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Background: This study evaluated efficacy and safety of sugammadex 4 mg kg(-1) for deep neuromuscular blockade (NMB) reversal in patients with severe renal impairment (creatinine clearance [CLCR] <30 ml min(-1)) vs those with normal renal function (CLCR ≥80 ml min(-1))., Methods: Sugammadex 4 mg kg(-1) was administered at 1-2 post-tetanic counts for reversal of rocuronium NMB. Primary efficacy variable was time from sugammadex to recovery to train-of-four (T4/T1) ratio 0.9. Equivalence between groups was demonstrated if two-sided 95% CI for difference in recovery times was within -1 to +1 min interval. Pharmacokinetics of rocuronium and overall safety were assessed., Results: The intent-to-treat group comprised 67 patients (renal n=35; control n=32). Median (95% CI) time from sugammadex to recovery to T4/T1 ratio 0.9 was 3.1 (2.4-4.6) and 1.9 (1.6-2.8) min for renal patients vs controls. Estimated median (95% CI) difference between groups was 1.3 (0.6-2.4) min; thus equivalence bounds were not met. One control patient experienced acceleromyography-determined NMB recurrence, possibly as a result of premature sugammadex (4 mg kg(-1)) administration, with no clinical evidence of NMB recurrence observed. Rocuronium, encapsulated by Sugammadex, was detectable in plasma at day 7 in 6 patients. Bioanalytical data for sugammadex were collected but could not be used for pharmacokinetics., Conclusions: Sugammadex 4 mg kg(-1) provided rapid reversal of deep rocuronium-induced NMB in renal and control patients. However, considering the prolonged sugammadex-rocuronium complex exposure in patients with severe renal impairment, current safety experience is insufficient to support recommended use of sugammadex in this population., Clinical Trial Registration: NCT00702715., (© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: A train-of-four ratio (TOFR) ≥0.9 measured by quantitative neuromuscular monitoring is accepted as an indication of sufficient neuromuscular recovery for extubation, even though many postsynaptic acetylcholine receptors may still be inhibited. We investigated whether antagonism with sugammadex after spontaneous recovery to TOFR≥0.9 further improves muscle function or subjective well-being., Methods: Following recovery to TOFR≥0.9 and emergence from anaesthesia, 300 patients randomly received either sugammadex 1.0 mg kg(-1) or placebo. Fine motor function (Purdue Pegboard Test) and maximal voluntary grip strength were measured before and after surgery (before and after test drug administration). At discharge from the postanaesthesia care unit, well-being was assessed with numerical analogue scales and the Quality-of-Recovery Score 40 (QoR-40)., Results: Patients' fine motor function [6 (sd 4) vs 15 (3) pegs (30 s)(-1), P<0.05] and maximal voluntary grip strength (284 (126) vs 386 (125) N, P<0.05) were significantly lower after anaesthesia compared with the pre-anaesthesia baseline. After sugammadex or placebo, motor function was significantly improved in both groups but did not reach the preoperative level. There was no difference between groups at any time. Global well-being was unaffected (QoR-40: placebo, 174 vs 185; sugammadex, 175 vs 186, P>0.05)., Conclusions: Antagonizing rocuronium at TOF≥0.9 with sugammadex 1.0 mg kg(-) (1) did not improve patients' motor function or well-being when compared with placebo. Our data support the view that TOFR≥0.9 measured by electromyography signifies sufficient recovery of neuromuscular function., Clinical Trial Registration: The trial is registered at ClinicalTrials.gov (NCT01101139)., (© The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A 61-year-old woman (57 kg, 171 cm) underwent surgery under general anaesthesia with desflurane 5.8-6.1 vol. % end-tidal, remifentanil 0.2-0.4 μg/kg/min and rocuronium 35 mg (0.61 mg/kg). On return of the second twitch in the train-of-four (TOF) stimulation measured by acceleromyography, sugammadex 120 mg (2.1 mg/kg) was given. After complete neuromuscular recovery, magnesium sulphate 3600 mg (60 mg/kg) was injected intravenously over 5 min to treat atrial fibrillation. This was associated with recurarisation with a nadir [first twitch=25%, TOF ratio (TOFR)=67%] 7 min after the start of the magnesium sulphate infusion (magnesium plasma level: 2.67 mM). A spontaneous twitch value and a TOFR of >90% were observed 45 min after the beginning of the magnesium sulphate infusion under general anaesthesia. Rapid infusion of magnesium sulphate may re-establish a sugammadex-reversed, rocuronium-induced neuromuscular block during general anaesthesia, probably because of the high plasma level of magnesium (2.67 mM). Desflurane and a small fraction of unbound rocuronium may amplify the known muscle relaxing effects of magnesium. Intravenous injection of magnesium sulphate is not recommended in patients after general anaesthesia with neuromuscular relaxants, particularly after sugammadex reversal. Quantitative neuromuscular monitoring should be used for reversing aminosteroid muscle relaxants with sugammadex--particularly in combination with magnesium injection--to prevent post-operative residual curarisation., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Total intravenous anaesthesia with propofol and remifentanil is widely used in neuroanaesthesiology and enables the quick recovery and early neurological assessment of patients. The administration of muscle relaxants carries a risk of residual relaxation following surgery. The administration of a suitable dose of sugammadex reverses the neuromuscular block irrespective of its depth and has none of the side effects associated with acetylcholinesterase inhibitors. The aim of the present study was to evaluate the usefulness of sugammadex for the reversal of vecuronium-induced effects following intracranial surgery., Methods: The study involved 38 women who underwent supratentorial tumour removal. These women were randomly divided into two groups. Total intravenous anaesthesia with propofol and remifentanil using target-controlled infusion was administered according to the Schnider and Minto models, respectively. Endotracheal intubation was performed after the target concentrations of propofol and remifentanil reached 4 μg mL⁻¹ and 4 ng mL⁻¹, respectively. Vecuronium (100 μg kg⁻¹) was administered, and no response to TOF stimulation was observed. Relaxation was continued via the continuous infusion of vecuronium (0.8-1.2 μg kg⁻¹ min⁻¹) to provide a TOF of 2 throughout the surgery. In group I, neuromuscular conduction was restored with intravenous sugammadex (2 mg kg⁻¹), whereas in group II, no reversal agents were administered., Results: The times of the return of spontaneous breathing, extubation, eye opening (both spontaneous and in response to a verbal command) were found to be longer in group II than group I., Conclusion: The use of sugammadex following craniotomy accelerates the achievement of optimal extubation conditions.

