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American Journal of Therapeutics 2017A growing proportion of patients undergoing surgical procedures are obese, providing anesthesiologists with numerous challenges for patient management. The current...
A growing proportion of patients undergoing surgical procedures are obese, providing anesthesiologists with numerous challenges for patient management. The current pooled analysis evaluated recovery times following sugammadex reversal of neuromuscular blockade by body mass index (BMI) in general, and in particular, in patients with BMIs ≥30 kg/m (defined as obese) and <30 kg/m (defined as non-obese). Data were pooled from 27 trials evaluating recommended sugammadex doses for reversal of moderate [reappearance of the second twitch of the train-of-four (TOF); sugammadex 2 mg/kg] or deep (1-2 post-tetanic counts or 15 minutes after rocuronium; sugammadex 4 mg/kg) rocuronium- or vecuronium-induced neuromuscular blockade. All doses of sugammadex were administered based on actual body weight. The recovery time from sugammadex administration to a TOF ratio ≥0.9 was the primary efficacy variable in all individual studies and in the pooled analysis. This analysis comprised a total of 1418 adult patients treated with sugammadex; 267 (18.8%) of these patients had a BMI ≥30 kg/m. The average time to recovery of the TOF ratio to 0.9 was 1.9 minutes for rocuronium-induced blockade and 3.0 minutes for vecuronium-induced blockade. No clinically relevant correlation was observed between BMI and recovery time. The recommended sugammadex doses based on actual body weight provide rapid recovery from neuromuscular blockade in both obese and non-obese patients; no dose adjustments are required in the obese patient.
Topics: Adult; Aged; Aged, 80 and over; Androstanols; Anesthesia Recovery Period; Body Mass Index; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Neuromuscular Blockade; Neuromuscular Monitoring; Neuromuscular Nondepolarizing Agents; Obesity; Rocuronium; Sugammadex; Surgical Procedures, Operative; Time Factors; Vecuronium Bromide; Young Adult; gamma-Cyclodextrins
PubMed: 26398716
DOI: 10.1097/MJT.0000000000000305 -
Veterinary Anaesthesia and Analgesia May 2015To compare baseline cardiovascular function in anesthetised pigs using either pancuronium or vecuronium as a neuromuscular blocker. (Clinical Trial)
Clinical Trial
OBJECTIVE
To compare baseline cardiovascular function in anesthetised pigs using either pancuronium or vecuronium as a neuromuscular blocker.
STUDY DESIGN
Retrospective, non-randomized comparison.
ANIMALS
Norwegian Land Race pigs (Sus scrofa domesticus) weighing mean 42 ± SD 3 kg.
METHODS
One hundred and sixteen animals from four different research protocols premedicated with identical doses of ketamine, diazepam, atropine and isoflurane, and anaesthetised with pentobarbital, fentanyl, midazolam and N(2)O were arranged into three uniform groups with respect to neuromuscular blocking agent: pancuronium bolus of 0.063 mg kg(-1) followed by 0.14 mg kg(-1) hour(-1) (n = 54), low-dose vecuronium 0.4 mg kg(-1) /0.2 mg kg(-1) hour(-1) (n = 29) and high-dose vecuronium 0.6 mg kg(-1) /0.3 mg kg(-1) hour(-1) (n = 33).
RESULTS
The majority of cardiovascular parameters demonstrated no significant differences between groups. For heart rate, there was an overall group difference, p = 0.036. Dromotropy was low in the pancuronium group, with an increased normalised PR-interval compared to the high-dose vecuronium group, median 0.200 interquartile range (0.190, 0.215) versus 0.182 (0.166, 0.199), p < 0.05. Left ventricular compliance was increased in pancuronium-treated animals, demonstrated as a reduction in the nonlinear end-diastolic pressure volume relationship β compared to both vecuronium groups, 0.021 (0.016, 0.025) versus 0.031 (0.025, 0.046) and 0.031 (0.022, 0.048), p < 0.05. The linear end-diastolic pressure volume relationship EDPVR(lin) was reduced as well in the pancuronium group, compared to the low-dose vecuronium group, 0.131 (0.116, 0.169) versus 0.181 (0.148, 0.247), p < 0.05.
CONCLUSIONS
There are only minor haemodynamic differences when using pancuronium compared to vecuronium in the fentanyl-pentobarbital-midazolam-N(2)O anesthetised domestic pigs. Furthermore, increasing doses of vecuronium have minimal haemodynamic effects.
CLINICAL RELEVANCE
Experimental studies in pigs using either pancuronium or vecuronium as a neuromuscular blocking agent are comparable with regard to cardiac and haemodynamic performance.
