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Journal of Clinical Anesthesia Sep 2017To summarize and compare efficacy of sugammadex with neostigmine or placebo for reversal of rocuronium- or vecuronium-induced neuromuscular blockade (NMB), and to... (Comparative Study)
Comparative Study
STUDY OBJECTIVE
To summarize and compare efficacy of sugammadex with neostigmine or placebo for reversal of rocuronium- or vecuronium-induced neuromuscular blockade (NMB), and to demonstrate consistency of sugammadex results across various patient populations.
DESIGN
Pooled analysis on data from 26 multicenter, randomized, Phase II and III studies.
SETTING
Operating room.
PATIENTS
1855 adults undergoing surgery under general anesthesia and receiving rocuronium or vecuronium for NMB.
INTERVENTIONS
Sugammadex (2.0mg/kg at second twitch reappearance [T; moderate NMB], 4.0mg/kg at 1-2 post-tetanic counts [PTC; deep NMB] or 16.0mg/kg at 3min after rocuronium 1.2mg/kg), neostigmine or placebo.
MEASUREMENTS
Time to recovery of the train-of-four (TOF) ratio to 0.9.
MAIN RESULTS
Geometric mean (95% CI) times to recovery to TOF ratio of 0.9 were 1.9 (1.8-2.0) min following sugammadex 2.0mg/kg and 10.6 (9.8-11.6) min following neostigmine administration at T after rocuronium, and 2.9 (2.5-3.4) min and 17.4 (13.4-22.6) min, respectively, after vecuronium. Recovery times were 2.2 (2.1-2.3) min following sugammadex 4.0mg/kg and 19.0 (14.8-24.6) min following neostigmine administered at a target of 1-2 PTC after rocuronium, and 3.8 (3.0-5.0) min and 67.6 (56.3-81.2) min after vecuronium. Sugammadex administered 3min after rocuronium 1.2mg/kg resulted in rapid recovery (1.7 [1.5-2.0] min). Modest increases in mean recovery time were associated with vecuronium use (+1.6min [78%; (61%-98%)] versus rocuronium), mild-to-moderate renal impairment (+0.4min [20%; (9%-32%)] versus normal renal function) and geographic location (+1.0min [38%; (25%-52%)] in subjects in USA/Canada versus Europe/Japan).
CONCLUSIONS
Sugammadex administered at recommended doses provides rapid and predictable reversal of rocuronium and vecuronium-induced moderate and deep NMB, and effective reversal 3min after rocuronium 1.2mg/kg. Robust recovery was seen across various patient factors, providing further confirmation of labeled dose recommendations.
Topics: Adult; Aged; Androstanols; Anesthesia Recovery Period; Anesthesia, General; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Placebos; Randomized Controlled Trials as Topic; Rocuronium; Sugammadex; Time Factors; Treatment Outcome; Vecuronium Bromide; gamma-Cyclodextrins
PubMed: 28802619
DOI: 10.1016/j.jclinane.2017.06.006 -
The Journal of Pediatric Pharmacology... 2022Neuromuscular blockade may be required in critically ill pediatric patients to facilitate ventilator synchrony or maintain safety during high-risk procedures. Vecuronium...
Neuromuscular blockade may be required in critically ill pediatric patients to facilitate ventilator synchrony or maintain safety during high-risk procedures. Vecuronium is one neuromuscular blocking agent used for this purpose; however, there are limited data regarding its use in pediatric patients with renal failure. Although predominantly considered to be metabolized by the liver, there are numerous adult cases and 1 pediatric case report that have described extended paralysis from vecuronium due to renal failure. The proposed mechanism is accumulation of renally cleared active metabolites. This case report describes an infant with vecuronium exposure during continuous renal replacement therapy who experienced prolonged neuromuscular blockade for several days after the agent was stopped. This highlights the importance of considering renal function when selecting neuromuscular blocking agent.
PubMed: 35558355
DOI: 10.5863/1551-6776-27.4.400 -
American Journal of Veterinary Research Apr 2015To evaluate the potency of vecuronium and duration of vecuronium-induced neuromuscular blockade in dogs with centronuclear myopathy (CNM).
