Sugammadex Research Articles

Molecular encapsulation of the aminosteroid phytotoxins solanidine and α-solanine by sugammadex: new insights into atomic-level interactions.

Background/Objectives: Laparoscopic gynecologic surgery is widely utilized due to its minimally invasive nature. Postoperative discomfort, including intra-abdominal and referred shoulder pain, remains a challenge. This study evaluates the impact of deep neuromuscular blockade (NMB) reversed with sugammadex compared to moderate NMB reversed with neostigmine on postoperative pain, recovery, and surgical conditions in patients undergoing laparoscopic hysterectomy. Methods: This double-blind, randomized controlled trial included 228 patients undergoing laparoscopic hysterectomy under standardized pneumoperitoneum pressure (12 mmHg). Participants were randomized into two groups: deep NMB with sugammadex (SUG) and moderate NMB with neostigmine (NEO). Primary outcomes included postoperative pain (NRS) and neuromuscular recovery time (TOF ratio ≥ 0.9). Secondary outcomes were surgical conditions, surgeon satisfaction, extubation and recovery times, incidence of postoperative nausea and vomiting (PONV), and analgesic consumption. Results: The SUG group exhibited lower pain scores up to 24 h compared to the NEO group (p < 0.05). Pain reductions remained statistically significant up to 6 h postoperatively after Bonferroni correction, while differences beyond this time were not significant after adjustment. Neuromuscular recovery was markedly faster in the SUG group (147.58 ± 82.26 sec vs. 488.02 ± 223.07 sec, p < 0.05). Patients in the SUG group had shorter extubation (ΔT1), awakening (ΔT2), and recovery room transfer times (ΔT3). PONV was significantly lower in the SUG group. Deep NMB did not contribute to the improvement of surgical workspace conditions. Conclusions: Deep NMB with sugammadex enhances postoperative pain control and accelerates neuromuscular recovery in laparoscopic hysterectomy. These findings support the adoption of deep NMB with sugammadex as a valid anesthetic approach in laparoscopic hysterectomy procedures.

Postoperative urinary retention (POUR) is common after inguinal hernia repairs (IHR). General anesthesia often utilizes paralytic agents such as vecuronium and rocuronium, which are subsequently reversed with neostigmine upon surgery completion. Neostigmine has undesired cholinergic effects, however, and is typically co-administered with glycopyrrolate, an anticholinergic agent which can impair bladder contraction, leading to urinary retention. Early studies have investigated sugammadex, an alternative reversal agent without cholinergic properties, to reduce POUR after IHR, yet none have focused on an exclusively laparoscopic cohort. This retrospective cohort study included adult male patients who underwent elective laparoscopic IHR procedures performed by a single surgeon from October 2021 to June 2024. Patients were divided into two groups: neostigmine/glycopyrrolate (NG-G) vs. sugammadex (SG). POUR rates and secondary outcomes were compared. Of the total n = 228 patients, NG-G included n = 122 and SG n = 106. Median age was 61.6years. Procedures were predominantly totally extraperitoneal (92.5%). Age, prostate disease history, International Prostate Symptom Scores, anesthesia/operative times, intraoperative/PACU opioid use, steroid use, and anticholinergic use were similar between groups (p > 0.05). NG-G patients received more intravenous fluids, but still < 500mL (375 vs. 250mL, p < 0.01). Twelve patients (9.8%) in the NG-G cohort experienced POUR versus none in SG (p < 0.01). Urinary symptoms were reported in 19.7% of NG-G cases and 0% of SG (p < 0.01). Post-void residual volumes were lower in the SG group (median 9 vs 136mL, p < 0.01). The SG cohort had shorter recovery times (191.5 vs 306.0min, p < 0.01). There were 2 readmissions for NG-G cases, both for urinary retention, and none in SG (p = 0.19). Patients who received sugammadex compared to neostigmine/glycopyrrolate had lower rates of POUR and shorter recovery times, suggesting that sugammadex should be the routine reversal agent in laparoscopic IHR, especially in older men with prostate disease at increased risk of retention.

