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1.
J Hazard Mater ; 469: 133875, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38457970

RESUMO

Selective relaxant binding agents (SRBA) have great potential in clinical surgeries for the precise reversal of neuromuscular blockades. Understanding the relationship between the structure-affinity-reversal effects of SRBA and neuromuscular blockade is crucial for the design of new SRBAs, which has rarely been explored. Seven anionic pillar[5]arenes (AP5As) with different aliphatic chains and anionic groups at both edges were designed. Their binding affinities to the neuromuscular blocking agent decamonium bromide (DMBr) were investigated using 1H NMR, isothermal titration calorimetry (ITC), and theoretical calculations. The results indicate that the capture of DMBr by AP5As is primarily driven by electrostatic interactions, ion-dipole interactions and C-H‧‧‧π interactions. The optimal size matching between the carboxylate AP5As and DMBr was ∼0.80. The binding affinity increased with an increase in the charge quantity of AP5As. Further animal experiments indicated that the reversal efficiency increased with increasing binding affinity for carboxylate or phosphonate AP5As. However, phosphonate AP5As exhibited lower reversal efficiencies than carboxylate AP5As, despite having stronger affinities with DMBr. By understanding the structure-affinity-reversal relationships, this study provides valuable insights into the design of innovative SRBAs for reversing neuromuscular blockade.


Assuntos
Bloqueadores Neuromusculares , Fármacos Neuromusculares não Despolarizantes , Organofosfonatos , gama-Ciclodextrinas , Animais , gama-Ciclodextrinas/farmacologia , Sugammadex , Bloqueadores Neuromusculares/farmacologia , Brometos
2.
Colloids Surf B Biointerfaces ; 237: 113841, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38492412

RESUMO

Geraniol (Ger) is an essential oil molecule with excellent biological activity. High hydrophobicity and volatility limit its practical application. Cyclodextrins (CDs) are water-soluble cyclic oligosaccharides with hydrophobic cavities. Physical encapsulation of CDs to improve the solubility and stability of essential oil molecules is not satisfactory. Therefore, this study synthesized the γ-CD derivative (γ-CD-Ger) by grafting Ger onto γ-CD using a bromide-mediated method. Compared to the inclusion complexes (γ-CD/Ger) formed by both, the derivatives exhibit better solubility and thermal stability. The derivative has better antibacterial activity when the ratio of γ-CD to Ger was 1:2. In addition, the derivatives did not exhibit cytotoxic and hemolytic properties. These results indicate that this research provides a water-soluble antibacterial agent with a wide range of promising applications and offers new ideas for the application of alcohol hydrophobic molecules in aqueous systems.


Assuntos
Monoterpenos Acíclicos , Ciclodextrinas , Óleos Voláteis , gama-Ciclodextrinas , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/química , Solubilidade , Antibacterianos/farmacologia , Ciclodextrinas/farmacologia , Ciclodextrinas/química , Água/química
5.
Vet Anaesth Analg ; 51(1): 60-63, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38072747

