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Background: The optimal pharmacological reversal strategy for neuromuscular blockade remains undefined even in the setting of strong recommendations for quantitative neuromuscular monitoring by several national and international anesthesiology societies. We evaluated a protocol for managing rocuronium blockade and reversal, using quantitative monitoring to guide choice of reversal agent and to confirm full reversal before extubation., Methods: We conducted a prospective cohort study and enrolled 200 patients scheduled for elective surgery involving the intraoperative use of rocuronium. Providers were asked to adhere to a protocol that was similar to local practice recommendations for neuromusculalr block reversal that had been used for >2 years; the protocol added quantitative monitoring that had not previously been routinely used at our institution. In this study, providers used electromyography-based quantitative monitoring. Pharmacological reversal was accomplished with neostigmine if the train-of-four (TOF) ratio was 0.40 to 0.89 and with sugammadex for deeper levels of blockade. The primary end point was the incidence of postoperative residual neuromuscular blockade (PRNB), defined as TOF ratio <0.9 at time of extubation. We further evaluated the difference in pharmacy costs had all patients been treated with sugammadex., Results: A total of 189 patients completed the study: 66 patients (35%) were reversed with neostigmine, 90 patients (48%) with sugammadex, and 33 (17%) patients recovered spontaneously without pharmacological reversal. The overall incidence of residual paralysis was 0% (95% CI, 0-1.9). The total acquisition cost for all reversal drugs was United States dollar (USD) 11,358 (USD 60 per patient) while the cost would have been USD 19,312 (USD 103 per patient, 70% higher) if sugammadex had been used in all patients., Conclusions: A protocol that includes quantitative monitoring to guide reversal with neostigmine or sugammadex and to confirm TOF ratio ≥0.9 before extubation resulted in the complete prevention of PRNB. With current pricing of drugs, the selective use of sugammadex reduced the total cost of reversal drugs compared to the projected cost associated with routine use of sugammadex for all patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Purpose of Review: This review article explores the evidence regarding sugammadex (MSD Australia) and its potential interaction with hormonal contraceptives. The impact of recent clinical trials and review articles is examined., Recent Findings: Recent clinical data suggest that the interaction between sugammadex and estrogen and progesterone concentrations may not be clinically significant and may confer some protection against ovulation. There are no clinical trials reporting interactions between sugammadex and the exogenous hormonal compounds found in oral contraceptive pills. The method of contraception is an important consideration, as sugammadex theoretically affects oral and nonoral, and combined versus single agent methods differently. Two large retrospective database studies have reported two cases of pregnancy postoperatively in patients on hormonal contraceptives whose anesthetic included sugammadex., Summary: Strong clinical evidence to support or refute claims of a significant impact of sugammadex on contraceptive efficacy in women on contraception is lacking. The existing evidence does not suggest a basis for concern regarding the impact of sugammadex on contraception in the perioperative setting., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Anterior uveitis is a sight-threatening inflammation inside the eyes. Conventional eye drops for anti-inflammatory therapy need to be administered frequently owing to the rapid elimination and corneal barrier. To address these issues, polypseudorotaxane hydrogels were developed by mixing Soluplus micelles (99.4 nm) and cyclodextrins solution. The optimized hydrogels exhibited shear-thinning and sustained release properties. The hydrogels exhibited higher transcorneal permeability coefficient (P app , 1.84 folds) than that of drug solutions. Moreover, animal study indicated that the hydrogels significantly increased the precorneal retention (AUC, 21.2 folds) and intraocular bioavailability of flurbiprofen (AUC Aqueous humor , 17.8 folds) in comparison with drug solutions. Importantly, the hydrogels obviously boosted anti-inflammatory efficacy in rabbit model of endotoxin-induced uveitis at a reduced administration frequency. Additionally, the safety of hydrogels was confirmed by cytotoxicity and ocular irritation studies. In all, the present study demonstrates a friendly non-invasive strategy based on γ-CD-based polypseudorotaxane hydrogels for ocular drug delivery., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

α-Lipoic acid (ALA) is a vitamin-like substance that is an indispensable supporting factor for a large number of enzymes. Due to its optical activity, ALA has optical isomers RALA and SALA. The major role of RALA is in energy metabolism. However, RALA cannot be used as a pharmaceutical or nutraceutical because it is sensitive to heat and acid conditions. Previous studies have shown that RALA complexed with γ-cyclodextrin (CD) has a higher antioxidant capacity than that of free RALA. The antioxidant enzyme system protects against intense exercise-induced oxidative damage and is related to the physical status of athletes. The aim of this study was to examine the effect of CD/RALA complex supplementation on antioxidant activity and performance during high-intensity exercise. Twenty-four male C3H/HeSlc mice were divided into four groups ( n = 6): swimming+distilled water administration (C), swimming+CD/RALA supplementation (CD/RALA), swimming+RALA suplementation (RALA), and swimming+CD supplementation (CD). Blood ammonia elevation due to exercise stress was repressed by CD/RALA supplementation. The oxidative stress in the kidney increased after exercise and was reduced by CD/RALA supplementation. Our findings suggest that CD/RALA supplementation may be useful for improving the exercise performance in athletes.

The malignancy of colorectal cancer (CRC) is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for CRC are limited. To integrate therapeutic targeting with tumor microenvironment (TME) reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified γ-cyclodextrin (M-γ-CD) with Regorafenib (RG), RG@M-γ-CD CNPs. In addition to its carrier role, M-γ-CD serves as a targeting device and participates in TME regulation. RG@M-γ-CD CNPs attenuate inflammation and inhibit TAM activation by targeting macrophages. They also improve RG's anti-tumor effect by potentiating kinase suppression. In vivo application shows that the channel-type formulation optimizes the pharmacokinetics and bio-distribution of RG. In colitis-associated cancer and CT26 mouse models, RG@M-γ-CD is proven to be a targeted, safe and effective anti-tumor nanomedicine that suppresses tumor cell proliferation, lesions neovascularization, and remodels TME. These findings indicate RG@M-γ-CD CNPs as a potential strategy for CRC treatment.

