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.     

Efficacy and safety of sugammadex compared to neostigmine for reversal of neuromuscular blockade: a meta-analysis of randomized controlled trials

Background and objectiveSugammadex has been introduced for reversal of rocuronium (or vecuronium)–induced neuromuscular blockade (NMB). Although its efficacy has been established, data are conflicting whether it is safer than neostigmine traditionally used for reversing NMB.DesignMeta-analysis of data about effectiveness and safety of sugammadex compared to neostigmine for reversing NMB in adults was performed using the PRISMA methodology.SettingUniversity medical hospital.MethodsA comprehensive search was conducted using PubMed, Web of Science, and Cochrane Library electronic databases to identify English-language randomized controlled trials. Two reviewers independently selected the trials; extracted data on reversal times, incomplete reversals of NMB, and adverse events (AEs); and assessed the trials' methodological quality and evidence level. Only AEs that were related to study drug by a blinded safety assessor were considered for meta-analysis.PatientsA total of 1384 patients from 13 articles were included in this meta-analysis.Main resultsCompared to neostigmine, sugammadex was faster in reversing NMB (P < .0001) and more likely to be associated with higher train-of-four ratio values at extubation (mean difference, 0.18; 95% confidence interval [CI], 0.14-0.22; P < .0001) and lower risk of postoperative residual curarization after extubation (odds ratio [OR], 0.05; 95% CI, 0.01-0.43; P = .0068). Compared to neostigmine, sugammadex was associated with a significantly lower likelihood of global AEs (OR, 0.47; 95% CI, 0.34-0.66; P < .0001), respiratory AEs (OR, 0.36; 95% CI, 0.14-0.95; P = .0386), cardiovascular AEs (OR, 0.23; 95% CI, 0.08-0.61; P = .0036), and postoperative weakness (OR, 0.45; 95% CI, 0.21-0.97; P = .0409). Sugammadex and neostigmine were associated with a similar likelihood of postoperative nausea and vomiting (OR, 1.23; 95% CI, 0.70-2.15; P = .4719), pain (OR, 1.06; 95% CI, 0.15-7.36; P = .9559), neurologic AEs (OR, 1.47; 95% CI, 0.52-4.17; P = .4699), general AEs (OR, 0.75; 95% CI, 0.47-1.21; P = .2448), and changes in laboratory tests' values (OR, 0.57; 95% CI, 0.18-1.78; P = .3368).ConclusionsResults from this meta-analysis suggest that sugammadex is superior to neostigmine, as it reverses NMB faster and more reliably, with a lower risk of AEs.     

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.     

Sugammadex reversal of rocuronium-induced neuromuscular blockade in two types of neuromuscular disorders: Myotonic dystrophy and spinal muscular atrophy

Neuromuscular disorders like myotonic dystrophy (dystrophia myotonica or Steinert's disease) and spinal muscular atrophy are associated with perioperative complications related to muscle weakness. These patients have an increased sensitivity to non-depolarising neuromuscular blocking agents, which can lead to postoperative residual curarization (PORC) and its associated respiratory complications. Adequate reversal of neuromuscular blockade is essential to prevent this. Sugammadex is the first selective relaxant binding agent and it reverses rocuronium- and vecuronium-induced neuromuscular block. Two cases are reported in which the patients received sugammadex to reverse a rocuronium-induced neuromuscular block. Reversal of the rocuronium-induced neuromuscular block (NMB) in both cases was fast, effective and without recurarization, and no safety concerns were observed.     

Sugammadex versus neostigmine for reversal of rocuronium-induced neuromuscular blockade: A randomized,double-blinded study of thoracic surgical patients evaluating hypoxic episodes in the early postoperative period

Study objectiveThis objective of this study was to determine if reversal of rocuronium-induced neuromuscular blockade with sugammadex versus neostigmine results in a decreased number of hypoxic episodes in the early postoperative period in patients undergoing thoracic surgery with single lung ventilation.DesignSingle-center, randomized, double-blind, two-arm clinical trial.SettingOperating room and postanesthesia care unit.Patients92 subjects aged ≥18, American Society of Anesthesiologists physical status II-IV, and undergoing a thoracic operation necessitating single lung ventilation.InterventionsSubjects received either 2 mg/kg sugammadex or 50 μg/kg neostigmine with 8 μg/kg glycopyrrolate for reversal of moderate neuromuscular blockade.MeasurementsFor the first 90 min postoperatively, all episodes of hypoxia were recorded. Neuromuscular monitoring was performed with acceleromyography (TOF-Watch® SX) and the train of four (TOF) was recorded at 2, 5, 10, and 15 min after administration of the neuromuscular reversal agent.Main resultsSubjects who received neostigmine had a median of 1 episode (interquartile range IQR: 0–2.2) of hypoxia versus subjects who received sugammadex who had a median of 0 episodes (IQR: 0–1) (p = 0.009). The mean time to recovery of TOF ≥ 0.9 was significantly faster with sugammadex at 10 min (95% confidence interval CI: 5–15) compared with neostigmine at 40 min (95% CI: 15–53) (p < 0.001).ConclusionsIn thoracic surgical patients necessitating single lung ventilation, sugammadex provides faster reversal of moderate neuromuscular blockade and results in a decreased number of postoperative hypoxic episodes compared with neostigmine.     

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.     

肝癌全身麻醉射频消融术后应用舒更葡糖钠逆转神经肌肉阻滞的回顾性研究

目的：探讨CT引导肝癌全身麻醉(全麻)射频消融术后、应用舒更葡糖钠逆转神经肌肉阻滞的作用。方法：回顾性分析2019年11月至2022年2月我院220例全麻肝癌射频消融术病人资料。根据不同逆转神经肌肉阻滞类型,即肌松拮抗剂分为：舒更葡糖钠组(S组)108例和新斯的明组(N组)112例。两组病人均采取全凭静脉麻醉,麻醉诱导和维持方式相同。S组术毕静脉给予舒更葡糖钠(2 mg/kg)拮抗肌松,N组静脉给予新斯的明(2 mg)+阿托品(0.5～1 mg)拮抗肌松。比较两组病人自主呼吸完全恢复时间、气管拔管时间、麻醉恢复室(postanesthesia care unit,PACU)停留时间和术后住院时间;以及拔管后10 min CT检查肺不张发生率,术后24 h肝功能,术后肺部并发症发生情况。结果：与N组比较,S组自主呼吸完全恢复时间、气管拔管时间与PACU停留时间明显缩短(P<0.05),拔管后10 min肺不张发生率[35例(32.4%)比59例(52.7%)]及术后肺部并发症发生率[4例(3.7%)比11例(9.8%)]明显降低(P<0.05)。两组术后24 h肝功能指标均较...     

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.     

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.