RESUMO

OBJECTIVE: To compare recovery times of sugammadex with spontaneous recovery from rocuronium-induced neuromuscular block (NMB) in dogs. STUDY DESIGN: Retrospective, unmatchedcase-control study. ANIMALS: A total of 10 dogs administered sugammadex and 10 dogs recovering spontaneously from rocuronium-induced NMB. METHODS: Files of dogs administered rocuronium between March and August 2023 were inspected. The train-of-four (TOF) count at the time of sugammadex administration and the time between administration and TOF ratio >90% (recovery time) were recorded. The recovery time for those not administered reversal agents was considered from the first TOF value >0 until TOF ratio >90%. The dose of sugammadex and the cumulative dose of rocuronium were recorded. Rocuronium doses and recovery times were compared using Mann-Whitney tests. The coefficient of determination (R2) between the cumulative rocuronium dose and sugammadex dose and the recovery time were calculated. RESULTS: Dogs in the sugammadex and spontaneous recovery groups were administered intravenously (IV) 0.76 (0.4-2.6) and 0.61 (0.3-2.9) mg kg-1 of rocuronium, respectively (p = 0.325). Recovery time after 3.9 (2.9-5.5) mg kg-1 of sugammadex IV was 1 (1-3) minutes and was 20 (10-35) min for spontaneous recovery (p < 0.0001). The R2 for rocuronium and sugammadex doses and recovery times were 0.19 (p = 0.2) and 0.012 (p = 0.758). CONCLUSIONS AND CLINICAL RELEVANCE: Sugammadex 2.9-5.5 mg kg-1 reversed moderate (TOF count 1-3) or deep (TOF count 0) rocuronium-induced NMB within 3 minutes, substantially faster than spontaneous recovery.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Cães , Animais , Sugammadex/farmacologia , Rocurônio , gama-Ciclodextrinas/farmacologia , Estudos Retrospectivos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Androstanóis/farmacologia , Fatores de Tempo , Bloqueio Neuromuscular/veterinária
7.
Anesth Prog ; 70(3): 116-119, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37850674

RESUMO

There are few reports on rocuronium infiltration under general anesthesia. We report a case of suspected accidental rocuronium infiltration during anesthesia induction. A 25-year-old woman with autism spectrum disorder, intellectual disability, and epilepsy was scheduled for the extraction of 4 impacted third molars under general anesthesia. After induction with sevoflurane, an intravenous (IV) line was established in the left cephalic vein. Rocuronium was administered; however, subcutaneous swelling at the IV site was observed immediately. Spontaneous ventilations were maintained until additional rocuronium was administered via a new IV line. After heat pack application, the swelling disappeared 60 minutes after infiltration, and no tissue damage was observed. A strategy was developed to continue neuromuscular monitoring until recovery occurred. Acceleromyography was used, and the train-of-4 ratios at 99, 130, and 140 minutes after infiltration were 0.79, 0.91, and 1.0, respectively. Sugammadex was administered to prevent neuromuscular blockade recurrence. The patient was extubated once adequate return of muscle function and consciousness were observed. No neuromuscular block prolongation or recurrence were observed postoperatively. When rocuronium infiltration is suspected, it is important to eliminate swelling at the infiltration site and determine a management strategy based on neuromuscular monitoring.


Assuntos
Transtorno do Espectro Autista , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Feminino , Humanos , Adulto , Rocurônio , gama-Ciclodextrinas/farmacologia , Androstanóis/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Anestesia Geral/efeitos adversos , Bloqueio Neuromuscular/efeitos adversos
8.
Pestic Biochem Physiol ; 194: 105501, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532321

RESUMO

The volatility of essential oils greatly limits their industrial applications. Here, we successfully prepared γ-cyclodextrin (γ-CD) inclusion compounds (γ-CDTL) containing thymol (TL) for the control of green mold caused by Penicillium digitatum (P. digitatum) in citrus fruit. In vitro experiment showed that the minimum fungicidal concentration (MFC) of γ-CDTL against the hyphae growth of P. digitatum was 2.0 g/L, and 8 × MFC treatment significantly reduced the occurrence of green mold in citrus fruit and had no adverse effect on fruit quality in vivo test compared to prochloraz. Scanning electron microscopy (SEM), x-ray diffraction (XRD), fourier transform-infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), physical properties and sustained release properties were also performed, results indicated that the hydrogen bonds between TL and γ-CD were the basis for the formation of γ-CDTL. We further investigated the inhibition mechanism of γ-CDTL. SEM and TEM experiments showed that γ-CDTL treatment caused severe damage to the hyphal morphology and cells in 30 min and disrupted the permeability of P. digitatum mycelial cell walls by increasing the chitinase activity, thus accelerating the leakage of intracellular lysates. However, the integrity of the cell membrane was obviously damaged only after 60 min of treatment. In conclusion, we prepared a novel inclusion complex γ-CDTL with obvious antifungal effects and preliminarily elucidated its inclusion mechanism and antifungal mechanism. γ-CDTL might be a potent alternative to chemical fungicides for controlling the postharvest decay of citrus.


