Neuromuscular blockade reversal - sugammadex sodium
Neuromuscular blockers such as rocuronium or pancuronium find wide use in critically ill patients to facilitate surgical access, mechanical ventilation and tracheal intubation. They are also used alongside anaesthetics in surgical procedures.
Neuromuscular blockers such as rocuronium or pancuronium find wide use in critically ill patients to facilitate surgical access, mechanical ventilation and tracheal intubation. They are also used alongside anaesthetics in surgical procedures.
However, once surgery is completed their effects must be reversed if full recovery of neuromuscular functions is to be achieved and residual paralysis is to be avoided.
This is generally done with the aid of acetylcholinesterase inhibitors, but side-effects are common. An alternative would be to chemically encapsulate the neuromuscular blockers, using, for example, cyclodextrins. These cyclic oligosaccharides can encapsulate lipophilic molecules, and so could be used to encourage the drugs to dissociate from their active site, reversing their activity without causing the side-effects.
Organon's sugammadex is a modified g-cyclodextrin that can encapsulate rocuronium's steroidal rings, promoting its dissociation from the nicotinic receptors where it binds.1 A Phase I trial to study its efficacy, safety and pharmacokinetics has been carried out in 29 healthy volunteers.2 Subjects were given general anaesthesia twice, using propofol and remifentanil for induction and maintenance, and a 0.6mg/kg dose of rocuronium bromide to aid intubation. Three minutes after the rocuronium was given, either placebo or a dose of sugammadex, from 0.1 to 8.0mg/kg, was administered. Those given doses of 4.0mg/kg recovered in around three minutes while those given the highest dose recovered in around a minute. The 10 patients given placebo took up to 69 minutes to recover. Adverse events were generally mild and short-acting.
A Phase II dose-response study was carried out in 87 patients.3 They were given 1.0mg/kg rocuronium with 2-16mg/kg sugammadex administered either three or 15 minutes later. Neuromuscular block lasted for two hours, with the effective reversal dose appearing to be 2-4mg/kg. Mean recovery time was 2.5 minutes for those given the 8mg dose. No serious side-effects were seen.