RESUMEN
BACKGROUND: Residual neuromuscular block at the end of surgery may compromise the patient's safety. The risk of airway complications can be minimized through monitoring of neuromuscular function and reversal of neuromuscular block if needed. Effective reversal can be achieved with selective relaxant binding agents, however, sugammadex is the only clinically approved drug in this group. We investigated the concentration-response properties of a novel selective relaxant binding agent, carboxymethyl-γ-cyclodextrin for the reversal of neuromuscular block. We evaluated the hypothesis that it is equally potent for reversing neuromuscular block as sugammadex. METHODS: Phrenic nerve - hemidiaphragm tissue preparations were isolated from male Wistar rats and suspended in a tissue holder allowing electrical stimulation of the nerve and monitoring of muscle contraction force. Concentration-response relationships were constructed for the neuromuscular blocking agents rocuronium, pipecuronium, and vecuronium. The half-effective concentrations of sugammadex and carboxymethyl-γ-cyclodextrin for reversal of neuromuscular block were determined. RESULTS: The half effective concentrations (95% confidence interval, CI) were 7.50 (6.93-8.12) µM for rocuronium, 1.38 (1.33-1.42) µM for pipecuronium, and 3.69 (3.59-3.80) µM for vecuronium. The half effective concentrations (95% CI) of carboxymethyl-γ-cyclodextrin and sugammadex were 35.89 (32.67-39.41) µM and 3.67 (3.43-3.92) µM, respectively, for the reversal of rocuronium-induced block; 10.14 (9.61-10.70) µM and 0.67 (0.62-0.74) µM, respectively, for the reversal of pipecuronium-induced block; and 376.1 (341.9-413.8) µM and 1.45 (1.35-1.56) µM, respectively, for the reversal of vecuronium-induced block. CONCLUSIONS: Carboxymethyl-γ-cyclodextrin is an effective, but less potent agent for reversal of neuromuscular block than sugammadex.
Asunto(s)
Bloqueo Neuromuscular , Bloqueantes Neuromusculares/antagonistas & inhibidores , gamma-Ciclodextrinas/farmacología , Animales , Ratas WistarRESUMEN
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.