Background/Objectives: No study has simulated rocuronium (Rb) effect-site concentrations (Ce_Rb) using real-time data-such as Rb concentrations, train-of-four (TOF) count (TOFC), and TOF ratio (TOFR)-under mechanical Rb administration. Therefore, we aimed to investigate post-operative recurarization and changes in the Ce_Rb after sugammadex (SGX) administration under conditions where Rb dosing was strictly administered using an automated delivery system for total intravenous anesthesia. Methods: This non-interventional, retrospective, observational study included 74 patients from an existing clinical trial who met the study criteria. Rb was automatically administered during surgery to maintain a TOFC of 1. SGX (2 mg/kg) was manually administered post-surgery, and the time until the TOFR reached ≥0.9 (if the time exceeded 3 min, 0.5 mg/kg SGX was added every minute). The results were analyzed using a pharmacokinetic (PK)-pharmacodynamic (PD) simulation model of the Rb-SGX complex. Results: The average total dose of administered SGX was 2.2 ± 0.4 mg/kg (mean ± standard deviation). The time from SGX administration till the TOFR reached ≥0.9 was 2.9 ± 1.1 min. Furthermore, Ce_Rb at recovery (Ce_r) was 0.3 ± 0.2 μg/mL. Notably, no cases showed post-operative recurarization within 24 h of surgery. PK-PD model simulations revealed that Ce_Rb increased again after reaching the lowest Ce_Rb in 72 cases, although no increase was recorded beyond Ce_r, suggesting no numerical risk of recurarization. Conclusions: Our results show that if TOFC of 1 is strictly maintained intraoperatively and SGX is administered till the TOFR reaches ≥0.9, post-operative recurarization does not occur.

Exceptional stability of the sugammadex-solasodine complex: Insights from experimental and theoretical studies

Sugammadex (SUG) is a novel antagonist of neuromuscular blocking agents (NMBAs). The NMBA rocuronium is usually employed to obtain better surgical conditions in kidney transplant. Nevertheless, rocuronium has several disadvantages, such as an increased risk of pulmonary complications. Thus, SUG is vital to kidney-transplant surgery. However, because SUG is excreted by the kidneys in prototypes, the pharmacokinetics (PK) may be affected in patients with renal impairment. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to monitor SUG in plasma samples to investigate the PK of SUG in kidney-transplant patients. Due to the complexity and limitation of other methods of sample preparation, magnetic solid-phase extraction (MSPE) was adopted to purify samples. Chromatographic separation was obtained using a reversed-phase Polaris® C18 column and gradient elution with 0.1% formic acid (FA) in water as phase A and in methanol (MeOH) as phase B as mobile phases. The transitions 999.7 → 963.9 (m/z) and 1055.7 → 1012.2 (m/z) were used to quantify SUG and ORG26265, respectively, under negative electrospray ionization. A linear calibration curve was achieved in concentrations varying from 100 to 10 000 ng mL-1. The acceptable accuracy varied from 95.7% to 106.4%, and intra- and inter-precision did not exceed 15% (20% at the lower limit of quantitation (LLOQ)). The matrix effect, stability, dilution integrity, and carry-over were validated. This method was applied successfully for the PK study of 13 recipients and 12 donors of kidney transplant after intravenous injection of SUG (2 mL per kg bodyweight).

