Search

Sugammadex, a selective antagonist of steroidal non-depolarizing neuromuscular blocking agents, has been used in children in limited circumstances. However, neither pharmacokinetics (PKs) nor recovery profile of sugammadex for intense neuromuscular blockade reversal in children have been reported. This prospective study aimed to obtain a PK model of sugammadex and evaluate its efficacy and safety for intense neuromuscular blockade reversal in children. Forty children (age, 2-17 years) who underwent surgery that required early neuromuscular blockade reversal were enrolled. After neuromuscular blockade with 1 mg·kg-1 of rocuronium, sugammadex (2, 4, and 8 mg·kg-1) or a conventional dose of neostigmine (0.03 mg·kg-1) was administered randomly after confirmation of zero post-tetanic count. The plasma concentrations of rocuronium and sugammadex were measured 2 min after rocuronium injection; immediately before, 2, 5, 15, 60, 120, 240, and 480 min after the study drug injection. Response to train-of-four stimulation was continuously recorded. Noncompartmental analysis and population PK modeling were performed. For pharmacodynamics, the recovery profile was measured. Three-compartment PK model was established for sugammadex. The median (interquartile range [IQR]) time from injection of 8 mg·kg-1 of sugammadex to recovery of T4/T1 greater than or equal to 0.9 at train-of-four stimulation was 1.1 (IQR: 0.88-1.8) min. No adverse events related to sugammadex were observed. We present a PK analysis of sugammadex for rocuronium-induced intense neuromuscular blockade reversal in children with its recovery profile. The time to recover T4/T1 greater than or equal to 0.9 at train-of-four stimulation with 8 mg·kg-1 of sugammadex was less than 3 min and comparable to that in adults. [ABSTRACT FROM AUTHOR]

Postoperative pulmonary complications are a source of morbidity after major surgery. In patients at increased risk of postoperative pulmonary complications we sought to assess the association between neuromuscular blocking agent reversal agent and development of postoperative pulmonary complications. We conducted a retrospective matched cohort study, a secondary analysis of data collected in the prior STRONGER study. Data were obtained from the Multicenter Perioperative Outcomes Group. Included patients were aged 18 yr and older undergoing non-emergency surgery under general anaesthesia with tracheal intubation with neuromuscular block and reversal, who were predicted to be at elevated risk of postoperative pulmonary complications. This risk was defined as American Society of Anesthesiologists Physical Status 3 or 4 in patients undergoing either intrathoracic or intra-abdominal surgery who were either aged >80 yr or underwent a procedure lasting >2 h. Cohorts were defined by reversal with neostigmine or sugammadex. The primary composite outcome was the occurrence of pneumonia or respiratory failure. After matching by institution, sex, age (within 5 yr), body mass index, anatomic region of surgery, comorbidities, and neuromuscular blocking agent, 3817 matched pairs remained. The primary postoperative pulmonary complications outcome occurred in 224 neostigmine cases vs 100 sugammadex cases (5.9% vs 2.6%, odds ratio 0.41, P <0.01). After adjustment for unbalanced covariates, the adjusted odds ratio for the association between sugammadex use and the primary outcome was 0.39 (P <0.0001). In a cohort of patients at increased risk for pulmonary complications compared with neostigmine, use of sugammadex was independently associated with reduced risk of subsequent development of pneumonia or respiratory failure. [ABSTRACT FROM AUTHOR]

We investigated the influence of different neuromuscular blocking agents and reversal agents during anaesthesia on early removal of chest tube drainage after video-assisted thoracoscopic surgery (VATS). This retrospective single-centre study included patients who underwent VATS after tracheal intubation under general anaesthesia. Patients received either cisatracurium and neostigmine (n =547) or rocuronium and sugammadex (n =151). Quantitative neuromuscular monitoring was used and one chest tube (size 24 Fr) was inserted. To reduce potential bias, 140 patients from each group were matched by propensity score for sex, age, body mass index and indication for VATS. Primary outcome was duration of chest tube drainage after surgery. Use of rocuronium and sugammadex was associated with a shorter duration of chest tube drainage (2 [1–2] vs 2 [1–3] days; P =0.049) and a 63% reduction in delayed chest tube removal (odds ratio 0.37; 95% confidence interval [CI]: 0.20–0.67; P =0.005). This group also had a lower incidence of postoperative atelectasis (P =0.047) and consolidation (P =0.008). Each 1 h increase in the duration of anaesthesia was associated with a 1.57-fold increase in the delayed removal of the chest tube (95% CI: 1.25–1.96; P =0.005). During general anaesthesia for VATS, compared with cisatracurium and neostigmine, use of rocuronium and sugammadex was associated with a significant decrease in the incidence of postoperative delayed removal of the chest tube, atelectasis, and pulmonary consolidation. [ABSTRACT FROM AUTHOR]

In 2020, the Sugammadex vs Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER) study provided evidence for the first time that use of sugammadex is associated with fewer postoperative pulmonary complications than use of neostigmine. In a recent publication in the British Journal of Anaesthesia , a secondary analysis of the same data, the Association Between Neuromuscular Blockade Reversal Agent Choice and Postoperative Pulmonary Complications (STIL-STRONGER) study, has produced similar evidence of the advantages of sugammadex over neostigmine in high-risk and older patients undergoing prolonged, elective surgery. Here we consider the implications of the detailed statistical analysis used in these two studies and how its limitations could possibly have enhanced the statistical differences between the two drugs with respect to postoperative pulmonary complications. [ABSTRACT FROM AUTHOR]

Sugammadex has several pharmacological advantages over neostigmine, including faster reversal of neuromuscular blockade and fewer adverse effects. However, the economic impact of sugammadex remains controversial due to the considerable heterogeneity of study designs and clinical settings in previous studies. In a post-hoc analysis of a randomized controlled trial, we evaluated patients who underwent elective surgeries and general anesthesia with endotracheal intubation in a medical center in Taiwan between March 2020 and August 2020. Patients were divided into either the sugammadex or neostigmine group based on the neuromuscular blocking drug used. Propensity score matching was used to balance the baseline patient characteristics between the two groups. The patient's recovery from anesthesia and the putative cost-effectiveness of sugammadex versus neostigmine was assessed. Derived cost-effectiveness using personnel costs in the operating room and the post-anesthesia care unit was estimated using multiple linear regression models. A total of 2587 and 1784 patients were included before and after matching, respectively. Time to endotracheal extubation was significantly shorter in the sugammadex group (mean 6.0 ± standard deviation 5.3 min) compared with the neostigmine group (6.6 ± 6.3 min; p = 0.0032). In addition, the incidence of bradycardia was significantly lower in the sugammadex group (10.2%) compared with the neostigmine group (16.9%; p < 0.001). However, the total costs were significantly lower in the neostigmine group (50.6 ± 21.4 United States dollars) compared with the sugammadex group (212.0 ± 49.5 United States dollars). Despite improving postoperative recovery, the benefits of sugammadex did not outweigh its higher costs compared with neostigmine, possibly due to the low costs of labor in Taiwan's healthcare system. [ABSTRACT FROM AUTHOR]