Topics: Animals; Dose-Response Relationship, Drug; Hemodynamics; Neuromuscular Nondepolarizing Agents; Pancuronium; Swine; Vecuronium Bromide
PubMed: 24985148
DOI: 10.1111/vaa.12198 -
Food and Chemical Toxicology : An... Jun 2019Prenatal nicotine exposure (PNE) could induce ovarian dysplasia in offspring. This study aimed to confirm its intrauterine origin and explore a programming mechanism of...
Decreased levels of H3K9ac and H3K27ac in the promotor region of ovarian P450 aromatase mediated low estradiol synthesis in female offspring rats induced by prenatal nicotine exposure as well as in human granulosa cells after nicotine treatment.
Prenatal nicotine exposure (PNE) could induce ovarian dysplasia in offspring. This study aimed to confirm its intrauterine origin and explore a programming mechanism of ovarian dysplasia caused by PNE. Pregnant Wistar rats were injected subcutaneously with nicotine (2 mg/kg.d) from gestation day (GD) 9 to GD20. Serum of female offspring was obtained for hormone assays and ovarian tissues were collected. The results showed that PNE impaired ovarian development, and inhibited estradiol production and cytochrome P450 aromatase (P450arom) expression before and after birth. Moreover, the nicotinic acetylcholine receptors (nAChRs) expression was increased in utero, while histone 3 lysine 9 acetylation (H3K9ac) and H3K27ac levels in the P450arom promoter region were decreased persistently in PNE group before and after birth. In vitro, nicotine decreased P450arom expression and estradiol production in human granulosa cell line KGN. Furthermore, nicotine treatment up-regulated nAChRα6 and α9 expression and down-regulated the H3K9ac and H3K27ac levels of the P450arom promoter region. Non-specific nAChRs inhibitor vecuronium bromide reversed these effects. These results suggest that PNE could induce ovarian dysplasia and inhibit estradiol synthesis in the female offspring rats, which was related to the decreased H3K9ac and H3K27ac levels in the promotor region of the P450arom via the nAChRs.
Topics: Acetylation; Animals; Aromatase; Estradiol; Female; Granulosa Cells; Histones; Humans; Maternal Exposure; Nicotine; Ovary; Pregnancy; Promoter Regions, Genetic; Rats; Rats, Wistar; Receptors, Nicotinic
PubMed: 30959089
DOI: 10.1016/j.fct.2019.03.055 -
Tugging force: A new objective index for evaluating acute changes in neuromuscular function in mice.Journal of Pharmacological and... 2015Many agents, including muscle relaxants, influence neuromuscular function. Although in vitro and in situ measurement systems of skeletal muscular contractility have been...
INTRODUCTION
Many agents, including muscle relaxants, influence neuromuscular function. Although in vitro and in situ measurement systems of skeletal muscular contractility have been developed and in use for years, no convenient device and parameter are available to examine the time course of the acute effects of such agents on neuromuscular function in conscious mice.
METHODS
We created a two-compartment device consisting of a transparent, wide, acrylic chamber with a foot shock grid, and an attached, opaque narrow tunnel to measure neuromuscular performance. A mouse placed into the wide chamber, quickly enters the narrow tunnel. We attached a string to the tail of the mouse to measure the developed tugging force when the mouse entered the narrow tunnel.
RESULTS
After administering the muscle relaxants suxamethonium, vecuronium, and pancuronium, the peak tugging force decreased maximally at 3 or 5 min after administration, and recovered within 20 min. These responses to the muscle relaxants were dose-dependent.
DISCUSSION
Tugging force is an objective and reproducible parameter for examining the time course of an acute change in neuromuscular function.
Topics: Animals; Biomechanical Phenomena; Male; Mice, Inbred ICR; Muscle Strength; Muscle Strength Dynamometer; Muscle, Skeletal; Neuromuscular Agents; Neuromuscular Diseases
PubMed: 26190647
DOI: 10.1016/j.vascn.2015.07.003 -
American Journal of Respiratory and... Apr 2018The neuromuscular blocking agent cisatracurium may improve mortality for patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Other neuromuscular... (Comparative Study)
Comparative Study Observational Study
RATIONALE
The neuromuscular blocking agent cisatracurium may improve mortality for patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Other neuromuscular blocking agents, such as vecuronium, are commonly used and have different mechanisms of action, side effects, cost, and availability in the setting of drug shortages.
OBJECTIVES
To determine whether cisatracurium is associated with improved outcomes when compared with vecuronium in patients at risk for and with ARDS.
