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Steroids Dec 2021Vecuronium bromide (Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide; Norcuron®) has been extensively...
Vecuronium bromide (Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide; Norcuron®) has been extensively used in anesthesiology practice as neuromuscular blocking agent since its launch on the market in 1982. However, a detailed crystallographic and NMR analysis of its advanced synthetic intermediates is still lacking. Hence, with the aim of filling this literature gap, vecuronium bromide was prepared starting from the commercially available 3β-hydroxy-5α-androstan-17-one (epiandrosterone), implementing some modifications to a traditional synthetic procedure. A careful NMR study allowed the complete assignment of the H, C, and N NMR signals of vecuronium bromide and its synthetic intermediates. The structural and stereochemical characterization of 2β,16β-bispiperidino-5α-androstane-3α,17β-diol, the first advanced synthetic intermediate carrying all the stereocenters in the final configuration, was described by means of single-crystal X-ray diffraction and Hirshfeld surface analysis, allowing a detailed conformational investigation.
Topics: Crystallography, X-Ray; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Neuromuscular Blocking Agents; Vecuronium Bromide
PubMed: 34655596
DOI: 10.1016/j.steroids.2021.108928 -
British Journal of Anaesthesia Mar 2024The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium...
The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium were well recognised 60 years ago. But the incidence seemed to decline with the introduction of atracurium and vecuronium. However, recently there have been an increasing number of reports of residual and recurrent neuromuscular block. Some of these reports are a result of inappropriate doses of rocuronium, sugammadex or both, together with inadequate neuromuscular monitoring. We urge clinicians to review their practice to ensure the highest standards of clinical care when using neuromuscular blocking drugs and reversal agents. This includes the use of quantitative neuromuscular monitoring whenever neuromuscular blocking drugs are administered.
Topics: Humans; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Androstanols; Rocuronium; Vecuronium Bromide; Neuromuscular Blocking Agents
PubMed: 38135525
DOI: 10.1016/j.bja.2023.12.001 -
Contact in Context 2023This study employed Fourier Transform near-infrared spectrometry to assess the quality of vecuronium bromide, a neuromuscular blocking agent. Spectral data from two lots...
This study employed Fourier Transform near-infrared spectrometry to assess the quality of vecuronium bromide, a neuromuscular blocking agent. Spectral data from two lots of vecuronium were collected and analyzed using the BEST metric, principal component analysis (PCA) and other statistical techniques. The results showed that there was variability between the two lots and within each lot. Several outliers in the spectral data suggested potential differences in the chemical composition or sample condition of the vials. The outliers were identified and their spectral features were examined. A total of eight unique outliers were found in the PC space from PCs 1 to 9, so 22% of the total vials were outliers. The study findings suggest that the manufacturing process of vecuronium bromide may have been operating outside of a state of process control. Further investigation is needed to determine the source of these variations and their impact on the safety and efficacy of the drug product.
PubMed: 38187821
DOI: 10.6084/m9.figshare.24846285 -
The Journal of Allergy and Clinical... Feb 2023Skin testing (ST) concentrations of neuromuscular blocking agents (NMBAs), NMBA-reversal agents, and the sugammadex-rocuronium inclusion complex (S-R-Cx) vary widely...
BACKGROUND
Skin testing (ST) concentrations of neuromuscular blocking agents (NMBAs), NMBA-reversal agents, and the sugammadex-rocuronium inclusion complex (S-R-Cx) vary widely among reports.
OBJECTIVE
To determine maximal ST nonirritant concentrations (NICs) of NMBAs (cisatracurium, rocuronium, succinylcholine, and vecuronium), NMBA-reversal agents (neostigmine and sugammadex), and S-R-Cx in NMBA-tolerant and NMBA-naïve participants.
METHODS
A single-center, prospective study between October 2019 and November 2021 of adult participants with or without a planned surgical procedure. The reference standard was tolerance of medication tested during a procedure (NMBA-tolerant group) before ST. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at 5-7 increasing concentrations of 1 or more medications. All medications were reconstituted according to package insert instructions and diluted with 0.9% saline. A concentration was considered irritant when more than 5% of participants had a positive test per ST positivity criteria (wheal ≥3 mm than initial wheal and associated erythema of the same size or greater than wheal). We also compared our results with current guidelines.
