCl2 alone, MgCl2 and ropivacaine, or MgCl2, ropivacaine, and gentamicin. The concentration of ropivacaine, gentamicin, or rocuronium was then progressively increased until an 80 to 90% reduction in ST was reached. The effective concentrations were estimated with a probit model.

Results: The potency of MgCl2 was greater than that of MgSO4, and pretreatment with MgCl2 increased the potency of gentamicin and rocuronium. Unexpectedly, MgCl2 did not potentiate ropivacaine, and the potency of gentamicin and rocuronium failed to show an increase when premixed with 0.5 µM ropivacaine.

Conclusions: The concomitant administration of high concentrations of magnesium and ropivacaine together with clinically relevant concentrations of gentamicin or rocuronium potentiated NM blockade but not with clinically relevant concentrations of ropivacaine.