Sugammadex affects GH/GHR’s signaling transduction on muscle cells by regulating the membrane-localized GHR level

Objectives 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. Methods Confocal laser scanning microscope (CLSM), flow cytometry, indirect immunofluorescence, Western-blot, and IP-WB were used to explore the effect of Sugammadex on GH’s bioactivities. Results We found that Sugammadex reduced the activity of GH on muscle cells, which down-regulated GH/GHR-mediated intracellular signaling pathway, such as Janus kinase 2 (JAK2) and signal transducers and activators of transcription 5 (STAT5). We further study the potential biological mechanism by which Sugammadex down-regulated GH/GHR-mediated signaling pathway, a series of related experiments were conducted, and found that Sugammadex may inhibit the proliferation of C2C12 cell via regulating the membrane-localized GHR, which may be the underlying mechanism by which Sugammadex suppressed GHR-induced signaling transduction. This work has laid the theoretical and experimental basis for further exploring the relationship between Sugammadex and GH’s activity. Conclusions In conclusion, this study laid a foundation for further study on the relationship between Sugammadex and GH’s activity.

Impact on grafted kidney function of rocuronium-sugammadex vs cisatracurium-neostigmine strategy for neuromuscular block management. An Italian single-center, 2014-2017 retrospective cohort case-control study

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.

Quantitative Neuromuscular Monitoring and Postoperative Outcomes: A Narrative Review

Over the past five decades, quantitative neuromuscular monitoring devices have been used to examine the incidence of postoperative residual neuromuscular block in international clinical practices, and to determine their role in reducing the risk of residual neuromuscular block and associated adverse clinical outcomes. Several clinical trials and a recent meta-analysis have documented that the intraoperative application of quantitative monitoring significantly reduces the risk of residual neuromuscular blockade in the operating room and postanesthesia care unit. In addition, emerging data show that quantitative monitoring minimizes the risk of adverse clinical events, such as unplanned postoperative reintubations, hypoxemia, and postoperative episodes of airway obstruction associated with incomplete neuromuscular recovery, and may improve postoperative respiratory outcomes. Several international anesthesia societies have recommended that quantitative monitoring be performed whenever a neuromuscular blocking agent is administered. Therefore, a comprehensive review of the literature was performed to determine the potential benefits of quantitative monitoring in the perioperative setting.

Safety and Efficacy of Neostigmine Against Residual Neuromuscular Blockade in Pediatric Patients During Recovery From General Anesthesia: A Retrospective Cohort Study

Introduction: with the wide application of muscle relaxants in clinic, the anesthesiologists pay more and more attention to the residual neuromuscular block. While the pediatric patients have poor tolerance to hypoxia, compared to adult patients, the residual neuromuscular block do more harm to them in recovery period of anesthesia, such as respiratory failure, hypoxia, asphyxia and even death. In order to reduce the risk of the residual neuromuscular block complications, we design the following regression cohort study to conform the safety and effectiveness of routine use of neostigmine after operation.Methods: This study was a retrospective cohort study (ChiCTR1900028048), approved by the ethics committee of West China Hospital, Sichuan University. We reviewed pediatric patients who received surgical treatment in West China Hospital, Sichuan University from January 1, 2018 to September 30, 2019.The exposure factor was the use of neostigmine during the period of anesthesia recovery. Inclusion criteria: the pediatric surgery department patients who underwent general anesthesia in West China Hospital, Sichuan University. Exclusion criteria: cases without medical electronic records; Cases with missing outcome data; No muscle relaxants were used during general anesthesia. The outcomes included: lowest pulse oxygen saturation after endotracheal extubation; incidence of hypoxemia after endotracheal extubation; in-hospital mortality; length of hospital stay; medical expenses. IBM SPSS Statistics 23.0 software was used for statistical analysis.1:1 propensity score matching was used to eliminate the influence of confounding factors. For continuous variables, student t test was used . For categorical variables, the chi-square test was used. The results were considered statistically significant, if p value < 0.05. Subgroup analysis was performed according to the age (<2 years / 3-5 years or >6 years) and the dose of neostigmine (low dose group <=0.02mg/kg or high dose group >0.02mg/kg).Results: A total of 4358 pediatric patients were included. After 1:1 propensity score matching, 1820 pediatric patients were included for statistical analysis. In-hospital mortality (1/910 vs 0/910, p = 0.32), lowest pulse oxygen saturation after endotracheal extubation (98.90±3.05 vs 98.78±3.48, p = 0.43), incidence of hypoxemia after endotracheal extubation (23/910 vs 21/910, p=0.76), length of hospital stay (5.66±6.11 vs 5.88±6.59, p= 0.46), and medical expenses (17967.04±21325.86 vs 17406.96±18358.17, p=0.55) showed no significantly statistical differences between the pediatric patients with or without neostigmine application to reverse the neuromuscular blockade during anesthesia recovery. Subgroup analysis found no significant associations between the outcomes and age of the patients or the dose of neostigmine.Conclusion: For pediatric patients, neostigmine application to reverse the neuromuscular blockade was not significantly associated with in hospital mortality, lowest pulse oxygen saturation after endotracheal extubation, incidence of hypoxemia after endotracheal extubation, medical expenses, or length of hospital stay. However, as some confounding factors cannot be eliminated in this retrospective study, the results of this study are needed to be confirmed by future prospective studies.Trial registration: Medical records based study for the recovery effect of antagonitst of muscle relaxant in pediatric patients, ChiCTR1900028048, Registered 8 September 2019, https://www.chictr.org.cn/showproj.aspx?proj=46686

A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants

Background The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest. Methods Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias. Results Of 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m2, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate. The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate. No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate. There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study. Conclusions Compared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg. These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants. Trial registration ClinicalTrials.gov Identifier: NCT03346057.

The impact of deep versus standard neuromuscular block on intraoperative safety during laparoscopic surgery: an international multicenter randomized controlled double-blind strategy trial — EURO-RELAX TRIAL

Background Muscle relaxants are routinely used during anesthesia to facilitate endotracheal intubation and to optimize surgical conditions. However, controversy remains about the required depth of neuromuscular block (NMB) needed for optimal surgical working conditions and how this relates to other outcomes. For instance, a deep neuromuscular block yields superior surgical working conditions compared to a standard NMB in laparoscopic surgery, however, a robust association to other (safety) outcomes has not yet been established. Methods Trial design: an international multicenter randomized controlled double-blind strategy trial. Trial population: 922 patients planned for elective, laparoscopic or robotic, abdominal surgery. Intervention: Patients will be randomized to a deep NMB (post-tetanic count 1–2 twitches) or standard care (single-dose muscle relaxant administration at induction and repeated only if warranted by surgical team). Main trial endpoints: Primary endpoint is the difference in incidence of intraoperative adverse events during laparoscopic surgery graded according to ClassIntra® classification (i.e., ClassIntra® grade ≥ 2) between both groups. Secondary endpoints include the surgical working conditions, 30-day postoperative complications, and patients’ quality of recovery. Discussion This trial was designed to analyze the effect of deep neuromuscular block compared to standard neuromuscular block on intra- and postoperative adverse events in patients undergoing laparoscopic surgery. Trial registration ClinicalTrials.gov NCT04124757(EURO-RELAX); registration URL: https://clinicaltrials.gov/ct2/show/NCT04124757, registered on October 11th, 2019.