Since its launch in 2008, sugammadex has been considered one of the most significant developments in anaesthesia-related pharmacology. With almost 500 sugammadex-related publications and over nine million patient exposures worldwide, user experience and scientific data have grown exponentially. However, several important questions are yet to be answered. This article reviews the sugammadex-related literature in 2013 and 2014 to determine which of these questions have been answered more fully over the last 18 months and which questions require more information and research.

Background: We tested the hypothesis that neostigmine reversal of neuromuscular blockade reduced the incidence of signs and symptoms of postoperative respiratory failure., Methods: We enrolled 3,000 patients in this prospective, observer-blinded, observational study. We documented the intraoperative use of neuromuscular blocking agents and neostigmine. At postanesthesia care unit admission, we measured train-of-four ratio and documented the ratio of peripheral oxygen saturation to fraction of inspired oxygen (S/F). The primary outcome was oxygenation at postanesthesia care unit admission (S/F). Secondary outcomes included the incidence of postoperative atelectasis and postoperative hospital length of stay. Post hoc, we defined high-dose neostigmine as more than 60 μg/kg and unwarranted use of neostigmine as neostigmine administration in the absence of appropriate neuromuscular transmission monitoring., Results: Neostigmine reversal did not improve S/F at postanesthesia care unit admission (164 [95% CI, 162 to 164] vs. 164 [161 to 164]) and was associated with an increased incidence of atelectasis (8.8% vs. 4.5%; odds ratio, 1.67 [1.07 to 2.59]). High-dose neostigmine was associated with longer time to postanesthesia care unit discharge readiness (176 min [165 to 188] vs. 157 min [153 to 160]) and longer postoperative hospital length of stay (2.9 days [2.7 to 3.2] vs. 2.8 days [2.8 to 2.9]). Unwarranted use of neostigmine (n = 492) was an independent predictor of pulmonary edema (odds ratio, 1.91 [1.21 to 3.00]) and reintubation (odds ratio, 3.68 [1.10 to 12.4])., Conclusions: Neostigmine reversal did not affect oxygenation but was associated with increased atelectasis. High-dose neostigmine or unwarranted use of neostigmine may translate to increased postoperative respiratory morbidity.

A 70-year-old man with Becker muscular dystrophy (BMD) underwent laparoscopic rectopexy under general anesthesia. For anesthetic induction, we administered total 0.6 mg · kg-1 of rocuronium with titration. Eight minutes later, train-of-four (TOF) count reached to 0 and the patient was intubated smoothly. One hundred and five minutes later, TOF ratio recovered to 100% and we administered rocuronium 10 mg additionally. Surgery was finished without any problems 95 minutes after thereafter. TOF ratio was 45% and we administered sugammadex 3 mg · kg-1, reversing neuromuscular blockade to TOF ratio 100% within 1.5 minute. The patient awoke clearly and respiratory condition was good. He was extubated without remaining neuromuscular blockade. Postoperative course was stable and there was no serious adverse effect on his muscular function intra- and post-operatively. In conclusion, rocuronium and sugammadex can be used safely and effectively in general anesthetic management for patients with muscular dystrophy. However, as the onset times and durations of these agents can be longer, we should administer these agents with titration carefully under periodic neuromuscular monitoring.

The anesthetic management of patients affected by myasthenia gravis is usually challenging in elective surgery and even more so in emergency procedures. The difficulties involved are several-fold, ranging from the choice of an appropriate muscle relaxant (i.e. one that enables safe and rapid airway management) to neuromuscular monitoring and normal muscular recovery. Additionally, optimizing patient conditions - either pharmacologically or with plasmapheresis - before intervention is well beyond the realm of possibility. We discuss the anesthetic management of two myasthenic patients undergoing emergency surgery (for sigmoid perforation and upper gastrointestinal bleeding respectively). In both cases, we opted for rapid-sequence induction with high-dose rocuronium to prevent inhalation of gastric contents. We also report on the implication of neuromuscular monitoring. We found that the rocuronium-sugammadex combination was a useful and effective option in the emergency setting., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients., Methods: We studied 98 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional doses of rocuronium or vecuronium for maintenance of moderate block. At T2 reappearance sugammadex 0-4.0 mg . kg-1 was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation., Results: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 82.1 min in the placebo group to 1.8 min in the 4.0 mg . kg-1 sugammadex group. For the vecuronium-induced neuromuscular block, it decreased from 83.2 min in the placebo group to 2.1 min in the sugammadex 4.0 mg . kg-1 group. Plasma concentrations of sugammadex were approximately dose proportional over the dose range of 0.5 to 4.0 mg . kg-1 and independent of the neuromuscular blocking agents used. No clinical evidence of recurarization or residual curarization was observed., Conclusions: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients.

Background: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients., Methods: We studied 99 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional dose of rocuronium or vecuronium for maintenance of deep block. At 1-2 PTC, 0.5-8.0 mg . kg-1 of sugammadex was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation., Results: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 66.9 min in the sugammadex 0.5 mg kg-1 group to 1.3 min in the sugammadex 8.0 mg kg-1 group. For the vecuronium-induced neuromuscular block it decreased from 79.5 min in the sugammadex 0.5 mg . kg-1 group to 2.9 min in the sugammadex 8.0 mg . kg-1 group. No clinical evidence of recurarization or residual curarization was observed., Conclusions: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients for reversal from deep block.