Assuntos
Citrus , Fungicidas Industriais , Penicillium , gama-Ciclodextrinas , Timol/farmacologia , Antifúngicos/farmacologia , Citrus/química , Citrus/microbiologia , Espectroscopia de Infravermelho com Transformada de Fourier , gama-Ciclodextrinas/análise , gama-Ciclodextrinas/farmacologia , Fungicidas Industriais/farmacologia , Frutas/microbiologia , Doenças das Plantas/microbiologia
9.
BMC Anesthesiol ; 23(1): 254, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37507689

RESUMO

BACKGROUND: Cranial nerve injury is an uncommon but significant complication of neck dissection. We examined the association between the use of intraoperative neuromuscular blockade and iatrogenic cranial nerve injury during neck dissection. METHODS: This was a single-center, retrospective, electronic health record review. Study inclusion criteria stipulated patients > 18 years who had ≥ 2 neck lymphatic levels dissected for malignancy under general anesthesia with a surgery date between 2008 - 2018. Use of neuromuscular blockade during neck dissection was the primary independent variable. This was defined as any use of rocuronium, cisatracurium, or vecuronium upon anesthesia induction without reversal with sugammadex prior to surgical incision. Univariate tests were used to compare variables between those patients with, and those without, iatrogenic cranial nerve injury. Multivariable logistic regression determined predictors of cranial nerve injury and was performed incorporating Firth's estimation given low prevalence of the primary outcome. RESULTS: Our cohort consisted of 925 distinct neck dissections performed in 897 patients. Neuromuscular blockade was used during 285 (30.8%) neck dissections. Fourteen instances (1.5% of surgical cases) of nerve injury were identified. On univariate logistic regression, use of neuromuscular blockade was not associated with iatrogenic cranial nerve injury (OR: 1.73, 95% CI: 0.62 - 4.86, p = 0.30). There remained no significant association on multivariable logistic regression controlling for patient age, sex, weight, ASA class, paralytic dose, history of diabetes, stroke, coronary artery disease, carotid atherosclerosis, myocardial infarction, and cardiac arrythmia (OR: 1.87, 95% CI: 0.63 - 5.51, p = 0.26). CONCLUSIONS: In this study, use of neuromuscular blockade intraoperatively during neck dissection was not associated with increased rates of iatrogenic cranial nerve injury. While this investigation provides early support for safe use of neuromuscular blockade during neck dissection, future investigation with greater power remains necessary.


Assuntos
Anestésicos , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Humanos , gama-Ciclodextrinas/farmacologia , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Estudos Retrospectivos , Sugammadex , Doença Iatrogênica , Androstanóis
10.
Can J Anaesth ; 70(9): 1529-1538, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37407856

RESUMO

BACKGROUND: Preoperative neoadjuvant chemotherapy plays a critical role in multidisciplinary therapy for a variety of malignant tumours. Although oncologists consider myocardial injury to be the most concerning side effect of chemotherapy, unique chemotherapy-mediated skeletal muscular damage has received attention recently. CLINICAL FEATURES: We report two unusual cases of postoperative delayed respiratory failure following administration of the recommended sugammadex dosage for patients undergoing lengthy operations with deep neuromuscular blockade (NMB) after neoadjuvant chemotherapy. Based on clinical outcomes, especially the comparison of muscle imaging results in patients at different treatment time points, we concluded that NMB recurrence had a possible correlation with neoadjuvant chemotherapy-induced muscular damage. CONCLUSION: The early identification of neoadjuvant chemotherapeutic side effects on NMB could be instrumental for clinical safety, especially in cases of major surgery requiring deep NMB. Thus, the timing of NMB antagonism and the recommended dosage of sugammadex warrant special consideration in these patients. In addition to neuromuscular monitoring during the operation, a more extended and closer observation period in the postanesthesia care unit is warranted.


