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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 -
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 -
Clinical and Translational Science Mar 2021This analysis of a published study (NCT03346070) evaluated the pharmacokinetics (PKs) of sugammadex dosed by actual body weight (ABW) or ideal body weight (IBW) for... (Randomized Controlled Trial)
Randomized Controlled Trial
This analysis of a published study (NCT03346070) evaluated the pharmacokinetics (PKs) of sugammadex dosed by actual body weight (ABW) or ideal body weight (IBW) for reversal of moderate or deep neuromuscular block (M-NMB or D-NMB) in adults with morbid obesity. Adults with body mass index ≥ 40 kg/m , ABW ≥ 100 kg, and American Society of Anesthesiologists (ASA) Class 3 were stratified by NMB agent (rocuronium or vecuronium) and randomized 1:1:1:1:1 to (i) M-NMB, sugammadex 2 mg/kg ABW; (ii) M-NMB, sugammadex 2 mg/kg IBW; (iii) M-NMB, neostigmine 5 mg + glycopyrrolate 1 mg; (iv) D-NMB, sugammadex 4 mg/kg ABW; and (v) D-NMB, sugammadex 4 mg/kg IBW. Plasma samples for sugammadex quantification were collected predose, 2, 5, 15, 60, and 120 minutes, and 4, 6 hours postdose. Natural log PK parameters were analyzed using linear fixed effect model with treatment, mode (ABW and IBW), and mode by treatment interaction as fixed terms. The sugammadex PK profile showed rapid distribution followed by monophasic decline consistent with a two-compartment model examined by dose and mode. Absolute sugammadex exposures were ~ 50% higher in the ABW vs. IBW group; dose-independent parameters (clearance and volume of distribution) and terminal half-life remained constant. Sugammadex PK parameter values increased in dose-dependent, linear manner following dosing by ABW or IBW, such that PK continues to be predictive across the clinical dose range. In conjunction with previously published results showing faster recovery with ABW vs. IBW dosing across NMB agent and depth of NMB, these PK findings continue to support dosing by ABW in patients with morbid obesity irrespective of depth of NMB.
Topics: Adult; Body Mass Index; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Humans; Ideal Body Weight; Male; Middle Aged; Models, Biological; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Obesity, Morbid; Rocuronium; Sugammadex; Vecuronium Bromide
PubMed: 33278332
DOI: 10.1111/cts.12941 -
Anales de Pediatria Oct 2020It has been suggested that neuromuscular blockade (NMB) affects the capacity of bispectral index (BIS) monitoring to measure consciousness in sedated children. Our aim... (Observational Study)
Observational Study
INTRODUCTION
It has been suggested that neuromuscular blockade (NMB) affects the capacity of bispectral index (BIS) monitoring to measure consciousness in sedated children. Our aim was to analyse the impact of NMB on BIS values in critically ill children.
METHODS
We conducted a prospective observational study of children monitored with a BIS system that received a continuous infusion of vecuronium. We analysed data on clinical, diagnostic and haemodynamic variables, sedatives, analgesics, muscle relaxants, and BIS parameters. We compared BIS parameters before the use of a muscle relaxant, during its administration, before its discontinuation and for the 24h following the end of the infusion.
RESULTS
The analysis included 35 patients (median age, 30 months). The most common diagnosis was heart disease (85%). The most frequent indication for initiation of NMB was low cardiac output (45%), followed by adaptation to mechanical ventilation (20%). Neuromuscular blockade did not produce a significant change in BIS values. We found a decrease was observed in electromyography (EMG) values at 6h (34.9±9.4 vs 31.2±7; P=.008) and 12h after initiation of NMB (34.9±9.4 vs 28.6±4.8; P =.006). We observed a small significant increase in BIS after discontinuation of NMB (from 42.7±11 to 48.4±14.5, P=.001), and 6 and 12h later (51.3±16.6; P=.015). There were no differences in the doses of sedatives or analgesics except for fentanyl, of which the dose was lowered after discontinuation of vecuronium.
CONCLUSION
Continuous NMB produces small changes on BIS values that are not clinically significant and therefore does not interfere with BIS consciousness monitoring in critically ill children.
Topics: Child, Preschool; Consciousness Monitors; Critical Illness; Electromyography; Humans; Neuromuscular Blockade; Vecuronium Bromide
PubMed: 34092338
DOI: 10.1016/j.anpede.2019.07.003 -
The Journal of International Medical... Jun 2020This study aimed to investigate the effects of neuromuscular blocking drugs on the viability of human umbilical vein endothelial cells (HUVECs) and to investigate...
OBJECTIVE
This study aimed to investigate the effects of neuromuscular blocking drugs on the viability of human umbilical vein endothelial cells (HUVECs) and to investigate whether they cause vascular complications due to cell proliferation.