Summary: A 68‐year‐old man underwent elective surgical repair of an abdominal wall hernia under general anaesthesia. The operation required muscle relaxation, for which we used rocuronium. Following completion of surgery, 180 mg sugammadex was administered intravenously. Shortly afterwards, the patient became severely bradycardic with hypotension, refractory to treatment with ephedrine. This progressed to a pulseless electrical activity cardiac arrest. After 4 min of cardiopulmonary resuscitation, there was return of spontaneous circulation and, following a period of haemodynamic stability in which general anaesthesia was maintained, the patient emerged from anaesthesia without incident. He remained haemodynamically stable until discharge. Post‐resuscitation investigations including the serum tryptase level were unremarkable except for a mild respiratory acidosis and slightly elevated D‐dimers. Sugammadex‐induced bradycardia has previously been described, but its mechanism remains unknown. We believe that sugammadex was the cause of cardiac arrest in this case because of the timing and sequence of events, the evolution to pulseless electric activity and the relatively uneventful post‐arrest clinical course. We hope that our report will help to promote awareness about this potential complication of a now commonly‐used drug. [ABSTRACT FROM AUTHOR]

Andexanet alfa is a modified recombinant human factor Xa (FXa) that was designed to serve as a binding target for FXa inhibitors as decoy protein. It sequesters FXa inhibitors from binding to endogenous FXa, thereby reversing anticoagulant effect of FXa inhibitors. Andexanet alfa has been approved in March 2022 in Japan for patients with life-threatening or uncontrolled bleeding while on treatment with a FXa inhibitor, apixaban, rivaroxaban, or edoxaban tosilate hydrate. It is administered via two dosing regimens, based on the type of FXa inhibitor, dose, and time since the last dose. In nonclinical studies, andexanet alfa significantly inhibited bleeding induced by FXa inhibitors in animal bleeding models. In the development for Japanese patients, the following two clinical studies have been conducted to confirm the efficacy and safety. First, safety and the reversal effect of andexanet alfa on the FXa inhibitor-mediated anticoagulant activity in healthy adults were confirmed in the overseas phase 2 study including Japanese subjects. Next, the reversal effect of andexanet alfa on the anticoagulation activity and the hemostasis were demonstrated in patients with acute major bleeding while on FXa inhibitor treatment in the global phase 3b/4 study (ANNEXA-4 study). The subgroup analysis of Japanese population showed that the efficacy and safety results were consistent with those of overall population. Andexanet alfa is the first approved reversal agent for FXa inhibitors in Japan and is expected to contribute to the improvement of prognosis in patients with fatal and/or uncontrolled bleeding by timely reversing anticoagulant effect of FXa inhibitors. [ABSTRACT FROM AUTHOR]

The primary sources of reactive oxygen species (ROS) that cause ischemia-reperfusion (I/R) injuries are enzymes xanthine oxidase (XO) and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in the literature, whereby one of the main ROS producing cells via NOX activity are polymophonuclear leukocytes (PNL). Sugammadex, the effect of which we plan to research against gastric I/R damage, is a modified gamma-cyclodextrin that antagonizes the action of steroidal neuromuscular blocking drugs. Previous studies have reported that sugammadex inhibits PNL infiltration. However, it is unknown whether an inhibitory effect on XO is present. We aimed to biochemically and histopathologically investigate the effects of sugammadex on I/R-induced stomach damage in rats. The animals were divided into groups that underwent gastric ischemia-reperfusion (GIR), 4 mg/kg sugammadex + gastric ischemia-reperfusion (SGIR), and a sham operation group (SG). The effect of sugammadex was evaluated by measuring oxidant-antioxidant and PNL parameters. There was no significant difference in XO levels between the SGIR and GIR groups. In the SGIR group, sugammadex inhibited the increase in myeloperoxidase (MPO) and malondialdehyde (MDA) levels (p < 0.001). The amount of MDA and MPO in the SGIR group was similar as in the SG group. Sugammadex significantly suppressed the decrease in tGSH levels in the SGIR group (p < 0.001). The difference between tGSH levels in the SG and SGIR groups was slight. In the SGIR group, sugammadex significantly suppressed the increase in tumor necrosis factor alpha (TNF-a) and interleukin 1 beta (IL1-ß) levels compared to the GIR group (p < 0.001). Additionally, sugammadex corrected histopathological modifications as much as sham group. In conclusion, sugammadex may be beneficial in preventing oxidative stress. [ABSTRACT FROM AUTHOR]

Patients requiring neuromuscular block for anaesthesia have a higher risk of adverse postoperative outcomes. The choice of reversal drug and its corresponding dose is critical for improving clinical outcomes. Although drug costs are higher for sugammadex relative to neostigmine, additional factors need to be considered when choosing one drug over the other. New data from a recent study in the British Journal of Anaesthesia indicate cost advantages for sugammadex in low-risk and ambulatory patients, but for neostigmine in high-risk patients. These findings highlight the need to take local and temporal factors into consideration in addition to clinical effectiveness when performing cost analyses for administrative decision-making. [ABSTRACT FROM AUTHOR]

Abstract Background A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. Methods PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. Results Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. Conclusion Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future.

Background With increasing use, the incidence of adverse events associated with sugammadex, a neuromuscular blockade reverser, is increasing. This study aimed to identify and analyze cases of adverse events caused by sugammadex reported in Korean population. Methods Out of a total of 12 cases detected using various keywords in the Korean Journal of Anesthesia, Anesthesia and Pain Medicine (Seoul), KoreaMed, PubMed, EMBASE, Web of Science, and The Cochrane Library-CENTRAL from 2013 to December 2020, 10 cases directly associated with sugammadex were selected. Results Adverse events included five cases of anaphylaxis, one case of cardiac arrest, one case of profound bradycardia, one case of negative pressure pulmonary edema, and two cases of incomplete recovery. Three patients had American Society of Anesthesiologists physical status ≥ 3, two had emergency surgery, and two had a history of allergic reaction. Neuromuscular monitoring was applied in nine cases. The average dose of sugammadex was 2.87 mg/kg, and there were six cases in which one full vial was used, regardless of the state of neuromuscular recovery. Sugammadex was administered immediately after surgery in two cases, at train of four (TOF) 0 in four cases, at TOF 3 in one case, and after evaluation of the clinical signs only with no neuromuscular monitoring in one case. Conclusions Even with neuromuscular monitoring, an excessive dose of sugammadex was observed. Given that adverse events tend to occur within 10 min of administration, continuous monitoring is important even after administration.

The definition of postoperative pulmonary complications (PPCs) is inconsistent in literature; however, PPCs include pulmonary abnormalities that adversely affect patient outcomes, such as respiratory failure, atelectasis, pneumonia, pleural effusion, and exacerbation of underlying lung conditions. Furthermore, although the incidence of PPCs varies according to its definition, surgery type, and patient population, they can lead to increased morbidity, mortality, duration of hospitalization, and medical costs; thus, efforts to identify and reduce the risk factors are important to improve patient outcomes. Among the risk factors for PPCs, residual neuromuscular block is a representative and preventable anesthesia-related risk factor that is affected by the choice of the reversal agent. However, it is not clear whether the chosen reversal agent, i.e., sugammadex, reduces PPCs better when compared to anticholinesterases. Additionally, the effects of the reversal agents on PPCs in high-risk patients, such as elderly patients, pediatric patients, those with end-stage renal disease, obesity, obstructive sleep apnea, or those undergoing specific surgeries, are diverse. To reduce the PPCs associated with the use of neuromuscular blocking agents, it is important to confirm complete reversal of the neuromuscular block under neuromuscular monitoring. Additionally, efforts to reduce the incidence of PPCs through interdisciplinary communication are required.

