Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial.

BACKGROUND AND OBJECTIVE: Sugammadex, a modified gamma-cyclodextrin, is a selective relaxant-binding agent designed to reverse the effects of the steroidal neuromuscular blocking agents rocuronium or vecuronium. This study compared the efficacy of sugammadex and neostigmine for reversal of neuromuscular blockade induced by rocuronium for facilitating elective surgery. METHODS: This randomised, multicentre, parallel-group trial included 98 adult patients. Patients received intravenous propofol for induction followed by sevoflurane maintenance anaesthesia. Neuromuscular blockade was monitored using acceleromyography and a train-of-four (TOF) mode of stimulation. Patients were randomly allocated to receive sugammadex 2.0 mg kg(-1) or neostigmine 50 microg kg (-1) (with glycopyrrolate 10 microg kg(-1)) at reappearance of the second response of the TOF (mean 16% twitch height of first response) after the last dose of rocuronium. Safety was evaluated by assessing adverse events, laboratory variables and vital signs. RESULTS: Time to recovery of the TOF ratio of 0.9 after sugammadex compared with neostigmine was significantly shorter (P < 0.0001), being 1.5 versus 18.6 min (geometric means). Predictability of response was greater with sugammadex than neostigmine: with 98% of sugammadex patients versus 11% of neostigmine patients recovering to a TOF ratio of 0.9 within 5 min. There were no clinical events related to residual neuromuscular blockade or reoccurrence of blockade. Serious adverse events were observed in two sugammadex-treated patients and in three neostigmine-treated patients, respectively, but none were considered related to study drugs. CONCLUSION: Sugammadex achieved significantly faster recovery of neuromuscular function after rocuronium to a TOF ratio of 0.9 compared with neostigmine (Clinicaltrials.gov identifier: NCT00451217).

A randomized simultaneous comparison of acceleromyography with a peripheral nerve stimulator for assessing reversal of rocuronium-induced neuromuscular blockade with sugammadex.

BACKGROUND AND OBJECTIVE: We investigated the relationship between acceleromyography and a peripheral nerve stimulator for measuring reversal in patients administered sugammadex following rocuronium. METHODS: In this randomized, active and within-participant controlled study, patients received rocuronium 0.6 mg kg for intubation with 0.15 mg kg maintenance doses as required. Single-dose sugammadex 4.0 or 1.0 mg kg was given 15 min after the last rocuronium dose. Neuromuscular monitoring was performed simultaneously: acceleromyography on one forearm and a peripheral nerve stimulator on the other. The peripheral nerve stimulator assessor was blinded to acceleromyography results. The primary efficacy end point was the difference between time from start of sugammadex 4.0 mg kg administration to recovery of the train-of-four ratio to 0.9 (acceleromyography) and time to reappearance of the fourth twitch (T4) (peripheral nerve stimulator). RESULTS: Sixty-one patients received sugammadex 4.0 mg kg. With acceleromyography, mean (SD) recovery time to a train-of-four ratio of at least 0.9 was 1.5 (0.7) min. With both the peripheral nerve stimulator and acceleromyography, mean (SD) time to T4 reappearance was 0.8 (0.3) min. Mean (95% confidence interval) difference between time to T4 reappearance (peripheral nerve stimulator) and recovery to a train-of-four ratio of at least 0.9 (acceleromyography) was 0.8 (0.6-0.9) min. CONCLUSION: T4 is detected at similar times when measured by a peripheral nerve stimulator or acceleromyography following sugammadex 4.0 mg kg administration 15 min after rocuronium. The mean interval between T4 reappearance (peripheral nerve stimulator) and recovery to a train-of-four ratio of at least 0.9 (acceleromyography) was 0.8 min. These findings provide guidance for evaluating the reversal effect of sugammadex in clinical situations.

Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial.

BACKGROUND: Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evaluated. METHODS: A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.9. Neuromuscular monitoring was performed using acceleromyography. RESULTS: Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg/kg sugammadex), respectively. After 1.2 mg/kg rocuronium, sugammadex decreased time to recovery of train-of-four from 124.3 min (3-min group) and 94.2 min (15-min group) to 1.3 min and 1.9 min with 16 mg/kg sugammadex, respectively. There was no clinical evidence of reoccurrence of neuromuscular blockade or residual neuromuscular blockade. Exploratory analysis revealed that prolongation of the corrected QT interval considered as possibly related to sugammadex occurred in one patient. Another two patients developed markedly abnormal arterial blood pressure after sugammadex that lasted approximately 15 min. CONCLUSION: Sugammadex provides a rapid and dose-dependent reversal of profound neuromuscular blockade induced by high-dose rocuronium (1.0 or 1.2 mg/kg) in adult surgical patients.

Reversal of rocuronium-induced neuromuscular block with the novel drug sugammadex is equally effective under maintenance anesthesia with propofol or sevoflurane.

In this study we investigated whether the novel reversal drug, sugammadex, is equally effective at reversing rocuronium-induced neuromuscular block (NMB) in patients under propofol or sevoflurane maintenance anesthesia. After receiving propofol for induction, patients were randomized to propofol (n = 21) or sevoflurane (n = 21). Rocuronium 0.6 mg/kg was administered for tracheal intubation. NMB was monitored using acceleromyography. At reappearance of the second twitch of the train-of-four ratio, sugammadex 2.0 mg/kg was administered by IV bolus. The primary end-point was time from start of sugammadex administration to recovery of train-of-four ratio to 0.9. Mean recovery time was 1.8 min after both propofol and sevoflurane anesthesia. The 95% confidence interval for the difference in recovery time between the 2 groups (-0.5 to +0.4 min) was well within the predefined equivalence interval (-1 to +1 min), indicating that recovery from NMB was unaffected by maintenance anesthesia. Thirteen patients (propofol n = 4; sevoflurane n = 9) experienced adverse events; these were treatment-related in 4 patients (propofol n = 3; sevoflurane n = 1). There were no treatment-related serious adverse events and no discontinuations or deaths. No residual paralysis occurred. The safety profile of sugammadex was somewhat more favorable under propofol than under sevoflurane anesthesia.

Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study.

BACKGROUND: Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block. METHODS: Twenty-seven male surgical patients aged 18-64 yr were randomly assigned to receive placebo or sugammadex (0.5, 1.0, 2.0, 3.0, or 4.0 mg/kg) for reversal of 0.6 mg/kg rocuronium-induced neuromuscular block. Anesthesia was induced and maintained using intravenous fentanyl and propofol. Neuromuscular function was assessed using acceleromyography. Sugammadex or placebo was administered at reappearance of T2 of the train-of-four. The primary efficacy variable was the time required for recovery to a train-of-four ratio of 0.9. RESULTS: Sugammadex decreased median recovery time in a dose-dependent manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0 mg/kg sugammadex. Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium-induced neuromuscular block within 3 min. A median of 59-77% of sugammadex was excreted unchanged in the urine within 16 h, mostly in the first 8 h. Sugammadex increased the proportion of the rocuronium dose excreted unchanged in the urine (from a median of 19% in the placebo group to 53% in the 4.0-mg/kg group within 16 h). Sugammadex was safe and well tolerated. No evidence of recurarization was observed in any patient. CONCLUSION: At doses of 2.0 mg/kg or greater, sugammadex safely reversed 0.6 mg/kg rocuronium-induced neuromuscular block in a dose-dependent manner. Sugammadex enhanced renal excretion of rocuronium and was excreted unchanged by the kidneys.