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Anaesthesia induced with remimazolam and a fentanyl-series opioid can be reversed with flumazenil and naloxone. Concomitant paralysis with rocuronium can facilitate tracheal intubation whilst being reversible with sugammadex. Together, this combination might offer full reversibility of a 'routine' or a 'rapid-sequence' induction anaesthesia. Whether this is useful, or even safe, requires careful evaluation., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Congenital muscular dystrophies are characterised by progressive skeletal muscle weakness from birth or early infancy. Maternal respiratory compromise, joint contractures and presence of spinal instrumentation or fusion are some of the anaesthetic challenges that may be encountered in the obstetric setting. The choice of anaesthetic technique for surgical delivery needs to be considered on an individual basis. Multidisciplinary involvement is paramount to optimise peripartum care and outcomes. In this case report, we present the use of dexmedetomidine, humidified high-flow nasal oxygen, rocuronium and sugammadex in the anaesthetic management of a wheelchair-bound, non-invasive bilevel positive airway pressure ventilation-dependent parturient with congenital muscular dystrophy, who was presenting for caesarean section., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To determine if reversing a deep or moderate block with sugammadex, compared with a shallow block reversed with neostigmine, reduces the time to operating room discharge after surgery and the time spent in the postanesthesia care unit., Design: A randomized controlled trial., Setting: Monocentric study performed from February 2011 until May 2012., Patients: One hundred consenting women with American Society of Anesthesiologists grade I or II were randomized into 2 groups., Intervention: Laparoscopic hysterectomy was performed under desflurane general anesthesia. For the neostigmine (N) group, 0.45 mg · kg -1 rocuronium was followed by spontaneous recovery. A 5-mg rescue bolus was administered only if surgical evaluation was unacceptable. At the end of surgery, 50 μg · kg -1 neostigmine with glycopyrrolate was administered. For the sugammadex (S) group, a higher intubating rocuronium dose (0.6 mg · kg -1 ) was followed by 5-mg boluses each time the train-of-four count exceeded 2. Sugammadex (2-4 mg · kg -1 ) was administered to reverse the block. All patients were extubated after obtaining a train-of-four ratio of 0.9., Measurements: The duration between the end of surgery and operating room discharge and the time spent in the postanesthesia care unit., Main Results: The time till operating room discharge was shorter and more predictable in group S (9.15±4.28 minutes vs 13.87±11.43 minutes in group N; P=.005). The maximal duration in group S was 22 minutes, compared with 72 minutes in group N. The time spent in the postanesthesia care unit was not significantly different (group S: 47.75±31.77 minutes and group N: 53.43±40.57 minutes; P=.543)., Conclusion: Maintaining a deep neuromuscular block during laparoscopic hysterectomy reversed at the end of the procedure with sugammadex enabled a faster and more predictable time till operating room discharge than did the classical combination of a shallower block reversed with neostigmine., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objective: Sugammadex 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., Design: Meta-analysis of data about effectiveness and safety of sugammadex compared to neostigmine for reversing NMB in adults was performed using the PRISMA methodology., Setting: University medical hospital., Methods: A 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., Patients: A total of 1384 patients from 13 articles were included in this meta-analysis., Main Results: Compared 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)., Conclusions: Results 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Study Objective: To evaluate the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in infant patients., Design: Retrospective observational study., Setting: University teaching hospital., Patients: Twenty-six infants (2-12 months of age; 3-11 kg) with an American Society of Anesthesiologists classification I, II, or III who were scheduled to undergo neurosurgical procedures were included in the study., Interventions: Anesthesia was induced with 5 mg/kg thiopental, 1 μg/kg fentanyl and 0.6 mg/kg rocuronium. Sevoflurane was administered to all patients after intubation., Methods: The neuromuscular block was monitored with acceleromyography using train-of-four (TOF) stimuli. Patients received additional doses of rocuronium to maintain a deep block during surgery. If profound neuromuscular block (TOF, 0) persisted at the end of the surgery, 3mg/kg sugammadex was administered., Measurements: The demographic data, surgeries, and anesthetic agents were recorded. The time from sugammadex administration to recovery of neuromuscular function (TOF ratio, >0.9) and complications during and after extubation were also recorded., Main Results: Twenty-six infants who had a deep neuromuscular block (TOF, 0) at the end of surgery