OBJECTIVE
To evaluate the potency of vecuronium and duration of vecuronium-induced neuromuscular blockade in dogs with centronuclear myopathy (CNM).
ANIMALS
6 Labrador Retrievers with autosomal-recessive CNM and 5 age- and weight-matched control dogs.
PROCEDURES
Dogs were anesthetized on 2 occasions (1-week interval) with propofol, dexmedetomidine, and isoflurane. Neuromuscular function was monitored with acceleromyography and train-of-four (TOF) stimulation. In an initial experiment, potency of vecuronium was evaluated by a cumulative-dose method, where 2 submaximal doses of vecuronium (10 μg/kg each) were administered IV sequentially. For the TOF's first twitch (T1), baseline twitch amplitude and maximal posttreatment depression of twitch amplitude were measured. In the second experiment, dogs received vecuronium (50 μg/kg, IV) and the time of spontaneous recovery to a TOF ratio (ie, amplitude of TOF's fourth twitch divided by amplitude of T1) ≥ 0.9 and recovery index (interval between return of T1 amplitude to 25% and 75% of baseline) were measured.
RESULTS
Depression of T1 after each submaximal dose of vecuronium was not different between groups. Median time to a TOF ratio ≥ 0.9 was 76.7 minutes (interquartile range [IQR; 25th to 75th percentile], 66.7 to 99.4 minutes) for dogs with CNM and 75.0 minutes (IQR, 47.8 to 96.5 minutes) for controls. Median recovery index was 18.0 minutes (IQR, 9.7 to 23.5 minutes) for dogs with CNM and 20.2 minutes (IQR, 8 to 25.1 minutes) for controls.
CONCLUSIONS AND CLINICAL RELEVANCE
For the study dogs, neither potency nor duration of vecuronium-induced neuromuscular blockade was altered by CNM. Vecuronium can be used to induce neuromuscular blockade in dogs with autosomal-recessive CNM.
Topics: Anesthesia Recovery Period; Anesthetics, Intravenous; Animals; Case-Control Studies; Dog Diseases; Dogs; Electromyography; Female; Male; Monitoring, Physiologic; Muscle Contraction; Muscular Diseases; Neuromuscular Nondepolarizing Agents; Vecuronium Bromide
PubMed: 25815571
DOI: 10.2460/ajvr.76.4.302 -
Lab on a Chip May 2021Engineered three-dimensional models of neuromuscular tissues are promising for use in mimicking their disorder states in vitro. Although several models have been...
Engineered three-dimensional models of neuromuscular tissues are promising for use in mimicking their disorder states in vitro. Although several models have been developed, it is still challenging to mimic the physically separated structures of motor neurons (MNs) and skeletal muscle (SkM) fibers in the motor units in vivo. In this study, we aimed to develop microdevices for precisely compartmentalized coculturing of MNs and engineered SkM tissues. The developed microdevices, which fit a well of 24 well plates, had a chamber for MNs and chamber for SkM tissues. The two chambers were connected by microtunnels for axons, permissive to axons but not to cell bodies. Human iPSC (hiPSC)-derived MN spheroids in one chamber elongated their axons into microtunnels, which reached the tissue-engineered human SkM in the SkM chamber, and formed functional neuromuscular junctions with the muscle fibers. The cocultured SkM tissues with MNs on the device contracted spontaneously in response to spontaneous firing of MNs. The addition of a neurotransmitter, glutamate, into the MN chamber induced contraction of the cocultured SkM tissues. Selective addition of tetrodotoxin or vecuronium bromide into either chamber induced SkM tissue relaxation, which could be explained by the inhibitory mechanisms. We also demonstrated the application of chemical or mechanical stimuli to the middle of the axons of cocultured tissues on the device. Thus, compartmentalized neuromuscular tissue models fabricated on the device could be used for phenotypic screening to evaluate the cellular type specific efficacy of drug candidates and would be a useful tool in fundamental research and drug development for neuromuscular disorders.