METHODS
Using a nationally representative database, patients who were admitted to the ICU with a diagnosis of ARDS or an ARDS risk factor, received mechanical ventilation, and were treated with a continuous infusion of neuromuscular blocking agent for at least 2 days within 2 days of hospital admission were included. Patients were stratified into two groups: those who received cisatracurium or vecuronium. Propensity matching was used to balance both patient- and hospital-specific factors. Outcomes included hospital mortality, duration of mechanical ventilation, ICU and hospital duration, and discharge location.
MEASUREMENTS AND MAIN RESULTS
Propensity matching successfully balanced all covariates for 3,802 patients (1,901 per group). There was no significant difference in mortality (odds ratio, 0.932; P = 0.40) or hospital days (-0.66 d; P = 0.411) between groups. However, patients treated with cisatracurium had fewer ventilator days (-1.01 d; P = 0.005) and ICU days (-0.98 d; P = 0.028) but were equally likely to be discharged home (odds ratio, 1.19; P = 0.056).
CONCLUSIONS
When compared with vecuronium, cisatracurium was not associated with a difference in mortality but was associated with improvements in other clinically important outcomes. These data suggest that cisatracurium may be the preferred neuromuscular blocking agent for patients at risk for and with ARDS.
Topics: Atracurium; Cohort Studies; Female; Humans; Male; Middle Aged; Neuromuscular Blocking Agents; Respiratory Distress Syndrome; Risk; Treatment Outcome; Vecuronium Bromide
PubMed: 29241014
DOI: 10.1164/rccm.201706-1132OC -
Acta Parasitologica Jun 2018The neuroimmunoregulation of inflammation has been well characterized. Entamoeba histolytica provokes an inflammatory response in the host in which macrophages and...
The neuroimmunoregulation of inflammation has been well characterized. Entamoeba histolytica provokes an inflammatory response in the host in which macrophages and neutrophils are the first line of defense. The aim of this study was to analyze the effect of the 220 kDa lectin of Entamoeba histolytica on stimulation of human macrophages and neutrophils, especially the secretion of cytokines and the relation of these to neurotransmitters. Human cells were interacted with L220, epinephrine, nicotine, esmolol and vecuronium bromide. The concentrations of IL-1β, IFN-γ, TNF-α and IL-10 were determined by ELISA at, 4 h of interaction. L220 has a cytokine stimulating function of macrophages and neutrophils for secretion of IL-1β, and IL-10 only by macrophages, which was modulated by the effect of vecuronium on cholinergic receptors in this immune cells.
Topics: Adolescent; Cytokines; Entamoeba histolytica; Epinephrine; Humans; Lectins; Macrophage Activation; Macrophages; Neurotransmitter Agents; Neutrophil Activation; Neutrophils; Nicotine; Protozoan Proteins; Vecuronium Bromide; Young Adult
PubMed: 29654688
DOI: 10.1515/ap-2018-0031 -
Journal of Clinical Monitoring and... Jun 2019There is a growing body of literature documenting the use of deep neuromuscular block (NMB) during surgery. Traditional definitions of depth of NMB rely on train-of-four... (Observational Study)
Observational Study
There is a growing body of literature documenting the use of deep neuromuscular block (NMB) during surgery. Traditional definitions of depth of NMB rely on train-of-four assessment, which can be less reliable in retrospective studies. The goal of our study was to investigate the real-world practice pattern of dosing of neuromuscular blocking agents (NMBA), utilizing the amount of NMBA used during the course of a case, adjusted for patient weight and case duration, as a surrogate measure of depth of NMB. We also aimed to identify case factors associated with larger NMBA doses. In this retrospective observational analysis of our anesthesia information management system, we analyzed all general endotracheal anesthesia cases from 2012 to 2015 in which an intermediate-acting NMBA was used. Cases using a long-acting NMBA or only succinylcholine were excluded. The expected duration of the case was calculated based on the cumulative dose of NMB used, normalized to the patient's ideal body weight and the ED95 of the drug. If the expected duration of the case was greater than the actual case duration documented in the case record, it was classified as higher dosing (HD). If the expected duration was equal to or less than the actual duration, it was considered predicted dosing (PD). Categorical comparisons between HD and PD groups were made for various patient, procedural, and provider factors. 72,684 cases were included in the final analysis, of which 46,358, or 64% of cases, used HD. Cases with patients who were morbidly obese, younger than 65 years, and who were lower ASA Physical Status classification (I or II) used more HD as opposed to PD. Cases that were non-open, used total intravenous anesthesia, emergent cases, or used non-rapid sequence anesthesia induction had higher rates of HD than their matched counterparts. All results were statistically significant. HD was more common in cases that documented train-of-four and used the reversal agent neostigmine. Approximately two-thirds of general endotracheal anesthesia cases using an intermediate-acting NMBA used HD. Cases with higher rates of HD may be those that are traditionally technically complex or emergent, would benefit from greater paralysis, or do not use adjunctive medications for muscle relaxation. Age greater than 65 years was shown to have lower rates of HD, likely due to provider awareness of age-related changes in pharmacokinetics and pharmacodynamics. Intraoperative monitoring and NMB antagonism with neostigmine were used more frequently with HD.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Androstanols; Anesthesia, General; Atracurium; Body Mass Index; Electronic Health Records; Female; Humans; Male; Middle Aged; Monitoring, Intraoperative; Muscle Relaxation; Neostigmine; Neuromuscular Blockade; Neuromuscular Blocking Agents; Neuromuscular Nondepolarizing Agents; Prevalence; Retrospective Studies; Rocuronium; Sugammadex; Vecuronium Bromide; Young Adult
PubMed: 30094585
DOI: 10.1007/s10877-018-0186-4 -
Journal of Biomedical Optics Jan 2017The purpose of this study is to evaluate the suitability of five different anesthetic protocols (isoflurane, isoflurane–xylazine, pentobarbital, ketamine–xylazine,...