received 3 mg/kg sugammadex. The mean recovery time of the T4/T1 ratio of 0.9 was 112 seconds. No clinical evidence of recurarization or residual curarization was observed., Conclusions: The efficacy and safety of sugammadex were confirmed in infant surgical patients for reversal of deep neuromuscular block induced by rocuronium., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Study Objective: Sugammadex is an alternative drug to traditional decurarization by cholinesterase inhibitors. It has been examined the effect of sugammadex on steroid hormones in this study., Design: Randomized clinical trial., Setting: The study was conducted in a University Teaching Hospital from January 2013 to May 2014., Patients: Fifty male patients between 18 and 45years of age with an American Society of Anesthesiology (ASA) class I or II undergoing elective lower extremity surgery were included in this study., Interventions: Patients were categorized into two groups (neostigmin group, Group N; and sugammadex group, Group S). In addition to standard monitorization, train-of-four (TOF) was also used to monitorize the level of neuromuscular blockade. Standard induction and maintenance of anesthesia were performed. At the termination of surgery, neuromuscular blockade was antagonized using 0.05mg/kg of neostigmine and 0.01mg/kg of atropin when spontaneous recovery of neuromuscular blockade occurred with the reappearance of T2 in Group N and using 4mg/kg sugammadex in Group S., Measurements: The primary outcome in this study was to determine serum aldosterone, cortisol, progesterone, and free testosterone levels. Three blood samples were obtained in each patient just before and 15minutes and 4hours after antagonism,, Main Results: No significant differences were found in demographic characteristics between the groups. While there were no differences in serum progesterone levels, patients in neostigmin group had significantly higher cortisol levels at 15minutes as compared to baseline. Also, patients in sugammadex group had significantly higher serum aldosterone and testosterone levels 15minutes after antagonism as compared to those in the neostigmine group., Conclusions: Our findings suggest that sugammadex is not associated with adverse effects on steroid hormones progesterone and cortisol, while it may lead to a temporary increase in aldosterone and testosterone., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Wolff-Parkinson-White (WPW) syndrome is a rare pre-excitation syndrome which develops when atrioventricular conduction occurs through a pathologic accessory pathway known as the bundle of Kent instead of atrioventricular node, hence resulting in tachycardia. Patients with WPW syndrome may experience various symptoms arising from mild-to-moderate chest disease, palpitations, hypotension, and severe cardiopulmonary dysfunction. These patients are most often symptomatic because of cardiac arrhythmias. In this case report, we present an uneventful anesthetic management of a pregnant patient with WPW syndrome undergoing cesarean delivery. A 23-year-old American Society of Anesthesiologists class 2 pregnant patient was diagnosed with WPW syndrome. Her preoperative 12-lead electrocardiogram showed a sinus rhythm at 82 beats per minute, a delta wave, and a short PR interval. After an uneventful surgery, sugammadex 2mg/kg was administered as a reversal agent instead of neostigmine. Then she was discharged to her obstetrics service. Serious hemodynamic disorders may occur in patients with WPW syndrome due to development of fatal arrhythmias. Neostigmine used as a reversal agent in general anesthesia can trigger such fatal arrhythmias by leading changes in cardiac conduction. We believe that sugammadex, which is safely used in many areas in the scope of clinical practice, can be also used for patients diagnosed with WPW syndrome., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Study Objective: The aim of this study was to evaluate the efficacy of sugammadex in reversing profound rocuronium-induced neuromuscular block at the laryngeal adductor muscles using motor-evoked potentials (mMEPs)., Design: A prospective observational study., Setting: University surgical center., Patients: Twenty patients with American Society of Anesthesiologists physical class I-II status who underwent propofol-remifentanil anesthesia for the surgery of the thyroid gland., Interventions: Patients were enrolled for reversal of profound neuromuscular block (sugammadex 16 mg/kg, 3 minutes after rocuronium 1.2 mg/kg). To prevent laryngeal nerve injury during the surgical procedures, all patients underwent neurophysiologic monitoring using mMEPs from vocal muscles. At the same time, the registration of TOF-Watch acceleromyograph at the adductor pollicis muscle response to ulnar nerve stimulation was performed; recovery was defined as a train-of-four (TOF) ratio ≥0.9., Measurement and Main Results: After injection of 16 mg/kg of sugammadex, the mean time to recovery of the basal mMEPs response at the laryngeal adductor muscles was 70 ± 18.2 seconds. The mean time to recovery of the TOF ratio to 0.9 was 118 ± 80 seconds. In the postoperative period, 12 patients received follow-up evaluation