Background Sugammadex is a specific antagonist of aminosteroidal neuromuscular blocking agents with 1:1 binding to guest molecules. Sugammadex can also bind to other drugs having a steroid component in its chemical structure. In this in vivo experiment, we investigated the differences in the recovery of rocuronium-induced neuromuscular blockade using sugammadex pre-exposed with two different concentrations of hydrocortisone. Methods The sciatic nerves and tibialis anterior muscles of 30 adult Sprague–Dawley rats were prepared for the experiment. The sciatic nerves were stimulated using a train-of-four (TOF) pattern with indirect supramaximal stimulation at 20 s intervals. After 15 min of stabilization, a 250 μg loading dose and 125 μg booster doses of rocuronium were serially administered until > 95% depression of the first twitch tension of TOF stimulation (T1) was confirmed. The study drugs were prepared by mixing sugamadex with the same volume of three different stock solutions (0.9% normal saline, 10 mg/ml hydrocortisone, and 100 mg/ml hydrocortisone). The recovery of rats from neuromuscular blockade was monitored by assessing T1 and the TOF ratio (TOFR) simultaneously until T1 was recovered to > 95% and TOFR to > 0.9. Results In the group injected with sugammadex premixed with a high concentration of hydrocortisone, statistically significant intergroup differences were observed in the recovery progression of T1 and TOFR (P < 0.050). Conclusions When sugammadex was pre-exposed to a high dose of hydrocortisone only, recovery from neuromuscular blockade was delayed. Delayed recovery from neuromuscular blockade is not always plausible when sugammadex is pre-exposed to steroidal drugs.

Abstract Background The AF-201P, a new electromyography (EMG)-based neuromuscular monitor has been developed recently. The aim of this clinical study was to compare two ulnar nerve innervated muscles: the adductor pollicis (AP) muscle and the abductor digiti minimi (ADM) muscle during the recovery from rocuronium-induced neuromuscular block by using EMG AF-201P. Methods Twenty patients undergoing surgery with general anesthesia were enrolled in the study. During total intravenous general anesthesia, train-of-four (TOF) and post-tetanic counts (PTC) responses following 0.9 mg/kg rocuronium administration were concurrently monitored at the AP and the ADM muscles with EMG AF-201P on the opposite arms. At the end of the surgery, sugammadex 2 mg/kg was administered when TOF counts of 2 (TOFC2) was observed at both muscles. The primary outcome of the study was time from administration of rocuronium to first appearance of PTC response (first PTC). The secondary outcomes of the study were time from administration of rocuronium to TOF count of 1 (TOFC1), time from first PTC to TOFC1 (PTC-TOF time), time to TOFC2, and time from administration of sugammadex to TOF ratio ≥ 0.9. Agreement between the two muscles was assessed using the Bland–Altman analysis. Data are expressed as mean ± standard deviation. Results Nineteen patients were included in the analysis. Time to first PTC was significantly faster at the ADM muscle than the AP muscle (24.4 ± 11.4 min vs 32.4 ± 13.1 min, p = 0.006). PTC-TOF time was significantly longer with the ADM muscle than the AP muscle (19.4 ± 7.3 min vs 12.4 ± 10.6 min, p = 0.019). There were no significant differences in time to TOFC2 and sugammadex-facilitated recovery between the two muscles. Bland–Altman analyses showed acceptable ranges of bias and limits of agreement of the two muscles. Conclusions The ADM muscle showed a good agreement with the AP muscle during rocuronium-induced neuromuscular block but faster recovery of PTC response when using EMG. Trial registration UMIN-CTR (Registration No. UMIN000044904 ). Registered 19 July 2021 -Retrospectively registered, https://center6.umin.ac.jp/cgi-bin/ctr_e/ctr_view.cgi?recptno=R000051290 .

Chris H Martini,1 GH Maarten Honing,1 Lori D Bash,2 Erik Olofsen,1 Marieke Niesters,1 Monique van Velzen,1 Albert Dahan,1 Martijn Boon1 1Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands; 2Center for Observational and Real- World Evidence (CORE), Merck & Co., Inc, Kenilworth, NJ, USACorrespondence: Chris H Martini, Department of Anesthesiology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333, ZA, the Netherlands, Tel +31 71 526 2301, Email c.h.martini@lumc.nlIntroduction: Muscle relaxants are often given during general anesthesia to facilitate endotracheal intubation. However lingering effects after anesthesia-end may lead to respiratory compromise in the PACU. Strategies to reduce these adverse events include monitoring neuromuscular block, the use of short-acting agents and active pharmacological reversal before extubation. At Leiden University Medical Center (LUMC), a tertiary care academic hospital in the Netherlands, various muscle relaxants and reversal agents are freely available to all clinicians without restrictions. In this setting, we intended to evaluate how patient and surgical characteristics impacted the use of these agents for a variety of non-cardiac surgeries.Material and Methods: This is a retrospective database study of adult patients that had received elective, non-cardiac surgery and general anesthesia with endotracheal intubation between 2016 and 2020 at LUMC in the Netherlands. Exclusion criteria consisted of patients pharmacologically reversed with both sugammadex and neostigmine during the same procedure, diagnosed with myasthenia gravis, receiving pyridostigmine therapy, or with renal failure (eGFR < 30 mL.min.1.73m2).Results: We retrieved 23,373 patient records of which 9742 were excluded because one or more exclusion criteria were met. The final cohort consisted of 13,631 cases. Rocuronium was the most commonly used muscle relaxant (88.5%); sugammadex was the most commonly used reversal agent (99.9% of those pharmacologically reversed). Of all cases that received rocuronium as muscle relaxant, 76.9% of patients were not reversed, while 23.1% were reversed with sugammadex. The odds of reversal increased with age, BMI, ASA class (1– 3) and shorter duration of surgery.Conclusion: In an unrestricted clinical environment, rocuronium and sugammadex are the preferred agents for muscle relaxation and reversal. Pharmacologic reversal of neuromuscular block was uncommon overall, but more likely in older and obese patients, higher ASA classification and shorter lasting procedures. Sugammadex has largely replaced neostigmine for this purpose.Keywords: neuromuscular blockade, muscle relaxants, sugammadex

The article titled "Response to Letters to the Editor regarding 'Analysis of the factors contributing to residual weakness after sugammadex administration in pediatric patients under 2 years of age'" acknowledges and appreciates the feedback received from Nhan et al and Faulk et al regarding their previous article. The authors aim to stimulate further discussion and research on the management of paralytic administration, neuromuscular blockade monitoring, and reversal in pediatric patients. They agree with the reviewers that the inconsistent use of neuromuscular blockade monitoring is a significant flaw in current practice and emphasize the need for standardization. The authors also acknowledge the uncertainty surrounding optimal management in this patient population and suggest future studies, including a propensity score matched case-control study design, to address these concerns. [Extracted from the article]

This article discusses a study on the dosing challenges of sugammadex in pediatric patients under 2 years of age. The study found that patients under 3 months of age and weighing less than 4.7 kg are at an increased risk of residual weakness and may require additional doses of sugammadex. However, the study lacked a standardized neuromuscular monitoring protocol, which may have affected the results. The authors suggest the need for a well-designed clinical trial to determine effective sugammadex doses for pediatric patients. [Extracted from the article]