Background: Quality of postoperative recovery is an important outcome after surgery. An observational cohort study was designed to assess the quality of postoperative recovery using the Portuguese version of the Postoperative Quality Recovery Scale (PQRS) in patients treated with neostigmine vs. sugammadex as neuromuscular blocking reversal agents., Methods: A convenience sample of 101 adult patients undergoing elective surgery with general anaesthesia and treated with neostigmine (n=48) or sugammadex (n=53) as neuromuscular blocking reversal agents was included. Patients were evaluated using the Portuguese PQRS version at baseline and postoperatively at 15 (T15) and 40 (T40) min and also at days 1 and 3. Recovery was defined as return to baseline values (or better) at each time points., Results: The PQRS overall recovery rates were similar in both groups, but recoveries in the nociceptive (96.2% vs. 81.3%, P=0.02) and physiological (96.2% vs. 70.2%, P=0.001) domains at T40 were higher in the sugammadex group than in the neostigmine group. Also, there was a trend that patients treated with sugammadex reported significantly better global perspective on the impact of surgery on working capacity and daily activities, as well as higher satisfaction with anaesthetic care., Conclusions: This pilot study suggests that sugammadex may improve physiological and nociceptive postoperative recovery as well as patient satisfaction with anaesthetic care. Although we lack an explanation for a possible favourable impact of sugammadex on quality of recovery, our results may provide sufficient preliminary data to justify a randomised trial to explore this possibility., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: The effectiveness of sugammadex in reversing rocuronium-induced neuromuscular blockade (NMB) in the presence of drugs that may potentiate NMB remains to be fully established. The aim of this post-hoc analysis of data from a Phase III clinical trial (VISTA; NCT00298831) was to investigate the impact of antibiotics on recovery from rocuronium-induced NMB after administration of sugammadex for reversal, and compared the neuromuscular recovery in patients who received antibiotics preoperatively with those who did not., Methods: A Phase III, multicenter, open-label study designed to reflect potential use of sugammadex in clinical practice was conducted at 19 sites. Data obtained from patients who received antibiotics were compared with the cohort of patients who underwent the same protocol without antibiotics. Each subject received rocuronium 0.6 mg/kg for muscle relaxation, after which tracheal intubation was performed; patients were also permitted to receive maintenance doses of rocuronium 0.15 mg/kg to maintain the desired level of NMB throughout the operation, as required.. At least 15 min after the last rocuronium dose, patients received sugammadex 4.0 mg/kg for reversal. Neuromuscular monitoring was continued until a train-of-four (TOF) ratio of ≥0.9 was achieved or the anesthetic was discontinued., Results: The presence of antibiotics prior to the administration of sugammadex did not affect the recovery time from rocuronium-induced NMB when sugammadex 4.0 mg/kg was administered at least 15 min after the last dose of rocuronium. In the presence of antibiotics, the geometric mean (95% CI) time from administration of sugammadex 4.0 mg/kg to recovery of the TOF ratio to ≥0.9 was 1.6 (1.4-1.9) min (range: 0.7-10.5 min), compared with 2.0 (1.8-2.3) min (range: 0.7-22.3 min) for patients who did not receive antibiotics., Conclusions: These findings suggest that prophylactic antibiotic use is unlikely to have a major impact on the recovery time from rocuronium-induced NMB with sugammadex reversal., Trial Registration: ClinicalTrials.gov Identifier: NCT00298831.

Background: This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 μg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects., Methods: This was a randomized, active-controlled, multicenter, safety-assessor-blinded study (NCT00825812) in American Society of Anesthesiologists Class 1-3 subjects undergoing surgery with propofol anesthesia. Rocuronium 0.6 mg/kg was administered for endotracheal intubation, with 0.1-0.2 mg/kg maintenance doses given as required. NMB was monitored using TOF-Watch(®) SX. At second twitch reappearance, after last rocuronium dose, subjects received sugammadex 2 mg/kg or neostigmine 50 μg/kg plus atropine 10-20 μg/kg, according to randomization. Primary efficacy variable was time from sugammadex/neostigmine to recovery of the train-of-four (TOF) ratio to 0.9., Results: Overall, 230 Chinese subjects (sugammadex, n = 119, neostigmine, n = 111); and 59 Caucasian subjects (sugammadex, n = 29, neostigmine, n = 30) had evaluable data. Geometric mean (95% CI) time to recovery to TOF ratio 0.9 was 1.6 (1.5-1.7) min with sugammadex vs 9.1 (8.0-10.3) min with neostigmine in Chinese subjects. Corresponding times for Caucasian subjects were 1.4 (1.3-1.5) min and 6.7 (5.5-8.0) min, respectively. Sugammadex 2 mg/kg was generally well tolerated, with no serious adverse events reported. There was no residual NMB or recurrence of NMB., Conclusion: Both Chinese and Caucasian subjects recovered from NMB significantly faster after sugammadex 2 mg/kg vs neostigmine 50 μg/kg, with a ~5.7 times (p < 0.0001) faster recovery with sugammadex vs neostigmine in Chinese subjects. Sugammadex was generally well tolerated., Trial Registration: ClinicalTrials.gov Identifier: NCT00825812.

