Blocking Agents Research Articles

Adequacy of Reversal of Neuromuscular Blockade with or without Train-of-Four Monitoring: A Randomised Controlled Study

Introduction: Adequate reversal of Neuromuscular Blockade (NMB) is essential when using muscle relaxants to avoid residual paralysis postoperatively. Reversal can be achieved using clinical parameters or, alternatively, by Train-of-Four (TOF) monitoring. Aim: To evaluate the adequacy of successful NMB reversal using clinical parameters-based endpoints compared to using TOF monitoring. Materials and Methods: The hospital-based randomised controlled study conducted in the Department of Anaesthesiology, SDM Medical College, Dharwad, Karnataka, India for a peroid of two years from November 2019 to December 2021. Consisted of 120 subjects divided into two groups: Group-C (Clinical parameters) and group T (TOF monitoring), aged 18-60 years of either sex with American Soceity of Anaesthesiologists (ASA) physical status I and II, undergoing elective surgery under general anaesthesia requiring intubation. Extubation was achieved in group C using clinical parameters like return of spontaneous respiratory efforts, adequate Tidal Volume (TV) (≥5 mL/kg), obeying simple commands, absence of excessive secretions, and in group T using TOF monitoring. The t-test was used to compare the difference between the groups. The Chi-square test was done for contingency data. A p-value of less than or equal to 0.05 (p-value≤0.05) indicates statistical significance. Results: In the study, both group C and group T were comparable in terms of age {(41.15±10.23 years, 41.03±11.9 years) p-value=0.95}, sex (m/f) {(46.6%/53.3% and 63.3%/36.6%) p-value=0.06}, and Basal Metabolic Index (BMI) {≤25=59.1%, 25- 30=33.3%, ≥30=7.5%, p-value=0.57}, respectively. Five patients in group C had residual paralysis, whereas none in group T. Reversal-extubation time in minutes (min) in group C {5.9± 2.2, 5.4 (2-15.2)} and group T {6.6± 1.9, 6.24 (3.3-12.2)} (p-value=0.07), TOF value at the time of extubation in group C {72.1±11.6, 72 (41-91)}, group T {72.75±2.74, 72 (70-79)} (p-value=0.69). TOF value after 10 minutes of extubation in group C {92.5±7.1, 94 (66- 100)} and group T {95.6±2.7, 96 (90-100)} (p-value=0.006). Conclusion: The TOF monitoring is better compared to a clinical parameters-based reversal strategy in reducing the incidence of residual paralysis and resulting complications whenever Neuromuscular Blocking Agents (NMBAs) are used. Hence, it is desirable to use Neuromuscular Monitoring with the use of NMBAs.

Evaluation of the vasorelaxant effect of Sugammadex on the arterial smooth muscle in rats

Although NMBAs (Neuro Muscular Blocking Agents) have been used for a long time, postoperative residual curarization is still a significant problem. Nowadays, an agent named Sugammadex is used for the reversal of curarization. It has been presented as a safer agent than its predecessor, neostigmine. The main purpose of this study is to investigate the effects of Sugammadex on rat thoracic aorta and enlighten the mechanism of action and potential benefits in surgical operations with general anesthesia. Twenty Wistar albino rats were used for the experiments. Thoracic aorta segments have been removed and mounted to the organ bath. Contraction and relaxation responses were presented as a percentage of phenylephrine (3x10-5 M) contraction. After recording contractile responses of Sugammadex (10-8-10-4 M), relaxation responses of Sugammadex (10-8-10-4 M) have been recorded both in the presence and absence of L-NAME (3x10-5 M) (Potent Nitric Oxide Sentase Inhibitor). Finally, relaxation responses of sugammadex-rocuronium have been recorded. Sugammadex caused slightly noticeable and concentration-dependent contraction on isolated thoracic aorta strips. Sugammadex also caused potent and concentration-dependent relaxation on isolated rat thoracic aorta. The relaxation response caused by Sugammadex has been diminished significantly in the presence of L-NAME. Administration of rocuronium with Sugammadex did cause neither relaxation nor any additional contractile effect on isolated rat thoracic aorta strips. Sugammadex is a promising agent in reversing rocuronium-induced neuromuscular block. Although the adverse effects of this agent are not studied in detail, it seems Sugammadex is safer than neostigmine. The side effects of anesthetic agents are one of the main problems of surgical procedures, including neurosurgery, gynecology, and obstetrics. Especially acute hypotension may be fatal in neurosurgery and gynecological operations. Sugammadex should be used carefully in adjusted and individualized doses to avoid hypotension-related adverse effects.

