Sugammadex efficacy for reversal of rocuronium- and vecuronium-induced neuromuscular blockade: A pooled analysis of 26 studies.

STUDY OBJECTIVE: To summarize and compare efficacy of sugammadex with neostigmine or placebo for reversal of rocuronium- or vecuronium-induced neuromuscular blockade (NMB), and to demonstrate consistency of sugammadex results across various patient populations. DESIGN: Pooled analysis on data from 26 multicenter, randomized, Phase II and III studies. SETTING: Operating room. PATIENTS: 1855 adults undergoing surgery under general anesthesia and receiving rocuronium or vecuronium for NMB. INTERVENTIONS: Sugammadex (2.0mg/kg at second twitch reappearance [T2; moderate NMB], 4.0mg/kg at 1-2 post-tetanic counts [PTC; deep NMB] or 16.0mg/kg at 3min after rocuronium 1.2mg/kg), neostigmine or placebo. MEASUREMENTS: Time to recovery of the train-of-four (TOF) ratio to 0.9. MAIN RESULTS: Geometric mean (95% CI) times to recovery to TOF ratio of 0.9 were 1.9 (1.8-2.0) min following sugammadex 2.0mg/kg and 10.6 (9.8-11.6) min following neostigmine administration at T2 after rocuronium, and 2.9 (2.5-3.4) min and 17.4 (13.4-22.6) min, respectively, after vecuronium. Recovery times were 2.2 (2.1-2.3) min following sugammadex 4.0mg/kg and 19.0 (14.8-24.6) min following neostigmine administered at a target of 1-2 PTC after rocuronium, and 3.8 (3.0-5.0) min and 67.6 (56.3-81.2) min after vecuronium. Sugammadex administered 3min after rocuronium 1.2mg/kg resulted in rapid recovery (1.7 [1.5-2.0] min). Modest increases in mean recovery time were associated with vecuronium use (+1.6min [78%; (61%-98%)] versus rocuronium), mild-to-moderate renal impairment (+0.4min [20%; (9%-32%)] versus normal renal function) and geographic location (+1.0min [38%; (25%-52%)] in subjects in USA/Canada versus Europe/Japan). CONCLUSIONS: Sugammadex administered at recommended doses provides rapid and predictable reversal of rocuronium and vecuronium-induced moderate and deep NMB, and effective reversal 3min after rocuronium 1.2mg/kg. Robust recovery was seen across various patient factors, providing further confirmation of labeled dose recommendations.

Neostigmine injected 5 minutes after low-dose rocuronium accelerates the recovery of neuromuscular function.

STUDY OBJECTIVE: To determine whether neostigmine 5 minutes after 0.4 mg/kg rocuronium accelerates reversal. DESIGN: Prospective, randomized, comparative open-label study. SETTING: Operating room. PATIENTS: 60 ASA physical status I and II patients, aged 18 to 65 years. INTERVENTIONS: Patients received 0.4 mg/kg rocuronium during nitrous oxide (N(2)O)-propofol-opioid anesthesia. Reversal of neuromuscular blockade was achieved with neostigmine, either at 0.03 mg/kg or 0.05 mg/kg intravenously (IV), together with glycopyrrolate administered 5 minutes after relaxant and compared with spontaneous recovery. Onset, depth, and duration of neuromuscular block, as well as recovery of train-of-four (TOF) to 0.8 and 0.9 were evaluated. MAIN RESULTS: Times to achieve TOF ratios of 0.8 and 0.9 were significantly shorter when 0.03 mg/kg or 0.05 mg/kg neostigmine was administered 5 minutes after administration of rocuronium (20.2 ± 5 min and 22.6 ± 5.9 min or 17.8 ± 4.8 min and 19.4 ± 5.1 min, respectively) compared with controls (36.2 ± 8.5 min and 39.0 ± 8.7 min; P < 0.01). Duration to spontaneous T1 25% recovery after rocuronium was 15.5 ± 6.5 min versus 9.3 ± 2.3 min and 7.7 ± 1.6 min in the treatment groups (P < 0.01). Recovery index (T1 from 25% to 75%) was significantly shorter after neostigmine (7.1 ± 2.4 min and 5.7 ± 4.0 min) versus controls (13.3 ± 8.3 min; P < 0.01). Speed of reversal did not differ significantly between IV neostigmine doses of 0.03 mg/kg or 0.05 mg/kg. CONCLUSION: Neostigmine accelerates recovery when administered 5 minutes after injection of IV rocuronium 0.4 mg/kg.

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.

Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial.

BACKGROUND: Sugammadex, a specifically designed gamma-cyclodextrin, is a selective relaxant binding drug that rapidly reverses rocuronium-induced and, to a lesser extent, vecuronium-induced neuromuscular blockade. In this study, we compared the efficacy of sugammadex and neostigmine for the reversal of vecuronium-induced neuromuscular blockade in patients scheduled for elective surgery. METHODS: Patients aged > or = 18 yr, ASA Class I-III, and scheduled for a surgical procedure under sevoflurane/opioid anesthesia received an intubating dose of vecuronium (0.1 mg/kg) and maintenance doses of 0.02-0.03 mg/kg at reappearance of the second twitch (T(2)) of train-of-four (TOF) if required. Neuromuscular blockade was monitored using acceleromyography (TOF-Watch SX, Schering-Plough Ireland, Dublin, Ireland). At end of surgery, at reappearance of T(2) after the last dose of vecuronium, patients were randomized to receive either sugammadex (2 mg/kg) or neostigmine (50 microg/kg) plus glycopyrrolate (10 microg/kg) i.v.. The primary efficacy end-point was time from start of administration of sugammadex or neostigmine to recovery of TOF ratio to 0.9. RESULTS: The geometric mean time to recovery of the TOF ratio to 0.9 was significantly faster with sugammadex compared with neostigmine (2.7 min [95% confidence interval {CI}]: 2.2-3.3) versus 17.9 min [95% CI: 13.1-24.3], respectively; P < 0.0001). The mean recovery times to a TOF ratio of 0.8 and 0.7 were also significantly shorter with sugammadex. No serious adverse events or unexpected side effects were reported with either drug. CONCLUSION: Sugammadex provided significantly faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine.

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.