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The Journal of International Medical... Aug 2022To conduct a meta-analysis to compare different dosing scalars of sugammadex in a morbidly obese population for reversal of neuromuscular blockade (NMB). (Meta-Analysis)
Meta-Analysis
Appropriate dosing of sugammadex for reversal of rocuronium-/vecuronium-induced muscle relaxation in morbidly obese patients: a meta-analysis of randomized controlled trials.
OBJECTIVE
To conduct a meta-analysis to compare different dosing scalars of sugammadex in a morbidly obese population for reversal of neuromuscular blockade (NMB).
METHODS
PubMed®, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar were searched for relevant randomized controlled trials (RCTs) comparing lower-dose sugammadex using ideal body weight (IBW) or corrected body weight (CBW) as dosing scalars with standard-dose sugammadex based on total body weight (TBW) among morbidly obese people after NMB. Mean difference with SD was used to estimate the results.
RESULTS
The analysis included five RCT with a total of 444 morbidly obese patients. The reversal time was significantly longer in patients receiving sugammadex with dosing scalar based on IBW than in patients receiving sugammadex with dosing scalar based on TBW (mean difference 55.77 s, 95% confidence interval [CI] 32.01, 79.53 s), but it was not significantly different between patients receiving sugammadex with dosing scalars based on CBW versus TBW (mean difference 2.28 s, 95% CI -10.34, 14.89 s).
CONCLUSION
Compared with standard-dose sugammadex based on TBW, lower-dose sugammadex based on IBW had 56 s longer reversal time whereas lower-dose sugammadex based on CBW had a comparable reversal time.
Topics: Androstanols; Body Weight; Humans; Muscle Relaxation; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Obesity; Randomized Controlled Trials as Topic; Rocuronium; Sugammadex; Vecuronium Bromide; gamma-Cyclodextrins
PubMed: 35983671
DOI: 10.1177/03000605221116760 -
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 -
PloS One 2022Drug-induced QT prolongation is one of the most common side effects of drug use and can cause fatal outcomes such as sudden cardiac arrest. This study adopts the...
Drug-induced QT prolongation is one of the most common side effects of drug use and can cause fatal outcomes such as sudden cardiac arrest. This study adopts the data-driven approach to assess the QT prolongation risk of all the frequently used drugs in a tertiary teaching hospital using both standard 12-lead ECGs and intensive care unit (ICU) continuous ECGs. We used the standard 12-lead ECG results (n = 1,040,752) measured in the hospital during 1994-2019 and the continuous ECG results (n = 4,835) extracted from the ICU's patient-monitoring devices during 2016-2019. Based on the drug prescription frequency, 167 drugs were analyzed using 12-lead ECG data under the case-control study design and 60 using continuous ECG data under the retrospective cohort study design. Whereas the case-control study yielded the odds ratio, the cohort study generated the hazard ratio for each candidate drug. Further, we observed the possibility of inducing QT prolongation in 38 drugs in the 12-lead ECG analysis and 7 drugs in the continuous ECG analysis. The seven drugs (vasopressin, vecuronium, midazolam, levetiracetam, ipratropium bromide, nifedipine, and chlorpheniramine) that showed a significantly higher risk of QT prolongation in the continuous ECG analysis were also identified in the 12-lead ECG data analysis. The use of two different ECG sources enabled us to confidently assess drug-induced QT prolongation risk in clinical practice. In this study, seven drugs showed QT prolongation risk in both study designs.
Topics: Adult; Aged; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Female; Humans; Intensive Care Units; Long QT Syndrome; Male; Middle Aged; Retrospective Studies
PubMed: 35100302
DOI: 10.1371/journal.pone.0263117 -
Hospital Pharmacy Oct 2021Sugammadex (Bridion) was approved by the US Food and Drug Administration (FDA) in December 2015 for the reversal of neuromuscular block (NMB) induced by rocuronium and...
Sugammadex (Bridion) was approved by the US Food and Drug Administration (FDA) in December 2015 for the reversal of neuromuscular block (NMB) induced by rocuronium and vecuronium bromide in adults undergoing surgery and approved for use in both adults and children in the European Union in 2008. Sugammadex use in children has been reported in the United States, but to what extent is not clear. The aim was to describe the utilization pattern of NMB agents and factors associated with the use of reversal agents (neostigmine and sugammadex) in US children. Cross-sectional study of children with exposure to NMB agents between 2015 and 2017 in the Cerner Health Facts database, which is an electronic health record (EHR) database across 600 facilities in the United States. Logistic regression estimated factors associated with the use of sugammadex vs neostigmine. A total of 27 094 pediatric clinical encounters were exposed to neuromuscular blocking agents (NMBAs), in which 21 845 were exposed to rocuronium (76%), vecuronium (18%), or both (6%). Among children with exposure to rocuronium and vecuronium, the use of sugammadex was 1.7% in 2016 and 7.6% in 2017. The multivariable logistic model suggested that children who were older (age 12-17 years vs 0-1 year; odds ratio [OR] 1.96; 95% confidence interval [CI], 1.36-2.83), Hispanic or Latino ethnicity and other ethnicities (vs non-Hispanic or Latino; OR 2.03 and 1.56; 95% CI, 1.55-2.67 and 1.15-2.13, respectively), in teaching facilities (OR 1.26; 95% CI, 1.00-1.59), or admitted through emergency departments (OR 1.65; 95% CI, 1.06-2.58) were independently more likely to receive sugammadex than neostigmine after controlling for other covariates. In Cerner Health Facts database 2015 to 2017, among children, rocuronium was more commonly used than vecuronium, and sugammadex use was observed since 2016. Sugammadex and neostigmine users varied by demographic, clinical, and site-level characteristics.