The differences in the adrenergic receptors of proximal urethra between sexes.

The bladder and urethra work as a physiologically functional unit to facilitate continence in the storage and voiding phase. Sex differences have been found in the urethral contraction in response to α-adrenergic receptor activation. This study aimed to investigate the role of adrenergic receptors in the proximal urethra of male and female mice. Urinary bladder and proximal urethral smooth muscle (USM) samples from male and female C57BL/6 mice were isolated and mounted in an organ bath. Acetylcholine-induced contraction of the urinary bladder was compared in male and female mice. Phenylephrine and norepinephrine (NE) induced little contraction at a lower concentration, but a relaxing phase of female proximal USM was observed at a higher concentration. This contraction profile was inhibited by NG-nitro-L-arginine, lidocaine, and capsaicin. In addition, the NE-induced contraction was greater in the incubation of propranolol than that of L-NNA or lidocaine. These results suggested that the β-adrenoceptor may be the dominant receptor of female proximal USM, and the activity of calcitonin gene-related peptide sensory nerves and nitrergic nerves may pose an anti-contraction effect on the proximal urethra in female mice. β-adrenoceptor may be the dominant receptor of female proximal USM. The use of β-adrenergic receptor blocker agents might have the potential for the treatment of female voiding dysfunction.

Highly Water-Soluble Cucurbit[8]uril Derivative as a Broad-Spectrum Neuromuscular Block Reversal Agent.

Broad-spectrum agents for the reversal of residual curarization induced by neuromuscular blocking agents are of great significance. Here, we report a highly water-soluble cucurbit[8]uril (CB[8]) derivative as a broad-spectrum neuromuscular block reversal agent induced by both benzylisquinolinium and aminosteroid neuromuscular block agents by the supramolecular sequestration strategy. The UV/Vis competition titration assays suggest the high binding affinity of the CB[8] derivative toward both benzylisquinolinium-type cisatracurium besylate and aminosteroid-type rocuronium, vecuronium, and pancuronium, at the level of 107 M-1. In vivo studies demonstrate that the administration of the CB[8] derivative could significantly accelerate the recovery time compared to the placebo or neostigmine groups. The reversal activity of the CB[8] derivative is comparable to or higher than that of clinically approved sugammadex. Acute toxicity evaluations reveal that the CB[8]-derivative displays outstanding biocompatibility, with the maximum tolerance dose as high as 960 mg kg-1.

Abstract 12406: Sglt2i Dapagliflozin Associated to Berberine Reduces Cardiac Cell Apoptosis and Necrosis During Exposure to Her-2 Blocking Agents Through Induction of Pampk and Reduction of Inflammasome, Il-6, Methylglyoxal and Leukotrienes-B4 Levels

Introduction: Trastuzumab has improved the prognosis in patients with HER2-positive breast cancer, but it can induce left ventricular dysfunction with reduced ejection fraction or HF during treatment. Dapagliflozin is a SGLT2i with cardio-renal benefits. In DAPA-HF trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin decreased the risk of worsening HF events and cardiovascular death in patients with HF and reduced ejection fraction. Berberine is a nutraceutical compound characterized by multiple metabolic effects in patients with/without cardiovascular diseases. Hypothesis: To investigate on the potential cardioprotective properties of Berberine associated to SGLT2i Dapagliflozin against HER-2 blocking agent-induced cardiotoxicity Methods: Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of trastuzumab (200 nM) alone or co-incubated with Berberine (200 mM) or Dapagliflozin (50 nM) or both in combination for 48 h. After the incubation period, we performed the following tests: cell viability, apoptosis, expression of NLRP3 inflammasome, methylglyoxal and leukotrienes-B4. Expression of pAMPK was analyzed through western blot. Moreover, quantification of IL-6 was performed Results: Berberine and Dapagliflozin increased significantly the cell viability of cardiomyocytes exposed to Trastuzumab. When combined, Berberine and Dapagliflozin increased synergistically cell viability of cardiac cells (p<0.001 vs Trastuzumab). Cell apoptosis was reduced of 32.5, 41.8 and 72.7% for berberine, dapagliflozin and both combined (vs trastuzumab group). Methylglyoxal,a marker of AGEs, was strongly reduced compared to untreated cells. Western blot analysis clearly demonstrate that pAMPK was induced by berberine and Dapagliflozin, improving mitochondrial metabolism. No significant changes in Leukotriene B4 expression were seen. Intracellular levels of IL-6 were reduced of 46.3, 62.7 and 86.3% for berberine, dapagliflozin and both combined (vs trastuzumab group). Conclusions: Berberine and Dapagliflozin in combination induces an anti-inflammatory phenotype to myocardial cells through the reduction of biomarkers involved in heart failure and apoptosis.