Background: Magnesium enhances the effect of rocuronium. Sugammadex reverses rocuronium-induced neuromuscular block. The authors investigated whether magnesium decreased the efficacy of sugammadex for the reversal of rocuronium-induced neuromuscular block., Methods: Thirty-two male patients were randomized in a double-blinded manner to receive magnesium sulfate (MgSO4) 60 mg/kg or placebo intravenously before induction of anesthesia with propofol, sufentanil, and rocuronium 0.6 mg/kg. Neuromuscular transmission was monitored using TOF-Watch SX acceleromyography (Organon Ltd., Dublin, Ireland). In 16 patients, sugammadex 2 mg/kg was administered intravenously at reappearance of the second twitch of the train-of-four (moderate block). In 16 further patients, sugammadex 4 mg/kg was administered intravenously at posttetanic count 1 to 2 (deep block). Primary endpoint was recovery time from injection of sugammadex to normalized train-of-four ratio 0.9. Secondary endpoint was recovery time to final T1., Results: Average time for reversal of moderate block was 1.69 min (SD, 0.81) in patients pretreated with MgSO4 and 1.76 min (1.13) in those pretreated with placebo (P = 0.897). Average time for reversal of deep block was 1.77 min (0.83) in patients pretreated with MgSO4 and 1.98 min (0.58) in those pretreated with placebo (P = 0.572). Times to final T1 were longer compared with times to normalized train-of-four ratio 0.9, without any difference between patients pretreated with MgSO4 or placebo., Conclusion: Pretreatment with a single intravenous dose of MgSO4 60 mg/kg does not decrease the efficacy of recommended doses of sugammadex for the reversal of a moderate and deep neuromuscular block induced by an intubation dose of rocuronium.

Sugammadex is the first selective relaxant binding agent. It allows rapid reversal of any degree of neuromuscular blockade induced by steroidal neuromuscular blocking agents. Sugammadex acts by encapsulation of the neuromuscular blocking agent. This prevents the drug from acting on prejunctional and postjunctional nicotinic receptors, allowing acetylcholine to activate these receptors, and resulting in reversal of the neuromuscular blockade. Objective monitoring of the degree of neuromuscular blockade is strongly recommended to determine the optimal dose of sugammadex. A good understanding of the concept behind sugammadex is essential in order to use this reversal agent in clinical practice., (Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.)

A number of case reports now indicate that rocuronium can induce a number of serious side effects. We hypothesized that these side effects might be mediated by the inhibition of nicotinic acetylcholine receptors (nAChRs) at superior cervical ganglion (SCG) neurons. Conventional patch clamp recordings were used to study the effects of rocuronium on nAChR currents from enzymatically dissociated rat SCG neurons. We found that ACh induced a peak transient inward current in rat SCG neurons. Additionally, rocuronium suppressed the peak ACh-evoked currents in rat SCG neurons in a concentration-dependent and competitive manner, and it increased the extent of desensitization of nAChRs. The inhibitory rate of rocuronium on nAChR currents did not change significantly at membrane potentials between -70 and -20 mV, suggesting that this inhibition was voltage independent. Lastly, rocuronium preapplication enhanced its inhibitory effect, indicating that this drug might prefer to act on the closed state of nAChR channels. In conclusion, rocuronium, at clinically relevant concentrations, directly inhibits nAChRs at the SCG by interacting with both opened and closed states. This inhibition is competitive, dose dependent, and voltage independent. Blockade of synaptic transmission in the sympathetic ganglia by rocuronium might have potentially inhibitory effects on the cardiovascular system.

Unlabelled: The required characteristics of neuromuscular blockers for rapid sequence induction (RSI) are clearly defined: nearly immediate effectiveness and short duration of effect. These demands are not only necessary for ideal conditions of quick endotracheal intubation without mask-bag intermediate ventilation but are also essential to enable a quick return to sufficient spontaneous breathing in case of a cannot intubate cannot ventilate situation. Until recently only succinylcholine had these characteristics; however, a considerable number of dangerous side effects and contraindications had to be accepted. In 1996, rocuronium was introduced, which was capable of immediately establishing good intubation conditions similar to succinylcholine. However, the median duration of effect is 45-60 min and it therefore contains a risk if the patient cannot be ventilated and oxygenated. Therefore, rocuronium is considered a good alternative but not a complete substitute for succinylcholine. The introduction of sugammadex in 2008 for quick reversal of rocuronium changed matters. Comparative studies from the past 4 years dealing with rocuronium/sugammadex versus uccinylcholine in RSI showed that rocuronium and sugammadex combined enabled a significantly faster return to sufficient spontaneous ventilation in emergency situations and also proved that the use of rocuronium significantly reduced the degree of desaturation during the interval between injection and ventilation postintubation., Conclusion: rocuronium used in hospital is a very good substitute for succinylcholine as a neuromuscular blocker during RSI as long as sugammadex is at hand for reversal. It remains to be considered that in a situation with severe problems of the airway and breathing, which are the main preclinical indications for intubation, a forward strategy for ventilation of the patient is the only acceptable way in most cases and the return to spontaneous breathing is not an alternative. Therefore, the value of sugammadex and also of succinylcholine is limited for these situations. Additionally, economic factors such as storage conditions for rocuronium and the cost of sugammadex must also be considered.

Background: We investigated whether sugammadex could reverse neuromuscular blockade induced by rocuronium in patients for cesarean delivery treated with magnesium sulfate preoperatively., Methods: Twenty-three pregnant women received general anesthesia induced with thiopental and rocuronium. They were maintained by nitrous oxide, oxygen and sevoflurane (GOS) before delivery and after delivery by GOS, midazolam, and propofol. After the surgery, the patients with two or more counts of train-of-four (TOF), the moderate block group were classified into Mg (-) M and Mg (+) M, depending whether magnesium sulfate had been injected or not, and sugammadex 2 mg x kg(-1) was administered to both groups. Patients with PTC 2 or more, the profound block group, were classified into Mg (-) P or Mg (+) P and sugammadex 4 mg x kg(-1) was administered to both groups. Recovery time was defined as the time required to reach TOFR 0.9 or more after the injection of sugammadex., Results: Median recovery times of the Mg (-) M, the Mg (-) P, the Mg (+) M and the Mg (+) P were 63 seconds (range: 26-130, N = 7), 127 seconds (range: 63-228, N = 7), 104 seconds (range: 67-133, N = 5), and 142 seconds (range: 57-209, N = 4), respectively., Conclusions: Sugammadex could reverse rocuronium-induced neuromuscular blockade in a dose-response manner even in the patients treated with magnesium sulfate.

