Abstract
BACKGROUND: Magnesium dose-dependently potentiates the effect of non-depolarizing neuromuscular blocking agents. We investigated whether the potentiation of rocuronium-induced blockade by magnesium reduces the effect of sugammadex in an ex-vivo environment and how this influences the safety margin of reversal. METHODS: Phrenic nerve - hemidiaphragm tissue preparations were isolated from male Wistar rats. The specimens were suspended in a tissue holder that allowed registering muscle contraction amplitude following electrical stimulation of the nerve. Concentration-response relationships were elucidated for magnesium, as well as for rocuronium and sugammadex. RESULTS: The mean (95% confidence interval [CI]) half effective concentrations (EC(50)) of rocuronium in the presence of magnesium 1 mM or 1.5 mM were 7.50 μM (6.97-8.07 μM) and 4.25 μM (4.09-4.41 μM), respectively (p < 0.0001). Increasing magnesium from 1 mM to 1.5 mM during reversal of rocuronium-induced block increased the mean (95% CI) EC(50) of sugammadex from 3.67 μM (3.43-3.92 μM) to 5.36 μM (5.18-5.53 μM), whereas mean (95% CI) effective concentrations for 95% effect (EC(95)) were not significantly different at 7.22 μM (6.09-8.54 μM) and 7.61 μM (7.05-8.20 μM), respectively (p = 0.542). When rocuronium-induced block was reversed to a train-of-four (TOF) ratio > 0.9, but with still visible fade, increasing magnesium from 1 mM to 2 mM decreased the TOF ratio to below 0.9. If there was no visible fade after reversal, increasing magnesium concentration did not reduce the TOF ratio. CONCLUSIONS: Magnesium potentiates the neuromuscular effect of rocuronium and shifts the concentration-response curve to the left. Magnesium decreases the safety margin of reversal of rocuronium-induced neuromuscular block with sugammadex.