Therapeutic contact lenses were developed from bacterial cellulose (BC) by the Institute of Chemistry at Brazil's São Paulo State University (UNESP). In a previous study, cyclodextrins (CD) and medications such as ciprofloxacin (CP) and diclofenac sodium (DS) were incorporated into the lenses to provide therapeutic properties and control drug release. However, significant opacity was seen in the material inherent to cellulose. In order to achieve full material transparency, the lenses were coated with an organic-inorganic hybrid compound containing aluminum alkoxide and glycidoxypropyltrimethoxysilane (GPTS)(H), or chitosan (Q) nanoparticles. This study evaluated the toxicity of these contact lenses to ensure the safety of these materials for future availability to the medical device industry. Lenses composed of BC and coated with either GPTS (H) or chitosan (Q), incorporating ciclodextrin (CD) to release diclofenac sodium (DS) or ciprofloxacin (CP), were submitted to cytotoxicity assays (XTT and Clonogenic Survival), genotoxicity (Comet Assay) and mutagenicity (Cytokinesis-blocked micronucleus assay) directly in cell culture. Statistical analyses were performed using the Tukey and Dunnett or Kruskal-Wallis and Dunn tests. All of the nanoparticles used in the lense coatings did not show cytotoxic effects by the XTT test (p > 0.05; Dunnett). Only materials associated with diclofenac sodium (BC-H-CD-DS and BC-Q-CD-DS) presented significantly different survival fractions compared to negative control (p < 0.001; Dunnett). Genotoxicity evaluation revealed a genotoxic effect in BC-H-CD-DS (p < 0.05; Dunn). All tested lenses did not present any mutagenic effect. These results indicate that improvements in DS incorporation are needed to eliminate toxicity. We demonstrated promising results in the safety of employing BC lenses functionalized with a drug delivery system permitting the bioavailability of ophthalmic drugs. Further studies utilizing other specific tests, such as corneal lineage are required before safe and efficient ophthalmologic use., (Copyright © 2019 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Microvascular decompression (MVD) is associated with a particularly high risk of postoperative nausea and vomiting (PONV) among craniotomy patients. However, there is no information regarding the effect of prophylactic palonosetron and sugammadex on PONV in patients undergoing MVD under propofol-maintained anesthesia.Medical records of 274 adults who had undergone MVD under propofol-maintained anesthesia were reviewed. Patients were classified into 4 groups, based on the reversal agent used (sugammadex/pyridostigmine) and whether or not prophylactic palonosetron was used. The PONV incidence and risk factors were analyzed according to the use of these agents.The overall incidence of PONV was 30.7% during the first 24 hours postoperatively. The incidence of PONV was lower in the group using combination of prophylactic palonosetron and sugammadex (19.3%) compared with the group not using both agents (37.2%). The combined use of the prophylactic palonosetron and sugammadex was identified as a factor affecting the occurrence of PONV in both univariable (OR = 0.40, 95% CI: 0.21-0.77, P = .006) and multivariable (OR = 0.38, 95% CI: 0.20-0.75, P = .005) logistic regression analyses. In multivariable logistic regression analysis, female sex was also significant independent risk factor in PONV (OR = 2.62, 95% CI: 1.35-5.08, P = .004).In this retrospective observational study, the combined use of prophylactic palonosetron before anesthetic induction and sugammadex as a reversal of neuromuscular blockade are associated with a reduction in the incidence of PONV in patients undergoing MVD under propofol-maintained anesthesia.

Donor safety is the major concern in living donor liver transplantation, although hepatic resection may be associated with postoperative coagulopathy. Recently, the use of sugammadex has been gradually increased, but sugammadex is known to prolong prothrombin time (PT) and activated partial thromboplastin time (aPTT). We compared the postoperative coagulation profiles and outcomes of sugammadex versus pyridostigmine group in donors receiving living donor hepatectomy.Consecutive donor hepatectomy performed between September 2013 and August 2016 was retrospectively analyzed. For reversal of rocuronium-induced neuromuscular blockade, donors received sugammadex 4 mg/kg or pyridostigmine 0.25 mg/kg. The primary end-points were laboratory findings (PT, aPTT, hemoglobin, platelet count) and clinically evaluated postoperative bleeding (relaparotomy for bleeding, cumulative volume collected in drains). Secondary outcomes were anesthesia time, postoperative hospital day.Of 992 donors, 383 treated with sugammadex and 609 treated with pyridostigmine for the reversal of neuromuscular blockade. There were no significant differences between both groups for drop in hemoglobin and platelet, prolongation in PT, aPTT, and the amount of 24-h drain volume. Bleeding events within 24 h were reported in 2 (0.3%) for pyridostigmine group and 0 (0%) for sugammadex group (P = .262). Anesthesia time was significantly longer in pyridostigmine group than that in sugammadex group (438.8 ± 71.4 vs. 421.3 ± 62.3, P < .001). Postoperative hospital stay was significantly longer in pyridostigmine group than that in sugammadex group (P = .002).Sugammadex 4 mg/kg was not associated with increased bleeding tendency, but associated with reduced anesthesia time and hospital stay. Therefore, sugammadex may be safely used and will decrease morbidity in donor undergoing living-donor hepatectomy.

Context: Sugammadex has steroid-encapsulating effect., Aim: This study was undertaken to assess whether the clinical efficacy of sugammadex was altered by the administration of steroids., Setting and Design: Sixty patients between 18 and 60 years of age with the American Society of Anesthesiologists I-IV and undergoing elective direct laryngoscopy/biopsy were included in this study., Materials and Methods: Patients were assigned to two groups based on the intraoperative steroid use: those who received steroid (Group S) and who did not (Group C). After standard general anesthesia, patients were monitored with the train of four (TOF) monitoring. The preferred steroid and its dose, timing of steroid administration, and TOF value before and after sugammadex as well as the time to recovery (TOF of 0.9) were recorded., Statistical Analysis Used: SPSS software version 17.0 was used for statistical analysis., Results: There is no statistically significant difference between groups in terms of age, gender, preoperative medication use, and TOF ratio just before administering sugammadex. The reached time to TOF 0.9 after sugammadex administration was significantly shorter in Group S than Group C (P < 0.05). A within-group comparison in Group S showed no difference in TOF ratio immediately before sugammadex as well as the dose of sugammadex in those who received prednisolone; time to TOF 0.9 was higher in prednisolone receivers as compared to dexamethasone receivers (P < 0.05)., Conclusion: In patients receiving steroids, and particularly dexamethasone, an earlier reversal of neuromuscular block by sugammadex was found, in contrast with what one expect. Further studies are required to determine the cause of this effect which is probably due to a potential interaction between sugammadex and steroids., Competing Interests: There are no conflicts of interest.