METHODS
HUVECs were cultivated with 5% CO at 37°C in a predefined supplemented medium over 7 days until confluence of cell monolayers. Assays were conducted during the exponential growth phase. Suxamethonium chloride, vecuronium bromide, atracurium besylate, and rocuronium bromide were used at concentrations of 10, 10, and 10 M in proliferation assays in which cells were incubated with these drugs for 24, 48, and 72 hours. All experiments were performed in four replicates.
RESULTS
The neuromuscular blocking drugs used had comparable effects on the survivability of HUVECs. Overall, no significant difference was observed in the survivability of HUVECs in a dose-dependent manner after exposure to the study drugs. However, some significant differences in the viability of HUVECs were found among the different measurement times.
CONCLUSIONS
The findings of the current study support the safety of the studied neuromuscular blocking drugs in clinically relevant concentrations regarding their effects on endothelial cell proliferation.
Topics: Androstanols; Atracurium; Human Umbilical Vein Endothelial Cells; Humans; Neuromuscular Blockade; Pharmaceutical Preparations; Vecuronium Bromide
PubMed: 32588688
DOI: 10.1177/0300060520910888 -
Heliyon Mar 2020Neuromuscular blocker agent namely; Vecuronium bromide (VEC) was quantified through developing a simple reversed phase liquid chromatographic (RP-LC) method, in drug...
Neuromuscular blocker agent namely; Vecuronium bromide (VEC) was quantified through developing a simple reversed phase liquid chromatographic (RP-LC) method, in drug substance and in drug product. The proposed method could quantify VEC in the presence of its degradation products produced from exposing VEC to different stress conditions as recommended by the International Conference on harmonization (ICH) guidelines. Acidic (2M HCl), basic (2MNaOH) hydrolysis, oxidation (3% HO), photolysis (UV light at 254nm), and thermal (135 °C) degradation were estimated by exposing the drug substances to different stress conditions. The separation of the drug from its degradation products was successfully conducted on Tracer Extrasil CN (150 × 4.6mm; 5μm) column using O-phosphoric acid (pH6; 0.05M)-acetonitrile (50:50v/v) as mobile phase. The detection and quantification was done with UV detection at210nm.The validation data were found to be acceptable over a concentration range10-120 μg/ml. The limit of quantification (LOQ) and detection (LOD) were 8.10 and 2.67 μg/ml, respectively. The proposed method met all criteria for validation in accordance with the International Conference on harmonization (ICH) guidelines. The presented work monitored the degradation profile for VEC under various stress conditions and provided a simple LC method for its routine analysis. The structures of the forced degradation products had been described in details using the MS data and the possible degradation pathways were outlined. Besides, the results obtained from the developed method compared statistically with that of the official method indicting high accuracy and precision.
PubMed: 32195388
DOI: 10.1016/j.heliyon.2020.e03530 -
Antioxidants (Basel, Switzerland) Jan 2020Hypothermia enhances outcomes of patients after resuscitation after cardiac arrest (CA). However, the underlying mechanism is not fully understood. In this study, we...
Hypothermia enhances outcomes of patients after resuscitation after cardiac arrest (CA). However, the underlying mechanism is not fully understood. In this study, we investigated effects of hypothermic therapy on neuronal damage/death, microglial activation, and changes of endogenous antioxidants in the anterior horn in the lumbar spinal cord in a rat model of asphyxial CA (ACA). A total of 77 adult male Sprague-Dawley rats were randomized into five groups: normal, sham ACA plus (+) normothermia, ACA + normothermia, sham ACA + hypothermia, and ACA + hypothermia. ACA was induced for 5 min by injecting vecuronium bromide. Therapeutic hypothermia was applied after return of spontaneous circulation (ROSC) via rapid cooling with isopropyl alcohol wipes, which was maintained at 33 ± 0.5 °C for 4 h. Normothermia groups were maintained at 37 ± 0.2 °C for 4 h. Neuronal protection, microgliosis, oxidative stress, and changes of endogenous antioxidants were evaluated at 12 h, 1 day, and 2 days after ROSC following ACA. ACA resulted in neuronal damage from 12 h after ROSC and evoked obvious degeneration/loss of spinal neurons in the ventral horn at 1 day after ACA, showing motor deficit of the hind limb. In addition, ACA resulted in a gradual increase in microgliosis with time after ACA. Therapeutic hypothermia significantly reduced neuronal loss and attenuated hind limb dysfunction, showing that hypothermia significantly attenuated microgliosis. Furthermore, hypothermia significantly suppressed ACA-induced increases of superoxide anion production and 8-hydroxyguanine expression, and significantly increased superoxide dismutase 1 (SOD1), SOD2, catalase, and glutathione peroxidase. Taken together, hypothermic therapy was found to have a substantial impact on changes in ACA-induced microglia activation, oxidative stress factors, and antioxidant enzymes in the ventral horn of the lumbar spinal cord, which closely correlate with neuronal protection and neurological performance after ACA.