of the vocal cords and no lesions caused by the surface laryngeal electrode during electrophysiological monitoring were noted., Conclusions: Recovery from profound rocuronium-induced block on the larynx is fast and complete with sugammadex. In urgent scenarios, "early" extubation can be performed, even with a TOF ratio ≤0.9. However, all procedures to prevent postoperative residual curarization should still be immediately undertaken., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The isolated forearm technique is used to monitor intraoperative awareness. However, this technique cannot be applied to patients who must be kept deeply paralysed for >1h, because the tourniquet preventing the neuromuscular blocking agent from paralysing the forearm must be deflated from time to time. To overcome this problem, we tested the feasibility of a 'reversed' isolated forearm technique., Methods: Patients received rocuronium 0.6 mg kg(-1) i.v. to achieve muscle paralysis. A tourniquet was then inflated around one upper arm to prevent further blood supply to the forearm. Sugammadex was injected into a vein of this isolated forearm to antagonize muscle paralysis regionally. A dose titration of sugammadex to antagonize muscle paralysis in the isolated forearm was performed in 10 patients, and the effects of the selected dose were observed in 10 additional patients., Results: The sugammadex dose required to antagonize muscle paralysis in the isolated forearm was 0.03 mg kg(-1) in 30 ml of 0.9% saline. Muscle paralysis was antagonized in the isolated forearm within 3.2 min in nine of 10 patients; the rest of the patients' bodies remained paralysed. Releasing the tourniquet 15 min later did not affect the train-of-four count in the isolated forearm but significantly increased the train-of-four count in the other arm by 7%., Conclusions: Regional antagonization of rocuronium-induced muscle paralysis using a sugammadex dose of 0.03 mg kg(-1) injected into an isolated forearm was feasible and did not have relevant systemic effects., Clinical Trial Registration: The trial was registered at EudraCT (ref. no. 2013-002164-53) before patient enrolment began., (© The Author 2016. 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: The aim of this dose-finding study was to evaluate the dose-response relationship of sugammadex and neostigmine to reverse a commonly observed level of incomplete recovery from rocuronium-induced neuromuscular block, that is, a train-of-four ratio (TOFR) ≥0.2., Methods: Ninety-nine anaesthetized patients received rocuronium 0.6 mg kg(-1) i.v. for tracheal intubation and, if necessary, incremental doses of 0.1-0.2 mg kg(-1). Neuromuscular monitoring was performed by calibrated electromyography. Once the TOFR recovered to 0.2, patients were randomized to receive sugammadex (0.25, 0.5, 0.75, 1.0, or 1.25 mg kg(-1) i.v.), neostigmine (10, 25, 40, 55, or 70 µg kg(-1) i.v.), or saline (n=9 per group). Primary and secondary end points were the doses necessary to restore neuromuscular function to a TOFR≥0.9 with an upper limit of 5 and 10 min for 95% of patients, respectively., Results: Neostigmine was not able to fulfil the end points. Based on the best-fitting model, the sugammadex dose estimation for recovery to a TOFR≥0.9 for 95% of patients within 5 and 10 min was 0.49 and 0.26 mg kg(-1), respectively., Conclusion: A residual neuromuscular block of a TOFR of 0.2 cannot be reversed reliably with neostigmine within 10 min. In the conditions studied, substantially lower doses of sugammadex than the approved dose of 2.0 mg kg(-1) may be sufficient to reverse residual rocuronium-induced neuromuscular block at a recovery of TOFR≥0.2., Clinical Trial Registration: NCT01006720., (© The Author 2016. 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: This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness., Methods: Adult patients undergoing abdominal surgery received rocuronium, followed by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual neuromuscular blockade at PACU admission, defined as a train-of-four (TOF) ratio <0.9, using TOF-Watch® SX. Key secondary endpoint was time between reversal agent administration and operating room discharge-readiness; analysed with analysis of covariance., Results: Of 154 patients randomized, 150 had a TOF value measured at PACU entry. Zero out of 74 sugammadex patients and 33 out of 76 (43.4%) usual care patients had TOF-Watch SX-assessed residual neuromuscular blockade at PACU admission (odds ratio 0.0, 95% CI [0-0.06], P<0.0001). Of these 33 usual care patients, 2 also had clinical evidence of partial paralysis. Time between reversal agent administration and operating room discharge-readiness was shorter for sugammadex vs usual care (14.7 vs. 18.6 min respectively; P=0.02)., Conclusions: After abdominal surgery, sugammadex reversal eliminated residual neuromuscular blockade in the PACU, and shortened the time from start of study medication administration to the time the patient was ready for discharge from the operating room., Clinical Trial Registration: Clinicaltrials.gov:NCT01479764., (© 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: 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.)

