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https://www.readbyqxmd.com/read/29324898/the-etomidate-analog-et-26-hcl-retains-superior-myocardial-performance-comparisons-with-etomidate-in-vivo-and-in-vitro
#1
Xingxing Liu, Haibo Song, Jun Yang, Cheng Zhou, Yi Kang, Linghui Yang, Jin Liu, Wensheng Zhang
OBJECTIVE: (R)-2-methoxyethyl1-(1-phenylethyl)-1H-imidazole-5-carboxylate hydrochloride (ET-26 HCl) is a novel etomidate analogue. The purpose of this study was to characterize whether ET-26 HCl could retain the superior myocardial performance of etomidate in vivo and in vitro. METHODS: In vivo, the influence of ET-26 HCl and etomidate on the cardiac function of dogs was confirmed using echocardiography and electrocardiogram. In vitro, a Langendorff preparation was used to examine direct myocardial performance in isolated rat hearts, and a whole-cell patch-clamp technique was used to study effects on the human ether-a-go-go-related gene (hERG) channel...
2018: PloS One
https://www.readbyqxmd.com/read/29320738/trapping-of-syntaxin1a-in-presynaptic-nanoclusters-by-a-clinically-relevant-general-anesthetic
#2
Adekunle T Bademosi, James Steeves, Shanker Karunanithi, Oressia H Zalucki, Rachel S Gormal, Shu Liu, Elsa Lauwers, Patrik Verstreken, Victor Anggono, Frederic A Meunier, Bruno van Swinderen
Propofol is the most commonly used general anesthetic in humans. Our understanding of its mechanism of action has focused on its capacity to potentiate inhibitory systems in the brain. However, it is unknown whether other neural mechanisms are involved in general anesthesia. Here, we demonstrate that the synaptic release machinery is also a target. Using single-particle tracking photoactivation localization microscopy, we show that clinically relevant concentrations of propofol and etomidate restrict syntaxin1A mobility on the plasma membrane, whereas non-anesthetic analogs produce the opposite effect and increase syntaxin1A mobility...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29280926/critical-illness-related-corticosteroid-insufficiency-in-cardiogenic-shock-patients-prevalence-and-prognostic-role
#3
Nicolas Ducrocq, Pascal Biferi, Nicolas Girerd, Ichraq Latar, Simon Lemoine, Pierre Perez, Carine Thivilier, Bruno Levy, Antoine Kimmoun
BACKGROUND: Cardiogenic shock shares with septic shock common hemodynamic features, inflammatory patterns and most likely similar complications such as critical illness-related corticosteroid insufficiency. The aim of this study was to evaluate the prevalence of critical illness-related corticosteroid insufficiency in cardiogenic shock patients and to secondarily assess its prognostic value on 90-day mortality. METHODS: A single-centre prospective observational study conducted over a three-year period and including all patients with cardiogenic shock...
December 26, 2017: Shock
https://www.readbyqxmd.com/read/29233853/variation-in-pediatric-procedural-sedations-across-children-s-hospital-emergency-departments
#4
Andrew F Miller, Michael C Monuteaux, Florence T Bourgeois, Eric W Fleegler
OBJECTIVES: Describe the trends in pediatric sedation use over time and determine variation in use of procedural sedation across children's hospital emergency departments (EDs). METHODS: We analyzed ED data from 35 hospitals within the Pediatric Health Information System for patients <19 years old who received sedation medications and were discharged from 2009 to 2014. Patients with chronic comorbidities or undergoing intubation were excluded. We determined frequency and trends in use of sedation and compared these between EDs...
January 2018: Hospital Pediatrics
https://www.readbyqxmd.com/read/29214627/a-12-month-descriptive-analysis-of-emergency-intubations-at-brooke-army-medical-center-a-national-emergency-airway-registry-study
#5
Michael D April, Steven G Schauer, Calvin A Brown Rd, Patrick C Ng, Jessie Fernandez, Andrea E Fantegrossi, Joseph K Maddry, Shane Summers, Daniel J Sessions, Robert M Barnwell, Mark Antonacci
Emergency airway management is a critical skill for military healthcare providers. Our goal was to describe the Emergency Department (ED) intubations at Brooke Army Medical Center (BAMC) over a 12-month period. MATERIAL AND METHODS: Physicians performing endotracheal intubations in the BAMC ED complete data collection forms for each intubation event as part of the National Emergency Airway Registry, including patient demographics, intubation techniques, success and failure rates, adverse events, and patient disposition...