PubMed: 31906329
DOI: 10.3390/antiox9010038 -
BMC Anesthesiology Feb 2021This randomized, double-blind trial evaluated sugammadex-mediated recovery time from rocuronium- or vecuronium-induced moderate (M-) or deep (D-) neuromuscular block in... (Comparative Study)
Comparative Study Randomized Controlled Trial
Actual versus ideal body weight dosing of sugammadex in morbidly obese patients offers faster reversal of rocuronium- or vecuronium-induced deep or moderate neuromuscular block: a randomized clinical trial.
BACKGROUND
This randomized, double-blind trial evaluated sugammadex-mediated recovery time from rocuronium- or vecuronium-induced moderate (M-) or deep (D-) neuromuscular block in morbidly obese adults dosed by actual (ABW) or ideal body weight (IBW).
METHODS
Adults with BMI ≥40 kg/m were randomized to 1 of 5 groups: M-neuromuscular block, sugammadex 2 mg/kg ABW; M-neuromuscular block, sugammadex 2 mg/kg IBW; M-neuromuscular block, neostigmine 5 mg, and glycopyrrolate 1 mg; D-neuromuscular block, sugammadex 4 mg/kg ABW; or D-neuromuscular block, sugammadex 4 mg/kg IBW. Supramaximal train of four (TOF) stimulation of the ulnar nerve (TOF-watch SX®) monitored recovery. Primary endpoint was time to TOF ratio ≥ 0.9 for ABW and IBW groups pooled across neuromuscular blocking agent (NMBA)/blocking depth, analyzed by log-rank test stratified for agent and depth. Prespecified safety outcomes included treatment-emergent bradycardia, tachycardia, and other arrhythmias, and adjudicated hypersensitivity and anaphylaxis.
RESULTS
Of 207 patients randomized, 188 received treatment (28% male, BMI 47 ± 5.1 kg/m, age 48 ± 13 years). Recovery was 1.5 min faster with ABW vs IBW dosing. The sugammadex 2 mg/kg groups recovered 9-fold faster [time 0.11-fold, 95% CI 0.08 to 0.14] than the neostigmine group. ABW (5.3%) and IBW (2.7%) groups had similar incidences of recovery time > 10 min (95% CI of difference: - 4.8 to 11.0%); 84% for neostigmine group. Re-curarization occurred in one patient each in the 2 mg/kg IBW and neostigmine groups. Prespecified safety outcomes occurred with similar incidences.
CONCLUSIONS
ABW-based sugammadex dosing yields faster reversal without re-curarization, supporting ABW-based sugammadex dosing in the morbidly obese, irrespective of the depth of neuromuscular block or NMBA used.
TRIAL REGISTRATION
Registered on November 17, 2017, at ClinicalTrials.gov under number NCT03346070 .
Topics: Anesthesia Recovery Period; Body Weight; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Ideal Body Weight; Male; Middle Aged; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Obesity, Morbid; Rocuronium; Sugammadex; Time Factors; Vecuronium Bromide
PubMed: 33639839
DOI: 10.1186/s12871-021-01278-w -
Oncology Letters Feb 2021Anaesthetics have been implicated to influence cancer cells and progression. Similarly, crosstalk between cancer cells and stromal components within the microenvironment...
Anaesthetics have been implicated to influence cancer cells and progression. Similarly, crosstalk between cancer cells and stromal components within the microenvironment is also an important factor driving progression. Stromal cell-derived factor-1 (SDF-1) and hepatocyte growth factor (HGF) are key chemokines/cytokines produced by fibroblasts which have been established as influential factors in cancer progression. The present study explored the capacity of anaesthetics to influence the expression of these key molecules in fibroblasts. The anaesthetics rocuronium bromide (RB), vecuronium bromide (VB), suxamethonium chloride CRS (SCC), dexmedetomidine hydrochloride (DH) and lidocaine were used to treat MRC-5 fibroblasts over a range of concentrations. Following treatment, transcript expression of SDF-1 and HGF was quantified using quantitative PCR. Treatment of MRC-5 cells with RB brought about a reduction of SDF-1 expression which was found to be significant in the 45 µg/ml treatment group. Treatment with the other anaesthetics brought about some alterations in SDF-1 expression but these were not found to be statistically significant. Treatment with the tested anaesthetics did not have any significant effect on HGF transcript expression within MRC-5 cells, although again some alterations were observed. The results indicated that anaesthetics may have an impact on the fibroblast component of the tumour microenvironment, potentially influencing SDF-1 and HGF expression which in turn could influence tumour progression.
PubMed: 33552259
DOI: 10.3892/ol.2020.12401 -
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