Topics: Humans; Lab-On-A-Chip Devices; Motor Neurons; Muscle Fibers, Skeletal; Muscle, Skeletal; Neuromuscular Junction
PubMed: 34008665
DOI: 10.1039/d1lc00048a -
Anticancer Research Mar 2016Aggressive surgical removal of the primary tumour is the preferred treatment, but with tumour progression, some tumours cannot be completely removed surgically.... (Comparative Study)
Comparative Study
BACKGROUND
Aggressive surgical removal of the primary tumour is the preferred treatment, but with tumour progression, some tumours cannot be completely removed surgically. Anaesthetics are administered to facilitate surgery. However, anaesthetics act as a potential factor in tumour recurrence or metastasis.
MATERIALS AND METHODS
Normal breast cells and cancer breast cells were treated with different doses of muscle-relaxant anaesthetics. The effects on breast cancer cell invasion, adhesion and migration of these anaesthetics were then investigated using in vitro models.
RESULTS
With increasing dose of rocuronium bromide and suxamethonium chloride CRS, the number of MCF-10A and MCF-7 cells, but not that of MDA-MB-231 cells, decreased. There was almost no difference in the number of cells when the three cell lines were treated with different doses of vecuronium bromide. The study also demonstrated that rocuronium bromide promoted the invasion, adhesion and growth of MDA-231 cells, while suxamethonium chloride CRS had no effect. Interestingly, vecuronium bromide did not affect the motility and invasion of breast cancer cells significantly.
CONCLUSION
An understanding of the effect of anaesthetics and their impact on tumour metastasis is important, thus using an appropriate aesthetic strategy could improve long-term survival in some patients.
Topics: Androstanols; Breast Neoplasms; Cell Adhesion; Cell Movement; Cell Proliferation; Disease Progression; Dose-Response Relationship, Drug; Female; Humans; MCF-7 Cells; Neoplasm Invasiveness; Neuromuscular Depolarizing Agents; Risk Assessment; Rocuronium; Succinylcholine; Vecuronium Bromide
PubMed: 26977023
DOI: No ID Found -
International Journal of Medical... 2017Rocuronium (ROC) and Vecuronium (VEC) are the most currently used steroidal non-depolarizing neuromuscular blocking (MNB) agents. Sugammadex (SUG) rapidly reverses...
Rocuronium (ROC) and Vecuronium (VEC) are the most currently used steroidal non-depolarizing neuromuscular blocking (MNB) agents. Sugammadex (SUG) rapidly reverses steroidal NMB agents after anaesthesia. The present study was conducted in order to evaluate neuronal effects of SUG alone and in combination with both ROC and VEC. Using MTT, CASP-3 activity and Western-blot we determined the toxicity of SUG, ROC or VEC in neurons in primary culture. SUG induces apoptosis/necrosis in neurons in primary culture and increases cytochrome C (CytC), apoptosis-inducing factor (AIF), Smac/Diablo and Caspase 3 (CASP-3) protein expression. Our results also demonstrated that both ROC and VEC prevent these SUG effects. The protective role of both ROC and VEC could be explained by the fact that SUG encapsulates NMB drugs. In BBB impaired conditions it would be desirable to control SUG doses to prevent the excess of free SUG in plasma that may induce neuronal damage. A balance between SUG, ROC or VEC would be necessary to prevent the risk of cell damage.
Topics: Androstanols; Animals; Apoptosis Inducing Factor; Caspase 3; Cytochromes c; Dose-Response Relationship, Drug; Drug Combinations; Gene Expression Regulation; Humans; Neuromuscular Blocking Agents; Neurons; Primary Cell Culture; Rats; Rocuronium; Sugammadex; Vecuronium Bromide; gamma-Cyclodextrins
PubMed: 28367082
DOI: 10.7150/ijms.17545 -
Se Pu = Chinese Journal of... Jul 2021Vecuronium, rocuronium, and pancuronium are widely used as non-depolarizing muscle relaxants. There have been occasional cases of allergic reactions and even death when...