RESULTS
A total of 187 participants (78% NMBA-tolerant) underwent 7812 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT NICs (mg/mL): cisatracurium (0.02), rocuronium (0.05), succinylcholine (0.8), vecuronium (0.01), neostigmine (0.2), sugammadex (50), and S-R-Cx (sugammadex 7.14 + rocuronium 2).
CONCLUSION
Our results suggest that SPT may be performed with undiluted stock concentrations. We confirm maximal IDT NICs for cisatracurium and rocuronium. We also propose that currently recommended maximal IDT NICs of succinylcholine, neostigmine, sugammadex, and S-R-Cx could be increased, whereas the maximal IDT NIC of vecuronium could be decreased compared with current guidelines and prior reports.
Topics: Adult; Humans; Sugammadex; Rocuronium; Vecuronium Bromide; Neuromuscular Nondepolarizing Agents; Neostigmine; gamma-Cyclodextrins; Succinylcholine; Prospective Studies; Androstanols; Neuromuscular Blockade; Neuromuscular Blocking Agents
PubMed: 36108924
DOI: 10.1016/j.jaip.2022.08.049 -
Pediatric Emergency Care Jun 2020Sugammadex reverses neuromuscular blockade by the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. In 2015, it was approved in the... (Review)
Review
Sugammadex reverses neuromuscular blockade by the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. In 2015, it was approved in the United States by the Food and Drug Administration for adult use. However, there are ongoing clinical trials investigating its use in the pediatric population. Before approval in adult use in the United States, several adverse effects were noted to occur in patients receiving sugammadex in clinical trials including prolonged QT interval, bradycardia, hypersensitivity reactions, and prolongation of coagulation parameters. Additional investigations further elucidated the risks of these adverse events. Sugammadex is approved for use in children older than 2 years in other countries in Europe and Asia. Investigations suggest that the efficacy, safety, and pharmacokinetic profile is similar in children when compared with adults. Published pediatric data favor the use of sugammadex in children older than 2 years, but there are some data in young children younger than 2 years. Case reports discuss the use of sugammadex in pediatric patients with neuromuscular diseases. Although sugammadex is typically used in the operating room for reversing neuromuscular blockade for surgical procedures, there is a small but important role for sugammadex use in the emergency department. In cases where rapid neurological examination is required after neuromuscular blockage with rocuronium or vecuronium, sugammadex can assist in facilitating a timely comprehensive neurological examination where pharmacologic or surgical management may depend on examination findings such as in the case of cerebral vascular accident, status epilepticus, or traumatic brain injury. Some clinicians have advocated for the use of sugammadex in the cannot intubate, cannot ventilate scenario. However, caution should be exercised in this situation as reversal of paralysis can take up to 22 minutes to occur.
Topics: Child; Diagnostic Techniques, Neurological; Emergency Medicine; Humans; Neuromuscular Blockade; Rocuronium; Sugammadex; Vecuronium Bromide
PubMed: 32483081
DOI: 10.1097/PEC.0000000000002126 -
Critical Care Explorations Jan 2020We observed that patients treated with continuous vecuronium or esmolol infusions showed elevated plasma sodium measurements when measured by the routine chemistry...
OBJECTIVES
We observed that patients treated with continuous vecuronium or esmolol infusions showed elevated plasma sodium measurements when measured by the routine chemistry analyzer as part of the basic metabolic panel (Vitros 5600; Ortho Clinical Diagnostics, Raritan, NJ), but not by blood gas analyzers (RAPIDLab 1265; Siemens, Tarrytown, NY). Both instruments use direct ion-selective electrode technology, albeit with different sodium ionophores (basic metabolic panel: methyl monensin, blood gas: glass). We questioned if the basic metabolic panel hypernatremia represents artefactual pseudohypernatremia.