A Comparison of Midazolam and Propofol for Deep Sedation in Patients with Acute Respiratory Distress Syndrome Requiring Neuromuscular Blocking Agents

Purpose: The optimal agent for deep sedation in patients undergoing continuous infusion (CI) neuromuscular blocking agent (NMBA) use for acute respiratory distress syndrome (ARDS) is unknown. The purpose of this study is to compare the efficacy and safety of propofol and midazolam in ARDS patients requiring CI NMBA. Methods: A multi-center, retrospective study was performed in mechanically ventilated (MV) adult patients requiring CI NMBA for management of ARDS. The primary outcome was to compare the time to liberation from MV in patients sedated with propofol vs midazolam. Results: In the 109 patients included, there was no difference in time to MV liberation with propofol as compared to midazolam (121 hr [Interquartile range (IQR) 67 195] vs 98 hr [IQR 48, 292], P = .72). Median time to sedation emergence after NMBA discontinuation was shorter in patients receiving propofol (12.9 hr [IQR 19.8, 72.5] vs 31.5 hr [IQR 6.4, 34.6], P < .01). There were no significant differences in time to therapeutic sedation, ICU stay, mortality, and adverse events. Conclusion: Propofol may be an effective and safe alternative to midazolam for patients undergoing CI NMBA for ARDS. Additionally, patients receiving propofol may have a quicker return to light sedation after NMBA discontinuation.

S952 The Effect of Commonly Prescribed Renin-Angiotensin-Aldosterone System Blocking Agents on the 5- and 10-year Disease Course of Crohn’s Disease Patients With Hypertension

S952 The Effect of Commonly Prescribed Renin-Angiotensin-Aldosterone System Blocking Agents on the 5- and 10-year Disease Course of Crohn’s Disease Patients With Hypertension

A Peculiar Wide Complex Tachycardia During Flecainide Treatment.

A Peculiar Wide Complex Tachycardia During Flecainide Treatment.

The Nonirritating Concentrations of Neuromuscular Blocking Agents and Related Compounds

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. 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. 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. 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). 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.

A randomized controlled trial of intravenous magnesium sulphate as an adjunct to standard therapy in atrial fibrillation

Abstract Background Magnesium sulphate (MgSO4) has been proven as an analgesic, neuromuscular blocker agent, and treatment of acute asthma. Objective The study aimed to assess the safety and efficacy of magnesium sulphate infusion for the treatment of patients with atrial fibrillation. Methods A prospective, randomized, double-blind, placebo-controlled study was conducted on 55 atrial fibrillation patients at the Emergency Department. The treatment group consisting of 41 patients received 20 mEq (2.5 g, 10 mmol) magnesium sulphate over a 20-minute period, followed by 20 mEq (2.5 g, 10 mmol) over a 2-hour period intravenously in addition to the standard treatment, and the control group consisting of 14 patients received placebo with a standard treatment. ECG was repeated and monitored upto 24 hours after the infusion. Results 41 patients received magnesium sulphate and 14 patients received a placebo. The heart rate was 127 bpm – 210 bpm at the presentation to the emergency department and it was reached &lt;100bpm in 70%(n=31) patients after 150 minutes of MgSO4 infusion. Two patients attained a heart rate of &lt;100bpm in Placebo infusion. In the treatment group, 65% of subjects attained normal sinus rhythm at the end of 24 hours of infusion. Magnesium sulphate was more likely than placebo to achieve a heart rate of &lt;100bpm and more likely to convert to sinus rhythm. ECG report reverted to normal in 74.5% in the treatment group and 25.5 % in the Placebo group within 24 hours. The patients in the treatment group stay a mean of 2.25 days in ICU, while the patients in the Placebo group stayed 4.25 days in ICU. Seven patients in the treatment group had minor side effects like flushing, headache, and nausea, which came to normal after 48hrs. Conclusions Magnesium sulphate has been shown a better efficacy to control the heart rate and conversion to sinus rhythm when used along with the standard management of Atrial fibrillation.