Background: Studies on higher doses of sugammadex effect on QT interval and leading arrhythmia have been limited. In this study, we aimed to investigate possible proarrhythmic effect of higher doses of sugammadex in conditions that required urgent reversal of neuromuscular blockade during general anesthesia in an experimental animal model. Methods: It was experimental animal study. Total of 15 male New Zealand rabbits were randomly divided into three groups for low (4 mg/kg, n = 5), moderate (16 mg/kg, n = 5), and high dose of sugammadex (32 mg/kg, n = 5). All rabbits were premedicated by intramuscular ketamine 10 mg/kg, and general anesthesia was inducted by intravenous injection of 2 mg/kg of a propofol, 1 mcg/kg fentanyl, and 0.6 mg/kg rocuronium injection. Airway was provided by V-gel rabbit and connected to anesthetic device and ventilated at about 40 cycle/min and 10 ml/kg; oxygen 50% plus air 50% mixture was used with 1 MAC isoflurane to maintain anesthesia. Electrocardiographic monitorization and arterial cannulation were provided to follow-up mean arterial pressure and for arterial blood gas analyses. Intravenous sugammadex in three different doses were injected at 25th min of induction. After observing adequate respiration of all rabbits, V-gel rabbit was removed. Parameters and ECG recordings were taken basal value before induction and at the 5th, 10th, 20th, 25th, 30th, and 40th min to measure corrected QT intervals and were stored on digital media. QT interval was calculated as the time from the beginning of the Q wave to the end of the T wave. Corrected QT interval was calculated according to the Bazett's formula. Possible adverse effects were observed and recorded. Results: In all three groups, there was no significant statistical difference in mean arterial blood gases parameters, arterial pressures, heart rates, and Bazett QTc values, and no serious arrhythmia was recorded. Conclusion: We found in animal study that low, moderate, and high doses of sugammadex did not significantly altered corrected QT intervals and did not cause any significant arrhythmia. [ABSTRACT FROM AUTHOR]

Introduction: The composition of the nasal microbiota in surgical patients in the context of general anesthesia and nasal povidone-iodine decolonization is unknown. The purpose of this quality improvement study was to determine: (i) if general anesthesia is associated with changes in the nasal microbiota of surgery patients and (ii) if preoperative intranasal povidone-iodine decolonization is associated with changes in the nasal microbiota of surgery patients. Materials and methods: One hundred and fifty-one ambulatory patients presenting for surgery were enrolled in a quality improvement study by convenience sampling. Pre- and post-surgery nasal samples were collected from patients in the no intranasal decolonization group (control group, n = 54). Pre-decolonization nasal samples were collected from the preoperative intranasal povidone-iodine decolonization group (povidone-iodine group, n = 97). Intranasal povidone-iodine was administered immediately prior to surgery and continued for 20 minutes before patients proceeded for surgery. Post-nasal samples were then collected. General anesthesia was administered to both groups. DNA from the samples was extracted for 16S rRNA sequencing on an Illumina MiSeq. Results: In the control group, there was no evidence of change in bacterial diversity between pre- and post-surgery samples. In the povidone-iodine group, nasal bacterial diversity was greater in post-surgery, relative to pre-surgery (Shannon's Diversity Index (P = 0.038), Chao's richness estimate (P = 0.02) and Inverse Simpson index (P = 0.027). Among all the genera, only the relative abundance of the genus Staphylococcus trended towards a decrease in patients after application (FDR adjusted P = 0.06). Abundant genera common to both povidone-iodine and control groups included Staphylococcus, Bradyrhizobium, Corynebacterium, Dolosigranulum, Lactobacillus, and Moraxella. Conclusions: We found general anesthesia was not associated with changes in the nasal microbiota. Povidone-iodine treatment was associated with nasal microbial diversity and decreased abundance of Staphylococcus. Future studies should examine the nasal microbiota structure and function longitudinally in surgical patients receiving intranasal povidone-iodine. [ABSTRACT FROM AUTHOR]

Cerebrovascular abnormalities are a common feature of sickle cell disease that may be associated with risk of vaso-occlusive pain crises, microinfarcts, and cognitive impairment. An activated endothelium and adhesion factors, VCAM-1 and P-selectin, are implicated in sickle cell vasculopathy, including abnormal hemodynamics and leukocyte adherence. This study examined the association between cerebral expression of these adhesion factors and cortical microvascular blood flow dynamics by using in-vivo two-photon microscopy. We also examined the impact of blood transfusion treatment on thesemarkers of vasculopathy. Results showed that sickle cell mice had significantly higher maximum red blood cell (RBC) velocity (6.80 ± 0.25 mm/sec, p 0.01 vs. 5.35 ± 0.35 mm/sec) and more frequent blood flow reversals (18.04 ± 0.95/min, p = 0.01 vs. 13.59 ± 1.40/min) in the cortical microvasculature compared to controls. In addition, sickle cell mice had a 2.6-fold (RFU/mm2) increase in expression of VCAM-1 and 17-fold (RFU/mm2) increase in expression of P-selectin compared to controls. This was accompanied by an increased frequency in leukocyte adherence (4.83 ± 0.57/100 µm/min vs. 2.26 ± 0.37/100 µm/min, p = 0.001). We also found that microinfarcts identified in sickle cell mice were 50% larger than in controls. After blood transfusion, many of these parameters improved, as results demonstrated that sickle cell mice had a lower post-transfusionmaximumRBC velocity (8.30 ± 0.98mm/sec vs. 11.29 ± 0.95 mm/sec), lower frequency of blood flow reversals (12.80 ± 2.76/min vs. 27.75 ± 2.09/min), and fewer instances of leukocyte adherence compared to their pre-transfusion imaging time point (1.35 ± 0.32/100 µm/min vs. 3.46 ± 0.58/100 µm/min). Additionally, we found that blood transfusion was associated with lower expression of adhesion factors. Our results suggest that blood transfusion and adhesion factors, VCAM-1 and P-selectin, are potential therapeutic targets for addressing cerebrovascular pathology, such as vaso-occlusion, in sickle cell disease. [ABSTRACT FROM AUTHOR]

We theoretically analyze spin filtering in two‐terminal systems, induced by the spin‐orbit interaction (SOI), as a possible origin of the "chirality‐induced spin selectivity" (CISS) effect observed experimentally in chiral molecules, such as DNA. Due to Bardarson's theorem, spin filtering cannot be realized in a molecule containing one orbital‐channel. However, when two orbitals are involved, SOI can induce spin filtering in a molecule coupled to two terminals without braking time‐reversal symmetry. In particular, we provide an example of a 4×4 ${4\times 4}$ reflection matrix for a spinful electron passing through a molecule containing two orbital‐channels, which complies with Bardarson's theorem and produces a finite spin conductance. As a microscopic toy model realizing a single strand of DNA, we consider a p‐orbital helical atomic chain with intra‐atomic SOI's and a strong crystalline field along the helix. This model exhibits two‐orbital spin filtering: For various parameters preserving the helical symmetry, the model hosts spin asymmetric states carrying pairs of up and down spins propagating in opposite directions. The typical energy scale of the helical states is the product of the intra‐atomic SOI and the curvature. The spin filtering mechanism is associated with the intra‐atomic SOI, which would be larger than the inter‐atomic SOI. In this respect, the present model may be a more likely candidate for the CISS in organic material than other models associated with the inter‐atomic SOI. [ABSTRACT FROM AUTHOR]

