The effect of magnesium on the reversal of rocuronium-induced neuromuscular block with sugammadex: an ex vivo laboratory study.
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 (EC50) 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) EC50 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 (EC95) 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.
['Fábián|Ákos I|ÁI|', 'Csernoch|Vera|V|', 'Tassonyi|Edömér|E|', 'Fedor|Marianna|M|', 'Fülesdi|Béla|B|0000-0003-2541-9740']
D000818:Animals D003964:Diaphragm D004305:Dose-Response Relationship, Drug D008274:Magnesium D008297:Male D019148:Neuromuscular Blockade D003473:Neuromuscular Nondepolarizing Agents D009924:Organ Culture Techniques D051381:Rats D017208:Rats, Wistar D000077123:Rocuronium D000077122:Sugammadex D016896:Treatment Outcome
Magnesium Neuromuscular block Sugammadex Rocuronium Phrenic nerve-diaphragm preparation