We describe the case of a 3-week-old boy with pyloric stenosis who presented for laparoscopic pyloromyotomy in the setting of symptomatic transient neonatal myasthenia gravis. The patient received muscle relaxation with rocuronium, and neuromuscular blockade was successfully reversed with sugammadex with recovery guided by train-of-four monitoring. He was extubated uneventfully without complications. Because sugammadex binds directly to rocuronium rather than interfering with acetylcholine metabolism, it might provide a good option for reversal of neuromuscular blockade in transient neonatal myasthenia gravis.

Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of neuromuscular reversal dramatically. With the introduction of this selective relaxant binding agent, rapid and reliable neuromuscular reversal from any depth of block became possible. Sugammadex can reverse neuromuscular blockade without the muscarinic side effects typically associated with the administration of acetylcholinesterase inhibitors. However, what remained unchanged is the incidence of residual neuromuscular blockade. It is known that sugammadex cannot always prevent its occurrence, if appropriate dosing is not chosen based on the level of neuromuscular paralysis prior to administration determined by objective neuromuscular monitoring. Alternatively, excessive doses of sugammadex administered in an attempt to ensure full and sustained reversal may affect the effectiveness of rocuronium in case of immediate reoperation or reintubation. In such emergent scenarios that require onset of rapid and reliable neuromuscular blockade, the summary of product characteristics (package insert) recommends using benzylisoquinolinium neuromuscular blocking agents or a depolarizing agent. However, if rapid intubation is required, succinylcholine has a significant number of side effects, and benzylisoquinolinium agents may not have the rapid onset required. Therefore, prior administration of sugammadex introduces a new set of potential problems that require new solutions. This novel reversal agent thus presents new challenges and anesthesiologists must familiarize themselves with specific issues with its use (e.g., bleeding risk, hypermagnesemia, hypothermia). This review will address sugammadex administration in such special clinical situations.

Background: Cough on emergence has been reported as a common adverse reaction with sugammadex reversal. We investigated if staggering the dose of sugammadex will reduce emergence cough in a single-center, randomized, double-blinded study., Methods: A hundred and twenty ASA 1-3 adults were randomly reversed with 1 mg/kg sugammadex prior to extubation followed by another 1 mg/kg immediately after extubation (staggered group), single dose of 2 mg/kg sugammadex (single bolus group) or neostigmine 0.02 mg/kg with glycopyrrolate (neostigmine group)., Results: We found 70% of patients (n = 28) reversed with single boluses of sugammadex had Grade 3 emergence cough compared to 12.5% (n = 5) in the staggered sugammadex group and 17.5% (n = 7) in the neostigmine group (p < 0.001). Besides cough, emergence agitation also appeared highest in the single bolus sugammadex group (n = 14, 35%, p = 0.005). On the other hand, staggering sugammadex lowered risks of developing severe cough (RR 0.2, p < 0.001) and agitation (RR 0.43, p = 0.010) on emergence in addition to cough (RR 0.25, p = 0.039) and early sore throat (RR 0.70, p = 0.036) in the post-anesthetic care unit. The risks for severe emergence cough (RR 0.86, p = 0.762), severe cough in the post-anesthetic care unit (RR 1.0, p = 1.000) and sore throat (RR 1.17, p = 0.502) were also not different between the staggered sugammadex group and control given neostigmine. In terms of timing, there was no delay in time taken from discontinuing anesthetic agents to reversal and extubation if sugammadex was staggered (emergence time 6.0 ± 3.2 s, p = 0.625 and reversal time 6.5 ± 3.5, p = 0.809)., Conclusions: Staggering the dose of sugammadex for reversal will effectively decrease common emergence and early postoperative complications., Trial Registration: ANZCTR Number ACTRN12616000116426 . Retrospectively registered on 2nd February 2016.

Study Objective: To summarize and compare efficacy of sugammadex with neostigmine or placebo for reversal of rocuronium- or vecuronium-induced neuromuscular blockade (NMB), and to demonstrate consistency of sugammadex results across various patient populations., Design: Pooled analysis on data from 26 multicenter, randomized, Phase II and III studies., Setting: Operating room., Patients: 1855 adults undergoing surgery under general anesthesia and receiving rocuronium or vecuronium for NMB., Interventions: Sugammadex (2.0mg/kg at second twitch reappearance [T 2 ; moderate NMB], 4.0mg/kg at 1-2 post-tetanic counts [PTC; deep NMB] or 16.0mg/kg at 3min after rocuronium 1.2mg/kg), neostigmine or placebo., Measurements: Time to recovery of the train-of-four (TOF) ratio to 0.9., Main Results: Geometric mean (95% CI) times to recovery to TOF ratio of 0.9 were 1.9 (1.8-2.0) min following sugammadex 2.0mg/kg and 10.6 (9.8-11.6) min following neostigmine administration at T 2 after rocuronium, and 2.9 (2.5-3.4) min and 17.4 (13.4-22.6) min, respectively, after vecuronium. Recovery times were 2.2 (2.1-2.3) min following sugammadex 4.0mg/kg and 19.0 (14.8-24.6) min following neostigmine administered at a target of 1-2 PTC after rocuronium, and 3.8 (3.0-5.0) min and 67.6 (56.3-81.2) min after vecuronium. Sugammadex administered 3min after rocuronium 1.2mg/kg resulted in rapid recovery (1.7 [1.5-2.0] min). Modest increases in mean recovery time were associated with vecuronium use (+1.6min [78%; (61%-98%)] versus rocuronium), mild-to-moderate renal impairment (+0.4min [20%; (9%-32%)] versus normal renal function) and geographic location (+1.0min [38%; (25%-52%)] in subjects in USA/Canada versus Europe/Japan)., Conclusions: Sugammadex administered at recommended doses provides rapid and predictable reversal of rocuronium and vecuronium-induced moderate and deep NMB, and effective reversal 3min after rocuronium 1.2mg/kg. Robust recovery was seen across various patient factors, providing further confirmation of labeled dose recommendations., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study aimed to assess the effects of sugammadex and neostigmine/atropine on postoperative cognitive dysfunction (POCD) in adult patients after elective surgery. A randomised, double-blind controlled trial was carried out on 160 American Society of Anesthesiologists physical status I to III patients who were >40 years. The Mini-Mental State Evaluation, clock-drawing test and the Isaacs Set test were used to assess cognitive function at three timepoints: 1) preoperatively, 2) one hour postoperatively, and 3) at discharge. The anaesthetic protocol was the same for all patients, except for the neuromuscular block reversal, which was administered by random allocation using either sugammadex or neostigmine/atropine after the reappearance of T2 in the train-of-four sequence. POCD was defined as a decline ≥1 standard deviation in ≥2 cognitive tests. The incidence of POCD was similar in both groups at one hour postoperatively and at discharge (28% and 10%, in the neostigmine group, 23% and 5.4% in the sugammadex group, P =0.55 and 0.27 respectively). In relation to individual tests, a significant decline of clock-drawing test in the neostigmine group was observed at one hour postoperatively and at discharge. For the Isaacs Set test, a greater decline was found in the sugammadex group. These findings suggest that there are no clinically important differences in the incidence of POCD after neostigmine or sugammadex administration.