ABSTRACT Objectives To compare using deep neuromuscular blockade during low abdominal insufflation pressure (DNMB/LAIP; n = 67) to conventional blockade and pressure (CNMB/CAIP; n = 68) for laparoscopic cholecystectomy and to evaluate the speed and efficacy of NMB recovery using sugammadex (SGX) as assessed by the Postoperative Quality Recovery Scale. Patients & Methods Rocuronium initiation and maintenance doses were 0.6 and 0.15 mg/Kg, respectively, and neostigmine or SGX was used as reverse agent for CNMB and DNMB, respectively. Abdominal insufflation was terminated at 15 and 8-mmHg, for CAIP and LAIP, respectively. The study outcome is the surgical feasibility under DNMB/LAIP, as judged by the frequency of shift-to-CAIP, surgical field visibility and operative time. Results The frequency of shift-to-CAIP was 2.9% due to surgeons’ inconvenience of LAIP. DNMB allowed significant control of intraoperative (IO) hemodynamic response to surgical manipulations. SGX allowed 3.2 times faster NMB-reversal with significantly higher percentages of patients returned to baseline physiologic statuses. The percentage of patients free of pain and nausea was significantly higher after DNMB/LAIP. At hospital discharge and day-7 PO, 86.6% and 98.5% of patients regained normalcy of their overall perspectives after DNMB/LAIP with a significant difference than after CNMB/CIAP. At 2-week PO, the frequency of shoulder-tip pain (STP) was significantly lower and surgeons’ satisfaction rate was significantly with DNMB/LAIP. Conclusion Laparoscopic cholecystectomy under DNMB/LAIP procedure is feasible and safe with lower incidence and severity of STP and high surgeons’ satisfaction. Sugammadex hastened the recovery of DNMB 3.2 times that of neostigmine-induced recovery of CNMB. Registration NO: RC.3.9.2023

(Int J Obstet Anesth. 2023;53:103620) Sugammadex (SGX) quickly and reliably reverses neuromuscular blockade. It also is known to bind progesterone and maintaining proper progesterone levels is critical during pregnancy, especially during the first trimester. Little is known about the impact of SGX exposure during pregnancy on pregnancy and fetal outcomes. This study aimed to compare fetal outcomes in pregnant patients who underwent nonobstetric surgery who were and were not exposed to SGX.

Background: There is no consensus regarding reversing neuromuscular blockade (NMB) under general anesthesia. For obese patients, complete and rapid recovery from NMB is essential. Objective: This study compared the effectiveness of methods to restore spontaneous breathing for obese patients who underwent laparoscopic sleeve gastrectomy after general anesthesia. Materials and Methods: Medical records were reviewed for those who underwent laparoscopic sleeve gastrectomy between January 2019 and December 2020. Patients were divided into two groups: (1) reversal of NMB (REV), who received a muscle relaxant antagonist; (2) received nothing (NONE). The REV group had two subgroups: sugammadex (SUG) and neostigmine (NEO). Groups were compared for extubation, recovery, hospitalization after surgery, and total hospitalization times. Major metabolic parameters were evaluated postoperatively at 1 and 6 months. Results: Time to extubation, recovery, hospitalization after surgery, and total hospitalization in the REV group were significantly shorter than in the NONE group. Moreover, the extubation time and hospitalization after surgery in the SUG group were significantly lower than in the NEO group. At each postoperative follow-up, both groups were comparable for all metabolism-related indicators. Conclusion: SUG was more effective for obese patients who underwent bariatric surgery with general anesthesia. The metabolism of obese patients might not be affected by the means to restore spontaneous breathing.

Sugammadex (SUG) is a synthetically modified γ-cyclodextrin derivative used in hospitals after surgeries to reverse the neuromuscular blockade induced by rocuronium or vecuronium. In this study, we aimed to develop the first electroanalytical quantification method for sugammadex by using molecular imprinting (MIP) via the electropolymerization (EP) technique. An EP-MIP film was formed by EP on a screen-printed gold electrode (SPAuE) and a new electrochemical sensor, EP-MIP(SUG)/SPAuE, was fabricated using the 4-aminophenol monomer with copper ions to enhance the MIP-binding site. Surface and electrochemical characterization of the EP-MIP(SUG)/SPAuE sensor have been done via scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). After screening and optimization studies were carried out to fabricate a MIP-based electrochemical sensor, the analytical performance of EP-MIP(SUG)/SPAuE and the validation parameters were tested according to the ICH guidelines. The specificity/selectivity of the developed sensor has been shown by using common interferents found in the biological fluids and also molecules having similar structures, such as α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. As a result, a quantitative analysis method has been developed and validated by using the EP-MIP(SUG)/SPAuE sensor in the concentration range of 0.1-1.0 pM with very high sensitivity (limit of detection: 27.3 fM). The applicability of the method has been shown for bulk drug substances, pharmaceutical dosage forms, and commercial serum samples with good recovery and RSD% results. The EP-MIP(SUG)/SPAuE is the first electrochemical sensor developed for the determination of sugammadex serving the aims of simplicity, short analysis time, and low cost, and has the potential to be adapted in the future as a portable and/or wearable sensor via miniaturization.