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.

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.)

Neuromuscular blocking agents have been implicated in 60-70% of anaphylactic events associated with anaesthesia. We report two cases of probable hypersensitivity reaction to sugammadex and an additional suspected but less supported case of possible immune-mediated reaction or other adverse reaction. The patients were given a bolus of sugammadex 100 mg immediately before extubation. In all three patients, a possible allergic reaction was suspected within 4 min of sugammadex administration, but with different degrees of severity. Skin testing was positive in two of these patients. Hypersensitivity to sugammadex unaccompanied by cardiovascular or respiratory symptoms might be missed during the course of anaesthesia. Careful monitoring for possible allergic responses is required in patients who have received sugammadex.

Study Objective: To evaluate the safety and efficacy of sugammadex for reversal of rocuronium-induced neuromuscular blockade in patients with pulmonary disease., Design: Phase III, randomized, multicenter, parallel-group, comparative, safety-assessor blinded study., Setting: Nine hospital sites., Patients: 77 ASA physical status 2 and 3 patients, aged ≥ 18 years, with a history of pulmonary disease, and scheduled for surgery with general anesthesia requiring neuromuscular blockade., Interventions: Following anesthesia induction, patients received rocuronium 0.6 mg/kg with 0.15 mg/kg maintenance doses as needed. Patients were randomized to receive sugammadex 2 mg/kg or 4 mg/kg after the last rocuronium dose at reappearance of the second twitch., Measurements: Safety evaluations included adverse events, laboratory parameters, vital signs, and evidence of recurrent or residual neuromuscular blockade. Efficacy was evaluated as the time from sugammadex administration to recovery of the train-of-four (TOF) ratio to ≥ 0.9., Main Results: Safety was comparable between doses, with no evidence of residual or recurrent neuromuscular blockade. Two bronchospasm cases were reported (4 mg/kg group), both in patients with asthma who received desflurane for anesthesia maintenance. Geometric mean (95% confidence interval) times to a TOF ratio of ≥ 0.9 were 2.1 (1.7 - 3.1) min (2 mg/kg) and 1.8 (1.5 - 2.7) min (4 mg/kg)., Conclusion: Sugammadex 2 mg/kg and 4 mg/kg were well tolerated and effective in patients with a history of pulmonary disease. Bronchospasm is a possibility when administering sugammadex to patients with underlying pulmonary disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A 78-yr-old woman presented for a panendoscopy to investigate dysphonia and dysphagia. Intubation was anticipated to be difficult but possible, and mask ventilation was anticipated to be possible. After induction of anaesthesia and after three attempts at intubation, a 'can't intubate, can ventilate' situation deteriorated to a 'can't intubate, can't ventilate' (CICV) situation. Rocuronium-induced neuromuscular block was successfully reversed with sugammadex, as evidenced by the restoration of diaphragmatic movement, the ability of the patient to move her limbs, and the presence of a train-of-four nerve stimulation with no fade; however, ventilation was still not possible. A cricothyroid puncture using a Ravussin needle was performed successfully to provide emergency oxygenation. A tracheostomy was performed to allow the panendoscopy. CICV situations are rare anaesthetic emergencies. While sugammadex can be relied upon to reverse rocuronium-induced neuromuscular block, it should not be relied upon to rescue all CICV events, especially where airway instrumentation has led to airway swelling. The availability of sugammadex does not obviate the need for emergency tracheal access in the event of failed oxygenation. The presence of head and neck pathology should lead to the consideration of securing the airway awake.

Background: Sugammadex is a modified γ-cyclodextrin with a novel mechanism of action for reversing the steroidal neuromuscular blocking agent rocuronium. Bispectral index (BIS) is an EEG-derived measure which can be sensitive to frontal electromyographic (EMG) artifacts. We compared BIS values before and after sugammadex or neostigmine neuromuscular block (NMB) reversal in patients with or without high EMG activity., Methods: During stable propofol/remifentanil anaesthesia and rocuronium-induced block, 48 patients were randomly allocated to receive sugammadex 4 mg kg(-1) or neostigmine 50 μg kg(-1)/glycopyrrolate 10 μg kg(-1), 10 min after the end of surgery., Results: Five minutes after sugammadex administration, mean BIS 50.1 (10.3) increased (P=0.018) to 61.7 (7.9) in 11 patients with high EMG activity. In contrast, BIS 49.3 (4.9) remained at 51.9 (5.4) in 13 patients who had no EMG activity. Fifteen minutes after neostigmine administration, mean BIS 51.9 (8.1) increased (P=0.007) to 63.9 (8.1) in 13 patients who had reappearance of muscle activity. However, in 11 patients who had no EMG activity, BIS 52.3 (7.4) remained at 53.3 (6.8). There was no significant difference between the sugammadex and neostigmine groups over time., Conclusions: We have shown that reversal of NMB with sugammadex or neostigmine increased BIS values dependent on the presence of EMG activity. Thus, the effect of muscle activity reappearance during rocuronium NMB reversal spuriously increasing the BIS value should be taken into consideration when relying on BIS monitoring for evaluating propofol/remifentanil recovery.