October 2017: U.S. Army Medical Department Journal
https://www.readbyqxmd.com/read/29210709/alphaxalone-binds-in-inner-transmembrane-%C3%AE-%C3%AE-interfaces-of-%C3%AE-1%C3%AE-3%C3%AE-2-%C3%AE-aminobutyric-acid-type-a-receptors
#6
Alexis M Ziemba, Andrea Szabo, David W Pierce, Marian Haburcak, Alex T Stern, Anahita Nourmahnad, Elizabeth S Halpin, Stuart A Forman
BACKGROUND: Neurosteroids like alphaxalone are potent anxiolytics, anticonvulsants, amnestics, and sedative-hypnotics, with effects linked to enhancement of γ-aminobutyric acid type A (GABAA) receptor gating in the central nervous system. Data locating neurosteroid binding sites on synaptic αβγ GABAA receptors are sparse and inconsistent. Some evidence points to outer transmembrane β-α interfacial pockets, near sites that bind the anesthetics etomidate and propofol. Other evidence suggests that steroids bind more intracellularly in β-α interfaces...
November 28, 2017: Anesthesiology
https://www.readbyqxmd.com/read/29209787/-different-levels-of-experience-with-anesthetic-agents-of-german-emergency-physicians-results-of-an-online-survey
#7
A Luckscheiter, M Fischer, W Zink
BACKGROUND AND OBJECTIVE: In 2015 practice management guidelines on prehospital emergency anesthesia in adults were published in Germany. The aim of the present study was to evaluate whether emergency physicians follow these guidelines in daily practice and to assess their level of experience with the use of anesthetic agents. MATERIAL AND METHODS: In an online survey the way of induction of preclinical anesthesia (including preoxygenation time and applied monitoring techniques) was assessed with the help of virtual scenarios based on the guidelines...
December 5, 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/29203576/dimethoxy-etomidate-a-non-hypnotic-etomidate-analog-that-potently-inhibits-steroidogenesis
#8
Megan McGrath, Celena Ma, Douglas Raines
Cushing's syndrome is characterized by the overproduction of adrenocortical steroids. Steroidogenesis inhibitors are mainstays of medical therapy for Cushing's syndrome; unfortunately, adverse side effects and treatment failures are common with currently available drugs. The general anesthetic induction agent etomidate is among the most potent inhibitors of adrenocortical steroidogenesis. However, its use as a treatment for Cushing's syndrome is complicated by its sedative-hypnotic activity and ability to produce myoclonus, central nervous system actions thought to be mediated by the GABAA receptor...
December 4, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29161398/role-of-gabaa-receptor-subtypes-in-the-behavioural-effects-of-intravenous-general-anaesthetics
#9
C J Weir, S J Mitchell, J J Lambert
Since the introduction of general anaesthetics into clinical practice, researchers have been mystified as to how these chemically disparate drugs act to produce their dramatic effects on central nervous system function and behaviour. Scientific advances, particularly during the last 25 years, have now begun to reveal the molecular mechanisms underpinning their behavioural effects. For certain i.v. general anaesthetics, such as etomidate and propofol, a persuasive case can now be made that the GABAA receptor, a major inhibitory receptor in the mammalian central nervous system, is an important target...
December 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29157794/analgosedative-interventions-after-rapid-sequence-intubation-with-rocuronium-in-the-emergency-department
#10
Emily Kilber, Daniel H Jarrell, John C Sakles, Christopher J Edwards, Asad E Patanwala
OBJECTIVES: The use of etomidate and rocuronium for rapid sequence intubation (RSI) results in a duration of paralysis that exceeds the duration of sedation. The primary objective of this study was to compare the number of analgosedative (AGS) interventions early versus late post-RSI, with this drug combination. The secondary objective was to descriptively assess time to first AGS intervention. METHODS: This was a retrospective cohort study conducted in an academic ED in the United States between January 2015 and June 2016...