A Meta-analysis of the Hospital Stay and Hypoxic Effect of Neuromuscular Blocking Agent Antagonists, Sugammadex and Neostigmine

A Meta-analysis of the Hospital Stay and Hypoxic Effect of Neuromuscular Blocking Agent Antagonists, Sugammadex and Neostigmine

Utilization of SUMO Tag and Freeze-thawing Method for a High-level Expression and Solubilization of Recombinant Human Angiotensinconverting Enzyme 2 (rhACE2) Protein in E. coli

SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a receptor for entering the host cells. Production of the ACE2 molecule is important because of its potency to use as a blocker and therapeutic agent against SARS-CoV-2 for the prophylaxis and treatment of COVID-19. The recombinant human ACE2 (rhACE2) is prone to form an inclusion body when expressed in the bacterial cells. We used the SUMO tag fused to the rhACE2 molecule to increase the expression level and solubility of the fusion protein. Afterward, the freeze-thawing method plus 2 M urea solubilized aggregated proteins. Subsequently, the affinity of solubilized rhACE2 to the receptor binding domain (RBD) of the SARS-CoV-2 spike was assayed by ELISA and SPR methods. SUMO protein succeeded in increasing the expression level but not solubilization of the fusion protein. The freeze-thawing method could solubilize and recover the aggregated fusion proteins significantly. Also, ELISA and SPR assays confirmed the interaction between solubilized rhACE2 and RBD with high affinity. The SUMO tag and freeze- Conclusion: The SUMO tag and freeze-thawing method would be utilized for high-level expression and solubilization of recombinant rhACE2 protein.

Development of a UV visible spectrophotometric method for simultaneous estimation of Ranolazine and Metoprolol

Ranolazine being Na+ channel blocker agent, decreases the chances of angina attacks. Metoprolol exerts specific β1 blocking effect which results into decreased cardiac contractility and heart Rate (1). Ultimately reduces oxygen demand of heart. Metoprolol enhances the pharmacological activity of Ranolazine so the combination gives better therapeutic activity (2).&#x0D; There is no UV visible method present for the simultaneous estimation of Ranolazine and Metoprolol. To formulate and evaluate such a formulation involving mentioned drugs this simultaneous equation method was developed using 0.1 N HCl as a solvent. Chosen wavelengths were 272 nm and 242 nm for Ranolazine and Metoprolol Succinate respectively. Linearity range was seen to be 7.5 to 40 ppm for Ranolazine and 1 to 5 ppm for Metoprolol. Recovery studies and Validation were successfully performed according to ICH guidelines. This method can be applied for any formulation consisting mentioned drugs without interference of other excipients.&#x0D; Keywords: UV visible spectrophotometry, Simultaneous estimation, Ranolazine, Metoprolol succinate, Analytical Method development, Angina Pectoris

The 2021–2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD

BackgroundDiabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021–2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice.MethodsThe methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease].ResultsThe extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75–89% of agreement; IIb 50–74% of agreement, and III, when most of the panelist recommends against a defined treatment.ConclusionsTo prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin–angiotensin–aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients’ survival.

Association between choice of reversal agent for neuromuscular block and postoperative pulmonary complications in patients at increased risk undergoing non-emergency surgery: STIL-STRONGER, a multicentre matched cohort study