This current phase II clinical trial was to compare the effect and safety of adamgammadex, a new cyclodextrin-based selective relaxant binding agent, with sugammadex to reverse rocuronium-induced neuromuscular block. Patients were randomised to receive adamgammadex (4 or 6 mg kg−1) or sugammadex (2 mg kg−1, as a positive control group) at the reappearance of the second twitch (T2) in response to TOF stimulation. The standard safety data were collected. The 4 mg kg−1 (n = 16) and 6 mg kg−1 (n = 20) adamgammadex- and 2 mg kg−1 (n = 20) sugammadex-induced recovery time of TOF ratio to 0.9 were 2.3, 1.6, and 1.5 min, respectively (p = 0.49). The 4 mg kg −1 adamgammadex-induced median recovery time was longer than that of 2 mg kg−1 sugammadex (p = 0.01), and there was no difference between the 6 mg kg −1 adamgammadex group and 2 mg kg−1 sugammadex group (p = 0.32). Then, the number of patients who experienced adverse events (AEs) was 6, 11, and 14 for adamgammadex at 4, 6 mg kg−1 and sugammadex at 2 mg kg−1, respectively. The treatment emergent AEs that occurred more than twice were detailed as follows: incision site pain, hypotension, emesis, fever, throat pain, blood bilirubin increase, abnormal T-wave of ECG, dizziness, incision site swelling, postoperative fever, expectoration, and nausea. For drug-related AEs, the increased urine acetone bodies and first-degree atrioventricular block were observed in two patients from sugammadex group. Then, the previously reported AEs were not observed in this study, including anaphylaxis, haemorrhage, recurarization, abnormal basic vital signs, or lengthened QRS intervals and QT intervals. Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block as sugammadex. [ABSTRACT FROM AUTHOR]

Background: Studies have proposed that the routine use of the modified gamma-cyclodextrin, sugammadex, could provide perioperative time savings. However, these investigations have been limited to small group analyses. The purpose of this study was to test the effectiveness of sugammadex on perioperative times when compared to neostigmine under general clinical practice conditions following rocuronium-induced neuromuscular blockade for laparoscopic cholecystectomy. Methods: Following institutional review board approval, data from 1,611 consecutive surgical records for laparoscopic cholecystectomy were reviewed. Patient characteristics, type of primary neuromuscular blocking reversal agent, operating room (OR) discharge times, and postanesthesia care unit (PACU) recovery times were the measures of interest. Equivalence testing was used to determine the between-group differences of the reversal agents in the two perioperative time periods of interest. Results: OR discharge times averaged 10.9 (95% CI, 10-11.8) minutes for patients administered sugammadex and 8.9 (95% CI, 8.2-9.7) minutes for patients administered neostigmine. PACU recovery times averaged 77.6 (95% CI, 74.1-81.1) minutes for sugammadex and 68.6 (95% CI, 65.9-71.3) minutes for neostigmine. Equivalence testing demonstrated no improvement in the two perioperative times with sugammadex. Conclusion: These results suggest no perioperative time savings with sugammadex when compared to neostigmine following laparoscopic cholecystectomy under general clinical practice conditions. [ABSTRACT FROM AUTHOR]

Background: Hydroxyethyl Ester of Mefenamic acid (HEMA), which is an available derivative of mefenamic acid (MFA) in the literature, was shown to exert a strong resistance to enzymatic hydrolysis in various buffer solutions as well as in the plasma. However, there are no studies yet that investigate the biological effects of HEMA as a possible active drug in-vivo. This study provides an in-vivo investigation of the efficacy and toxicity of HEMA in comparison to those of a related drug, MFA, that has a similar chemical structure. Methods: Acute toxicity evaluations were conducted in various groups of mice following administration of high equimolar doses of HEMA and MFA and were measured at various parameters including the percentage of catalepsy, seizure score, percentage of clonic-tonic seizure and death, grimace scale score (GSS) and locomotor activity. In addition, the anti-inflammatory and anti-nociceptive effects of HEMA were evaluated in the carrageenan-induced paw edema test and acetic acid-induced writhing test, respectively. Results: The findings of this study revealed that the percentage of catalepsy, clonic-tonic seizure and death as well as seizure and grimace scale scores were lower in mice treated with HEMA than those treated with equimolar doses of MFA. In addition, treatment with HEMA caused a comparable anti-inflammatory activity in the carrageenan-induced paw edema test and a significantly (p<0.05) higher anti-nociceptive effect in the acetic acidinduced writhing test than that of MFA. Conclusion: Results obtained from this study may indicate that HEMA has superior therapeutic advantages for the management of acute and inflammatory events with a less potential risk of neuromuscular adverse effects. [ABSTRACT FROM AUTHOR]

Sugammadex is a direct reversal agent of aminosteroid muscle relaxants, particularly rocuronium, with promptly and completely reverse of deep neuromuscular block (NMB), which allows better surgical conditions. Sugammadex exhibits advantages over indirect reversal agent acetylcholinesterase inhibitor neostigmine with less adverse effects. In this retrospective review, we compared the incidence of postoperative vomiting (POV), postoperative urinary retention (POUR), and hemodynamic changes between sugammadex and neostigmine/glycopyrrolate in reversal of muscular blockade. Sugammadex showed superior in all three aspects. The heart rate was 7.253 lower (P < 0.0001) and mean arterial pressure was 5.213 lower (P < 0.0001) in sugammadex group. The POV of neostigmine/glycopyrrolate group was 3.16 times more than sugammadex group (OR = 3.16, p < 0.0001), and POUR of neostigmine/glycopyrrolate group was 4.291 times more than sugammadex group (OR = 4.291, p < 0.0001). Sugammadex showed better hemodynamic stability, and lower incidence of POV and POUR than neostigmine/glycopyrrolate. [ABSTRACT FROM AUTHOR]

The activity of a molecule is related to its structure, and thus any mathematical or topological technique that can specify the underlying topological building of a molecule is important and useful. Recently, mathematical techniques have been used to characterize their structures, topologically, to find statistical correlations between their structures and drug activity. Among them, topological indices and their developments have absorbed significant consideration from both mathematical and medicinal chemists. Sugammadex is a relaxant binding agent that can be sought after the management of the aminosterioid non-depolarizing neuromuscular-blocking factors. The role of topological indices in drug development research is updated. A series of definitions in the fields of topological indices and drug discovery technologies are introduced. The aim of this paper is to investigate several well-known topological descriptors for Sugammadex. [ABSTRACT FROM AUTHOR]

Rocuronium is a non‐depolarising neuromuscular block drug extensively used in canine patients due to its favourable characteristics, including the fastest onset of action among all non‐depolarising neuromuscular blocking agents, lack of active metabolites and intermediate duration of effect. Although rocuronium elimination is relatively independent of kidney function, in the past few years, a growing number of reports describing a prolonged duration of the effect of rocuronium in human patients with renal failure have been published. However, to date, the mechanism behind this phenomenon is unclear. The present case describes the development of extremely prolonged neuromuscular blockade (>5 hours) following a single dose of 0.5 mg/kg rocuronium in a female English bulldog with renal disease where neostigmine failed to provide adequate reversal, which was only subsequently achieved following administration of sugammadex. Aside from renal disease, other possible causes of this prolonged duration (relative drug overdose, hypoalbuminaemia, co‐administered drugs, neostigmine‐induced neuromuscular blockade and idiosyncratic reaction to rocuronium) are also discussed. [ABSTRACT FROM AUTHOR]