A growing proportion of patients undergoing surgical procedures are obese, providing anesthesiologists with numerous challenges for patient management. The current pooled analysis evaluated recovery times following sugammadex reversal of neuromuscular blockade by body mass index (BMI) in general, and in particular, in patients with BMIs ≥30 kg/m (defined as obese) and <30 kg/m (defined as non-obese). Data were pooled from 27 trials evaluating recommended sugammadex doses for reversal of moderate [reappearance of the second twitch of the train-of-four (TOF); sugammadex 2 mg/kg] or deep (1-2 post-tetanic counts or 15 minutes after rocuronium; sugammadex 4 mg/kg) rocuronium- or vecuronium-induced neuromuscular blockade. All doses of sugammadex were administered based on actual body weight. The recovery time from sugammadex administration to a TOF ratio ≥0.9 was the primary efficacy variable in all individual studies and in the pooled analysis. This analysis comprised a total of 1418 adult patients treated with sugammadex; 267 (18.8%) of these patients had a BMI ≥30 kg/m. The average time to recovery of the TOF ratio to 0.9 was 1.9 minutes for rocuronium-induced blockade and 3.0 minutes for vecuronium-induced blockade. No clinically relevant correlation was observed between BMI and recovery time. The recommended sugammadex doses based on actual body weight provide rapid recovery from neuromuscular blockade in both obese and non-obese patients; no dose adjustments are required in the obese patient.

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).

Background: The aim of this study is to assess the effect of sugammadex on postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy., Methods: Eighty patients who were scheduled for elective laparoscopic cholecystectomy surgery were enrolled in this prospective study. Patients were randomly assigned to neostigmine (group N) or sugammadex (group S) for neuromuscular antagonism at the end of anesthesia. The incidence of PONV and antiemetic consumption were recorded., Results: Nausea and vomiting were observed in 60% of the patients given sugammadex and 77.5% given neostigmine during the initial 24 hours postoperatively. The incidence of nausea and the need for rescue antiemetic were lower in group S than group N during all time intervals but there were no significant differences between the groups., Conclusions: Sugammadex seems to be effective in decreasing the incidence of PONV, severity of nausea, number of patients who suffered from nausea and vomiting, and need for rescue antiemetic, although there were no significant differences.

Study Objective: Sugammadex has been introduced for reversal of neuromuscular blockade (NMB) induced by rocuronium (or vecuronium). Although its efficacy and safety have been established, data are conflicting as to whether it accelerates discharge to the surgical ward compared with neostigmine, which is traditionally used for reversing NMB. The object of this systematic review and meta-analysis was to review the research comparing sugammadex and neostigmine in the context of patient discharge after general anesthesia., Design: Systematic review and meta-analysis., Setting: University medical hospital., Patients: Five-hundred eighteen patients from six studies were included., Methods: A comprehensive search was conducted using PubMed, Web of Science, Google Scholar, and Cochrane Library electronic databases to identify randomized controlled trials written in English. Two reviewers independently selected the studies, extracted data regarding postoperative discharge, and assessed the trials' methodological quality and evidence level. Postoperative discharge time was determined from the operating room (OR) to the postanesthesia care unit (PACU) and from the PACU to the surgical ward. This study was conducted using PRISMA methodology., Measurements: Time to discharge after NMB reversal with sugammadex or neostigmine., Main Results: Compared with neostigmine, sugammadex was associated with a significantly faster discharge from the OR to the PACU (mean difference [MD]=22.14min, 95% CI (14.62, 29.67), P<0.0001, I 2 =0%) and from the PACU to the surgical ward (MD=16.95min, 95% CI (0.23, 33.67), P=0.0469, I 2 =98.4%). Similarly, discharge-readiness was shorter for sugammadex than for neostigmine from the OR to the PACU (MD=5.58min, 95% CI (3.03, 8.14), P≤0.0001, I 2 =0%). However, discharge-readiness was similar in both groups for patients moving from the PACU to the surgical ward (MD=-1.10min, 95% CI (-5.69, 3.50), P=0.6394, I 2 =25.3%)., Conclusions: Results from this meta-analysis suggest that sugammadex accelerates postoperative discharge of patients after general anesthesia compared with neostigmine., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose of Review: The aim of this review is to examine data relating to perioperative management of the patient with neuromuscular disorders RECENT FINDINGS: Patients with pre-existing neuromuscular disorders are at risk for a number of postoperative complications that are related to anesthetic drugs that are administered intraoperatively. Careful preoperative assessment is necessary to reduce morbidity and mortality. In particular, the risk of postoperative respiratory failure and need for long-term ventilation should be reviewed with patients. The use of succinylcholine should be avoided in muscular dystrophies, motor neuron diseases, and intrinsic muscle disease due to a risk of malignant hyperthermia, hyperkalemia, rhabdomyolysis, and cardiac arrest. The use of quantitative neuromuscular monitoring should be strongly considered whenever nondepolarizing neuromuscular blocking agents are administered. A number of case series and reports have been recently published demonstrating that sugammadex can be safely used in patients with neuromuscular disease; the risk of residual neuromuscular is nearly eliminated when this agent is administered intraoperatively., Summary: Careful assessment and management of patients with underlying neuromuscular diseases is required to reduce postoperative complications. This article reviews the anesthetic implications of patients undergoing surgery with neuromuscular disorder.

