With the growing number of elderly patients undergoing surgical procedures, the use of neuromuscular blocking agents (NMBAs) in geriatric anesthesia has become increasingly relevant. Aging is associated with physiological and pathological changes that affect drug pharmacokinetics and pharmacodynamics, including reduced renal and hepatic function, altered body composition, and decreased plasma protein levels. These changes influence the onset, duration, and recovery from neuromuscular blockade, increasing the risk of postoperative residual curarization (PORC) and respiratory complications. This narrative review summarizes current knowledge on the use of depolarizing and non-depolarizing NMBAs in elderly patients, including benzylisoquinolines (atracurium, cisatracurium, mivacurium) and aminosteroids (rocuronium, vecuronium, pancuronium, pipecuronium). Age-related differences in drug metabolism, distribution, and elimination are discussed, along with the clinical implications for dosing, recovery, and safety. The role of reversal agents, including neostigmine and sugammadex, is emphasized, highlighting their efficacy and safety profiles in older adults. Special attention is given to neuromuscular monitoring, particularly objective quantitative methods as a critical tool to prevent residual blockade. Individualized management strategies, careful agent selection, and vigilant monitoring are essential to optimize safety and outcomes in elderly patients. Despite age-related pharmacological changes, appropriate use of short-acting or organ-independent NMBAs, combined with reversal agents and neuromuscular monitoring, allows for effective and safe anesthesia in the geriatric population. Future research should focus on large-scale studies to better define age-specific NMBA dosing and monitoring guidelines.

Inappropriate use of muscle relaxants leads to postoperative residual neuromuscular block (PORNB), which is still a significant problem nowadays and is an independent risk factor for postoperative pulmonary complications. To decrease its incidence, the European Society of Anesthesiology and Intensive Care and the American Society of Anesthesiologists published their guidelines on the safe use of muscle relaxants in 2023. In this publication, the Edömér Tassonyi Neuromuscular Task Force of the University of Debrecen Clinical Center summarizes its recommendations. Based on international guidelines, objective neuromuscular monitoring should be performed in every patient who received non-depolarizing muscle relaxants during surgery. Since postoperative residual neuromuscular block can lead to several complications, it is essential for patient safety to ensure that the effect of the muscle relaxants is gone and train-of-four (TOF) ratio has returned to 0.9 (90%) before extubation. Clinical signs and subjective neuromuscular monitoring are not suitable for diagnosing residual curarization at the end of surgery. Therefore, whenever a patient receives non-depolarizing muscle relaxant, objective neuromuscular monitoring should be performed to exclude residual neuromuscular block. Neuromuscular monitoring should be performed in the hand. Objective neuromuscular monitoring should be started before muscle relaxant administration by calibrating the monitoring device. To ensure optimal intubating conditions and prevent airway injuries, TOF count should drop to 0 (all muscle responses evoked by nerve stimulation should disappear). TOF measurements should be repeated at regular intervals during surgery to follow the course of muscle relaxation. The effect of reversal agents (both neostigmine and sugammadex) should always be objectively monitored. The effect of bensilisoquinolin muscle relaxants can only be reversed with neostigmine when there is twitch response to TOF stimulation. Sugammadex is the most effective reversal agent for steroidal muscle relaxants (vecuronium, rocuronium and pipecuronium), but neostigmine can be used as well when there is twitch response to TOF stimulation. Orv Hetil. 2025; 166(15): 569–577.

We tested the feasibility of maintaining low intraabdominal pressures during pipecuronium-induced deep block (post-tetanic count ≥1, train-of-four count = 0) in patients undergoing laparoscopic surgery.

Muscle relaxants have broad application in anesthesiology. They can be used for safe intubation, preparing the patient for surgery, or improving mechanical ventilation. Muscle relaxants can be classified based on their mechanism of action into depolarizing and non-depolarizing muscle relaxants and centrally acting muscle relaxants. Non-depolarizing neuromuscular blocking drugs (NMBDs) (eg, tubocurarine, atracurium, pipecuronium, mivacurium, pancuronium, rocuronium, vecuronium) act as competitive antagonists of nicotine receptors. By doing so, these drugs hinder the depolarizing effect of acetylcholine, thereby eliminating the potential stimulation of muscle fibers. Depolarizing drugs like succinylcholine and decamethonium induce an initial activation (depolarization) of the receptor followed by a sustained and steady blockade. These drugs do not act as competitive antagonists; instead, they function as more enduring agonists compared to acetylcholine itself. Many factors can influence the duration of action of these drugs. Among them, electrolyte disturbances and disruptions in acid-base balance can have an impact. Acidosis increases the potency of non-depolarizing muscle relaxants, while alkalosis induces resistance to their effects. In depolarizing drugs, acidosis and alkalosis produce opposite effects. The results of studies on the impact of acid-base balance disturbances on non-depolarizing relaxants have been conflicting. This work is based on the available literature and the authors' experience. This article aimed to review the use of anesthetic muscle relaxants in patients with acid-base disturbances.

Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.

Hepatitis C virus (HCV) infection causes viral hepatitis leading to hepatocellular carcinoma. Despite the clinical use of direct-acting antivirals (DAAs) still there is treatment failure in 5-10% cases. Therefore, it is crucial to develop new antivirals against HCV. In this endeavor, we developed the "Anti-HCV" platform using machine learning and quantitative structure-activity relationship (QSAR) approaches to predict repurposed drugs targeting HCV non-structural (NS) proteins. We retrieved experimentally validated small molecules from the ChEMBL database with bioactivity (IC50/EC50) against HCV NS3 (454), NS3/4A (495), NS5A (494) and NS5B (1671) proteins. These unique compounds were divided into training/testing and independent validation datasets. Relevant molecular descriptors and fingerprints were selected using a recursive feature elimination algorithm. Different machine learning techniques viz. support vector machine, k-nearest neighbour, artificial neural network, and random forest were used to develop the predictive models. We achieved Pearson's correlation coefficients from 0.80 to 0.92 during 10-fold cross validation and similar performance on independent datasets using the best developed models. The robustness and reliability of developed predictive models were also supported by applicability domain, chemical diversity and decoy datasets analyses. The "Anti-HCV" predictive models were used to identify potential repurposing drugs. Representative candidates were further validated by molecular docking which displayed high binding affinities. Hence, this study identified promising repurposed drugs viz. naftifine, butalbital (NS3), vinorelbine, epicriptine (NS3/4A), pipecuronium, trimethaphan (NS5A), olodaterol and vemurafenib (NS5B) etc. targeting HCV NS proteins. These potential repurposed drugs may prove useful in antiviral drug development against HCV.

Bitter taste receptors (TAS2R) are expressed in many non-sensor tissues including skeletal muscles but their function remains unexplored. The aim of this study is to investigate the role of TAS2R in rat abdominal skeletal muscles contractions using denatonium, a TAS2R agonist. Low concentration of denatonium (0.01 mmol/l) caused a significant decrease of amplitudes of the electrical field stimulation (EFS)-induced contractions in abdominal skeletal muscles preparations in vitro. This inhibitory effect was significantly reduced when the preparations were pre-incubated with gentamicin (0.02 mmol/l) used as a non-specific inhibitor of IP3 formation or with BaCl(2) (0.03 mmol/l) applied to block the inward-rectifier potassium current. All experiments were performed in the presence of pipecuronium in order to block the nerve stimulation of the contractions. The data obtained suggest that denatonium decreases the force of rat abdominal muscles contractions mainly via activation of TAS2R, phosphatidylinositol 4,5-biphosphate and its downstream signal metabolites.