The purpose of this study is to evaluate the suitability of five different anesthetic protocols (isoflurane, isoflurane–xylazine, pentobarbital, ketamine–xylazine, and ketamine–xylazine–vecuronium) for functional blood flow imaging in the rat eye. Total retinal blood flow was measured at a series of time points using an ultrahigh-speed Doppler OCT system. Additionally, each anesthetic protocol was qualitatively evaluated according to the following criteria: (1) time-stability of blood flow, (2) overall rate of blood flow, (3) ocular immobilization, and (4) simplicity. We observed that different anesthetic protocols produced markedly different blood flows. Different anesthetic protocols also varied with respect to the four evaluated criteria. These findings suggest that the choice of anesthetic protocol should be carefully considered when designing and interpreting functional blood flow studies in the rat eye.
Topics: Anesthesia; Anesthetics; Animals; Eye; Isoflurane; Ketamine; Pentobarbital; Rats; Regional Blood Flow; Retina; Vecuronium Bromide; Xylazine
PubMed: 28056146
DOI: 10.1117/1.JBO.22.1.016005 -
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 -
Experimental and Clinical... Aug 2017Organ transplant in humans is an established therapy for a variety of end-stage organ diseases. However, due to organ shortages and lack of donors, the need for...
OBJECTIVES
Organ transplant in humans is an established therapy for a variety of end-stage organ diseases. However, due to organ shortages and lack of donors, the need for xenotransplant has gradually increased. Xenotransplantation has great potential to solve many of the problems facing organ transplantation. Pigs are being developed as xenogeneic organ donors for use in humans. In this study, we propose a novel and simple method for tracheal intubation in a swine model using neuromuscular blocking agents and laryngeal mask airway.
MATERIALS AND METHODS
Eight Yorkshire pigs were used for the 2 separate experiments, which were conducted 1 week apart. In the first experiment, an anesthesiologist with no previous comparable experience performed endotracheal intubation of pigs. One week later, using the same pig, a second experiment was performed by an experienced anesthesiologist. Anesthesia was induced with intramuscular injection of a mixture of 1 mg/kg xylazine (Rompun, Bayer Korea Ltd., Seoul, Korea) and 7 mg/kg Zoletil (a mixture of tiletamine hydrochloride and zolazepam hydro-chloride, Virbac Laboratory, Carros, France). The laryngeal mask was then placed, and 0.15 mg/kg vecuronium bromide was injected intravenously. Tracheal intubation was attempted after mask removal. The duration and number of intubation attempts were recorded, and the degree of intubation difficulty was scored.
RESULTS
In all cases, the laryngeal mask was easily inserted, and endotracheal intubation was successfully completed. Oxygen saturation did not fall below 95%, and there were no hypoxemia episodes. Degree of intubation difficulty and duration were not significantly different between the 2 anesthesiologists.
CONCLUSIONS
Tracheal intubation in our swine model was successfully performed using neuromuscular blocking agents and laryngeal masks without resulting in hypoxemia, with even anesthesiologists who are unfamiliar with endotracheal intubation of pigs easily able to do so using our protocol. Therefore, our protocol will enable all investigators to perform successful tracheal intubation in swine models.
Topics: Anesthesia, General; Animals; Female; Injections, Intravenous; Intubation, Intratracheal; Laryngeal Masks; Learning Curve; Male; Models, Animal; Neuromuscular Blocking Agents; Sus scrofa; Time Factors; Transplantation, Heterologous; Vecuronium Bromide
PubMed: 28447930
DOI: 10.6002/ect.2016.0123