Objectives/hypothesis: Laser microlaryngeal surgery (LMS) is a short operation requiring brief and intense paralysis. Adequate muscle relaxation and rapid recovery of neuromuscular function are essential for improving surgical conditions and reducing the incidence of complications during LMS. However, the ideal muscle relaxant with a rapid onset and short duration of action is not yet available. Rocuronium has rapid onset at higher doses, but with a prolonged duration of action. Sugammadex is a selective relaxant-binding agent that allows for rapid reversal of rocuronium-induced neuromuscular blockade. This study aimed to compare the surgical conditions and anesthesia time between two combinations of neuromuscular blocker and reversal agent, rocuronium-sugammadex (R-S) and succinylcholine-cisatracurium-pyridostigmine (S-C-P), and propose an optimal anesthetic regimen for improving the surgical conditions in LMS patients., Study Design: Prospective, randomized, double-blinded clinical study., Methods: Patients in the R-S group received 1 mg/kg rocuronium bromide, whereas those in the S-C-P group received 1 mg/kg succinylcholine. After endotracheal intubation, 0.08 mg/kg cisatracurium was injected in S-C-P patients. After the procedure, R-S patients received 2 mg/kg sugammedex, whereas S-C-P patients received 0.2 mg/kg pyridostigmine plus 10 μg/kg atropine., Results: In the R-S group, surgical condition scores were significantly higher and anesthesia time was significantly shorter. The use of additive neuromuscular blocking agents was significantly higher in the S-C-P group., Conclusions: Muscle relaxation with rocuronium and reversal with sugammadex resulted in better surgical conditions and a shorter anesthesia time in patients undergoing LMS when compared to the S-C-P regimen., Level of Evidence: 1b Laryngoscope, 127:1135-1139, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Competing Interests: Les auteurs ne déclarent aucun conflit d'intérêts.

Sugammadex encapsulates and inactivates rocuronium and vecuronium. It is used to reverse neuromuscular blockade from these nondepolarizing agents. The safety of sugammadex in patients with neuromuscular disease has not been established. Guillain-Barre Syndrome (GBS) is a neuromuscular disease characterized by acute inflammatory polyneuropathy. Patients with GBS may exhibit autonomic dysfunction, chronic pain, abnormal reactions to neuromuscular blocking agents, and may require postoperative mechanical ventilation. We report the successful use of sugammadex to reverse rocuronium in a patient with chronic GBS, who presented for a hemicolectomy.

Previous studies have shown that sugammadex decreases the anesthetic depth when administered to reverse the neuromuscular blockade produced by rocuronium/vecuronium. The aim of the present study was to investigate the effect of sugammadex alone on anesthetic depth and hemodynamics. Sixty patients scheduled for abdominal surgery participated in the study. Anesthesia was induced with thiopental/fentanyl and maintained with N 2 O/oxygen and sevoflurane concentrations adjusted to maintain Entropy and Bispectral Index (BIS) values between 40 and 50. Cis-atracurium 0.2 mg/kg was administered for neuromuscular blockade which was monitored with a TOF-Watch ® SX acceleromyograph. State entropy (SE), response entropy (RE), Bispectral Index (BIS), systolic (SAP) and diastolic blood pressure (DAP), heart rate (HR), SpO 2 , end-tidal CO 2 and sevoflurane concentrations were recorded every 3 min intraoperatively. Sugammadex 2 mg/kg (Group-2), 4 mg/kg (Group-4) or 16 mg/kg (Group-16) was given intravenously when a count of two responses of the train-of-four (TOF) or a post-tetanic count (PTC) 1-3 appeared or when no response at all (PTC = 0) was observed, respectively. The overall SE values, thus the primary outcome of the study, were 44 ± 11, 43 ± 10 and 43 ± 11 for Group-2, Group-4 and Group-16, respectively (p = 0.812). Also, the secondary endpoints, namely RE, BIS, SAP and DAP, HR and SpO 2 did not differ between the three groups. Comparisons between Group-2 versus Group-4, Group-2 versus Group-16 and Group-4 versus Group-16 showed no differences (p > 0.05) for all the studied variables. Sugammadex alone at low, medium or high clinical doses has no effect on anesthetic depth as assessed by Entropy and BIS or on hemodynamics.

[60]Fullerene (C 60 ) derivatives were incorporated into liposomes using a fullerene exchange method involving the transfer of the fullerene from the cavity of two γ-cyclodextrin molecules to a liposome. A lipid-membrane-incorporated C 60 derivative bearing a polar group showed much higher photodynamic activity than the analogous system incorporating pristine C 60 .

Background and Objectives: The aim of our study is to compare the effects of sugammadex and neostigmine, used for neuromuscular blockage antagonism, on postoperative nausea and vomiting (PONV)., Methods: Our study was completed with 98 ASA I-II risk patients undergoing endotracheal intubation under general anesthesia. At the end of the surgery patients were randomly divided into two groups given 2mgkg -1 sugammadex (Group S) or 50μgkg -1 neostigmine plus 0.2mgkg -1 atropine (Group N). Monitoring and recording times were set as 1 hour postoperative and from 1-6, 6-12, and 12-24hours. The anti-emetic amounts administered were recorded., Results: In the first hour postoperative 13 patients in Group N (27%) and 4 in Group S (8%) were observed to have nausea and/or vomiting and the difference was statistically significant (p=0.0016). During the 24 hours of monitoring there was no significant difference in the incidence and severity of PONV (p>0.05), however the number of patients given ondansetron for PONV treatment in Group N was statistically significantly higher than the number in Group S (16 in Group N, 6 in Group S, p<0.011)., Conclusions: At the end of our study comparing neostigmine with sugammadex for neuromuscular blockage antagonism, we found use of sugammadex had lower incidence of PONV in the postoperative 1st hour and less anti-emetic use in 24 hours of monitoring., (Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Myasthenia gravis is an autoimmune disorder that is characterized by muscle weakness that fluctuates, worsening with exertion, and improving with rest. Diagnosis of myasthenia gravis is made following clinical and physical examination and is confirmed by serum immunoassays to measure autoantibody levels. Myasthenia gravis especially when associated with pregnancy is a high-risk disease, and its course is unpredictable. We described the second report about use of sugammadex after rocuronium for a caesarean delivery with myasthenia gravis, but, unlike our case that formerly was diagnosed with myasthenia gravis, the patient was extubated on postoperative successfully and we did not encounter any respiratory problems., (Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Rocuronium (ROC) and Vecuronium (VEC) are the most currently used steroidal non-depolarizing neuromuscular blocking (MNB) agents. Sugammadex (SUG) rapidly reverses steroidal NMB agents after anaesthesia. The present study was conducted in order to evaluate neuronal effects of SUG alone and in combination with both ROC and VEC. Using MTT, CASP-3 activity and Western-blot we determined the toxicity of SUG, ROC or VEC in neurons in primary culture. SUG induces apoptosis/necrosis in neurons in primary culture and increases cytochrome C (CytC), apoptosis-inducing factor (AIF), Smac/Diablo and Caspase 3 (CASP-3) protein expression. Our results also demonstrated that both ROC and VEC prevent these SUG effects. The protective role of both ROC and VEC could be explained by the fact that SUG encapsulates NMB drugs. In BBB impaired conditions it would be desirable to control SUG doses to prevent the excess of free SUG in plasma that may induce neuronal damage. A balance between SUG, ROC or VEC would be necessary to prevent the risk of cell damage., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