Background: The routine use of neuromuscular blocking agents reduces the occurrence of unacceptable surgical conditions. In some surgeries, such as retroperitoneal laparoscopies, deep neuromuscular block (NMB) may further improve surgical conditions compared with moderate NMB. In this study, the effect of deep NMB on surgical conditions was assessed., Methods: Twenty-four patients undergoing elective laparoscopic surgery for prostatectomy or nephrectomy were randomized to receive moderate NMB (train-of-four 1-2) using the combination of atracurium/mivacurium, or deep NMB (post-tetanic count 1-2) using high-dose rocuronium. After surgery, NMB was antagonized with neostigmine (moderate NMB), or sugammadex (deep NMB). During all surgeries, one surgeon scored the quality of surgical conditions using a five-point surgical rating scale (SRS) ranging from 1 (extremely poor conditions) to 5 (optimal conditions). Video images were obtained and 12 anaesthetists rated a random selection of images., Results: Mean (standard deviation) SRS was 4.0 (0.4) during moderate and 4.7 (0.4) during deep NMB (P<0.001). Moderate block resulted in 18% of scores at the low end of the scale (Scores 1-3); deep block resulted in 99% of scores at the high end of the scale (Scores 4 and 5). Cardiorespiratory conditions were similar during and after surgery in both groups. Between anaesthetists and surgeon, there was poor agreement between scores of individual images (average κ statistic 0.05)., Conclusions: Application of the five-point SRS showed that deep NMB results in an improved quality of surgical conditions compared with moderate block in retroperitoneal laparoscopies, without compromise to the patients' peri- and postoperative cardiorespiratory conditions. Trial registration The study was registered at clinicaltrials.gov under number NCT01361149.

A 32-year-old pregnant woman (height 162 cm, weight 86 kg, age of fetus 25 weeks) without preoperative complications underwent an emergent cesarean section under general anesthesia. She was intubated with a 7.0-mm tracheal tube 40 s after receiving rocuronium 0.93 mg x kg(-1) and thiamilal 375 mg. Anesthesia was maintained with oxygen, air, sevoflurane 1.0-2.5%, and fentanyl 425 microg. Nine minutes after the end of surgery (operation time 71 minutes), a train-of-four count of 2 with 20 spontaneous breaths was noted, and sugammadex 2.3 mg x kg(-1) was administered. However, the train-of-four count was 3 even five minutes after sugammadex administration. Fifteen minutes after sugammadex administration (train-of-four ratio 14%), she received atropine 0.5 mg and neostigmine 1.0 mg. Ten minutes later, the train-of-four ratio increased to 89%, and the patient was successfully extubated with no respiratory suppression. We speculate that the rocuronium dose (0.93 mg x kg(-1)) was too high in this obese patient, and sugammadex dose at the end of the surgery was not enough for reversal of rocuronium-induced neuromuscular blockade.

This study evaluated and explored time course, efficacy, relation, safety, changes in heart rate, and blood pressure after a bolus dose of sugammadex or neostigmine for reversal of a prolonged rocuronium and vecuronium induced neuromuscular block. A total of 60 patients of both sexes, 'ASA' grade I, II and all were scheduled for elective surgery of 30-45 minutes duration. Informed oral consent was obtained from all patients to participate in this study. The results showed statistically significant progressive decrease of heart rate and blood pressure at 2, 5 and 10 minutes when compared to their basal values before anesthesia, then it starts to gain its normal value at 5 and 10 minutes, regardless the dose of sugammadex (effect of anesthesia). Also, heart rate and blood pressure showed statistically non-significant variance between groups of sugammadex when compared at any time of the study with the neostigmine groups (i.e. no effect of the dose on heart rate).

Introduction: Seven Neuromuscular Blocking Agents (NMBA) are commercialized in France. Four of them have an intermediate duration of action. Sugammadex required the use of NMBA slightly employed in clinical practice in France. Its introduction in routine practice could have an impact on NMBA use in clinical practice. This study was then conducted to assess and compare NMBA use before and after the commercialization of sugammadex., Materials and Methods: A longitudinal, retrospective, observational study was conducted between 2008 and 2011 in French university hospitals and military hospitals. The consumption data for sugammadex and NMBA were collected using a collection grid which was filled by pharmacists or anesthesiologists. Drug use was measured by the number of vials used divided by the annual number of hospitalizations in surgery and obstetrics (HSO). An overall analysis of the annual frequency of NMBA use was firstly performed, then individual data of each hospital were analyzed. Descriptive statistical analysis including mean, standard deviation, median, minimum and maximum was achieved., Results: Thirty-four out of 39 hospitals participated in the study (87%) and analysis was performed on 26 of them (7%). The data of eight institutions were excluded due to missing values or because of the non-admission of sugammadex in their formulary. The NMBA mostly used were non-steroidal NMBA (75% of market share) with an increased use between 2008 and 2011 concerning atracurium (from 41 to 51 vials of 50mg atracurium used per 100 HSO). The overall analysis revealed an increase of the occurrence of rocuronium (between 2008 and 2011: from 1 to 4.8 vials of 50mg rocuronium used per 100 HSO). Individual analyses on each hospital showed a possible effect of sugammadex introduction on NMBA use in nine hospitals., Discussion and Conclusions: The commercialization of sugammadex seems to have induced a discrete increase of steroidal NMBA but non-steroidal NMBA remain the leading agent in France. A long-term follow-up is deserved., (Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Blockade of neuromuscular conductivity is a considered one of basic part of a patient protection in a concept of a balanced multicomponent anesthesia. The controlled neuromuscular paralysis in a combination of a sedation, an analgesia and a hyporeflection not only provides comfortable conditions to surgeons for carrying out surgeries, but also allows to manage a gas exchange, blood circulation and a metabolism in a patient. However in clinical practice there is such complication after application of muscular relaxant (not depolarizing) as a residual curarization. The residual curarization is interfaced to deterioration of the respiratory answer to a hypoxemia, swallowing dysfunction that significantly increased risk of aspiration and risk of postoperative pulmonary complications. Until recent time acetylcholinesterase inhibitors or prolonged ALV before spontaneous regression of the neuromuscular block were applied in clinical practice for the purpose of restoration of adequate neuromuscular conductivity and elimination of a residual curarization. However there are number of the circumstances limiting application of preparations of this group including it is related with rather high frequency of side effects and lack of efficiency at the deep neuromuscular block. Today in an arsenal of the anesthesiologist there was the latest chemical - sugammadex. Sugammadex realizes a new approach to restoration of the neuromuscular conductivity.

