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Objective: To investigate the efficacy and safety of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope. Methods: One hundred patients undergoing radical resection of lung cancer under thoracoscope in Affiliated Cancer Hospital of Zhengzhou University from March to September in 2019, were randomly divided into control group (group C) and sugammadex group (group S). All patients were anaesthetized (induced and maintained) with intravenous target-controlled infusion of propofol and remifentanil, and intermittent intravenous injection of the neuromuscular block of rocuronium. During the operation, the bispectral index (BIS) was used to monitor the depth of anesthesia, and the neuromuscular block was assessed with TOF. Single-lung mechanical ventilation and double-lumen endotracheal intubation were carried out, and patient-controlled analgesia after operation were enforced. Patients in group C received neostigmine (2 mg) combined with atropine (0.5-1.0 mg) after thoracic closure, while patients in group S received sugammadex (2 mg/kg) at TOF count (≥2) after thoracic closure, and then double-lumen endotracheal tubes were extubated according to extubation indications. At these time points: T(0) (immediate before anesthesia induction), T(1) (immediate before tracheal intubation), T(2) (immediately after thoracic closure), T(3) (1 h after operation), T(4) (6 h after operation), T(5) (24 h after operation), T(6)(48 h after operation), the heart rate(HR) and mean arterial pressure (MAP) were recorded, QT interval (V3 ECG) were measured and calculated, indicators of liver function [alanine transaminase (ALT), aspartate transaminase(AST)], renal function [blood urea nitrogen (BUN), creatinine (Cre)] and clotting function [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The duration of operation, postoperative conditions within 48 hours after operation(the time of tracheal tube extubation, respiratory suppression/dysfunction, allergy, nausea and vomiting, itching of skin, abnormal sensation), pathological types and the postoperative hospital stay were recorded. Results: There were no significant differences of the age, sex ratio, body mass index (BMI), American Society of Anesthesiologists (ASA) grading ratio, duration of operation, pathological types and the postoperative hospital stay, HR, MAP and QT interval between two groups (all P> 0.05). There were no remarkable differences of the levels of serum histamine, ALT, AST, BUN, Cre, TT, PT, APTT and FIB before and after administration of neuromuscular blockade antagonists (neostigmine or Sugammadex) in the same group patients (all P> 0.05), also no significant differences between group C and group S at the same time points (all P> 0.05). Average time of tracheal tube extubation in group S [(3.7±1.3) min] was sharply shorter than that in group C [(14.5±4.4) min, t= 2.266, P< 0.05)]. There were no patients with allergy, skin itching, sensory abnormality in these two groups. There were no significant difference of the incidence of postoperative nausea and vomiting between these two groups. There were 5 patients with respiratory depression in group C and no respiratory depression patient in group S, the difference was statistically significant between these two groups (χ(2)=5.263, P< 0.05). Conclusion: Sugammadex is effective for antagonizing the neuromuscular blockade of rocuronium in patients with radical resection of lung cancer under thoracoscope, and can shorten the time of tracheal tube extubation after surgery.

Sugammadex (SDX), a neuromuscular blocking-reversal agent, quickly reverses neuromuscular blockade induced by rocuronium (RCR). SDX dosage is set according to the state of neuromuscular blockade determined with a neuromuscular monitoring device. However, in clinical situations, such a devise is not frequently used. Here, we report construction of a method for theoretically setting SDX dose by which the optimum reverse time (RT) can be obtained for individual patients even when the device is not available. The subjects were 42 adult female patients who underwent laparoscopic surgery from 1 August 2015 to 31 March 2016, during which RCR and SDX were administered. We formulated an equation for theoretically calculating the RCR residual ratio (RR) in blood after SDX administration. Furthermore, we examined the relationship between RR and RT. Based on the results obtained, we developed a method for predicting RT using RR. We excluded 1 subject as the RT value was detected as an outlier in our analysis. Multiple regression analysis was performed using standard body weight, serum creatinine, total bilirubin, and RR as explanatory variables. The number of subjects with a prediction error of RT within ±1 min was 36 (87.8%) of 41 in multiple regression analysis. We could predict RT following SDX administration by using the RT prediction expression with RR obtained for subjects administered RCR during the surgery. Furthermore, our results suggest that the SDX dose able to achieve optimum RT may be set prior to surgery on the basis of the present methodology.