We present a case in which rocuronium was applied for muscle relaxation following the administration of sugammadex. An emergency surgery under general anesthesia was planned for a 43-year-old male patient due to an L1 vertebral corpus and right tibia-fibula shaft fracture. Anesthesia was induced with fentanyl, propofol and lidocaine. After applying only 30mg of the total induction dose of rocuronium, it was learned that the neurological examination should be controlled again from the surgeon because of the controversial of the neurological deficit. As a result, patient awakened from anesthesia. We administered 2mg/kg sugammadex and spontaneous breathing of patient returned immediately. The patient became conscious and orientated immediately afterwards. The neurological examination of the lower extremities was performed. The patient was anesthetized once again and 0.6mg/kg rocuronium was given in order to gain neoromuscular block approximately 10min after sugammadex administration. 2min later, the patient was smoothly intubated. Neuromuscular monitorization was not used because of emergency. We administered 2mg/kg sugammadex at the end of the procedure and the patient was extubated. The most suitable time for the re-establishment of rocuronium following sugammadex is currently unclear. This case showed that neuromuscular block can be effectively re-induced by rocuronium following the reversal of rocuronium-induced neuromuscular block with sugammadex. In this case, we consider that the ability to effectively reuse normal induction doses of rocuronium is an important clinical observation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Myaesthenia Gravis is an autoimmune disorder that results in increased sensitivity to neuromuscular blockers. Anaesthesia and surgery in patients with Myaesthenia Gravis is associated with an increased incidence of complications, including post operative ventilation. We report the successful use of intra-operative train of four ratio monitoring and Sugammadex to reverse rocuronium induced neuromuscular blockade in an elderly octagenarian with Myaesthenia Gravis undergoing an emergency laporotomy., Case Report: An 87year old man with Myaesthenia Gravis underwent an emergency laporotomy for a perforated sigmoid diverticulum. Induction of anaesthesia was performed with 100μg of fentanyl, 120mg propofol and 25mg rocuronium. Intraoperative boluses of 5mg rocuronium were guided by train of four ratio of 50%. At the end of the procedure 4mg/kg of Sugammadex was given to reverse neuromuscular blockade as observed by return of four twitches on the train of four. He was then successfully extubated and did not require any post operative ventilation., Conclusion: We report the successful use of intra-operative neuromuscular monitoring and Sugammadex to reverse rocuronium induced neuromuscular blockade in an elderly octagenarian with Myaesthenia Gravis undergoing emergency laporotomy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Neuroleptics are a group of drugs widely used in the treatment of psychotic symptoms. Among their adverse effects is the ability to trigger a neuroleptic malignant syndrome (NMS). The diagnosis of NMS is determined by exclusion, and its initial therapeutic management should be the withdrawal of neuroleptics, the administration of benzodiazepines, and electroconvulsive therapy (ECT). ECT is an effective treatment in these patients, and in those cases with a poor response to treatment with antipsychotic drugs. A review is presented on the treatment options and anaesthetic implications of ECT used to handle a patient diagnosed with paranoid schizophrenia in the context of NMS., (Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

An anaphylactic reaction during a cesarean section occurs rarely, and rocuronium is thought to be one of the common agents causing perioperative anaphylaxis. Here we report an anaphylactic shock after cesarean section that is suggested to be induced by the rocuronium-sugammadex complex. A 36-year-old primigravida underwent an elective cesarean section under general anesthesia due to placenta previa. While the operation was completed uneventfully, she developed anaphylactic shock following sugammadex administration. She was successfully managed with rapid treatments. Serum tryptase level was significantly elevated. Although sugammadex was first suspected to be the causative agent, the result of intradermal skin tests with sugammadex were negative. Surprisingly, a subsequent intradermal test with undiluted rocuronium caused the patient to fall into a state of shock. Furthermore, a later skin-prick test with pre-mixed rocuronium-sugammadex complex also revealed a strong positive reaction, and a test with only rocuronium showed negative. We finally concluded that the rocuronium-sugammadex complex is the causative agent in this case. To the best of our knowledge, this is the first report suggesting anaphylaxis caused by the rocuronium-sugammadex complex. This case highlights the importance of appropriate examinations to determinate the pathogenesis of anaphylaxis in order to establish risk reduction strategies., Competing Interests: Masakazu Yamaoka has no conflict of interest.