Vecuronium, rocuronium, and pancuronium are widely used as non-depolarizing muscle relaxants. There have been occasional cases of allergic reactions and even death when using such muscle relaxants. Rapid determination of the concentration of these muscle relaxants in blood can provide valuable information for early clinical diagnosis. As quaternary ammonium compounds, these muscle relaxants are highly polar. Hence, they cannot be retained effectively on reversed-phase chromatographic columns with conventional mobile phases. These quaternary ammonium muscle relaxants are mainly separated by ion-pair chromatography. Using an ion-pairing reagent can help improve the retention capabilities of quaternary ammonium muscle relaxants. Nevertheless, the sensitivity of MS detection is significantly decreased because of ionic inhibition caused by the ion-pairing reagent in the mobile phase. Furthermore, ion-pairing reagents can pollute the MS system. A method based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for the simultaneous determination of the three quaternary ammonium muscle relaxants in blood. The blood samples were diluted and subjected to high-speed centrifugation. The supernatant was purified on a Bond Elut AL-N solid phase extraction column and then filtered through a 0.45 μm microporous membrane. The quaternary ammonium muscle relaxants were separated on a ZIC-cHILIC analytical column (50 mm×2.1 mm, 3.0 μm) with gradient elution. Acetonitrile and 0.1% formic acid aqueous solution were used as mobile phases. The separated compounds were analyzed by tandem MS with an electrospray ionization (ESI) source in positive and multiple reaction monitoring (MRM) modes. The matrix effects of vecuronium, rocuronium, and pancuronium in blood were 88.1% to 95.4%. The calibration curves for vecuronium, rocuronium, and pancuronium showed good linear relationships in each range, and all correlation coefficients () were > 0.996. The limits of detection of vecuronium, rocuronium, and pancuronium were 0.2-0.8 ng/mL, with the corresponding limits of quantification being 0.5-2.0 ng/mL. The recoveries of vecuronium, rocuronium, and pancuronium were 92.8% to 110.6%, with relative standard deviations (RSDs) of 3.2%-9.4%. This method is sensitive, accurate, and easy to operate, and it can be used to rapidly determine vecuronium, rocuronium, and pancuronium in blood.
Topics: Ammonium Compounds; Chromatography, High Pressure Liquid; Humans; Neuromuscular Agents; Pancuronium; Rocuronium; Solid Phase Extraction; Tandem Mass Spectrometry; Vecuronium Bromide
PubMed: 34227366
DOI: 10.3724/SP.J.1123.2020.09020 -
Spectrochimica Acta. Part A, Molecular... Feb 2023Near-infrared (NIR) spectroscopy is a non-destructive, efficient and convenient detection technology, with the emergence of portable NIR spectrometers, NIR mobile...
Near-infrared (NIR) spectroscopy is a non-destructive, efficient and convenient detection technology, with the emergence of portable NIR spectrometers, NIR mobile applications (APPs) come into being. The popularity of intelligent mobile phones provides an impetus to the research and development of NIR APPs, however, the primary functions such as operating the NIR spectrometers and collecting data cannot satisfy NIR users in the field of data processing. Herein, we propose an APP processing NIR data locally at the mobile terminal, by the comprehensive utilization of Principal Component Analysis (PCA) and Cuckoo Search algorithm optimized Support Vector Classifier with radial basis function (RBFSVC) kernel (CS-RBFSVC). 738 NIR samples of four drugs (Cydiodine Buccal Tablets, Sulfasalazine Enteric-coated Tablets, Dexamethasone Acetate Tablets, Vecuronium Bromide for Injection) were used as the validation objects to train and test the data classification model. Firstly, the original data were subjected to dimensional reduction through PCA for the purpose of compressing calculation amount. Secondly, the CS-RBFSVC model was utilized to classify the types of drugs and their manufacturers, moreover, the improved accuracy and efficiency by introducing Cuckoo Search (CS) algorithm into RBFSVC were proven in comparison with the conventional grid optimized RBFSVC (Grid-RBFSVC) and Linear Support Vector Classifier (Linear-SVC). Last but not least, an APP based on the proposed PCA and CS-RBFSVC model is developed and demonstrated to be able to classify the type of drugs with an accuracy of 100%, the accuracies of classifying the drugs' manufacturers were 100%, 100%, 98.3% and 90.7%, respectively. Conclusively, the proposed PCA and CS-RBFSVC based model can provide a low-consumption, high accuracy and quick strategy for NIR data classification and overcome the limitations of internal storage and operating speed at phone terminals, in conjunction with the portable NIR spectrometer, it is believed to push forward NIR technology into the instant detection and on-site inspection.