Background: Acetylcholinesterase inhibitors, such as neostigmine, have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents. However, these drugs have significant limitations, such as indirect mechanisms of reversal, limited and unpredictable efficacy, and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety, reduced incidence of residual block on recovery, and more efficient use of healthcare resources., Objectives: The main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents in adults., Search Methods: We searched the following databases on 2 May 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (WebSPIRS Ovid SP), Embase (WebSPIRS Ovid SP), and the clinical trials registries www.controlled-trials.com, clinicaltrials.gov, and www.centerwatch.com. We re-ran the search on 10 May 2017., Selection Criteria: We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We included adults, classified as American Society of Anesthesiologists (ASA) I to IV, who received non-depolarizing neuromuscular blocking agents for an elective in-patient or day-case surgical procedure. We included all trials comparing sugammadex versus neostigmine that reported recovery times or adverse events. We included any dose of sugammadex and neostigmine and any time point of study drug administration., Data Collection and Analysis: Two review authors independently screened titles and abstracts to identify trials for eligibility, examined articles for eligibility, abstracted data, assessed the articles, and excluded obviously irrelevant reports. We resolved disagreements by discussion between review authors and further disagreements through consultation with the last review author. We assessed risk of bias in 10 methodological domains using the Cochrane risk of bias tool and examined risk of random error through trial sequential analysis. We used the principles of the GRADE approach to prepare an overall assessment of the quality of evidence. For our primary outcomes (recovery times to train-of-four ratio (TOFR) > 0.9), we presented data as mean differences (MDs) with 95 % confidence intervals (CIs), and for our secondary outcomes (risk of adverse events and risk of serious adverse events), we calculated risk ratios (RRs) with CIs., Main Results: We included 41 studies (4206 participants) in this updated review, 38 of which were new studies. Twelve trials were eligible for meta-analysis of primary outcomes (n = 949), 28 trials were eligible for meta-analysis of secondary outcomes (n = 2298), and 10 trials (n = 1647) were ineligible for meta-analysis.We compared sugammadex 2 mg/kg and neostigmine 0.05 mg/kg for reversal of rocuronium-induced moderate neuromuscular blockade (NMB). Sugammadex 2 mg/kg was 10.22 minutes (6.6 times) faster then neostigmine 0.05 mg/kg (1.96 vs 12.87 minutes) in reversing NMB from the second twitch (T2) to TOFR > 0.9 (MD 10.22 minutes, 95% CI 8.48 to 11.96; I 2 = 84%; 10 studies, n = 835; GRADE: moderate quality).We compared sugammadex 4 mg/kg and neostigmine 0.07 mg/kg for reversal of rocuronium-induced deep NMB. Sugammadex 4 mg/kg was 45.78 minutes (16.8 times) faster then neostigmine 0.07 mg/kg (2.9 vs 48.8 minutes) in reversing NMB from post-tetanic count (PTC) 1 to 5 to TOFR > 0.9 (MD 45.78 minutes, 95% CI 39.41 to 52.15; I 2 = 0%; two studies, n = 114; GRADE: low quality).For our secondary outcomes, we compared sugammadex, any dose, and neostigmine, any dose, looking at risk of adverse and serious adverse events. We found significantly fewer composite adverse events in the sugammadex group compared with the neostigmine group (RR 0.60, 95% CI 0.49 to 0.74; I 2 = 40%; 28 studies, n = 2298; GRADE: moderate quality). Risk of adverse events was 28% in the neostigmine group and 16% in the sugammadex group, resulting in a number needed to treat for an additional beneficial outcome (NNTB) of 8. When looking at specific adverse events, we noted significantly less risk of bradycardia (RR 0.16, 95% CI 0.07 to 0.34; I 2 = 0%; 11 studies, n = 1218; NNTB 14; GRADE: moderate quality), postoperative nausea and vomiting (PONV) (RR 0.52, 95% CI 0.28 to 0.97; I 2 = 0%; six studies, n = 389; NNTB 16; GRADE: low quality) and overall signs of postoperative residual paralysis (RR 0.40, 95% CI 0.28 to 0.57; I 2 = 0%; 15 studies, n = 1474; NNTB 13; GRADE: moderate quality) in the sugammadex group when compared with the neostigmine group. Finally, we found no significant differences between sugammadex and neostigmine regarding risk of serious adverse events (RR 0.54, 95% CI 0.13 to 2.25; I 2 = 0%; 10 studies, n = 959; GRADE: low quality).Application of trial sequential analysis (TSA) indicates superiority of sugammadex for outcomes such as recovery time from T2 to TOFR > 0.9, adverse events, and overall signs of postoperative residual paralysis., Authors' Conclusions: Review results suggest that in comparison with neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular block regardless of the depth of the block. Sugammadex 2 mg/kg is 10.22 minutes (˜ 6.6 times) faster in reversing moderate neuromuscular blockade (T2) than neostigmine 0.05 mg/kg (GRADE: moderate quality), and sugammadex 4 mg/kg is 45.78 minutes (˜ 16.8 times) faster in reversing deep neuromuscular blockade (PTC 1 to 5) than neostigmine 0.07 mg/kg (GRADE: low quality). With an NNTB of 8 to avoid an adverse event, sugammadex appears to have a better safety profile than neostigmine. Patients receiving sugammadex had 40% fewer adverse events compared with those given neostigmine. Specifically, risks of bradycardia (RR 0.16, NNTB 14; GRADE: moderate quality), PONV (RR 0.52, NNTB 16; GRADE: low quality), and overall signs of postoperative residual paralysis (RR 0.40, NNTB 13; GRADE: moderate quality) were reduced. Both sugammadex and neostigmine were associated with serious adverse events in less than 1% of patients, and data showed no differences in risk of serious adverse events between groups (RR 0.54; GRADE: low quality).

