Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study

BACKGROUND: Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular blockade at 5 min in American Society of Anesthesiologists physical status I and II patients. METHODS: Forty-five American Society of Anesthesiologists physical status I and II patients (aged 18-64 yr) scheduled to undergo surgical procedures (anticipated anesthesia duration >/= 90 min) were randomly assigned to a phase II, multicenter, assessor-blinded, placebo-controlled, parallel, dose-finding study. Anesthesia was induced and maintained with propofol and an opioid. Profound neuromuscular blockade was induced with 1.2 mg/kg rocuronium bromide. Sugammadex (2.0, 4.0, 8.0, 12.0, or 16.0 mg/kg) or placebo (0.9% saline) was then administered 5 min after the administration of rocuronium. Neuromuscular function was monitored by acceleromyography, using train-of-four nerve stimulation. Recovery time was the time from the start of administration of sugammadex or placebo, to recovery of the train-of-four ratio to 0.9. Safety assessments were performed on the day of the operation and during the postoperative and follow-up period. RESULTS: A total of 43 patients received either sugammadex or placebo. Increasing doses of sugammadex reduced the mean recovery time from 122 min (spontaneous recovery) to less than 2 min in a dose-dependent manner. Signs of recurrence of blockade were not observed. No serious adverse events related to sugammadex were reported. Two adverse events possibly related to sugammadex were reported in two patients (diarrhea and light anesthesia); however, both patients recovered without sequelae. CONCLUSIONS: Sugammadex rapidly and effectively reversed profound rocuronium-induced neuromuscular blockade in humans and was well tolerated.     

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.     

Reversal of profound rocuronium neuromuscular blockade by sugammadex in anesthetized rhesus monkeys

BACKGROUND: Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the anesthetized rhesus monkey using train-of-four stimulation. METHODS: Four female rhesus monkeys each underwent three experiments. In each experiment, first, a 100-microg/kg dose of rocuronium was injected and spontaneous recovery was monitored. After full recovery, a 500-microg/kg dose of rocuronium was injected. Up to this point, all three experiments in a single monkey were identical. One minute after this rocuronium injection, either one of the two tested dosages of sugammadex (1.0 or 2.5 mg/kg) was injected or saline was injected. RESULTS: Injection of 100 microg/kg rocuronium resulted in a mean neuromuscular blockade of 93.0% (SD = 4%), and profound blockade was achieved by injection of 500 microg/kg. In all experiments, a 100% neuromuscular blockade was achieved at this dose. After injection of the high rocuronium dose, the 90% recovery of the train-of-four ratio took 28 min (SD = 7 min) after saline, 26 min (SD = 9.5 min) after 1 mg/kg sugammadex, and 8 min (SD = 3.6 min) after 2.5 mg/kg sugammadex. Signs of residual blockade or recurarization were not observed. Injection of sugammadex had no significant effects on blood pressure or heart rate. CONCLUSIONS: Chemical encapsulation of rocuronium by sugammadex is a new therapeutic mechanism allowing effective and rapid reversal of profound neuromuscular blockade induced by rocuronium in anesthetized rhesus monkeys.     

Effect of magnesium sulphate on sugammadex reversal time for neuromuscular blockade: a randomised controlled study

Magnesium potentiates neuromuscular blockade. Sugammadex reverses rocuronium‐induced blockade. The aim of this study was to determine the effect of pre‐treatment with magnesium sulphate on sugammadex reversal time for neuromuscular blockade. Seventy‐three patients were randomly assigned to receive magnesium sulphate (40 mg.kg^?1) or saline intravenously. After anaesthetic induction, continuous train‐of‐four monitoring was performed and rocuronium was administered (0.6 mg.kg^?1). When a second twitch appeared, the patients received sugammadex (2 mg.kg^?1). The median (IQR [range]) reversal time of moderate neuromuscular blockade to a train‐of‐four ratio of 0.9 facilitated by sugammadex was 115 (93?177.5 [68?315]) s in the magnesium group and 120 (105?140 [70?298]) s in the saline group (p = 0.79). The median (IQR [range]) clinical duration was 45 (35.5?53 [22?102]) min in the magnesium group and 37 (31?43 [19?73]) min in the saline group (p = 0.031). Pre‐treatment with magnesium did not significantly affect sugammadex reversal time of moderate neuromuscular blockade induced by rocuronium.     