PubMed: 34720141
DOI: 10.1177/0018578720918332 -
BMC Anesthesiology Oct 2021The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from... (Randomized Controlled Trial)
Randomized Controlled Trial
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/m, 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 .
Topics: Aged; Bradycardia; Cholinergic Agents; Double-Blind Method; Female; Glycopyrrolate; Humans; Male; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Tachycardia; Vecuronium Bromide
PubMed: 34711192
DOI: 10.1186/s12871-021-01477-5 -
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 -
Drug Design, Development and Therapy 2021High intra-abdominal pressure induced by artificial pneumoperitoneum can obviously impair respiratory and circulatory functions and has a negative effect on the... (Review)
Review
High intra-abdominal pressure induced by artificial pneumoperitoneum can obviously impair respiratory and circulatory functions and has a negative effect on the prognosis of patients undergoing conventional and robot-assisted laparoscopic surgery. The application of deep neuromuscular blockade during the operation is reported to lower the intra-abdominal pressure and improve patients' outcome. However, concern lies in the risks of postoperative residual muscular paralysis with the use of deep neuromuscular blockade. Sugammadex, a specific antagonist for aminosteroids muscle relaxants, can effectively and rapidly reverse rocuronium and vecuronium induced neuromuscular blockade of different depths. Thus, sugammadex allows the ability to safeguard the application of deep neuromuscular blockade in laparoscopic operations and helps to alleviate the adverse complications associated with pneumoperitoneum. Here, we review the application of deep neuromuscular blockade in different laparoscopic surgeries and discuss the benefits and possible risks of sugammadex administration in the reversal of deep neuromuscular blockade in these operations.
Topics: Humans; Laparoscopy; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Robotic Surgical Procedures; Rocuronium; Sugammadex; Vecuronium Bromide
PubMed: 34548781
DOI: 10.2147/DDDT.S328682 -
Clinical and Translational Science Jan 2022Residual shallow neuromuscular block (NMB) is potentially harmful and contributes to critical respiratory events. Evidence for the optimal dose of sugammadex required to...
Residual shallow neuromuscular block (NMB) is potentially harmful and contributes to critical respiratory events. Evidence for the optimal dose of sugammadex required to reverse vecuronium-induced shallow NMB is scarce. The aims of the present study were to find suitable doses of sugammadex and neostigmine to reverse a residual vecuronium-induced NMB from a time of flight (TOF) ratio of 0.3-0.9 and evaluate their safety and efficacy. In total, 121 patients aged 18-65 years were randomly assigned to 11 groups to receive placebo, sugammadex (doses of 0.125, 0.25, 0.5, 1.0, or 2.0 mg/kg), or neostigmine (doses of 10, 25, 40, 55, or 70 μg/kg). The reversal time of sugammadex and neostigmine to antagonize a vecuronium-induced shallow residual NMB (i.e., TOF ratio of 0.3) and related adverse reactions were recorded. Several statistical models were tested to find an appropriate statistical model to explore the suitable doses of sugammadex and neostigmine required to reverse a residual vecuronium-induced NMB. Based on a monoexponential model with the response variable on a logarithmic scale, sugammadex 0.56 mg/kg may be sufficient to reverse vecuronium-induced shallow residual NMB at a TOF ratio of 0.3 under anesthesia maintained with propofol. Neostigmine may not provide prompt and satisfactory antagonism as sugammadex, even in shallow NMB.
Topics: Delayed Emergence from Anesthesia; Dose-Response Relationship, Drug; Humans; Neostigmine; Sugammadex; Vecuronium Bromide
PubMed: 34435439
DOI: 10.1111/cts.13143 -
Biochemical Pharmacology Oct 2021Endogenous neurosteroids and their synthetic analogues-neuroactive steroids-have been found to bind to muscarinic acetylcholine receptors and allosterically modulate...
Endogenous neurosteroids and their synthetic analogues-neuroactive steroids-have been found to bind to muscarinic acetylcholine receptors and allosterically modulate acetylcholine binding and function. Using radioligand binding experiments we investigated their binding mode. We show that neuroactive steroids bind to two binding sites on muscarinic receptors. Their affinity for the high-affinity binding site is about 100 nM. Their affinity for the low-affinity binding site is about 10 µM. The high-affinity binding occurs at the same site as binding of steroid-based WIN-compounds that is different from the common allosteric binding site for alcuronium or gallamine that is located between the second and third extracellular loop of the receptor. This binding site is also different from the allosteric binding site for the structurally related aminosteroid-based myorelaxants pancuronium and rapacuronium. Membrane cholesterol competes with neurosteroids/neuroactive steroids binding to both high- and low-affinity binding site, indicating that both sites are oriented towards the cell membrane..
Topics: Allosteric Regulation; Androstanes; Androstenes; Animals; Benzimidazoles; Binding Sites; CHO Cells; Cholesterol; Cricetinae; Cricetulus; Gallamine Triethiodide; Humans; Neuromuscular Nondepolarizing Agents; Neurosteroids; Receptors, Muscarinic; Vecuronium Bromide
PubMed: 34324870
DOI: 10.1016/j.bcp.2021.114699 -
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