RéSUMé: CONTEXTE: La chimiothérapie néoadjuvante préopératoire joue un rôle crucial dans le traitement multidisciplinaire de diverses tumeurs malignes. Bien que les oncologues considèrent les lésions myocardiques comme l'effet secondaire le plus inquiétant de la chimiothérapie, des lésions musculosquelettiques spécifiques induites par la chimiothérapie ont récemment fait l'objet d'une attention plus précise. CARACTéRISTIQUES CLINIQUES: Nous signalons deux cas inhabituels d'insuffisance respiratoire postopératoire retardée suite à l'administration de la posologie recommandée de sugammadex chez des patient·es bénéficiant d'opérations prolongées avec blocage neuromusculaire (BNM) profond après une chimiothérapie néoadjuvante. Sur la base des résultats cliniques, en particulier de la comparaison des résultats d'imagerie musculaire chez les patient·es à différents moments du traitement, nous avons conclu que la récurrence du BNM avait une corrélation intéressante avec les lésions musculaires induites par la chimiothérapie néoadjuvante. CONCLUSION: L'identification précoce des effets secondaires de la chimiothérapie néoadjuvante sur le BNM pourrait jouer un rôle déterminant dans l'innocuité clinique, en particulier en cas de chirurgie majeure nécessitant un BNM profond. Ainsi, le moment de l'antagonisme du BNM et la posologie recommandée de sugammadex nécessitent une attention particulière chez ces patient·es. En plus du monitorage neuromusculaire pendant l'opération, une période d'observation plus longue et plus étroite en salle de réveil est justifiée.


Assuntos
Bloqueio Neuromuscular , gama-Ciclodextrinas , Humanos , Sugammadex , gama-Ciclodextrinas/farmacologia , Terapia Neoadjuvante , Bloqueio Neuromuscular/métodos , Período Pós-Operatório
11.
Am J Vet Res ; 84(7)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37253449

RESUMO

OBJECTIVE: To evaluate the effects of rocuronium and sugammadex on the patient state index (PSI) in dogs anesthetized with propofol. ANIMALS: 6 intact healthy male Beagles. PROCEDURES: Anesthesia was induced with and maintained on a propofol infusion. The estimated plasma propofol concentration (ePC) was recorded. Baseline PSI and train-of-four ratio (TOFR) readings were collected for 2 minutes in stable general anesthesia. Neuromuscular blockade (NMB) was induced with 0.6 mg/kg, IV, rocuronium, and full NMB was confirmed with a TOFR of 0. After 5 minutes, the neuromuscular function was restored with 4 mg/kg sugammadex, IV (reversal), and monitored for 5 minutes. Throughout the data collection, ePC, PSI, and TOFR were recorded every 15 seconds and compared with mixed-effect ANOVA. RESULTS: Baseline ePC, PSI, and TOFR were 3.63 ± 0.38, 41 ± 6, and 0.97 ± 0.08 µg/mL, respectively. There was no difference between the baseline of ePC and PSI from NMB or reversal. Compared to the baseline, the TOFR decreased to 0 with NMB (P < .001) and returned to 0.96 ± 0.08 (P = .721) on reversal. After 5 minutes, sugammadex fully reversed 5 out of 6 dogs to TOFR > 0.90 and partially reversed 1 animal to TOFR = 0.80. CLINICAL RELEVANCE: There was no evidence that NMB with rocuronium and sugammadex-induced reversal interfered with PSI readings under steady-state total intravenous anesthesia with propofol. Further evaluation of PSI is warranted to assess its utility in a clinical population to detect changes in levels of consciousness during NMB.