Background: Electromyographic activity of the diaphragm (EMGdi) during weaning from mechanical ventilation is increased after sugammadex compared with neostigmine., Objective: To determine the effect of neostigmine on EMGdi and surface EMG (sEMG) of the intercostal muscles during antagonism of rocuronium block with neostigmine, sugammadex and neostigmine followed by sugammadex., Design: Randomised, controlled, double-blind study., Setting: Intensive care research unit., Participants: Eighteen male volunteers., Interventions: A transoesophageal EMGdi recorder was inserted into three groups of six anaesthetised study participants, and sEMG was recorded on their intercostal muscles. To reverse rocuronium, volunteers received 50 μg kg neostigmine, 2 mg kg sugammadex or 50 μg kg neostigmine, followed 3 min later by 2 mg kg sugammadex., Main Outcome Measures: We examined the EMGdi and sEMG at the intercostal muscles during recovery enhanced by neostigmine or sugammadex or neostigmine-sugammadex as primary outcomes. Secondary objectives were the tidal volume, PaO2 recorded between the onset of spontaneous breathing and extubation of the trachea and SpO2 during and after anaesthesia., Results: During weaning, median peak EMGdi was 0.76 (95% confidence interval: 1.20 to 1.80) μV in the neostigmine group, 1.00 (1.23 to 1.82) μV in the sugammadex group and 0.70 (0.91 to 1.21) μV in the neostigmine-sugammadex group (P < 0.0001 with EMGdi increased after sugammadex vs. neostigmine and neostigmine-sugammadex). The median peak intercostal sEMG for the neostigmine group was 0.39 (0.65 to 0.93) μV vs. 0.77 (1.15 to 1.51) μV in the sugammadex group and 0.82 (1.28 to 2.38) μV in the neostigmine-sugammadex group (P < 0.0001 with sEMG higher after sugammadex and after neostigmine-sugammadex vs. neostigmine)., Conclusion: EMGdi and sEMG on the intercostal muscles were increased after sugammadex alone compared with neostigmine. Adding sugammadex after neostigmine reduced the EMGdi compared with sugammadex alone. Unlike the diaphragm, intercostal EMG was preserved with neostigmine followed by sugammadex., Trial Registration: EudraCT: 2015-001278-16; ClinicalTrials.gov: NCT02403063.

Objective: to determine the ED90 (minimum effective dose in 90% of patients) of sugammadex for the reversal of rocuronium-induced moderate neuromuscular blockade (NMB) in patients with grade III obesity undergoing bariatric surgery., Methods: we conducted a prospective study with the biased coin up-and-down sequential design. We chosen the following doses: 2.0mg/Kg, 2.2mg/Kg, 2.4mg/Kg, 2.6mg/Kg, 2.8mg/Kg. The complete reversal of rocuronium-induced NMB considered a T4/T1 ratio ≥0.9 as measured by TOF. After induction of general anesthesia and calibration of the peripheral nerve stimulator and accelerometer, we injected rocuronium 0.6mg/kg. We administered propofol and remifentanil by continuous infusion, and intermittent boluses of rocuronium throughout the procedure., Results: we evaluated 31 patients, of whom 26 had displayed successful reversal of the NMB with sugammadex, and failure in five. The mean time to complete moderate NMB reversal was 213 seconds (172-300, median 25-75%). The ED90 of sugammadex calculated by regression was 2.39mg/kg, with a 95% confidence interval of 2.27-2.46 mg/kg., Conclusion: the ED90 of sugammadex in patients with grade III obesity or higher was 2.39mg/kg.

Postoperative paralysis of the vocal cords resulting from intraoperative surgical injury of the recurrent laryngeal nerve is one of the most serious complications of elective thyroid surgery. The chance of injury is reduced by using intraoperative neuromonitoring (IONM). This educational report describes a case of IONM failure resulting from residual muscle relaxation that was restored by administration of sugammadex. It discusses possible pharmacology explanations and provides recommendations for how to prevent this situation in daily practice.

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.)

Background: The objective of this analysis is to explore potential impact on operating room (OR) efficiency and incidence of residual neuromuscular blockade (RNMB) with use of sugammadex (Bridion™, Merck & Co., Inc., Kenilworth, NJ USA) versus neostigmine for neuromuscular block reversal in Canada., Methods: A discrete event simulation (DES) model was developed to compare ORs using either neostigmine or sugammadex for NMB reversal over one month. Selected inputs included OR procedure and turnover times, hospital policies for paid staff overtime and procedural cancellations due to OR time over-run, and reductions in RNMB and associated complications with sugammadex use. Trials show sugammadex's impact on OR time and RNMB varies by whether full neuromuscular recovery (train-of-four ratio ≥0.9) is verified prior to extubation in the OR. Scenarios were therefore evaluated reflecting varied assumptions for neuromuscular reversal practices., Results: With use of moderate neuromuscular block, when full neuromuscular recovery is verified prior to extubation (93 procedures performed with sugammadex, 91 with neostigmine), use of sugammadex versus neostigmine avoided 2.4 procedural cancellations due to OR time over-run and 33.5 h of paid staff overtime, while saving an average of 62 min per OR day. No difference was observed between comparators for these endpoints in the scenario when full neuromuscular recovery was not verified prior to extubation, however, per procedure risk of RNMB at extubation was reduced from 60% to 4% (reflecting 51 cases prevented), with associated reductions in risks of hypoxemia (12 cases avoided) and upper airway obstruction (23 cases avoided). Sugammadex impact in reversing deep neuromuscular block was evaluated in an exploratory analysis. When it was hypothetically assumed that 30 min of OR time were saved per procedure, the number of paid hours of staff over-time dropped from 84.1 to 32.0, with a 93% reduction in the per patient risk of residual blockade., Conclusions: In clinical practice within Canada, for the majority of patients currently managed with moderate neuromuscular block, the principal impact of substituting sugammadex for neostigmine is likely to be a reduction in the risk of residual blockade and associated complications. For patients maintained at a deep level of block to the end of the procedure, sugammadex is likely to both enhance OR efficiency and reduce residual block complications.

A 50-year-old man developed a severe anaphylactic reaction shortly after the administration of sugammadex at the end of an uneventful laparoscopic appendectomy. Subsequent skin testing was negative to all agents to which the patient was exposed including sugammadex. Because of the temporal relationship to the administration of sugammadex, further skin testing was performed with premixed sugammadex and rocuronium that produced a markedly positive response. This is the first case report of anergy to the individual components but sensitivity to the inclusion complex of rocuronium and sugammadex. Written informed consent was obtained from the patient for skin testing, photography, laser perfusion imaging, and publication of this case report.

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.)