Background: Complete and fast recovery of neuromuscular function is very important in morbidly obese patients because of the possible influence of postoperative residual curarization (PORC) on respiratory function in the postoperative period. Recent reports underline incidences of the residual influence of neuromuscular blocking agents., Methods: Seventy morbidly obese (BMI >40 kg m(-2)) patients requiring general anaesthesia and receiving rocuronium for muscle relaxation were randomly assigned into two groups: at the end of the anaesthetic procedure, one group received sugammadex 2 mg kg(-1) of corrected body weight (Group SUG) and the other group received neostigmine 0.05 mg kg(-1) of CBW (Group NEO). At the end of surgery and when response reached a train-of-four (TOF) score of 2, patients received the study drugs. The neuromuscular function was recorded and time to achieve 90% of TOF (safe extubation) was measured. Patients were examined directly after arrival to the post-anaesthesia care unit (PACU) by a blinded investigator for the presence of PORC., Results: Thirty-five patients received sugammadex and 35 neostigmine. Mean dose of rocuronium was 87.9 vs 85.6 mg (P>0.05), mean time to 90% of TOF was 2.7 vs 9.6 min (P<0.05), and TOF at the PACU was 109.8% vs 85.5% (P<0.05) in Groups SUG and NEO, respectively., Conclusions: Administration of sugammadex provides fast recovery of neuromuscular function and prevents PORC in the morbidly obese, however neostigmine does not.

Postoperative curarization in patients has been established. Nevertheless, extremely prolonged neuromuscular blockades are rare. We report the case of a prolonged neuromuscular blockade (lasting 10 hours) following a single dose of rocuronium, in an elderly patient with severe renal failure. We have studied the possible causes of prolonged curarization, and discussed the interest of the use of sugammadex in such cases., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

We report a case of delayed rocuronium-induced deep block antagonization with sugammadex, thus requiring a total of three injections and a cumulative dose of 12 mg/kg over a 30 min period. The patient was an emergency case with full stomach that had required a rapid sequence induction. Because of hyperkaliemia due to an acute renal failure, rocuronium was preferred to succinylcholine. Use of sugammadex in the acute renal failure context is discussed., (2011 Elsevier Masson SAS. All rights reserved.)

Objective: Sugammadex reverses neuromuscular blockade by chemical encapsulation of nondepolarizing neuromuscular blocking drugs (rocuronium and vecuronium). The imprint of this new molecule has recently been supplemented with a section on haemostasis notifying a longer clotting time without documented clinical consequences. This has resulted in recommendations on the use of sugammadex in the presence of coagulation disorders (pharmacologically-induced or not). The objective of this study was to analyze the experience gathered with this molecule on clinically-evaluated bleeding. No study on this subject is currently available., Methods: This is a retrospective study over 1 year between August 2009 and August 2010. All patients with laparotomies for cancer surgery requiring suction drains were included. Patients were allocated to groups according to the type of reversal (without sugammadex versus sugammadex 2 or 4 mg/kg). The endpoint was clinically-evaluated postoperative bleeding (reoperation for haemostasis, blood-stained laparotomy dressings in the post-anaesthesia care unit [PACU], cumulative volume collected in suction drains upon arrival in PACU and then after 2 hours and the next morning at 6a.m)., Results: One hundred and ninety-three patients were included in three groups, 78 in the group "without sugammadex", 95 in "sugammadex 2mg/kg" and 20 in "sugammadex 4 mg/kg". There were no reoperations for haemostasis. The comparison among different groups for the endpoint of bleeding showed no significant difference., Conclusion: In this retrospective study performed in patients at high risk of postoperative bleeding, sugammadex at doses of 2 and 4 mg/kg was not associated with increased bleeding. This study, the first in this field, suggests that future prospective investigations should target patients receiving 4 or 16 mg/kg of sugammadex and/or with documented preoperative abnormal coagulations tests., (2011 Elsevier Masson SAS. All rights reserved.)

Background: This study compared the reversibility of rocuronium-induced profound neuromuscular block with sugammadex in younger and older patients., Methods: Fifteen younger (20-50 yr) and 15 older (≥70 yr) patients were sequentially enrolled in this study. After induction of anaesthesia and laryngeal mask insertion, contraction of the adductor pollicis muscle in response to ulnar nerve stimulation was quantified using acceleromyography during 1.0-1.5% end-tidal sevoflurane and remifentanil anaesthesia. All patients initially received rocuronium 1 mg kg(-1), followed by 0.02 mg kg(-1) when a post-tetanic count (PTC) of 1 or 2 was observed. After completion of surgery, at reappearance of 1-2 PTC, the time required for a single bolus dose of 4 mg kg(-1) sugammadex to produce recovery to a train-of-four (TOF) ratio of 0.9 was recorded., Results: There were no differences in the total dose of rocuronium administered between the younger [mean (sd): 93.4 (17.5) mg] and the older [97.5 (32.2) mg] groups. In all patients, adequate recovery of the TOF ratio to 0.9 was achieved after administration of sugammadex, although it was significantly slower in the older [3.6 (0.7) min, P<0.0001] than in the younger group [1.3 (0.3) min]. There were no clinical events attributable to recurarization., Conclusions: Sugammadex can adequately restore neuromuscular function in older patients, although a longer time is required to recover from profound rocuronium-induced neuromuscular block than in younger patients.