The use of neuromuscular blocking agent (NMBA) during anesthesia may interfere with facial nerve monitoring (FNM) during parotid surgery. Sugammadex has been reported to be an effective and safe reversal of rocuronium-induced neuromuscular block (NMB) during surgery. This study investigated the feasibility and clinical effectiveness of sugammadex for NMB reversal during FNM in Parotid surgery. Fifty patients undergoing parotid surgery were randomized allocated into conventional anesthesia group (Group C, n = 25) and sugammadex group (Group S, n = 25). Group C did not receive any NMBA. Group S received rocuronium 0.6 mg/kg at anesthesia induction and sugammadex 2 mg/kg at skin incision. The intubating condition and influence on FNM evoked EMG results were compared between groups. The intubation condition showed significantly better in group S patients than C group patients (excellent in 96% v.s. 24%). In group S, rapid reverse of NMB was found and the twitch (%) recovered from 0 to >90% within 10 min. Positive and high EMG signals were obtained in all patients at the time point of initial facial nerve stimulation in both groups. There was no significant difference as comparing the EMG amplitudes detected at the time point of initial and final facial nerve stimulation in both groups. Implementation of sugammadex in anesthesia protocol is feasible and reliable for successful FNM during parotid surgery., (Copyright © 2017. Published by Elsevier Taiwan.)

Background: Sugammadex reverses the effect of rocuronium more rapidly and effectively than neostigmine, at all levels of neuromuscular blockade (NMB). However, its cost is prohibitive. The combination of half dose sugammadex with neostigmine would be non-inferior to full dose sugammadex for the reversal of deep NMB. This approach would reduce the cost of sugammadex while preserving its efficacy., Methods: Patients were randomly allocated to receive sugammadex 4 mg/kg (Group S) or sugammadex 2 mg/kg with neostigmine 50 μg/kg and glycopyrrolate 10 μg/kg (Group NS) for reversal of rocuronium deep NMB. The primary outcome was the percentage of patients who recovered to 90% Train of Four (TOF) ratio within 5 min. The non-inferiority margin was set at 10%., Results: Twenty eight patients were enrolled in each group. The number of patients who reached 90% TOF ratio within 5 min was 27 out of 28 (96%) in group S versus 25 out of 28 (89%) in group NS by intention-to-treat (difference: 7%, 95% CI of the difference: -9% to 24%). The number of patients who reached 90% TOF ratio within 5 min was 26 out of 26 (100%) in group S versus 23 out of 25 (92%) in group NS by per-protocol (difference: 8%, 95% CI of the difference: -6% to 25%)., Conclusions: Sugammadex 2 mg/kg with neostigmine 50 μg/kg was at worst 9% and 6% less effective than sugammadex 4 mg/kg by intention-to-treat and by per-protocol analysis respectively. Hence, the combination is non-inferior to the recommended dose of sugammadex., Trial Registration: Clinicaltrials.gov NCT 02375217 , registered on February 11, 2015.

