Reversal Of Rocuronium-induced Block Research Articles

Carboxymethyl-\u03b3-cyclodextrin, a novel selective relaxant binding agent for the reversal of neuromuscular block induced by aminosteroid neuromuscular blockers: an ex vivo laboratory study

BackgroundResidual 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.MethodsPhrenic 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.ResultsThe 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.ConclusionsCarboxymethyl-γ-cyclodextrin is an effective, but less potent agent for reversal of neuromuscular block than sugammadex.

The effect of magnesium on the reversal of rocuronium-induced neuromuscular block with sugammadex: an ex vivo laboratory study

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.

Sugammadex in antagonism of neuromuscular block in anesthesia: a clinical and economic profile

Sugammadex is a modified cyclodextrin which acts by encapsulating and inactivating the neuromuscular blocking agents (NMBAs) rocuronium and vecuronium, used to induce relaxation of skeletal muscles during surgery and to facilitate endotracheal intubation. The procedure of reversal of the block at the end of surgery can influence the time to discharge from the operating room and post-operative residual curarization (PORC) incidence, which is related to an increased rate of adverse respiratory events in the post-anaesthesia care unit. Cholinesterase inhibitors are frequently used to reverse neuromuscular block, but their use is associated with potential cardiovascular and respiratory side-effects. The recommended dose-range for sugammadex is 2-16 mg/kg, depending on the level of block: the dose is approximately 2 mg/kg for reversal of moderate blockade, 4 mg/kg for deep blockade and 16 mg/kg for the immediate reversal of a neuromuscular blockade as early as 3 minutes after 1-1.2 mg/kg of rocuronium. Four pivotal, phase III trials studied sugammadex in routine reversal of moderate, deep neuromuscular block and in the immediate reversal of rocuronium-induced block. In all the cases the drug demonstrated of being significantly more efficient than other reversal strategies, providing a faster reversal than the most used anticholinesterase comparator neostigmine. Sugammadex also appeared to have an acceptable safety profile. Acquisition cost of sugammadex is greater than that of neostigmine, but cost-savings related to the reduced theatre time and to the reduced incidence of PORC episodes can offset it. A Budget Impact analysis in the perspective of the hospital has been conducted for the Italian setting resulting in a total cost-save of 7,420 € for one year of activity. In conclusion, sugammadex appears to be a valuable innovation in anesthesiology. This drug represents a safe and effective alternative to anticholinesterase agents.