Background: This 'real-life' study aimed to analyze the time from the start of neostigmine or sugammadex administration to recovery to a train of four ratio (TOFr) of 0.9 in a real-life in patients receiving rocuronium. The secondary aims were to assess the proportion of patients: presenting TOFr < 0.9 after 5, 10, and 20 min from reversal agent administration, receiving opioids for intraoperative analgesia and extubated in the post-anesthesia care unit (PACU)., Methods: This was a multisite, prospective, nonrandomized, observational real-life study. Reversal agent was administered at either T2 reappearance or at a post-tetanic count of 1 or 2. Drugs dosages were free according to each investigator's usual practice., Results: Three hundred fifty-nine patients were enrolled onto the study. Time from reversal administration to TOFr to 0.9 is significantly faster in the sugammadex group than in the neostigmine group (shallow block: 2.2 vs. 6.9 min, respectively; P < 0.0001; deep block: 2.7 vs. 16.2 min, respectively; P < 0.0001). The number of patients with TOFr < 0.9 at 5, 10, and 20 min post-reversal agent administration was higher in the neostigmine than in the sugammadex group. Just five patients did not receive opioids. All patients were extubated in the operative room except for a single patient in the sugammadex group who was extubated following PACU admission., Conclusions: This real-life study confirms that reversal time is faster in patients receiving sugammadex than in those receiving neostigmine. TOFr < 0.9 20 min after reversal was only present in patients treated with neostigmine., (© 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Myotonic dystrophy type 1 (MD1) is the commonest muscular dystrophy found in adults; however, it may present in the neonatal period with hypotonia, talipes, poor feeding, and respiratory failure. Inheritance is autosomal dominant with a defect in the DMPK gene found on the long arm of chromosome 19 with variable expansion of the cytosine-thymine-guanine (CTG) triplet repeat. A 14-month-old boy with congenital MD type 1 was scheduled for percutaneous endoscopic gastrostomy (PEG) insertion, orchidopexy, and division of tongue-tie. Following induction of anesthesia, acceleromyography was used to monitor neuromuscular function. This revealed a very rapid onset of profound neuromuscular block which lasted significantly longer than would be expected in a child without MD1. Sugammadex reversed the block rapidly. The anesthetic management of children with MD1 has been well described but not the acceleromyographic monitored use of rocuronium and its subsequent reversal with the new cyclodextrin sugammadex., (© 2013 John Wiley & Sons Ltd.)

Introduction: To evaluate whether calabadion 1, an acyclic member of the Cucurbit[n]uril family of molecular containers, reverses benzylisoquinoline and steroidal neuromuscular-blocking agent effects., Methods: A total of 60 rats were anesthetized, tracheotomized, and instrumented with IV and arterial catheters. Rocuronium (3.5 mg/kg) or cisatracurium (0.6 mg/kg) was administered and neuromuscular transmission quantified by acceleromyography. Calabadion 1 at 30, 60, and 90 mg/kg (for rocuronium) or 90, 120, and 150 mg/kg (for cisatracurium), or neostigmine/glycopyrrolate at 0.06/0.012 mg/kg were administered at maximum twitch depression, and renal calabadion 1 elimination was determined by using a H NMR assay. The authors also measured heart rate, arterial blood gas parameters, and arterial blood pressure., Results: After the administration of rocuronium, resumption of spontaneous breathing and recovery of train-of-four ratio to 0.9 were accelerated from 12.3 ± 1.1 and 16.2 ± 3.3 min with placebo to 4.6 ± 1.8 min with neostigmine/glycopyrrolate to 15 ± 8 and 84 ± 33 s with calabadion 1 (90 mg/kg), respectively. After the administration of cisatracurium, recovery of breathing and train-of-four ratio of 0.9 were accelerated from 8.7 ± 2.8 and 9.9 ± 1.7 min with placebo to 2.8 ± 0.8 and 7.6 ± 2.1 min with neostigmine/glycopyrrolate to 47 ± 13 and 87 ± 16 s with calabadion 1 (150 mg/kg), respectively. Calabadion 1 did not affect heart rate, mean arterial blood pressure, pH, carbon dioxide pressure, and oxygen tension. More than 90% of the IV administered calabadion 1 appeared in the urine within 1 h., Conclusion: Calabadion 1 is a new drug for rapid and complete reversal of the effects of steroidal and benzylisoquinoline neuromuscular-blocking agents.

A 53-year-old man with hypopharyngeal stenosis following curative chemoradiotherapy for a tongue base tumour presented three years later for an attempt at pharyngeal dilatation. The first attempt 6 months previously was abandoned when awake fibreoptic intubation failed due to partial airway obstruction and desaturation when the fibrescope was advanced. As mask ventilation was anticipated to be possible, a further attempt at intubation after induction of anaesthesia was judged appropriate. The backup plan was jet ventilation via a cricothyroid cannula sited pre-induction. However, neither mask nor jet ventilation proved possible after the induction of anaesthesia and neuromuscular blockade with rocuronium. Swift administration of sugammadex on a background of thorough pre-oxygenation allowed return of spontaneous breathing before the development of hypoxia and so avoided the need for surgical airway rescue. This case demonstrates the utility of sugammadex in restoring spontaneous respiration in a 'can't ventilate' scenario, provided that the airway has not been traumatised by instrumentation., (© 2013 The Association of Anaesthetists of Great Britain and Ireland.)