Sugammadex is a selective relaxant-binding agent, which reverses rocuronium-induced neuromuscular blocks of any depth by chemical encapsulation of rocuronium in the plasma in various groups of patients. We reported seven Caesarean section cases, undergoing general anaesthesia with thiopental (6 mg kg⁻¹) and rocuronium (0.6 mg kg⁻¹) who were given desflurane and fentanyl for maintenance of anaesthesia after delivery. The action of rocuronium may be prolonged in pregnant women. At the end of the operation, all patients had a significant degree of neuromuscular block. In five patients, there was no single twitch response and no TOF ratio, one patient had one twitch detectable, and in one patient, a TOF ratio of 3% was detected. The recommended dose of sugammadex for reversal of profound block (4 mg kg⁻¹) or moderate block (2 mg kg⁻¹) was given. In all patients, sugammadex provided rapid and sufficient reversal to TOF >0.9 within 2 min. All patients were monitored after operation, and no signs of recurarization occurred in any patient and no signs of neuromuscular weakness were observed.

Sugammadex 16 mg kg⁻¹ can be used for the immediate reversal of neuromuscular block 3 min after administration of rocuronium and could be used in place of succinylcholine for emergency intubation. We have systematically reviewed the efficacy and cost-effectiveness and made an economic assessment of sugammadex for immediate reversal. The economic assessment investigated whether sugammadex appears cost-effective under various assumptions about the value of any reduction in recovery time with sugammadex, the likelihood of a 'can't intubate, can't ventilate' (CICV) event, the age of the patient, and the length of the procedure. Three trials were included in the efficacy review. Sugammadex administered 3 or 5 min after rocuronium produced markedly faster recovery than placebo or spontaneous recovery from succinylcholine-induced block. No published economic evaluations were found. Our economic analyses showed that sugammadex appears more cost-effective, where the value of any reduction in recovery time is greater, where the reduction in mortality compared with succinylcholine is greater, and where the patient is younger, for lower probabilities of a CICV event and for long procedures which do not require profound block throughout. Because of the lack of evidence, the value of some parameters remains unknown, which makes it difficult to provide a definitive assessment of the cost-effectiveness of sugammadex in practice. The use of sugammadex in combination with high-dose rocuronium is efficacious. Further research is needed to clarify key parameters in the analysis and to allow a fuller economic assessment.

Background: Sugammadex shows a dose-response relationship for reversal of neuromuscular block (NMB) during propofol anaesthesia. Sevoflurane, unlike propofol, can prolong the effect of neuromuscular blocking agents (NMBAs), increasing recovery time. This open-label, randomized, dose-finding trial explored sugammadex dose-response relationships, safety, and pharmacokinetics when administered for reversal of moderate rocuronium- or vecuronium-induced NMB during sevoflurane maintenance anaesthesia., Methods: After anaesthesia induction with propofol, adult patients were randomized to receive single-dose rocuronium 0.9 mg kg⁻¹ or vecuronium 0.1 mg kg⁻¹, with maintenance doses as needed. Anaesthesia was maintained with sevoflurane. NMB was monitored using acceleromyography. After the last dose of NMBA, at reappearance of T(2), single-dose sugammadex 0.5, 1.0, 2.0, or 4.0 mg kg⁻¹ or placebo was administered. The primary efficacy variable was time from the start of sugammadex administration to recovery of T₄/T₁ ratio to 0.9. Safety assessments were performed throughout., Results: The per-protocol population comprised 93 patients (rocuronium, n=46; vecuronium, n=47). A statistically significant dose-response relationship was demonstrated for mean recovery times of T₄/T₁ ratio to 0.9 with increasing sugammadex dose with both NMBAs: rocuronium, 96.3 min (placebo) to 1.5 min (sugammadex 4.0 mg kg⁻¹); vecuronium, 79.0 min (placebo) to 3.0 min (sugammadex 4.0 mg kg⁻¹). Plasma sugammadex concentrations indicated linear pharmacokinetics, independent of NMBA administered. No study drug-related serious adverse events occurred. Evidence of reoccurrence of block was reported in seven patients [sugammadex 0.5 mg kg⁻¹ (suboptimal dose), n=6; 2.0 mg kg⁻¹, n=1]., Conclusions: During sevoflurane maintenance anaesthesia, sugammadex provides well-tolerated, effective, dose-dependent reversal of moderate rocuronium- and vecuronium-induced NMB.