Introduction: Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial., Clinical Features: An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward., Conclusion: A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD.

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: The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation., Methods: The dose-response relationship of drugs to reverse vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n = 34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps femoris muscle of the rat). Cumulative dose-response curves of calabadions, neostigmine, or sugammadex were created ex vivo at a steady-state deep NMB. In living rats, the authors studied the dose-response relationship of the test drugs to reverse deep block under physiologic conditions, and they measured the amount of calabadion 2 excreted in the urine., Results: In vitro experiments showed that calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (Ka = 3.4 × 10 M and Ka = 3.8 × 10 M-). The results of urine analysis (proton nuclear magnetic resonance), competition binding assays, and ex vivo study obtained in the absence of metabolic deactivation are in accordance with an 1:1 binding ratio of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2 dose-dependently and rapidly reversed all NMBAs tested. The molar potency of calabadion 2 to reverse vecuronium and rocuronium was higher compared with that of sugammadex. Calabadion 2 was eliminated renally and did not affect blood pressure or heart rate., Conclusions: Calabadion 2 reverses NMB induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in rats.

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.)

Purpose: To compare the effects of sugammadex and neostigmine, used to antagonize the effects of rocuronium, on the QTc interval., Methods: This study used 10 adult New Zealand white rabbits of 2.5-3.5 kg randomly divided into two groups: sugammadex group (Group S, n:5) and neostigmine group (Group N, n:5). For general anesthesia administering 2 mg/kg iv propofol and 1 mcg/kg iv fentanyl, 0.6 mg/kg iv rocuronium was given. Later to provide reliable airway for all experimental animals V-Gel Rabbit was inserted. The rabbits were manually ventilated by the same anesthetist. After the V-Gel Rabbit was inserted at 2, 5, 10, 20, 25, 27, 30 and 40 minutes measurements were repeated and recorded. At 25 minutes after induction Group N rabbits were given 0.05 mg/kg iv neostigmine + 0.01 mg/kg iv atropine. Group S were administered 2 mg/kg iv sugammadex., Results: Comparing the QTc interval in the rabbits in Group S and Group N, in the 25th, 27th and 30th minute after muscle relaxant antagonist was administered the QTc interval in the neostigmine group rabbits was significantly increased (p<0.05)., Conclusion: While sugammadex, administered to antagonize the effect of rocuronium, did not significantly affect the QTc interval, neostigmine+atropine proloned the QTc interval.

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.

Objective: Sugammadex rapidly reverses neuromuscular blockade (NMB) induced by rocuronium. NMB induced by rocuronium is prolonged in patients with liver dysfunction, because the drug is mainly excreted into the bile. However, the efficacy and safety of sugammadex in terms of reversing rocuronium-induced NMB in patients with liver dysfunction undergoing hepatic surgery have not been evaluated. This observational study investigated the efficacy and safety of sugammadex after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery., Methods: Remifentanil/propofol anesthesia was administered to 31 patients: 15 patients in the control group, and 16 patients from a group with liver dysfunction. Rocuronium (0.6 mg/kg) was administered, followed by continuous infusion. The enrolled patients were then subdivided into two groups according to the dose of sugammadex. In the first group a single dose of sugammadex (2.0 mg/kg) was given at the reappearance of the second twitch (T2). In the second group a single dose of sugammadex (4.0 mg/kg) was given at the first twitch response if T2 did not reappear in 15 minutes after stopping rocuronium. The primary outcome was time from administration of sugammadex to recovery of a train-of-four ratio to 0.9., Results: The dose of rocuronium required in the liver dysfunction group was lower than that in the control group (6.2 vs. 8.2 μg/kg/min, p = 0.002). The mean time from the administration of sugammadex to recovery of the train-of-four ratio to 0.9 was not significantly different between the liver dysfunction group and the control group (2.2 minutes vs. 2.0 minutes in the 2 mg/kg administration group, p = 0.44 and 1.9 minutes vs. 1.7 minutes in the 4 mg/kg administration group, p = 0.70, respectively). No evidence of recurarization was observed in any of the patients. Most of the adverse events were found to be mild and such events were not related to the use of sugammadex. None of the patients was eliminated from the study because of an adverse event. One patient died due to cholestatic liver cirrhosis because of repeated hepatic surgery., Conclusion: Sugammadex can rapidly reverse NMB after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery. Sugammadex was found to be safe and well tolerated. However, further studies of sugammadex under similar conditions should be conducted involving a large number of patients with liver dysfunction undergoing hepatic surgery., (Copyright © 2014. Published by Elsevier B.V.)