We report a patient with myasthenia gravis whose rocuronium induced neuromuscular block was reversed with sugammadex. A 26-year-old man, 175 cm and 76 kg, with myasthenia gravis, was scheduled for extended thymectomy under general anesthesia. An epidural catheter was inserted at the T5-6 interspace before induction of general anesthesia. Anesthesia was induced with propofol and remifentanil. Rocuronium was given in divided doses to obtain > 95% neuromuscular block to intubate the trachea. The ED50 and ED95 of rocuronium for this patient were 0.18 mg x kg(-1) and 0.39 mg x kg(-1), respectively. The values were similar to the ED50 and ED95 of rocuronium for normal patients. General anesthesia was maintained with propofol and remifentanil. Additional doses of rocuronium were given intermittently. Sugammadex, 2 mg x kg(-1), was given at the end of the surgery. The train-of-four ratio reached 93% 105 sec later. His postoperative course was uneventful.

Background: Doses of sugammadex required to reverse deep, moderate, and shallow rocuronium-induced neuromuscular blockade have been established. However, no adequate doses for the reversal of reappearance of four twitches of train-of-four (TOF) stimulation (threshold TOF-count-four) have been established., Methods: This single-center, randomized, controlled, double-blind, four-groups parallel-arm study included 80 patients undergoing general anesthesia with propofol, sevoflurane, fentanyl, and rocuronium. Neuromuscular monitoring was performed with calibrated acceleromyography. Once rocuronium-induced neuromuscular blockade recovered spontaneously to threshold TOF-count-four, patients randomly received 0.5, 1.0, 2.0 mg/kg of sugammadex or 0.05 mg/kg of neostigmine. The time between study drug injection and reversal of TOF ratios to 1.0 was measured. Rapid reversal (≤2.0 min average, upper limit of 5.0 min) was the primary endpoint and slower reversal (≤5.0 min average, upper limit of 10 min) was the secondary endpoint of the study., Results: Sugammadex, in doses of 1.0 and 2.0 mg/kg, reversed threshold TOF-count-four to TOF ratios of 1.0 in 2.1±0.8 min (mean±SD) and 1.8±0.9 min, respectively. Sugammadex, 0.5 mg/kg, induced a similar degree of reversal in 4.1±1.9 min (P<0.001 vs. 1.0 and 2.0 mg/kg). Neostigmine, 0.05 mg/kg, reversed TOF ratios to 1.0 in 8.5±3.5 min (P<0.001 vs. sugammadex groups)., Conclusion: Sugammadex, 1.0 mg/kg, rapidly and effectively reverses rocuronium-induced block that has recovered spontaneously to a threshold TOF-count-four. A dose of 0.5 mg/kg was equally effective, but satisfactory antagonism took as long as 8 min to take place.

Background: The use of neuromuscular blocking agents is still controversial in myasthenic patients but rocuronium could be useful after the introduction of sugammadex as a selective antagonist. The aim of the study was to evaluate the use of rocuronium-sugammadex in myasthenic patients undergoing thoracoscopic thymectomy., Methods: After ethical approval, 10 myasthenic patients undergoing videothoracoscopic-assisted thymectomy were enrolled in the study. Neuromuscular block was achieved with 0.3 mg/kg rocuronium and additional doses were given according to train-of-four (TOF) monitoring or movement of the diaphragm. Sugammadex 2 mg/kg was given after surgery. Recovery time (time to obtain a TOF value > 0.9) was recorded for all subjects., Result: All patients were extubated in the operating room after administration of sugammadex. Mean rocuronium dose was 48 mg and the average operation time was 62 min. Recovery time after sugammadex administration was 111 s (min 35; max 240)., Conclusions: A rapid recovery of neuromuscular function was found in myasthenic patients receiving rocuronium when sugammadex was used for reversal. This combination could be a rational alternative for myasthenic patients for whom neuromuscular blockade is mandatory during surgery., (© 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Sugammadex, the first selective relaxant-binding agent indicated to reverse the neuromuscular blockade induced during general anesthesia, was recently introduced into clinical practice. In the present report, the following issues pertinent to the use of sugammadex in anesthesia practice are discussed: the intraoperative use of NMBAs and the incidence of postoperative residual curarization (PORC); the efficacy and safety of rocuronium plus sugammadex compared to succinylcholine for rapid sequence induction; the availability of sugammadex in hospitals; and, finally, some relevant legal medical aspects. Sugammadex is considerably more expensive than neostigmine, but its use can be advocated based on its safety and efficacy profile as a reversal agent of steroidal neuro muscular blocking agents (NMBAs), and as a mean to prevent PORC. The availability of sugammadex in Italian hospitals may have a beneficial impact on patient safety. This is due to the fact that PORC is a common and dangerous condition that may lead to postoperative inhalational events, hypoxemia, and pneumonia; and at the moment, it is not completely preventable even when advanced neuro-muscolar monitoring techniques are applied". In the case of rapid sequence intubation (RSI), rocuronium (1.2 mg/kg) administration followed by sugammadex represents a better choice in terms of efficacy and safety than succinylcholine. If a new drug is proven to be safer and more efficient than the one it is replacing, hospitals should consider the new drug and make it available, at least for selected patients or in situations at risk of severe complications. It is reasonable to hypothesize that, when discussing informed consent for elective procedures, patients and families may want to know if the admitting facilities have the superior agent available, and that the absence of such agent could create concerns and complains.

A 51-year-old male patient with a diagnosis of refractory major depressive disorder and unresponsive to antidepressants underwent 8 sessions of electroconvulsive therapy (ECT) every 48 hours. Succinylcholine was used for muscle relaxation until the sixth ECT session, and midazolam was administered for severe emergence agitation that recurred after each session. In the sixth ECT session, rocuronium, 0.4 mg/kg, was used for muscle relaxation and sugammadex, 2 mg/kg, for reversal of muscle paralysis. Subsequently, a clear decrease in post-ECT agitation was observed. We suggest that this combination might be a safe and effective alternative to succinylcholine for post-ECT agitation.