Background: Re-intubation and re-operation may occasionally be required after neuromuscular block (NMB) reversal. This study evaluated block onset times of a second dose of rocuronium (1.2 mg kg(-1)) after sugammadex reversal of rocuronium 0.6 mg kg(-1)., Methods: In this open-label study of healthy anaesthetized volunteers, subjects received rocuronium 0.6 mg kg(-1), were antagonized at 1-2 post-tetanic counts with sugammadex 4.0 mg kg(-1), and received rocuronium 1.2 mg kg(-1) at 5, 7.5, 10, 15, 20, 22.5, 25, 27.5, 30, 45, or 60 min after sugammadex. Spontaneous recovery occurred after repeat rocuronium dose. Primary endpoints were the onset time of maximal block (time to lowest T(1) value reached) and the clinical duration of block (until T(1)=25%) after repeat rocuronium dose., Results: Sixteen subjects were included. For subjects receiving rocuronium 1.2 mg kg(-1) 5 min after sugammadex (n=6), mean (sd) onset time (to T(1)=0) was 3.06 (0.97) min; range, 1.92-4.72 min. For repeat dose time points ≥25 min (n=5), mean onset was faster (1.73 min) than for repeat doses <25 min (3.09 min) after sugammadex. The duration of block ranged from 17.7 min (rocuronium 5 min after sugammadex) to 46 min (repeat dose at 45 min). Mean duration was 24.8 min for repeat dosing <25 min vs 38.2 min for repeat doses ≥25 min., Conclusions: Rapid re-onset of NMB occurred after repeat dose of rocuronium 1.2 mg kg(-1) as early as 5 min after sugammadex in healthy volunteers. Re-onset of block took longer if second rocuronium dose was <25 min after sugammadex. The duration of action of second rocuronium dose increased with later repeat dose time points.

Background: This clinical study evaluated the speed of reversal of profound rocuronium block in ponies using sugammadex and investigated the differences in onset and recovery from block in three different muscle groups., Methods: Anaesthesia was induced and maintained with isoflurane in oxygen 100% in eight ponies. Neuromuscular monitoring was performed at each site using acceleromyography: in the extensor muscles of the pelvic limb (peroneal nerve) and thoracic limb (radial nerve), and in the orbicularis oris muscle (OOM; facial nerve). Rocuronium 0.6 mg kg(-1) i.v. was administered, followed 5 min later by sugammadex 4 mg kg(-1) i.v. Onset time (onsetROC), maximum block, and time to recovery of the train-of-four ratio to 0.9 (TOFR=0.9) were recorded. The differences between monitored sites were compared using one-way anova followed by a post hoc Dunn's test., Results: Onset of ROC was significantly delayed in OOM compared with both limbs [pelvic limb, thoracic limb, and OOM: 43.1 (sd 16.9), 50.6 (15.9), and 204.4 (35.8) s, respectively; P<0.001]. Complete block was achieved in the pelvic and thoracic limbs, but in none of the eight ponies in the OOM [mean T1=15.3 (9.4)%; range: 7-36%]. No differences were observed between muscle sites in recovery to TOFR=0.9 [pelvic limb, thoracic limb, and OOM: 2.3 (0.9), 3.4 (1.7), and 2.8 (2.1) min, respectively]. No adverse effects of sugammadex were detected throughout the study period., Conclusions: Sugammadex can be used to reverse profound rocuronium-induced block in ponies during isoflurane anaesthesia. Thoracic limb muscles represent a suitable alternative for monitoring neuromuscular block compared with pelvic limb muscles.

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., (Copyright © 2010 Elsevier Inc. All rights reserved.)

A 38-year-old wheelchair-bound primigravida with transverse myelitis presented at 38 weeks of gestation for elective caesarean section. Transverse myelitis, which is characterised by bilateral inflammation of the spinal cord and myelin destruction, is associated with myopathy, autonomic dysreflexia and pulmonary aspiration. Regional anaesthesia was contraindicated in this case as the patient had undergone two previous lumbar spinal fusion procedures. Rocuronium 1.2 mg/kg was used to facilitate rapid intubating conditions. The caesarean section proceeded uneventfully, but even after administration of neostigmine the patient exhibited prolonged neuromuscular blockade. After 3 h and 15 min sugammadex was obtained to reverse neuromuscular blockade; the drug was not stocked in our hospital. Sugammadex 4 mg/kg resulted in complete reversal of blockade after 2 min. We believe that myopathy associated with transverse myelitis led to the prolonged duration of action of rocuronium. Sugammadex is a relatively new drug with few reported side effects. In this case it was used to reverse neuromuscular blockade and prevented prolonged postoperative ventilatory support., (2010 Elsevier Ltd. All rights reserved.)