Acid-base properties of cyclodextrins (CDs), persubstituted at C-6 by 3-mercaptopropionic acid, sualphadex (Suα-CD), subetadex (Suβ-CD) and sugammadex (Suγ-CD, the antidote of neuromuscular blocking steroids) were studied by 1H NMR-pH titrations. For each CD, the severe overlap in protonation steps prevented the calculation of macroscopic pKa values using the standard data fitting model. Considering the full symmetry of polycarboxylate structures, we reduced the number of unknown NMR parameters in the "Q-fitting" or the novel "equidistant macroscopic" evaluation approaches. These models already provided pKa values, but some of them proved to be physically unrealistic, deceptively suggesting cooperativity in carboxylate protonations. The latter problem could be circumvented by adapting the microscopic site-binding (cluster expansion) model by Borkovec, which applies pairwise interactivity parameters to quantify the mutual basicity-decreasing effect of carboxylate protonations. Surprisingly, only a single averaged interactivity parameter could be calculated reliably besides the carboxylate 'core' microconstant for each CD derivative. The speciation of protonation isomers hence could not be resolved, but the optimized microscopic basicity parameters could be converted to the following sets of macroscopic pKa values: 3.84, 4.35, 4.81, 5.31, 5.78, 6.28 for Suα-CD; 3.82, 4.31, 4.73, 5.18, 5.64, 6.06, 6.54 for Suβ-CD and 3.83, 4.28, 4.65, 5.03, 5.43, 5.81, 6.18, 6.64 for Suγ-CD. The pH-dependent charge of these compounds can now be accurately calculated, in support of designing new analytical methods to exploit their charge-dependent molecular recognition such as in cyclodextrin-aided chiral capillary electrophoresis. [ABSTRACT FROM AUTHOR]

Alternaria mycotoxins, including alternariol (AOH), alternariol-9-monomethylether (AME), and their masked/modified derivatives (e.g., sulfates or glycosides), are common food contaminants. Their acute toxicity is relatively low, while chronic exposure can lead to the development of adverse health effects. Masked/modified metabolites can probably release the more toxic parent mycotoxin due to their enzymatic hydrolysis in the intestines. Previously, we demonstrated the complex formation of AOH with serum albumins and cyclodextrins; these interactions were successfully applied for the extraction of AOH from aqueous matrices (including beverages). Therefore, in this study, the interactions of AME, alternariol-3-sulfate (AS), and alternariol-9-monomethylether-3-sulfate (AMS) were investigated with albumins (human, bovine, porcine, and rat) and with cyclodextrins (sulfobutylether-β-cyclodextrin, sugammadex, and cyclodextrin bead polymers). Our major results/conclusions are the following: (1) The stability of mycotoxin–albumin complexes showed only minor species dependent variations. (2) AS and AMS formed highly stable complexes with albumins in a wide pH range, while AME–albumin interactions preferred alkaline conditions. (3) AME formed more stable complexes with the cyclodextrins examined than AS and AMS. (4) Beta-cyclodextrin bead polymer proved to be highly suitable for the extraction of AME, AS, and AMS from aqueous solution. (5) Albumins and cyclodextrins are promising binders of the mycotoxins tested. [ABSTRACT FROM AUTHOR]

The magnetization reversal of atomic chains on metal surfaces has been theoretically studied using the analytical method developed earlier and the geodesic nudged elastic band method. The atomic chains can be divided into the following three types: chains with a small, intermediate, and large domain wall width. A dipole–dipole interaction is shown to cause an increase in the average spontaneous magnetization reversal time of FM|| and AFM⊥ chains and a decrease in the magnetization reversal time of FM⊥ and AFM|| chains. For FM⊥ and AFM⊥ chains with a medium-width domain wall, taking into account a dipole–dipole interaction leads to the appearance of an energy barrier between two states of a domain wall differing in the direction of rotation of magnetic moments. The magnetization reversal of atomic chains from the third type can occur in the following two ways: all magnetic moments are reversed either simultaneously or one by one. The transition from one magnetization reversal mode to another occurs at a critical length N0. The effect of a dipole–dipole interaction is most significant when the chain length is close to N0. Numerical estimations have shown that taking into account a dipole–dipole interaction can change the magnetization reversal time of a chain by an order of magnitude in some cases. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) has emerged as the second most common form of human neurodegenerative disorders. However, due to the severe side effects of the current antiparkinsonian drugs, the design of novel and safe compounds is a hot topic amongst the medicinal chemistry community. Herein, a convenient peptide method, TBTU (O-(benzotriazole-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate), was used for the synthesis of the amide (E)-N-(2-methylcinnamoyl)-amantadine (CA(2-Me)-Am; 3)) derived from amantadine and 2-methylcinnamic acid. The obtained hybrid was studied for its antiparkinsonian activity in an experimental model of PD induced by MPTP. Mice (C57BL/6,male, 8 weeks old) were divided into four groups as follows: (1) the control, treated with normal saline (i.p.) for 12 consecutive days; (2) MPTP (30 mg/kg/day, i.p.), applied daily for 5 consecutive days; (3) MPTP + CA(2-Me)-Am, applied for 12 consecutive days, 5 days simultaneously with MPTP and 7 days after MPTP; (4) CA(2-Me)-Am +oleanoic acid (OA), applied daily for 12 consecutive days. Neurobehavioral parameters in all experimental groups of mice were evaluated by rotarod test and passive avoidance test. Our experimental data showed that CA(2-Me)-Am in parkinsonian mice significantly restored memory performance, while neuromuscular coordination approached the control level, indicating the ameliorating effects of the new compound. In conclusion, the newly synthesized hybrid might be a promising agent for treating motor disturbances and cognitive impairment in experimental PD. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Incomplete recovery from residual neuromuscular block agent (NMBA) after anesthesia is a serious adverse event in the post-anesthesia care unit. Acetylcholinesterase neostigmine is usually used to reverse residual neuromuscular blockade and facilitate spontaneous breathing and endotracheal extubation. Case Report: A 40-year-old woman received general anesthesia for strabismus correction surgery. At the end of surgery, repeated doses of neostigmine up to 85 µg/kg failed to reverse the residual neuromuscular blockade (train-offour [TOF] ratio below 21%). Sugammadex (200 mg) provided immediate reversal, with the TOF ratio up to 100%. The patient regained spontaneous breathing, and the endotracheal tube was removed. After surgery, myasthenia gravis was diagnosed. Conclusions: When unexpected prolonged neuromuscular blockade presents, the TOF ratio should be used to detect its depth and guide a reasonable dose of reversal agents. Anticholinesterase has a ceiling effect; once acetylcholinesterase activity is fully inhibited, administration of additional anticholinesterase can result in no further recovery. Furthermore, excessive acetylcholine can cause muscle weakness. In contrast, sugammadex is a selective reversal agent for steroidal NMBA, which works by encapsulation via tight water-soluble complexes with amino steroids (eg, rocuronium) rather than increasing acetylcholine at the neuromuscular junction. In this case, the recovery from moderate neuromuscular blockade by sugammadex was more effective and rapid than that by neostigmine. When refractory and prolonged residual neuromuscular blockade presents after repeated doses of anticholinesterase, sugammadex should be considered as an effective reversal agent. Particularly in cases of myasthenia gravis, sugammadex is superior to neostigmine for reversing rocuronium-induced NMBA in patients undergoing surgery. [ABSTRACT FROM AUTHOR]