Purpose: This study was conducted to (1) compare the recovery times from rocuronium-induced muscle relaxation after reversal with sugammadex between young and elderly patients undergoing electroconvulsive therapy (ECT), and (2) to examine the existence of a correlation between cardiac index and reversibility of rocuronium-induced neuromuscular block with sugammadex after ECT., Methods: Seventeen patients (young group, 50 years or younger, n = 8; elderly group, 70 years or older, n = 9) who were scheduled to undergo ECT were studied. Anesthesia was induced using propofol (1.0 mg/kg) followed by rocuronium (0.6 mg/kg). Assisted mask ventilation was initiated with 100% oxygen. Cardiac index was monitored noninvasively throughout the procedure. After the first twitch of the train of four (TOF) was assessed as being zero by neuromuscular monitoring, an electroshock stimulus was applied bilaterally. Immediately after the seizure stopped, patients were given 8-mg/kg sugammadex intravenously to reverse the muscle relaxation. Neuromuscular monitoring was continued until recovery of the TOF ratio to 0.9 at the tibial nerve in the leg. The time to recovery of the TOF to 0.1 and 0.9 was compared in both groups., Results: Although no significant difference in return to a TOF of 0.1 was found between the groups, there were significant differences in both recovery to a TOF of 0.9 and the time interval to the first spontaneous breath between groups (time to recovery to a TOF of 0.9, young group, 403 ± 37 seconds; elderly group, 443 ± 36 seconds; P < 0.05). In contrast, there was no relationship between cardiac index after ECT and recovery time to TOF of 0.9., Conclusions: Although recovery time to TOF of 0.9 after the administration of 8.0-mg/kg sugammadex was longer in the elderly patients than in the young patients, it had no relationship with cardiac output after ECT.

Neuromuscular blockers (NMBs) provide good conditions for endotracheal intubation and surgery. NMBs have been associated with higher morbidity and mortality, mainly due to post-operative residual neuromuscular block. This may become history with the advent of sugammadex - an antidote to the NMB rocuronium - which within 1-3 minutes neutralizes the effects of rocuronium. High-dose rocuronium is now an alternative to suxamethonium in acute or short procedures and in a situation, where ventilation/intubating cannot be performed, sugammadex can reverse the rocuronium blockade within minutes.

Sugamnmadex is a new type agent for reversal of neuromuscular blockade in any stage. There are foreign and home sugammadex use studies; however the information of sugammadex use in Pediatric patients is not enough. The article deals with study results of sugammadex use in Pediatric surgical oncology for the reversal of neuromuscular blockade by the agent rocuronium. 42 Pediatric patients in age from 2 to 17 years after elective oncology surgeries were recruited in the study. The speed and entirety of myorelaxation shifting as an evidence of sugammadex effectiveness were assessed by the accelerometer.

Content: Strumpell-Lorrain disease--or familial spastic paraplegia (FSP)--is a rare hereditary neurological disorder, mainly characterized by variable degrees of stiffness and weakening of the muscles, with cognitive impairment, deafness, and ataxia in the more severe cases. We describe two female siblings with FSP programmed for cholecystectomy and subtotal colectomy, respectively, and also how we dealt with the anesthetic management in both cases and review the literature on this disease in relation to anesthesia., (Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Sugammadex was synthesized as a selective reversal agent for rocuronium, a steroidal non-depolarizing neuromuscular blocking (NMB) agent. Sugammadex exerts its effect by forming very tight water-soluble complexes at a 1 : 1 ratio with steroidal NMB agents. Because the reversal of NMB could not sufficiently be completed by anti-cholinesterase agents such as neostigmine, we often had to wait until their spontaneous recovery. Sugammadex altered the situation because of its rapid and potent antagonistic action. The rapid reversal can be explained by rapid redistribution of free rocuronium from the neuromuscular junction to the plasma. The reversal effects are not influenced by anesthetics. There is no interaction with cholinergic systems. Therefore, undesired side effects attendant with anti-cholinesterases are not seen. This article provides information on the characteristics and effectiveness of sugammadex.

We report here an intellectually compromised 7-year-old boy with cerebral palsy who developed a hypersensitivity reaction several minutes after the administration of sugammadex for subsequent extubation. He developed signs of upper airway stenosis and decreased oxygen saturation, as well as wheals on his neck, chest, and both upper extremities. He was successfully treated with immediate administration of adrenaline and hydrocortisone. A hypersensitivity reaction to sugammadex was suspected on the basis of the patient's clinical course., (Copyright © 2012. Published by Elsevier B.V.)

Purpose: Rocuronium has been associated with muscle weakness when administered in prolonged infusions. The effect of sugammadex and rocuronium together on muscle is unknown. In this study, we examined the effects of rocuronium and sugammadex, and the complex formed by these agents, on cardiac and diaphragmatic muscle cells., Methods: Forty-two Sprague-Dawley male rats were divided into six groups. Group I received only rocuronium at a dose of 1 mg/kg and groups II and III received sugammadex alone at doses of 16 and 96 mg/kg, respectively. Groups IV and V received 1 mg/kg rocuronium plus 16 mg/kg sugammadex and 1 mg/kg rocuronium plus 96 mg/kg sugammadex, respectively. Group six was the control group and received only 0.9 % NaCl without any drug., Results: Histopathological examination demonstrated that rocuronium and high doses of sugammadex accumulated in both cardiac and diaphragm muscle tissues. We also observed intense edema and degeneration in diaphragmatic and myocardial cells when the rocuronium-sugammadex complex was used. Rocuronium and sugammadex remain in the circulation for a long time and they may cause skeletal muscle myopathy, vacuolization, pyknotic nuclear clumps, and hypertrophy, and weaken the muscle fibers., Conclusion: Rocuronium, sugammadex, and rocuronium-sugammadex complexes cause histopathological changes and immunoreactivity to calcineurin in muscle cells.