BackgroundPostoperative pulmonary complications are a source of morbidity after major surgery. In patients at increased risk of postoperative pulmonary complications we sought to assess the association between neuromuscular blocking agent reversal agent and development of postoperative pulmonary complications. MethodsWe conducted a retrospective matched cohort study, a secondary analysis of data collected in the prior STRONGER study. Data were obtained from the Multicenter Perioperative Outcomes Group. Included patients were aged 18 yr and older undergoing non-emergency surgery under general anaesthesia with tracheal intubation with neuromuscular block and reversal, who were predicted to be at elevated risk of postoperative pulmonary complications. This risk was defined as American Society of Anesthesiologists Physical Status 3 or 4 in patients undergoing either intrathoracic or intra-abdominal surgery who were either aged >80 yr or underwent a procedure lasting >2 h. Cohorts were defined by reversal with neostigmine or sugammadex. The primary composite outcome was the occurrence of pneumonia or respiratory failure. ResultsAfter matching by institution, sex, age (within 5 yr), body mass index, anatomic region of surgery, comorbidities, and neuromuscular blocking agent, 3817 matched pairs remained. The primary postoperative pulmonary complications outcome occurred in 224 neostigmine cases vs 100 sugammadex cases (5.9% vs 2.6%, odds ratio 0.41, P<0.01). After adjustment for unbalanced covariates, the adjusted odds ratio for the association between sugammadex use and the primary outcome was 0.39 (P<0.0001). ConclusionsIn a cohort of patients at increased risk for pulmonary complications compared with neostigmine, use of sugammadex was independently associated with reduced risk of subsequent development of pneumonia or respiratory failure.

Prone Positioning and Neuromuscular Blocking Agents as Adjunctive Therapies in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome.

Neuromuscular blocking agents (NMBAs) and prone position (PP) are two major adjunctive therapies that can improve outcome in moderate-to-severe acute respiratory distress syndrome. NMBA should be used once lung-protective mechanical ventilation has been set, for 48 hours or less and as a continuous intravenous infusion. PP should be used as early as possible for long sessions; in COVID-19 its use has exploded. In nonintubated patients, PP might reduce the rate of intubation but not mortality. The goal of this article is to perform a narrative review on the pathophysiological rationale, the clinical effects, and the clinical use and recommendations of both NMBA and PP.

Neuroprotective association of preoperative renin-angiotensin system blocking agents use in patients undergoing carotid interventions.

The optimal medical management strategy in the periprocedural period for patients undergoing carotid artery interventions is not well described. Renin-angiotensin-system blocking (RASB) agents are considered to be among the first line anti-hypertensive agents; however, their role in the perioperative period is unclear. The objective of this study was to examine the relationship between the use of RASB agents on periprocedural outcomes in patients undergoing carotid interventions-carotid endarterectomy (CEA), transfemoral carotid artery stenting (CAS), and transcervical carotid artery revascularization (TCAR). The Society for Vascular Surgery Quality Initiative database was queried for all patients undergoing CAS, CEA, and TCAR between 2003 and 2020. Patients were stratified into two groups based upon their use of RASB agents in the periprocedural period. The primary endpoint was periprocedural neurologic events (including both strokes and transient ischemic attacks (TIAs)). The secondary endpoints were peri-procedural mortality and significant cardiac events, including myocardial infarction, dysrhythmia, and congestive heart failure. Over 150,000 patients were included in the analysis: 13,666 patients underwent TCAR, 13,811 underwent CAS, and 125,429 underwent CEA for carotid artery stenosis. Overall, 52.2% of patients were maintained on RASB agents. Among patients undergoing CEA, patients on RASB agents had a significantly lower rate of periprocedural neurologic events (1.7% versus 2.0%, p =0.001). The peri-procedural neurological event rate in the TCAR cohort was similarly reduced in those treated with RASB agents, but did not reach statistical significance (2.0% vs 2.4%, p = 0.162). Among patients undergoing CAS, there was no difference in perioperative neurologic events between the RASB treated and untreated cohorts (3.4% vs 3.2%, p = 0.234); however, the use of RASB agents was significantly associated with lower mortality (1.2% vs 1.7%, p =0.001) with CAS. The use of preoperative RAS-blocking agents did not appear to affect the overall rates of adverse cardiac events with any of the three carotid intervention types, or periprocedural mortality following CEA or TCAR. On multivariable analysis, the use of RAS-blocking agents was independently associated with lower rates of post-procedural neurologic events in patients undergoing CEA (OR 0.819, CI 0.747-0.898; p = 0.01) and TCAR (OR 0.869, CI 0.768-0.984; p = 0.026), but not in those undergoing CAS (OR 0.967, CI 0.884-1.057; p = 0.461). The use of peri-procedural RASB agents was associated with a significantly decreased rate of neurologic events in patients undergoing both CEA and TCAR. This effect was not observed in patients undergoing CAS. As carotid interventions warrant absolute minimization of perioperative complications in order to provide maximum efficacy with regard to stroke protection, the potential neuro-protective effect associated with RASB agents use following CEA and TCAR warrants further examination.