Background: Corticosteroids are frequently used during anesthesia to provide substitution therapy in patients with adrenal insufficiency, as a first-line treatment of several life-threatening conditions, to prevent postoperative nausea and vomiting, and as a component of multimodal analgesia. For these last 2 indications, dexamethasone is most frequently used. Due to the structural resemblance between aminosteroid muscle relaxants and dexamethasone, concerns have been raised about possible corticosteroid inhibition in the reversal of neuromuscular block by sugammadex. We thus investigated the influence of dexamethasone on sugammadex reversal of rocuronium-induced neuromuscular block, which could be relevant in certain clinical situations., Methods: The unique co-culture model of human muscle cells innervated in vitro with rat embryonic spinal cord explants to form functional neuromuscular junctions was first used to explore the effects of 4 and 10 μM rocuronium on muscle contractions, as quantitatively evaluated by counting contraction units in contraction-positive explant co-cultures. Next, equimolar and 3-fold equimolar sugammadex was used to investigate the recovery of contractions from 4 and 10 μM rocuronium block. Finally, 1, 100, and 10 μM dexamethasone (normal, elevated, and high clinical levels) were used to evaluate any effects on the reversal of rocuronium-induced neuromuscular block by sugammadex., Results: Seventy-eight explant co-cultures from 3 time-independent experiments were included, where the number of contractions increased to 10 days of co-culturing. Rocuronium showed a time-dependent effect on depth of neuromuscular block (4 μM rocuronium: baseline, 10, 20 minutes administration; P < 0.0001), while the dose-dependent effect was close to nominal statistical significance (4, 10 μM; P = 0.080). This was reversed by equimolar concentrations of sugammadex, with further and virtually complete recovery of contractions with 3-fold equimolar sugammadex (P < 0.0001). Dexamethasone diminished 10 μM sugammadex-induced recovery of contractions from rocuronium-induced neuromuscular block in a dose-dependent manner (P = 0.026) with a higher sugammadex concentration (30 μM) being close to statistically significantly improving recovery (P = 0.065). The highest concentration of dexamethasone decreased the recovery of contractions by equimolar sugammadex by 26%; this effect was more pronounced when 3-fold equimolar (30 μM) sugammadex was used for reversal (48%)., Conclusions: This is the first report in which the effects of rocuronium and sugammadex interactions with dexamethasone have been studied in a highly accessible in vitro experimental model of functionally innervated human muscle cells. Sugammadex reverses rocuronium-induced neuromuscular block; however, concomitant addition of high dexamethasone concentrations diminishes the efficiency of sugammadex. Further studies are required to determine the clinical relevance of these interactions.

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: 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.

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.

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.)

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.)

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.

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 and Objectives: Sugammadex is a reversal agent that acts as a selective antagonist of neuromuscular blockade induced by rocuronium and vecuronium. This is a case report of an elderly female patient who had sugammadex just after rocuronium induction., Case Report: An 88-year-old female patient, 34 kg, presented a femoral fracture and had to undergo general anesthesia after spinal anesthesia failure. Induction was performed with propofol 1.5mg.kg(-1), rocuronium 1.2mg.kg(-1), fentanyl 100 mcg, and lidocaine 2mg.kg(-1). There was no success in either tracheal intubation or laryngeal mask positioning maneuvers. The use of sugammadex at a dose of 16 mg.kg(-1) was required and respiratory function returned to normal., Conclusion: Literature recommends sugammadex at a dose of 16 mg.kg(-1) for patients with profound blockade. It was used in our patient with rapid and effective reversal of neuromuscular blockade allowing the patient to undergo another procedure to ensure the airway patency without clinical impairment of her general condition., (Copyright © 2012 Elsevier Editora Ltda. All rights reserved.)

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.