Study Objective: To evaluate the effect of neuromuscular blockade (NMB) upon the abdominal space during pneumoperitoneum establishment in laparoscopic surgery, comparing moderate NMB and deep NMB., Design: Prospective, randomized, crossover clinical trial., Setting: Operating room., Patients: Seventy-six American Society of Anesthesiologists 1 to 2 patients scheduled for elective laparoscopic surgery., Interventions: Two independent evaluations were performed at the establishment of pneumoperitoneum for a preset intraabdominal pressures (IAPs) of 8 and 12 mm Hg, both during moderate NMB (train-of-four count, 1-3) and deep NMB (posttetanic count, <5). Rocuronium was used to induce NMB, and sugammadex was used for reversal., Measurements: We evaluated (i) the volume of CO2 introduced in 41 patients and (ii) the skin-sacral promontory distance in 35 patients, at pneumoperitoneum establishment., Results: Compared to moderate NMB, deep NMB increased, in a significant manner, both the intraabdominal volume of CO2 insufflated (mean [SD], 2.24 [1.10] vs 2.81 [1.13] L at 8 mm Hg IAP, P<.001, and 3.52 [1.31] vs 4.09 [1.31] L at 12 mm Hg IAP, P<.001) and the skin-sacral promontory distance (11.78 [1.52] vs 12.16 [1.51] cm at 8 mm Hg IAP, P=.002, and 13.34 [1.87] vs 13.80 [1.81] cm at 12 mm Hg IAP, P<.001). Increase in intraabdominal volume after inducing deep NMB was observed in 88% and 81.7% of patients at 8 and 12 mm Hg pneumoperitoneum, with a volume increase of mean of 36.8% (95% confidence interval [CI], 22.8-50.8) and 25% (95% CI, 13.7-36.4), respectively (P=.003). Increase in distance was observed in 61% and 82% of patients at 8 and 12 mm Hg pneumoperitoneum, with a mean distance increase of 3.3% (95% CI, 1.3-5.4) and 3.6% (95% CI, 1.9-5.2), respectively (P=.840)., Conclusions: Deep NMB, in comparison to moderate NMB, increased in a significant manner the abdominal space at pneumoperitoneum establishment. However, the effective increase in the abdominal cavity dimensions could be low, the increase showed a great interindividual variability, and it was not observed in every patient. Clinical significance of this increase on surgical conditions is yet to be demonstrated., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Complex surgical procedures are increasingly performed in an outpatient setting, with emphasis on rapid recovery and case turnover. In this study, the combination of rocuronium for neuromuscular blockade (NMB) reversed by single-dose sugammadex was compared with succinylcholine followed by spontaneous recovery in outpatient surgery. This multicenter, randomized, safety assessor-blinded study enrolled adults undergoing a short elective outpatient surgical procedure requiring NMB and tracheal intubation. Patients were randomized to NMB with either rocuronium 0.6 mg/kg for tracheal intubation with incremental doses of rocuronium 0.15 mg/kg and subsequent reversal with sugammadex 4.0 mg/kg at 1-2 posttetanic counts or succinylcholine 1.0 mg/kg for intubation with spontaneous recovery. The primary efficacy end point was the time from sugammadex administration to recovery of the train-of-four ratio to 0.9; for succinylcholine, time from administration to recovery of the first twitch (T1) to 90% was assessed. From 167 patients enrolled, 150 received treatment. The all-subjects-treated population comprised 70 patients in the rocuronium-sugammadex group and 80 in the succinylcholine group. Geometric mean (95% confidence interval) time from the start of sugammadex administration to recovery of the train-of-four ratio to 0.9 was 1.8 (1.6-2.0) minutes. Geometric mean (95% confidence interval) time from succinylcholine administration to recovery of T1 to 90% was 10.8 (10.1-11.5) minutes. Health outcome variables were similar between the groups. Adverse events were reported in 87.1% and 93.8% of patients for rocuronium-sugammadex and succinylcholine, respectively. In conclusion, rocuronium for intubation followed by sugammadex for reversal of NMB offers a viable treatment option in outpatient surgery without prolonging recovery duration or jeopardizing safety.

Background: Sugammadex reverses neuromuscular block (NMB) through binding aminosteroid neuromuscular blocking agents. Although sugammadex appears to be highly selective, it can interact with other drugs, like corticosteroids. A prospective single-blinded randomized clinical trial was designed to explore the significance of interactions between dexamethasone and sugammadex., Methods: Sixty-five patients who were anesthetized for elective abdominal or urological surgery were included. NMB was assessed using train-of-four stimulation (TOF), with rocuronium used to maintain the desired NMB depth. NMB reversal at the end of anaesthesia was achieved using sugammadex. According to their received antiemetics, the patients were randomized to either the granisetron or dexamethasone group. Blood samples were taken before and after NMB reversal, for plasma dexamethasone and rocuronium determination. Primary endpoint was time from sugammadex administration to NMB reversal. Secondary endpoints included the ratios of the dexamethasone and rocuronium concentrations after NMB reversal versus before sugammadex administration., Results: There were no differences for time to NMB reversal between the control (mean 121 ± 61 s) and the dexamethasone group (mean 125 ± 57 s; P = 0.760). Time to NMB reversal to a TOF ratio ≥0.9 was significantly longer in patients with lower TOF prior to sugammadex administration (Beta = -0.268; P = 0.038). The ratio between the rocuronium concentrations after NMB reversal versus before sugammadex administration was significantly affected by sugammadex dose (Beta = -0.375; P = 0.004), as was rocuronium dose per hour of operation (Beta = -0.366; p = 0.007), while it was not affected by NMB depth before administration of sugammadex (Beta = -0.089; p = 0.483) and dexamethasone (Beta = -0.186; p = 0.131). There was significant drop in plasma dexamethasone after sugammadex administration and NMB reversal (p < 0.001)., Conclusions: Administration of dexamethasone to anesthetized patients did not delay NMB reversal by sugammadex., Trial Registration: The trial was retrospectively registered with The Australian New Zealand Clinical Trials Registry (ANZCTR) on February 28th 2012 (enrollment of the first patient on February 2nd 2012) and was given a trial ID number ACTRN12612000245897 and universal trial number U1111-1128-5104.

Background: Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially., Methods: Rabbits were randomly divided into 4 groups. Group Control (n=7); no intervention performed. Group Catheter (n=7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n=7); rabbits were given 4mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n=7); rabbits were given 1μg/kg dexmedetomidine into the central artery of the ear. After 72h, the ears were amputated and histologically investigated., Results: There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p<0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores., Conclusion: Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed., (Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)