November 14, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29155148/functional-properties-and-mechanism-of-action-of-pptq-an-allosteric-agonist-and-low-nanomolar-positive-allosteric-modulator-at-gabaa-receptors
#11
Nawid Madjroh, Emma Rie Olander, Christoffer Bundgaard, Pella Cecilia Söderhielm, Anders A Jensen
The former sedative-hypnotic and recreational drug methaqualone (Quaalude) is a moderately potent, non-selective positive allosteric modulator (PAM) at GABAA receptors (GABAARs) (Hammer et al., 2015). In the present study, we have identified a novel methaqualone analog, 2-phenyl-3-(p-tolyl)quinazolin-4(3H)-one (PPTQ), in a screening of 67 analogs at five αβ2γ2S GABAAR subtypes and delineated its functional properties and mechanism of action at wild-type and mutant GABAARs expressed in Xenopus laevis oocytes by two-electrode voltage clamp electrophysiology...
January 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29149702/an-hplc-tandem-mass-spectrometry-for-quantification-of-et-26-hcl-and-its-major-metabolite-in-plasma-and-application-to-a-pharmacokinetic-study-in-rats
#12
Xu Chen, Wensheng Zhang, Sandy Rios, Miriam B Morkos, Xiaoli Ye, Gen Li, Xuehua Jiang, Zhijun Wang, Ling Wang
ET-26-HCl is a new analog of etomidate, a short-acting anesthetic drug, with less adrenal cortex inhibition. The pharmacokinetics of ET-26-HCl in rats needs to be determined for future clinical trials in human subjects. In order to facilitate the pharmacokinetic study, a liquid chromatography based tandem mass spectrometric (HPLC-MS/MS) method was developed and validated for quantification of ET-26-HCl and its major metabolite, ET-26-acid. These two compounds and gabapentin (internal standard) were extracted using a protein precipitation method with methanol and detected by Multiple Reaction Monitoring of m/z transition of 275...
November 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29147790/-etomidate-for-intravenous-induction-of-anaesthesia
#13
C Dumps, D Bolkenius, E Halbeck
The pharmacological and historical knowledge about the currently available intravenous induction hypnotics form the basis for the daily work of anesthetists. Side effects of using hypnotic induction agents must be anticipated and adequately treated. Decades of experience with using intravenous induction hypnotics have led to theoretical requirements for an ideal narcotic agent with a best possible side effect profile. In the absence of this optimal hypnotic induction agent, a careful selection of one or a combination of narcotic drugs is necessary to meet the needs of the respective risk constellation of the patient...
November 16, 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/29064259/the-cardiovascular-implications-of-sedatives-in-the-cardiac-intensive-care-unit
#14
Sammy Zakaria, Helaine J Kwong, Jonathan E Sevransky, Marlene S Williams, Nisha Chandra-Strobos
Patients admitted to the cardiac intensive care unit frequently develop multi-organ system dysfunction associated with their cardiac disease. In many cases, invasive mechanical ventilation is required, which often necessitates sedation for patient-ventilator synchrony, reduction of work of breathing, and patient comfort. In this paper, we describe the use of common sedatives available in the endotracheally intubated critically ill patient and emphasize the clinical and cardiovascular effects. We review γ-aminobutyric acid agonists such as etomidate, benzodiazepines, and propofol, the centrally acting α2-agonist dexmedetomidine, and the N-methyl-D-aspartate receptor antagonist ketamine...
February 1, 2017: European Heart Journal. Acute Cardiovascular Care
https://www.readbyqxmd.com/read/29046518/pretreatment-with-oxycodone-simultaneously-reduces-etomidate-induced-myoclonus-and-rocuronium-induced-withdrawal-movements-during-rapid-sequence-induction
#15
Xiaoxia An, Caixia Li, Zayd Sahebally, Xiaohong Wen, Bing Zhao, Xiangming Fang
BACKGROUND Etomidate and rocuronium are often paired in rapid-sequence anesthesia induction. However, the effect of pretreatment with oxycodone on myoclonic and withdrawal movements has not been previously investigated. The aim of this study was to evaluate the effects of oxycodone on the incidence and severity of etomidate-induced myoclonus and rocuronium-induced nociceptive withdrawal movements during rapid-sequence anesthesia induction. MATERIAL AND METHODS We randomly divided 120 patients into the saline group (group S) and the oxycodone group (group O) (n=60 in each group)...
October 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29039138/the-role-of-gaba-receptor-agonists-in-anesthesia-and-sedation
#16
REVIEW
Janette Brohan, Basavana G Goudra
GABA (γ-aminobutyric acid) receptors, of which there are two types, are involved in inhibitory synapses within the central nervous system. The GABAA receptor (GABAAR) has a central role in modern anesthesia and sedation practice, which is evident from the high proportion of agents that target the GABAAR. Many GABAAR agonists are used in anesthesia practice and sedation, including propofol, etomidate, methohexital, thiopental, isoflurane, sevoflurane, and desflurane. There are advantages and disadvantages to each GABAAR agonist currently in clinical use...