Assuntos
Anestésicos , Bloqueio Neuromuscular , Propofol , gama-Ciclodextrinas , Masculino , Animais , Cães , Rocurônio/farmacologia , Sugammadex/farmacologia , Bloqueio Neuromuscular/veterinária , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico , Propofol/farmacologia , Androstanóis/farmacologia , Anestesia Geral/veterinária
12.
Carbohydr Polym ; 304: 120516, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36641162

RESUMO

Cyclodextrin metal-organic frameworks (CD-MOF) are a class of biocompatible MOF with a great potential in drug delivery applications. Original CD-MOF crystals are fragile and large (0.2-1 mm), which are less useful in pharmaceutical applications. Cetyltrimethylammonium bromide and long chain poly(ethylene) glycol, used in size modulation to produce nanosized CD-MOF can compromise the biocompatibility, and physiochemical properties of CD-MOF as their complete removal from frameworks is difficult. To avoid the use of above-mentioned modulators, herein, we demonstrate the synthesis of nanosized CD-MOF using triethylamine (TEA) as a modulator to reduce their size to ~254 nm. The MOF characteristics such as crystal and chemical structure remain unaffected and the surface area of CD-MOF synthesised with TEA is measured 1075.5 m2/g, almost 50 % higher than those of synthesised using bulky modulators. The improved CD-MOF architecture utilized for the in-situ synthesis of silver nanoparticles resulted in enhanced antimicrobial efficacy tested against Staphylococcus aureus and Escherichia coli bacteria and Candida albicans fungus. And minimum inhibitory concentration (MIC) is recorded in the range of 31-15 µg/mL. Overall, the structural improvement in CD-MOF supported with thorough comparative investigations and enhanced antimicrobial efficacy could be very helpful in further establishing them in biomedicine field.


Assuntos
Anti-Infecciosos , Ciclodextrinas , Nanopartículas Metálicas , Estruturas Metalorgânicas , gama-Ciclodextrinas , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/química , Prata/farmacologia , Ciclodextrinas/química , Estruturas Metalorgânicas/química , Polietilenoglicóis
13.
J Neurosurg Anesthesiol ; 35(2): 224-231, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34839318

RESUMO

INTRODUCTION: Neuromuscular blockade suppresses transcranial electrical motor evoked potential (TceMEP) amplitude and is usually avoided during TceMEP monitoring. In this randomized controlled trial, we investigated whether rocuronium-induced suppression of TceMEP amplitude could be reversed by sugammadex in patients undergoing spine surgery. METHODS: Seventy-six patients undergoing spinal surgery were randomly allocated into sugammadex and control groups. In the sugammadex group, a rocuronium infusion was titrated to maintain moderate neuromuscular blockade (2 twitches on train-of-four) until dural opening when the rocuronium infusion was discontinued and 2 mg/kg sugammadex administered. In the control group, no neuromuscular blockade was administered after induction of anesthesia. The primary outcome was a comparison between sugammadex and control groups of mean TceMEP amplitudes in the abductor pollicis brevis muscles of both upper extremities 5 minutes after dural. Secondary outcomes included TceMEP amplitudes at 10, 20, 30, and 60 minutes after dural opening. RESULTS: Sixty-six patients were included in the analysis. TceMEP amplitudes were significantly greater in the sugammadex group (629 µV, interquartile range: 987 µV) than in the control group (502 µV, interquartile range: 577 µV; P =0.033) at 5 minutes after dural opening. TceMEP amplitudes were also greater in the sugammadex group at 10 minutes ( P =0.0010), 20 minutes ( P =0.003), 30 minutes ( P =0.001), and 60 minutes ( P =0.003) after dural opening. CONCLUSIONS: Moderate neuromuscular blockade induced by continuous infusion of rocuronium was effectively reversed by sugammadex. This suggests that sugammadex could be used to enhance TceMEP waveform monitoring during spine surgery requiring muscle relaxation.