Topics: Principal Component Analysis; Spectroscopy, Near-Infrared; Algorithms; Tablets
PubMed: 36370633
DOI: 10.1016/j.saa.2022.122080 -
Anesthesiology Dec 2015The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation. (Comparative Study)
Comparative Study
BACKGROUND
The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation.
METHODS
The dose-response relationship of drugs to reverse vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n = 34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps femoris muscle of the rat). Cumulative dose-response curves of calabadions, neostigmine, or sugammadex were created ex vivo at a steady-state deep NMB. In living rats, the authors studied the dose-response relationship of the test drugs to reverse deep block under physiologic conditions, and they measured the amount of calabadion 2 excreted in the urine.
RESULTS
In vitro experiments showed that calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (Ka = 3.4 × 10 M and Ka = 3.8 × 10 M-). The results of urine analysis (proton nuclear magnetic resonance), competition binding assays, and ex vivo study obtained in the absence of metabolic deactivation are in accordance with an 1:1 binding ratio of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2 dose-dependently and rapidly reversed all NMBAs tested. The molar potency of calabadion 2 to reverse vecuronium and rocuronium was higher compared with that of sugammadex. Calabadion 2 was eliminated renally and did not affect blood pressure or heart rate.
CONCLUSIONS
Calabadion 2 reverses NMB induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in rats.
Topics: Androstanols; Animals; Atracurium; Dose-Response Relationship, Drug; Heterocyclic Compounds, 4 or More Rings; Male; Neostigmine; Neuromuscular Nondepolarizing Agents; Rats; Rocuronium; Sugammadex; Sulfonic Acids; Vecuronium Bromide; gamma-Cyclodextrins
PubMed: 26418697
DOI: 10.1097/ALN.0000000000000868 -
Journal of Photochemistry and... Nov 2014The interactions between an anesthetic, vecuronium bromide (VB) and human serum albumin (HSA) have been investigated systematically by steady-state/time-resolved...
The interactions between an anesthetic, vecuronium bromide (VB) and human serum albumin (HSA) have been investigated systematically by steady-state/time-resolved fluorescence, circular dichroism (CD), UV-vis absorption, Fourier transform infrared spectroscopy (FTIR), mass spectroscopy and differential scanning calorimetry (DSC) methods under physiological conditions. The fluorescence quenching observed is attributed to the formation of a complex between HSA and VB, and the reverse temperature effect of the fluorescence quenching has been found and discussed. Fluorescence analysis has proved that there is one classical binding site on HSA for VB with a relative weak binding constant of 1.07 × 10(4)M(-1) at 298 K. The primary binding pattern is determined by hydrogen bonding or van der Waals forces occurring in site I of HSA with ΔG°=-2.30 × 10(4)J mol(-1), ΔS°=-233 J mol(-1)K(-1) and ΔH°=-9.23 × 10(4)J mol(-1) at 298 K. VB could slightly change the secondary structure and induce unfolding of the polypeptides of protein. The DSC results provide quantitative information on the effect of VB on the stability of serum albumin. It is shown that VB can efficiently bind with HSA and be transported to the focuses needed.
Topics: Anesthetics; Biophysical Phenomena; Calorimetry; Humans; Hydrogen Bonding; Metals; Models, Molecular; Protein Binding; Protein Conformation; Serum Albumin; Spectrum Analysis; Thermodynamics; Vecuronium Bromide
PubMed: 25255425
DOI: 10.1016/j.jphotobiol.2014.08.019