Sugammadex (SUG) has been associated with changes in coagulation studies. Most reports have concluded a lack of clinical significance based on surgical blood loss with SUG use at the end of surgery. Previous reports have not measured its use intraoperatively during ongoing blood loss. Our hypothesis was that the use of SUG intraoperatively may increase bleeding. This was a single site retrospective study. Inclusion criteria were patients undergoing a primary posterior cervical spine fusion, aged over 18 years, between July 2015 and June 2021. The primary outcomes compared were intraoperative estimated blood loss (EBL) and postoperative drain output (PDO) between patients receiving SUG, neostigmine (NEO) and no NMB reversal agent. The objective was to determine if there was a difference in primary endpoints between patients administered SUG, NEO or no paralytic reversal agent. Primary endpoints were compared using analysis of variance with a P value of 0.05 used to determine statistical significance. Groups were compared using the Chi-squared test, rank sum or student's t test. A logistic regression model was constructed to account for differences between the groups. There was no difference in median EBL or PDO between groups. The use of SUG was not associated with an increase in odds for >500 milliliters (ml) of EBL. Increasing duration of surgery and chronic kidney disease were both associated with an increased risk for EBL >500 ml. Intraoperative use of SUG was not associated with increased bleeding. Any coagulation laboratory abnormalities previously noted did not appear to have an associated clinical significance.

Chlorpromazine (CPZ) is an antipsychotic drug which can cause several adverse effects and drug poisoning. Recent studies demonstrated that CPZ forms highly stable complexes with certain cyclodextrins (CDs) such as sulfobutylether-β-CD (SBECD) and sugammadex (SGD). Since there is no available antidote in CPZ intoxication, and considering the good tolerability of these CDs even if when administered parenterally, we aimed to investigate the protective effects of SBECD and SGD against CPZ-induced acute toxicity employing in vitro (SH-SY5Y neuroblastoma cells) and in vivo (zebrafish embryo) models. Our major findings and conclusions are the following: (1) both SBECD and SGD strongly relieved the cytotoxic effects of CPZ in SH-SY5Y cells. (2) SGD co-treatment did not affect or increase the CPZ-induced 24 h mortality in NMRI mice, while SBECD caused a protective effect in a dose-dependent fashion. (3) The binding constants of ligand–CD complexes and/or the in vitro protective effects of CDs can help to estimate the in vivo suitability of CDs as antidotes; however, some other factors can overwrite these predictions.

BackgroundPostoperative residual curarization (PORC) may be a potential risk factor of postoperative pulmonary complications (PPCs), and both of them will lead to adverse consequences on surgical patient recovery. The train-of-four ratio (TOFr) which is detected by acceleromyography of the adductor pollicis is thought as the gold standard for the measurement of PORC. However, diaphragm function recovery may differ from that of the peripheral muscles. Recent studies suggested that diaphragm ultrasonography may be useful to reveal the diaphragm function recovery, and similarly, lung ultrasound was reported for the assessment of PPCs in recent years as well. Sugammadex reversal of neuromuscular blockade is rapid and complete, and there appear to be fewer postoperative complications than with neostigmine. This study aims to compare the effects of neostigmine and sugammadex, on PORC and PPCs employing diaphragm and lung ultrasonography, respectively.Methods/designIn this prospective, double-blind, randomized controlled trial, patients of the American Society of Anesthesiologists Physical Status I–III, aged over 60, will be enrolled. They will be scheduled to undergo arthroplasty under general anesthesia. All patients will be allocated randomly into two groups, group NEO (neostigmine) and group SUG (sugammadex), using these two drugs for reversing rocuronium. The primary outcome of the study is the incidence of PPCs in the NEO and SUG groups. The secondary outcomes are the evaluation of diaphragm ultrasonography and lung ultrasound, performed by an independent sonographer before anesthesia, and at 10 min and 30 min after extubation in the post-anesthesia care unit, respectively.DiscussionElimination of PORC is a priority at the emergence of anesthesia, and it may be associated with reducing postoperative complications like PPCs. Sugammadex was reported to be superior to reverse neuromuscular blockade than neostigmine. Theoretically, complete recovery of neuromuscular function should be indicated by TOFr > 0.9. However, the diaphragm function recovery may not be the same matter, which probably harms pulmonary function. The hypothesis will be proposed that sugammadex is more beneficial than neostigmine to reduce the incidence of PPCs and strongly favorable for the recovery of diaphragm function in our study setting.Trial registrationClinicalTrials.gov NCT05040490. Registered on 3 September 2021