Assuntos
Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Humanos , Sugammadex/farmacologia , Rocurônio , gama-Ciclodextrinas/farmacologia , Fármacos Neuromusculares não Despolarizantes/farmacologia , Potencial Evocado Motor , Androstanóis
15.
Eur J Drug Metab Pharmacokinet ; 48(1): 101-114, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36477706

RESUMO

BACKGROUND AND OBJECTIVES: Probability of target attainment (PTA) curves are commonly used to support dose recommendations of antibiotics for different patient groups. In this study we propose PTA analysis to optimize sugammadex dosing in children. METHODS: This study involved data from an observational cohort study of 30 American Society of Anesthesiologists (ASA) Physical Status I and II children undergoing surgery requiring muscle relaxation. All patients received 0.6 mg/kg rocuronium, with sugammadex administered at the end of surgery in three different doses (0.5, 1.0, and 2.0 mg/kg) to reverse the neuromuscular blockade. RESULTS: The data were analyzed using a population Bayesian-based approach. The developed model was used to simulate pharmacokinetic-pharmacodynamic profiles for different patient groups and dosing regimens before the PTA analysis was performed to translate these simulations into a clinically useful measure. The target was defined as neuromuscular blockade reversal measured by Train-of-Four (TOF ratio > 90%) at 1.5, 3, and 5 min post sugammadex dose. The sugammadex doses leading to 90% PTA were determined for different patients' body weights, rocuronium doses, and time gaps between rocuronium and sugammadex administration assuming the model, priors, and gathered data. For comparison, PTA curves for a range of clinical scenarios are provided to illustrate the usefulness of PTA analysis in selecting the appropriate dose for a given patient. CONCLUSIONS: The proposed PTA analysis is useful to support the sugammadex dose selection in different clinical scenarios. TRIAL REGISTRATION: The study was registered by ClinicalTrials.gov under number NCT04851574 on 21 April 2021.


Assuntos
Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Humanos , Criança , Sugammadex , Rocurônio , gama-Ciclodextrinas/farmacologia , Teorema de Bayes , Fármacos Neuromusculares não Despolarizantes/farmacologia , Androstanóis/farmacologia , Probabilidade
16.
J Med Chem ; 65(24): 16893-16901, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36480913

RESUMO

Broad-spectrum agents for the reversal of residual curarization induced by neuromuscular blocking agents are of great significance. Here, we report a highly water-soluble cucurbit[8]uril (CB[8]) derivative as a broad-spectrum neuromuscular block reversal agent induced by both benzylisquinolinium and aminosteroid neuromuscular block agents by the supramolecular sequestration strategy. The UV/Vis competition titration assays suggest the high binding affinity of the CB[8] derivative toward both benzylisquinolinium-type cisatracurium besylate and aminosteroid-type rocuronium, vecuronium, and pancuronium, at the level of 107 M-1. In vivo studies demonstrate that the administration of the CB[8] derivative could significantly accelerate the recovery time compared to the placebo or neostigmine groups. The reversal activity of the CB[8] derivative is comparable to or higher than that of clinically approved sugammadex. Acute toxicity evaluations reveal that the CB[8]-derivative displays outstanding biocompatibility, with the maximum tolerance dose as high as 960 mg kg-1.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Fármacos Neuromusculares não Despolarizantes/uso terapêutico , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico , Água
17.
Am J Case Rep ; 23: e937128, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36229945

RESUMO

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-of-four [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.


Assuntos
Recuperação Demorada da Anestesia , Miastenia Gravis , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Acetilcolina , Acetilcolinesterase , Adulto , Androstanóis/farmacologia , Inibidores da Colinesterase/uso terapêutico , Feminino , Humanos , Miastenia Gravis/tratamento farmacológico , Neostigmina/farmacologia , Neostigmina/uso terapêutico , Rocurônio , Sugammadex , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico
18.
Medicine (Baltimore) ; 101(39): e30841, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181124