A temporary decrease in twitch response following reversal of rocuronium-induced neuromuscular block with a small dose of sugammadex in a pediatric patient

We report a temporary decrease in twitch response following reversal of rocuronium-induced neuromuscular block with a small dose of sugammadex in our dose-finding study in pediatric patients. A 19-month-old female infant (9.6 kg, 80 cm) was scheduled for elective cheiloplasty surgery. Anesthesia was induced with nitrous oxide 50 % and sevoflurane 5 % and maintained with air, oxygen, sevoflurane 3 %, and fentanyl (total, 3 μg/kg). Neuromuscular monitoring was performed at the adductor pollicis muscle after induction of anesthesia but before the administration of rocuronium. Total dose of rocuronium during the surgery was 0.9 mg/kg. Neuromuscular block was reversed with 0.5 mg/kg sugammadex when one response was observed with post-tetanic count stimulation. Twitch responses after sugammadex administration showed a temporary decrease after its initial recovery. Maximum decreases in twitch responses were observed 17 min after initial dose of sugammadex. Twitch responses recovered to their control values after additional doses of 3.5 mg/kg sugammadex (4 mg/kg in total). Time from sugammadex administration to maximum decreases in twitch responses is earlier than has been reported in adults (20–70 min). It is demonstrated that following neuromuscular block reversal with insufficient dose of sugammadex, there is a possibility of the recurrence of residual paralysis within less than 20 min in pediatric patients.     

Reversal of rocuronium-induced neuromuscular block by sugammadex is independent of renal perfusion in anesthetized cats

Purpose  

Sugammadex is a selective relaxant binding agent designed to encapsulate the aminosteroidal neuromuscular blocking agent rocuronium, thereby reversing its effect. Both sugammadex and the sugammadex–rocuronium complex are eliminated by the kidneys. This study investigated the effect of sugammadex on recovery of rocuronium-induced neuromuscular block in cats with clamped renal pedicles, as a model for acute renal failure.     

Prospective,randomized, multicenter study evaluating safety and efficacy of intragastric dual-balloon in obesity

BackgroundIntragastric balloons are designed to occupy space within the stomach and induce satiety. The present study evaluated the safety and efficacy of an intragastric dual balloon as an adjunct to diet and exercise in obese patients compared with diet and exercise alone.MethodsAfter approval from the institutional review board, patients provided written consent and were randomized to the treatment group (TG) or control group (CG) in a 2:1 ratio. Three sites randomized a total of 30 patients to the TG (n = 21) or CG (n = 9). Patients randomized to the TG underwent endoscopic placement of the dual balloon. Both groups received similar diet and exercise counseling. After 24 weeks, the device was removed. Patient weight, adverse events, and quality of life data were evaluated throughout the 48-week study duration.ResultsOur patient population included 26 women and 4 men aged 26–59 years. At 24 weeks, the mean excess weight loss in the TG and CG was 31.8% ± 21.3% and 18.3% ± 20.9%, respectively (P = .1371). At 48 weeks, 24 weeks after device removal, the TG maintained 64% of their weight loss. No deaths, unanticipated adverse effects, early removals, balloon deflations, or balloon migrations occurred. In the TG, 4 patients were readmitted for severe nausea, 1 had asymptomatic gastritis at balloon removal, and 1 patient experienced transient hypoxia during device removal.ConclusionIn the present small study, the dual balloon proved easy to use, was associated with a trend toward greater weight loss than the CG, and demonstrated a good safety profile.     

Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1)

Sugammadex is the first selective relaxant binding agent andreverses rocuronium-induced neuromuscular block. A case is reportedin which a patient accidentally received a high dose of sugammadex(40 mg kg^–1) to reverse a rocuronium-induced (1.2 mg kg^–1)profound neuromuscular block. A fast and efficient recoveryfrom profound neuromuscular block was achieved and no adverseevents or other safety concerns were reported.