Catalpol is an iridoid glycoside with rich content, rich nutrition, and numerous biological activities in Rehmanniae Radix contained in classic antidepressant prescriptions in Chinese clinical medicine. Catalpol has been confirmed previously its exact antidepressant-like effect involved heme oxygenase (HO)-1, but its antidepressant molecular targets and mechanism are still unclear. Here, catalpol's antidepressant-like molecular target was diagnosed and confirmed by ZnPP intervention [the antagonist of HO-1, (10 μg/rat), intracerebroventricular] for the first time, and its molecule mechanism network was determined through HO-1 related pathway and molecules in the hippocampus. Results showed that ZnPP significantly abolished catalpol's (10 mg/kg) reversal on depressive-like behaviors of chronic unpredictable mild stress rats, abolished catalpol's up-regulation on the phosphorylation level of extracellular regulated protein kinases (ERK)1/2 and brain-derived neurotrophic factor (BDNF)'s receptor tropomyosin-related kinase B (TrkB), the nuclear expression level of nuclear factor E 2-related factor 2 (Nrf2), the levels of anti-oxidant factors (such as HO-1, SOD, GPX, GST, GSH) and BDNF, and abolished catalpol's down-regulation on the levels of peroxide and neuroinflammation factors [cyclooxygenase-2 (COX-2), induced nitrogen monoxide synthase (iNOS), nitric oxide (NO)]. Thus, HO-1 could serve as an important potential molecular target for catalpol's antidepressant-like process, and the antidepressant-like mechanism of catalpol could at least involve the activation of HO-1 triggering the up-regulation of the ERK1/2/Nrf2/HO-1 pathway-related factors to enhance the anti-oxidant defense, triggering the down-regulation of the COX-2/iNOS/NO pathway-related factors to inhibit neuroinflammation, and triggering the up-regulation of the BDNF/TrkB pathway to enhance neurotrophy. [ABSTRACT FROM AUTHOR]

Residual neuromuscular paralysis, the presence of clinically significant weakness after administration of pharmacologic neuromuscular blockade reversal, is associated with postoperative pulmonary complications and is more common in older patients. In contemporary anesthesia practice, reversal of neuromuscular blockade is accomplished with neostigmine or sugammadex. Neostigmine, an acetylcholinesterase inhibitor, increases the concentration of acetylcholine at the neuromuscular junction, providing competitive antagonism of neuromuscular blocking drug and facilitating muscle contraction. Sugammadex, a modified gamma-cyclodextrin, antagonizes neuromuscular blockade by encapsulating rocuronium and vecuronium in a one-to-one ratio for renal clearance, a pharmacokinetic property that led to the recommendation that sugammadex not be administered to those with end-stage renal disease. While data are limited, reports suggest sugammadex is efficacious and well tolerated in individuals with reduced renal function. Sugammadex provides a more rapid and complete reversal of neuromuscular blockade than neostigmine. There is also accumulating evidence that sugammadex may provide a protective effect against the development of postoperative pulmonary complications, nausea, and vomiting, and that it may have beneficial effects on the rate of bowel and bladder recovery after surgery. Accordingly, sugammadex administration is beneficial for most older patients undergoing surgery. [ABSTRACT FROM AUTHOR]

Background: Recovery from neuroanesthesia requires stable hemodynamics and optimal cerebral oxygenation. Objective: The purpose of this study was to compare the effect of low dose sugammadex with neostigmine on recovery and cerebral hemodynamic profile after supratentorial tumor resection. Patients and Methods: In this double-blind randomized study, forty patients were allocated according to the reversal used after supratentorial tumor surgery into, sugammadex 2 mg·kg–1 (group S) or neostigmine 0.05 mg·kg–1 + atropine 0.02 mg·kg–1 (group N). Duration from reversal to train of four 0.9 was a primary outcome. Arterial and jugular bulb blood samples obtained after induction, before closure of dura, before reversal, ten minutes after reversal then one hourly for 3 hours postoperative for the calculation of arterial-jugular oxygen content difference “CaO2-jO2,” cerebral oxygen extraction “CEO2”, jugular venous oxygen saturation (SjvO2), estimated cerebral metabolic rate “eCMRO2,” and cerebral blood flow equivalent “CBFe,” as secondary outcomes. Results: We demonstrated that recovery time (duration from reversal to train of four 0.9) was significantly shorter with sugammadex (P=0.001). Sugammadex recorded significant increased CEO2 and CaO2-jO2 at 10 minutes after reversal, at 1 hour (hr), 2 hr and 3 hr postoperatively. Sugammadex resulted in significant decreased SjvO2 and CBFe at 10 minutes after reversal, at 1 hr, 2 hr and 3 hr postoperatively without significant effect on eCMRO2. Conclusion: Low dose sugammadex (2 mg.kg-1) provided rapid and effective reversal of rocuronium NMB superior to neostigmine with improved cerebral hemodynamic profile after supratentorial tumor surgery. [ABSTRACT FROM AUTHOR]

• Lingering rocuronium effects affect perceived patient neurologic status. • Rocuronium lingering effects can be prolonged in acute neurosurgical patients. • Rocuronium reversal can drastically impact neurosurgical decision making. • Sugammadex can serve as a useful tool in acute neurosurgical settings. Sugammadex reversal of neuromuscular blocking agents (NMBAs) is usually performed postoperatively. A scarcity of literature exists exploring sugammadex use for timely neurological examination of neurosurgical patients. NMBAs, like rocuronium, are used in the Emergency Department during intubation and their unpredictable duration of action often impedes timely and accurate assessment of patient neurological status. We aim to explore the role of sugammadex in evaluating patients in need of acute neurosurgical care. Retrospective assessment of patients presenting with traumatic brain injury or intracranial hemorrhage was conducted at our level 1 trauma center. Patients of interest were those for whom sugammadex reversal of rocuronium neuromuscular blockade, from intubating doses, was pursued to ensure timely neurologic assessment. Nine patients were identified for whom GCS pre-/post-sugammadex, rocuronium dosing, elapsed time between rocuronium administration and reversal, and clinical course data were retrieved. Arrival GCS was 5.2 ± 3.2, with intubation accomplished within 10 ± 2.5 min of presentation. Rocuronium dosing was consistent between patients, average single dose of 1.2 ± 0.3 mg/kg. Lingering neuromuscular blockade ranged from 28 to 132 min (87.3 ± 34.3 min). All patients exhibited a GCS of 3 T upon initial neurosurgical evaluation, prior to reversal. Post-reversal GCS rose to 6.0 T ± 2.2. Sugammadex facilitated more accurate clinical decision making in 8 of 9 patients, including prevention of unnecessary invasive procedures. Two of 9 patients were eventually discharged home or to a rehabilitation facility. Rocuronium neuromuscular blockade can linger beyond pharmacokinetic predictions, thus delaying timely and precise neurologic assessment. Our data suggests sugammadex may be a useful addition to the clinician's armamentarium for acute neurologic assessment in the neurosurgical population. Sugammadex may impact clinical decision-making in certain patients and allow for more informed decision-making by families and physicians alike. Prospective studies are needed to definitively assess the impact of sugammadex on outcomes in acute neurosurgical settings. [ABSTRACT FROM AUTHOR]