Backgraound: Myasthenia gravis is a rare immunological illness that impairs neuromuscular transmission. Myasthenic patients are usually hypersensitive to non-depolarising muscle relaxants, and reversal with neostigmine is rarely effective. We report the successful reversal of rocuroniuminduced neuromuscular block in a morbidly obese myasthenic patient., Case Report: A 38-year-old morbidly obese (body weight 160 kg, BMI 48.8 kg m⁻²) woman was scheduled for elective laparoscopic gastric banding. She was anaesthetised with propofol-based TIVA; intubation was facilitated by 24 mg of rocuronium. After spontaneous recovery of T1, she received 200 mg of sugammadex, which completely restored the NMT ratio (TOF=100%) within 2 min and 48 sec., and she was extubated. No postoperative complications were observed., Conclusion: Sugammadex can be successfully used in myasthenic patients, allowing for the safe use of muscle relaxants in these patients.

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 new pharmacological agent for neuromuscular block reversion. It is a cyclic oligosaccharide, a gamma cyclodextrin with lipophylic inner coat that enables forming of stable complexes with steroidal neuromuscular blocking drugs, especially with rocuronium. A physical encapsulation of the relaxants is a novel elimination pathway and it produces fast and complete reversion of both deep and shallow neuromuscular block. Consequently, sugammadex has no unwanted cholinergic muscarinic effects observed with cholinesterase inhibitors such as bradycardia, hypersalivation, and increased gastrointestinal motility. Since the effects of sugammadex are dose dependent it can very rapidly reverse the effects of rocuronium. After the adjusted dose of sugammadex was given, the duration of action of rocuronium can be made as short as that of succinylcholine. This characteristic is especially important in the 'can't intubate, can't ventilate' situation and after surgical procedure was unexpectedly finished. Clinical studies involving more patients are needed to show the real risk-benefit profile and safety in the special patients' populations.

We present a case where immediate muscle relaxation was needed following sugammadex administration. A 72 year-old female underwent surgery for a cerebral artery aneurysm. Upon conclusion of the operation sugammadex (9.3 mg/kg) was administered and the patient was noted to have left hemiplegia. Rocuronium (1.2 mg/kg × 2 doses) was given in order to gain neuromuscular block approximately 25 minutes after sugammadex had been injected. Although TOF monitoring was not utilized in this case and assessing residual muscular block was difficult, spontaneous respirations continued and breathing had to be controlled with sevoflurane and remifentanil. Sugammadex is a potent reversal agent for rocuronium-induced neuromuscular block, however, certain situations require immediate neuromuscular blockade following sugammadex. In this case, rocuronium was unable to induce neuromuscular blockade immediately after sugammadex and that higher concentrations were necessary in addition to intravenous analgesics and inhaled anesthetics.

Background: The management of elderly patients can be challenging for anesthesiologists for many reasons, including altered pharmacokinetics and dynamics. This study compared the efficacy, safety, and pharmacokinetics of sugammadex for moderate rocuronium-induced neuromuscular blockade reversal in adult (aged 18-64 yr) versus elderly adult (aged 65 yr or older) patients., Methods: This phase 3a, multicenter, parallel-group, comparative, open-label study enrolled 162 patients aged 18 yr and older, American Society of Anesthesiologists class 1-3, scheduled for surgery with general anesthesia and requiring neuromuscular blockade. After anesthesia induction, patients received rocuronium, 0.6 mg/kg, before tracheal intubation, with maintenance doses of 0.15 mg/kg as required. At the end of surgery, patients received sugammadex, 2.0 mg/kg, at reappearance of the second twitch of the train-of-four (TOF) for reversal. The primary efficacy variable was time from sugammadex administration to recovery of the TOF ratio to 0.9 or greater. Pharmacokinetics and safety were also evaluated., Results: Overall, 150 patients were treated and had at least one postbaseline efficacy assessment; 48 were aged 18-64 yr (adult), 62 were aged 65-74 yr (elderly), and 40 were aged 75 yr or older (old-elderly). The geometric mean time (95% confidence interval) from sugammadex administration to recovery of the TOF ratio to 0.9 increased with age, from 2.3 (2.0-2.6) min (adults) to 2.9 (2.7-3.2) min (elderly/old-elderly groups combined). Recovery of the TOF ratio to 0.9 was estimated to be 0.7 min faster in adults compared with patients aged 65 yr or older (P = 0.022). Sugammadex was well tolerated by all patients., Conclusion: Sugammadex facilitates rapid reversal from moderate rocuronium-induced neuromuscular blockade in adults of all ages.

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.