Journal: Anesthesiology 109(5):816-824, 2008. 36 References
Reprint: Accurate Clinical Trials Inc., Saddleback Memorial Medical Center, Laguna Hills, CA 92653 (RK Jones, MD)
Faculty Disclosure: Supported by Schering-Plough, Roseland, New Jersey. Abstracted by R. Ouellette, who has nothing to disclose.
Reversal of nondepolarizing neuromuscular blocking agents (NMBAs) has been achieved traditionally by using acetylcholinesterase inhibitors. However, these agents cannot adequately reverse profound neuromuscular blockade. Acetylcholinesterase inhibitors suppress the enzymatic breakdown of acetylcholine, allowing it to accumulate and displace the NMBA molecules from the binding sites on the nicotinic receptors. If the NMBA concentration is very high, the increase in acetylcholine concentration is insufficient to displace enough NMBA molecules to reverse blockade. Sugammadex is a novel reversal agent, reversing the effects of rocuronium by encapsulation. At this time sugammadex is not FDA-approved for clinical use in the USA.
This study assessed the efficacy and safety of sugammadex versus neostigmine for reversal of profound rocuronium-induced neuromuscular blockade. This phase III, multicenter, randomized, parallel-group, safety assessor-blinded study, known as the Signal study (NCT00473694), was conducted at 8 sites in the US, with the aim to compare the efficacy and safety of sugammadex versus neostigmine for reversal of profound rocuronium-induced blockade.
Eighty-eight patients, ages 18 years or older, ASA PS 1-4, were randomized to receive sugammadex 4.0 mg/kg or neostigmine 70 mcg/kg plus glycopyrrolate 14 mcg/kg. Anesthetized patients received an intubating dose of rocuronium, 0.6 mg/kg, with maintenance doses of 0.15 mg/kg as required. The primary efficacy parameter was the time from administration of sugammadex or neostigmine-glycopyrrolate to return of the train-of-four (TOF) ratio to 0.9.
In this study, 4 mg/kg sugammadex produced a significantly more rapid recovery from profound rocuronium-induced NM blockade when administered at post-tetanic counts of 1-2 than did neostigmine. In the intent-to-treat population of n=37 in each group, geometric mean time to recovery to a TOF ratio of 0.9 with sugammadex was 2.9 min versus 50.4 minutes with neostigmine-glycopyrrolate. Most sugammadex patients recovered to a TOF ratio of 0.9 within 5 min after administration. |