October 2017: CNS Drugs
https://www.readbyqxmd.com/read/28974833/comparing-hemodynamic-responses-to-diazepam-propofol-and-etomidate-during-anesthesia-induction-in-patients-with-left-ventricular-dysfunction-undergoing-coronary-artery-bypass-graft-surgery-a-double-blind-randomized-clinical-trial
#17
Aria Soleimani, Neda Heidari, Mohammad Reza Habibi, Farshad Hasanzadeh Kiabi, Mohammad Khademloo, Amir Emami Zeydi, Fatemeh Bozorg Sohrabi
BACKGROUND: Anesthesia induction is often accompanied by a period of hemodynamic instability, which could be deleterious in patients with coronary artery disease (CAD) and left ventricular dysfunction undergoing coronary artery bypass graft (CABG) surgery. The aim of this study was to compare the hemodynamic responses to propofol, etomidate, and diazepam following anesthesia induction, laryngoscopy and intubation in CABG surgery patients with low ejection fraction (EF). METHODS: A double-blind randomized, clinical study was performed on 150 patients with CAD and left ventricular dysfunction (EF≤35%) scheduled for elective CABG surgery with Cardiopulmonary bypass (CPB)...
June 2017: Medical Archives
https://www.readbyqxmd.com/read/28971155/comparison-of-ketamine-propofol-ketofol-and-etomidate-fentanyl-etofen-combinations-for-procedural-sedation-and-analgesia-in-the-emergency-department-an-observational-study
#18
Erkman Sanri, Sinan Karacabey, Haldun Akoglu, Bora Kaya, Ozlem Guneysel
OBJECTIVES: The primary aim of this study was to report the vital signs, hemodynamic parameters and pain scores of the patients who have received procedural sedation and analgesia (PSA) with either ketofol (combination of ketamine and propofol) or etofen (combination of etomidate and fentanyl) and compare the proportion of patients with airway or respiratory adverse events (AEs) requiring an intervention and calculate the relative risk of AEs with each combination. METHODS: This study is a prospective observational study with survey analysis...
September 2017: Turkish Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28890850/minimum-infusion-rate-and-adrenocortical-function-after-continuous-infusion-of-the-novel-etomidate-analog-et-26-hcl-in-rats
#19
Junli Jiang, Bin Wang, Zhaoqiong Zhu, Jun Yang, Jin Liu, Wensheng Zhang
BACKGROUND: Because etomidate induces prolonged adrenal suppression, even following a single bolus, its use as an infused anesthetic is limited. Our previous study indicated that a single administration of the novel etomidate analog methoxyethyletomidate hydrochloride (ET-26-HCl) shows little suppression of adrenocortical function. The aims of the present study were to (1) determine the minimum infusion rate of ET-26-HCl and compare it with those for etomidate and cyclopropyl-methoxycarbonylmetomidate (CPMM), a rapidly metabolized etomidate analog that is currently in clinical trials and (2) to evaluate adrenocortical function after a continuous infusion of ET-26-HCl as part of a broader study investigating whether this etomidate analog is suitable for long infusion in the maintenance of anesthesia...
2017: PeerJ
https://www.readbyqxmd.com/read/28883852/a-randomized-clinical-trial-comparing-hemodynamic-responses-to-ketamine-propofol-combination-ketofol-versus-etomidate-during-anesthesia-induction-in-patients-with-left-ventricular-dysfunction-undergoing-coronary-artery-bypass-graft-surgery
#20
Afshin Gholipour Baradari, Abbas Alipour, Mohammad Reza Habibi, Sajedeh Rashidaei, Amir Emami Zeydi
INTRODUCTION: Anesthesia induction is often accompanied by a period of hemodynamic instability, which could be a significant problem in patients with compromised ventricular function. The aim of this study is to compare the hemodynamic responses to etomidate versus a combination of ketamine and propofol (ketofol) for anesthetic induction in patients with left ventricular dysfunction undergoing coronary artery bypass graft (CABG) surgery. MATERIAL AND METHODS: In a double-blind randomized clinical study, a total of 84 patients with ischemic left ventricular dysfunction (EF < 40%) were randomly assigned to two groups (A and B)...
August 2017: Archives of Medical Science: AMS
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