DESIGN
We added vecuronium bromide or esmolol hydrochloric acid to pooled plasma samples and compared sodium values measured by both methodologies. We queried sodium results from the electronic medical records of patients admitted at Children's Hospital of Philadelphia from 2016 to 2018 and received vecuronium and/or esmolol infusion treatment during their admissions.
SETTING
PICU of a quaternary, free-standing children's hospital.
PATIENTS
Children admitted to the hospital who received vecuronium and/or esmolol infusion.
MEASUREMENTS AND MAIN RESULTS
Sodium was measured in pooled plasma samples by basic metabolic panel and blood gas methodologies after adding vecuronium bromide or esmolol hydrochloric acid, leading to a dose-response increase in basic metabolic panel sodium measurements. A repeated measures regression analysis of our electronic medical records showed that the vecuronium dose predicted the Δ sodium (basic metabolic panel-blood gas) sodium within 12 hours of the vecuronium administration ( < 0.0018). Esmolol showed a similar trend ( = 0.13). This occurred primarily in central line samples with continuous vecuronium or esmolol infusions.
CONCLUSIONS
Vecuronium and esmolol can falsely elevate direct ion-selective electrode sodium measurements on Vitros chemistry analyzers. Unexpectedly high sodium measurements in patients receiving vecuronium and/or esmolol infusions should be further investigated with an alternate sample type (i.e., peripheral blood) or measurement methodology (i.e., blood gas) to guide treatment decisions.
PubMed: 32166293
DOI: 10.1097/CCE.0000000000000073 -
BMC Cardiovascular Disorders Dec 2022Cardiac arrest (CA) is caused by a nonshockable rhythm with a low success rate of return of spontaneous circulation (ROSC) and a poor prognosis. This study intended to...
OBJECTIVE
Cardiac arrest (CA) is caused by a nonshockable rhythm with a low success rate of return of spontaneous circulation (ROSC) and a poor prognosis. This study intended to establish a nonshockable rhythm CA model caused by asphyxia.
MATERIALS AND METHODS
Healthy adult male Wistar rats were injected with vecuronium bromide to induce CA. After the CA duration reached the target time point, cardiopulmonary resuscitation was performed. The survival status and neurological and cardiac function were evaluated after ROSC. Brain histopathology, including hematoxylin staining, Nissl staining and Terminal dUTP nick-end labeling (TUNEL) staining, was performed to evaluate the surviving cells and apoptotic cells. Apoptosis-related proteins after ROSC for 72 h were analyzed by western blot.
RESULTS
CA was successfully induced in all animals. The time for the three groups of animals to PEA was 320 ± 22 s in the CA-8 group, 322 ± 28 s in the CA-12 group and 320 ± 18 s in the CA-15 group. The time to asystole was 436 ± 54 s in the CA-8 group, 438 ± 62 s in the CA-12 group and 433 ± 56 s in the CA-15 group. The NDS of rats in the CA group was significantly decreased after ROSC for 24 h. The NDS in the CA-15 group was 5-16 points, while it was 58-67 points and 15-43 points in the CA-8 and CA-12 groups, respectively. The cardiac function of animals in the CA group was impaired after ROSC, and the ejection fraction, fractional shortening, stroke volume and cardiac output, were all significantly decreased. Brain histopathology showed that the number of surviving neurons was decreased, and the number of apoptotic cells was increased in CA group, the longer the CA duration, the more apoptotic cells increased. The expression of the proapoptotic protein Bax and the apoptotic executive protein caspase3 in the hippocampus of CA rats was significantly increased, while the expression of the antiapoptotic protein Bcl-2 was significantly reduced.
CONCLUSIONS
The use of vecuronium can successfully induce CA caused by nonshockable rhythm in rats, which will help to further study the pathophysiological changes after CA by nonshockable rhythm.
Topics: Rats; Male; Animals; Asphyxia; Rats, Wistar; Heart Arrest; Cardiopulmonary Resuscitation; Brain
PubMed: 36581829
DOI: 10.1186/s12872-022-02996-w