Postoperative myasthenic crisis with respiratory failure is a potentially lethal complication, warranting careful perioperative planning and extended postoperative surveillance of patients. Data on the incidence of postoperative respiratory failure and optimal management of patients after robotic-assisted thymectomy are limited. The objective of this study was to evaluate the incidence of respiratory complications and the need for intensive care unit (ICU) capacities after robotic-assisted thymectomy in patients with myasthenia gravis. Retrospective cohort study. Single University hospital in Vienna, Austria, from January 2014 to December 2019. The authors included adult patients who underwent robotic-assisted thymectomy due to myasthenia gravis. Of 72 patients, 4 patients (5.6%) developed postoperative respiratory failure, needing noninvasive ventilation/intubation. Respiratory failure occurred within the first hours after extubation when patients still were under surveillance in the recovery room or in the ICU. One patient (1.4%) suffered from worsened myasthenic symptoms several days after surgery, and was treated with plasmapheresis. Sixty-five patients (90.3%) were extubated in the operating room, 35 of these (48.6%) were transferred to the ICU, and 30 patients (41.7%) primarily were transferred to the recovery room. Fourteen patients (19.4%) were transferred to the surgical ward after extended observation in the recovery room. Furthermore, after implementation of a standardized perioperative algorithm in 2020, a reduction of ICU admissions was achieved. After careful patient selection, planning, and postoperative patient evaluation, robotic-assisted thymectomy can be performed safely without postoperative surveillance in an ICU. [ABSTRACT FROM AUTHOR]

Background Residual neuromuscular blockade (RNMB) is a frequent event after general anesthesia, which can lead to serious complications, such as upper airway obstruction. Sugammadex is useful in reversing RNMB. However, its use in infants has not yet been approved by the Food and Drug Administration. Therefore, anesthesiologists can be hesitant use it, even in situations where no other choice is available. Case A two-month-old baby presented to the hospital for umbilical polypectomy. At the end of the surgery, neostigmine was administered. Even after waiting for 30 min and injecting an additional dose of neostigmine, neuromuscular blockade was not adequately reversed. Eventually, sugammadex was administered, and spontaneous breathing returned. Conclusions If there were no particular causes of delayed return to spontaneous breathing in infants, RNMB should be considered and reversal with sugammadex would be useful.

Perioperative anaphylaxis is a rare, but life-threatening hypersensitivity reaction for patients undergoing surgical procedures. Sugammadex is a relatively new drug used to reverse the neuromuscular blockade of specific anesthetics in surgery. Several case reports indicate that there may be a risk of anaphylaxis associated with the use of sugammadex This review examines the literature in order to evaluate the strength of the association between sugammadex use and anaphylaxis. A query of PubMed, EMBASE, and Web of Science was conducted using a combination of terms to identify relevant articles from inception until March 9, 2020. We included any primary study that identified sugammadex as a probable causative agent based on the World Allergy Organization diagnostic criteria for anaphylaxis. A total of 24 articles were reviewed. Across the three randomized controlled trials, there were only four cases of anaphylaxis identified. Incidence of anaphylaxis was reported in only one trial at 0.33%. Two retrospective observational studies conducted in Japan identified cases of anaphylaxis, with incidences of 0.02 and 0.04%. Among 19 case reports and series, 25 patient cases of anaphylaxis were confirmed via allergy testing to be caused by sugammadex or sugammadex–rocuronium complex. Commonly reported symptoms included hypotension, erythema, and decreased oxygen saturation. Based on the findings of this review, there appears to be a rare, but serious, association of sugammadex-induced perioperative anaphylaxis with an incidence between 0.02 and 0.04% in observational studies. It is unclear whether sugammadex on its own or in complex with rocuronium triggers this reaction, but it is clearly involved in inducing anaphylaxis. Further population studies are needed to get a more accurate global incidence rate, and more detailed allergy testing is required to better describe which step of the sugammadex reversal pathway initiates the anaphylactic attack.

Sugammadex (also known as bridion) is a modified γ-cyclodextrin, which is a reversal agent for the neuromuscular block. Growth hormone (GH) has an important biological effect on muscle, regulating muscle growth and development. In the current work, we explored the effect of Sugammadex on GH’s bioactivities.

Background: Evidences show that sugammadex may facilate extubation after surgery. Applying neuromuscular monitoring in general anesthesia may prevent postoperatrive reintubation. However, routine general anesthesia does not always include neuromuscular monitoring. Therefore, we investigated the relationship between the sugammadex use and postoperative reintubation in the absence of neuromuscular monitoring. Methods: We conducted a retrospective analysis of the incidence of postoperative reintubation in the operating room (OR) or postanesthesia care unit following sugammadex use in the absence of neuromuscular monitoring that involved a large number of patients over 4 years (from January 2017 to August 2020). Postoperative reintubation was applied for patients who had peripheric oxygen saturation

Abstract Background The impact of sugammadex in patients with end-stage renal disease undergoing kidney transplantation is still far from being defined. The aim of the study is to compare sugammadex to neostigmine for reversal of rocuronium- and cisatracurium-induced neuromuscular block (NMB), respectively, in patients undergoing kidney transplantation. Methods A single-center, 2014-2017 retrospective cohort case-control study was performed. A total of 350 patients undergoing kidney transplantation, equally divided between a sugammadex group (175 patients) and a neostigmine group (175 patients), were considered. Postoperative kidney function, evaluated by monitoring of serum creatinine and urea and estimated glomerular filtration rate (eGFR), was the endpoint. Other endpoints were anesthetic and surgical times, post-anesthesia care unit length of stay, postoperative intensive care unit admission, and recurrent NMB or complications. Results No significant differences in patient or, with the exception of drugs involved in NMB management, anesthetic, and surgical characteristics, were observed between the two groups. Serum creatinine (median [interquartile range]: 596.0 [478.0-749.0] vs 639.0 [527.7-870.0] μmol/L, p = 0.0128) and serum urea (14.9 [10.8-21.6] vs 17.1 [13.1-22.0] mmol/L, p = 0.0486) were lower, while eGFR (8.0 [6.0-11.0] vs 8.0 [6.0-10.0], p = 0.0473) was higher in the sugammadex group than in the neostigmine group after surgery. The sugammadex group showed significantly lower incidence of postoperative severe hypoxemia (0.6% vs 6.3%, p = 0.006), shorter PACU stay (70 [60-90] min vs 90 [60-105] min, p < 0.001), and reduced ICU admissions (0.6% vs 8.0%, p = 0.001). Conclusions Compared to cisatracurium-neostigmine, the rocuronium-sugammadex strategy for reversal of NMB showed a better recovery profile in patients undergoing kidney transplantation.

We introduce and study a non-oriented first passage percolation model having a property of statistical invariance by time reversal. This model is defined in a graph having directed edges and the passage times associated with each set of outgoing edges from a given vertex are distributed according to a generalized Bernoulli–Exponential law and i.i.d. among vertices. We derive the statistical invariance property by time reversal through a zero-temperature limit of the random walk in Dirichlet environment model. [ABSTRACT FROM AUTHOR]