Description of flecainide usage from 2005-2018 in the Danish population

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Flecainide is an antiarrhythmic class 1C agent used to treat cardiac arrhythmias. Due to the risk of pro-arrhythmia and 1:1 conduction with flecainide, concomitant treatment with atrioventricular nodal blocking (AVNB) agents is advised. However, little data exist pertaining to the real-world use of flecainide and concomitant AVNB therapy. Purpose We sought to investigate the change over time in the use of flecainide and AVNB agents in relation to patient characteristics. Methods Using the Nationwide Danish registers, all Danish patients above 18 years with a redeemed prescription for flecainide between January 1st, 2005, and December 31st, 2018, and included at the date of the first prescription. The use of AVNB agents was identified in the period from 180 days prior to and 180 days after the inclusion date. Individual AVNB agents were divided into beta-blockers, class IV calcium channel blockers, and digoxin. Results The study cohort consisted of 6,594 patients with a median [IQR] age increasing from 59 [53-65] years in 2005 to 63 [56-69] in 2018, 59 % were men, and the most frequent arrhythmia diagnosis was AF (90.1%). In total, there were 297 patients starting flecainide in 2005 and 491 in 2018, with the highest number of patients in 2011, with 613 new users (Figure 1). Compared to the 144,215 patients with prevalent atrial fibrillation in Denmark in 2018, the number of patients using flecainide was only 0.3% this year. The percentage of patients on concomitant AVNB treatment was high throughout the study period, with 93% in 2005 and 95% in 2018, giving an average increase of 0.3% per year over time. The most frequently used AVNB was beta-blockers, and the least frequently used were the class IV calcium channel blockers. (Figure 2) Over time, the number of patients with concomitant AVNB treatment to flecainide decreased from 94% the first year in flecainide treatment to 90% between the second and third years. Between the firth and sixth year in flecainide treatment, the number was down to 86%. The number of patients with a diagnosis of ischemic heart disease was 10% in 2005, dropping to 6% in 2018 Conclusions Flecainide use increased from 2005 to 2018. The use of AVNB was high in patients prescribed with flecainide and increased over time, with beta-blocker as the most frequent.

Neuromuscular Blocking Agents and Monitoring in China: A Cross-Sectional Survey of Current Management.

BackgroundLittle is known about the recent use of neuromuscular blocking agents (NMBAs) and monitoring in China. This paper presents the results of a nationwide survey conducted to obtain information regarding the current management of NMBAs in China.MethodsA questionnaire was sent to Chinese anesthesiologists inviting them to participate in the study. The questionnaire was available through the wenjuanxing website, and the link was sent to 1,488 anesthesiologists using the Wechat mini app.ResultsThe web-based survey consisted of 28 questions, and data were collected using an online tool. Between May 19, 2021 and June 16, 2021, 637 responses were collected (response rate = 42.8%). Only 10.2% of anesthesiologists reported using neuromuscular function monitors, and 6.59% of respondents reported that they had the relevant monitors in the operating room.ConclusionAlthough PORC is a potential safety issue, the frequency of using reversal agents and monitors remains extremely low in China. Surveys such as this are important to understand the use and application customs of NMBAs in China.

Design, synthesis and biological evaluation of novel 5-methyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives as potent potassium-competitive acid blockers

With the aim to discover a novel potent potassium-competitive acid blocker (P-CAB) agent, a series of 5-methyl-2,4,5,6-tetrahydropyrrolo[3,4–c]pyrazole derivatives were synthesized, and their H+/K+-ATPase inhibitory activities and inhibitory action on histamine-stimulated gastric acid secretion in rats were evaluated. Among the compounds synthesized, compound 3′-((3-(2-fluorophenyl)-5-methyl-5,6-dihydropyrrolo[3,4–c]pyrazol-2(4H)-yl)methyl)-[1,1′-biphenyl]-3-carboxamide not only exhibited potent H+/K+-ATPase inhibitory activity but olso showed potent inhibitory action in vivo on histamine-stimulated gastric acid secretion. In addition, the lead compound displayed favourable oral pharmacokinetic properties in rats, which was worthy of further study as a novel P-CAB agent.