The launch on the market of a new compound is always an important event for a specialty, particularly when the mechanism of action is completely new. It is the case with sugammadex, a cyclodextrin able to encapsulate specifically and only nondepolarizing steroidal muscles relaxant, rocuronium or vecuronium. The clinical trials which have been performed for sugammadex approval have demonstrated promising results. Sugammadex is able to rapidly reverse (2-5 min) different levels of neuromuscular blockade: moderate (e.g., T2 recovery), deep (e.g., PTC 1-2 recovery) and also few minutes (3-15) after rocuronium administration. Thus, the sugammadex's onset time is about 10 times more rapid than neostigmine without the need of concomitantly atropine administration. Sugammadex has only been tested in small sample size of patients. Therefore, the exact place in the anesthetic practice, the potential indications, the safety profile on a large-scale, thus remain to determine. In particular, how it will modify our current practices characterized to date by 1) under-use of neuromuscular monitoring, 2) a marginal practice of reversal and 3) a wide use of benzylisoquinolines : atracurium and cis-atracurium? Finally, what will be the medical strategies to justify an additional cost when compared to neostigmine?

Sugammadex, a cyclodextrin, is a novel agent designed to encapsulate selectively steroidal neuromuscular blocking agents such as rocuronium and vecuronium as well. One molecule of sugammadex is able to encapsulate only one molecule of muscle relaxant. This original pharmacological property allows a very rapid reversal of muscle paralysis. After sugammadex injection, a train of four ratio higher than 0.9 is obtained in less than 5 minutes in all the patients whatever the degree of muscle paralysis at the time of reversal and even when anesthesia is maintained with halogenated agents. However, in order to preserve this efficacy, the dose of sugammadex needs to be adjusted to the degree of muscle paralysis at the time of reversal : 2 mg/kg after obtaining 2 responses at the adductor pollicis muscle after a train of four stimulation, 4 mg/kg with a post-tetanic count between 1 and 3 responses, and 12 to 16 mg/kg in case of rescue reversal (3 to 15 minutes after 0.6 to 1.2 mg/kg rocuronium). Even if the original property of sugammadex lets us think that per-operative neuromuscular transmission monitoring would not be furthermore useful, the assessment of the exact degree of muscle paralysis before reversal is mandatory for choosing the right dose of sugammadex.

Sugammadex is a new molecule derived from a known pharmacological class : the cyclodextrins known and used in human for many years. It was recently demonstrated that cyclodextrins could encapsulate and bind strongly steroidal neuromuscular blocking agents. Among cyclodextrins gamma-cyclodextrins proved to be more efficient. The binding of cyclodextrins to rocuronium and compound's water solubility was greatly improved by addition of 8 side chains to glycopyranoses units and the presence of a negative charge to the end of these side-chains. Animal studies have clearly demonstrated that sugammadex is faster in onset than anticholinesterase agents and is specific of steroidal neuromuscular blocking agents. It cannot reverse neuromuscular block induced by succinylcholine or benzylisoquinolines such as atracurium or cisatracurium. In human, the dose of sugammadex required to reverse shallow block is 2 mg/kg approximately whereas 4 mg/kg is needed to reverse deep level of neuromuscular block with a few responses at the post tetanic count at the adductor pollicis. The use of sugammadex was not associated with recurrence of block when an adequate dose was administered.

Background: Sugammadex, a modified gamma-cyclodextrin, is the first selective relaxant binding agent that specifically encapsulates the steroidal neuromuscular blocking agent, rocuronium. The action of rocuronium is prolonged in patients with renal failure. As sugammadex is primarily cleared renally, this phase III trial investigated the efficacy and safety of sugammadex for reversal of rocuronium-induced neuromuscular block (NMB) in patients with end-stage renal failure., Methods: Thirty adult patients were studied: 15 renally impaired [creatinine clearance (CL(CR)) <30 ml min(-1)] and 15 controls (CL(CR)>80 ml min(-1)). Anaesthesia was induced and maintained using i.v. opiates and propofol. Neuromuscular monitoring was performed by acceleromyography and train-of-four (TOF) nerve stimulation. Rocuronium (0.6 mg kg(-1)) was given, followed by a single i.v. dose of sugammadex (2.0 mg kg(-1)) at reappearance of the second twitch of the TOF. The primary efficacy variable was time from administration of sugammadex to recovery of the TOF ratio to 0.9. Safety variables included clinical evidence of reoccurrence of NMB., Results: After sugammadex administration, the mean (sd) time to recovery of the TOF ratio to 0.9 was 2.0 (0.72) min in renal patients and 1.65 (0.63) min in controls (NS). Recurrence of NMB was not observed in any patient. No sugammadex-related serious adverse events were reported., Conclusions: Sugammadex administered at reappearance of T(2) rapidly and effectively reverses NMB induced by rocuronium in renal failure and healthy patients. Sugammadex was well tolerated by all patients. Further safety studies on sugammadex in patients with severe renal impairment are warranted.