Abstract
BackgroundMagnesium 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.MethodsPhrenic 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.ResultsThe 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.ConclusionsMagnesium 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.
Highlights
Magnesium dose-dependently potentiates the effect of non-depolarizing neuromuscular blocking agents
Several clinical studies found that magnesium administration prior to the injection of neuromuscular blocking agents (NMBA) does not Fábián et al BMC Anesthesiology (2019) 19:64 significantly impact the efficacy of sugammadex [16, 17], whereas case studies have reported that if magnesium was administered after spontaneous recovery [18] or reversal with sugammadex [19], the significant return of neuromuscular block was seen
From the concentration-response curve, we can see that increasing the concentration of magnesium from 1 mM to 1.5 mM resulted in a mean reduction of contraction force amplitude to 96.6% of the amplitude measured with 1 mM magnesium concentration
Summary
Magnesium dose-dependently potentiates the effect of non-depolarizing neuromuscular blocking agents. Magnesium has several neuromuscular effects, such as decreased liberation of acetylcholine from the presynaptic membrane in the neuromuscular junction [6, 7], a decreased depolarizing effect of acetylcholine on the motor end plate [7] and reduced excitability of the muscle fiber [7] These effects influence the action of neuromuscular blocking agents (NMBA): depolarizing NMBAs are antagonized by magnesium [8], while non-depolarizing NMBAs are potentiated, resulting in a faster onset time [9,10,11,12] and prolonged clinical effect [9, 12,13,14,15]. A recent pre-clinical study found that while time to recovery was not systematically increased by magnesium for reversal of rocuronium-induced block with equimolar sugammadex, maximal achieved TOF ratio was lower with higher magnesium concentrations [20]
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