RESUMO

Given neuromuscular blockade (NMB) can affect the amplitude and detection success rate of motor-evoked potentials (MEP), sugammadex may be administered intraoperatively. We evaluated the factors affecting the degree of residual NMB (i.e., the train-of-four [TOF] ratio) and the relationship between TOF ratio and MEP detection success rate in Japanese patients undergoing spine surgery. This single-center retrospective observational study included adults who underwent spine surgery under propofol/remifentanil anesthesia, received rocuronium for intubation, and underwent myogenic MEP monitoring after transcranial stimulation. TOF ratios were assessed using electromyography. Sugammadex was administered after finishing the MEP setting and the TOF ratio was ≤0.7. To identify factors affecting the TOF ratio, TOF ratio and MEP detection success rate were simultaneously measured after finishing the MEP setting; to compare the time from intubation to the start of MEP monitoring after NMB recovery between sugammadex and spontaneous recovery groups, multivariable analyses were performed. Of 373 cases analyzed, sugammadex was administered to 221 (59.2%) cases. Age, blood pressure, hepatic impairment, and rocuronium dose were the main factors affecting the TOF ratio. Patients with higher TOF ratios (≥0.75) had higher MEP detection success rates. The time from intubation to the start of MEP monitoring after NMB recovery was significantly shorter in patients administered sugammadex versus patients without sugammadex (P < .0001). The MEP detection success rate was higher in patients with a TOF ratio of ≥0.75. Sugammadex shortened the time from intubation to the start of MEP monitoring after NMB recovery.


Assuntos
Recuperação Demorada da Anestesia , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Propofol , gama-Ciclodextrinas , Adulto , Androstanóis , Recuperação Demorada da Anestesia/etiologia , Potencial Evocado Motor , Humanos , Japão , Bloqueio Neuromuscular/efeitos adversos , Monitoração Neuromuscular , Remifentanil , Rocurônio , Sugammadex/farmacologia , gama-Ciclodextrinas/farmacologia
19.
Anaesth Crit Care Pain Med ; 41(6): 101145, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36057386

RESUMO

BACKGROUND: The study aimed to compare the responses obtained simultaneously from the newly developed electromyography (EMG)-based neuromuscular monitors, AF-201P and TetraGraph™, during rocuronium-induced neuromuscular block. METHODS: Twenty patients were enrolled in this study. During total intravenous general anesthesia, train-of-four (TOF) responses following 0.9-mg/kg-rocuronium administration were monitored at the abductor digiti minimi muscle with AF-201P and TetraGraph on the contralateral arms. Sugammadex 2 mg/kg was administered when both devices showed TOF counts (TOFC) = 2. The primary outcome was time from rocuronium administration to the first appearance of the post-tetanic count (PTC) response (first PTC). The secondary outcomes were supramaximal current, baseline compound muscle action potential, onset time, time to TOFC = 1, time to TOFC = 2, and time from sugammadex administration to TOF ratio ≥ 0.9. We used the paired t-test and Wilcoxon signed-rank test to analyze parametric and non-parametric data, respectively. P < 0.05 defined statistical significance. RESULTS: A total of 19 patients were analyzed. The supramaximal current was significantly lower with AF-201P than TetraGraph (31.7 ± 13.2 vs. 43.2 ± 8.2, p = .002). The time to first PTC (24.9 ± 9.4 vs. 27.3 ± 8.9 min, p = .026), time to TOFC = 1 (42.3 ± 9.0 vs. 45.1 ± 10.4 min, p = .03), and time to TOFC = 2 (52.0 ± 10.5 vs. 54.6 ± 11.7 min, p = .014) were significantly faster with AF-201P than with TetraGraph. There were no significant differences in the other outcomes between the devices. CONCLUSIONS: AF-201P showed faster recovery of rocuronium-induced neuromuscular block compared with TetraGraph.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Humanos , Rocurônio , Sugammadex , Androstanóis , Estudos Prospectivos , Eletromiografia , gama-Ciclodextrinas/farmacologia , Período de Recuperação da Anestesia
20.
Drugs Aging ; 39(10): 749-761, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35934764

RESUMO

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.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Acetilcolina , Acetilcolinesterase , Idoso , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Humanos , Neostigmina/farmacologia , Neostigmina/uso terapêutico , Bloqueio Neuromuscular/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/uso terapêutico , Complicações Pós-Operatórias/etiologia , Rocurônio , Sugammadex/farmacologia , Brometo de Vecurônio , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêutico
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