Objective: Sugammadex (SUG) quickly reverses steroidal neuromuscular blocking drugs after anesthesia. It has been reported that SUG has a toxic effect on neurons in primary culture. This study aims to examine the effect of SUG on glial cell viability, oxidative stress, and apoptosis in C6 glial cells after exposure to H2O2. Method: In this study, C6 glioma cell line was used to study the effect of SUG on the glial cell in four cell groups. The control group was untreated. Cells in the H2O2group were treated with 0.5 mM H2O2 for 24 h. Cells in the SUG group were treated with 50 μg/mL SUG for 24 h. Cells in the SUG+ H2O2 group were pre-treated with 50 μg/mL of SUG for 1 h before 24-h exposure to 0.5 mM H2O2. Cell viability was evaluated using XTT assay. Total antioxidant status (TAS), total oxidant status (TOS), caspase-3, Bax, 8-hydroxy-2′ -deoxyguanosine (8-OHdG), and cleaved-PARP levels in the cells were measured by commercial kits. Results: SUG significantly decreased the viability of C6 cells after H2O2-induced oxidative stress (p < 0.05). SUG pretreatment also raised TOS levels and led to increased Bax, Caspase-3, 8-OHdG, and cleaved PARP levels after H2O2-induced oxidative damage in C6 cells (p < 0.05).

BackgroundPostoperative cognitive dysfunction affects the quality of recovery, particularly affecting the elderly, and poses a burden on the health system. We hypothesize that the use of sugammadex (SG) could optimize the quality of postoperative cognitive function and overall recovery through a neuroprotective effect.MethodsA pilot observational study on patients undergoing cardiac surgery with enhanced recovery after cardiac surgery (ERACS) approach, was designed to compare SG-treated (n = 14) vs. neostigmine (NG)-treated (n = 7) patients. The Postoperative Quality Recovery Scale (PQRS) was used at different times to evaluate cognitive function and overall recovery of the patients. An online survey among anesthesiologists on SG use was also performed. Additionally, an animal model study was designed to explore the effects of SG on the hippocampus.ResultsSugammadex (SG) was associated with favorable postoperative recovery in cognitive domains particularly 30 days after surgery in patients undergoing aortic valve replacement by cardiopulmonary bypass and the ERACS approach; however, it failed to demonstrate a short-term decrease in length of intensive care unit (ICU) and hospital stay. The survey information indicated a positive appreciation of SG recovery properties. SG reverts postoperative memory deficit and induces the expression of anti-inflammatory microglial markers.ConclusionThe results show a postoperative cognitive improvement by SG treatment in patients undergoing aortic valve replacement procedure by the ERACS approach. Additionally, experimental data from an animal model of mild surgery confirm the cognitive effect of SG and suggest a potential effect over glia cells as an underlying mechanism.

IntroductionThe use of muscle relaxants is an indispensable in the general anaesthesia but is prone to accidents, which are often related to residual muscle relaxant. Therefore, how to timely and...

Reversal of residual neuromuscular block with neostigmine or sugammadex and postoperative pulmonary complications: a prospective, randomised, double-blind trial in high-risk older patients

Sugammadex

Sugammadex

Sugammadex