Comparison of Inhalational and Intravenous Anesthesia Induction on Electroencephalogram and Cerebral Perfusion in Children With Congenital Heart Disease: A Secondary Analysis of a Randomized Controlled Trial

Article

Author: Ou, Yangchuan ; Xie, Siyuan ; Han, Ding ; Pan, Shoudong

OBJECTIVESThe effects of anesthetics on electroencephalograms and cerebral perfusion remain understudied in children with congenital heart disease. With regard to this, we compared inhalational anesthesia induction and intravenous anesthesia induction.DESIGNA randomized controlled trial.SETTINGOperating room in 2 tertiary hospitals.PARTICIPANTSA cohort of 116 pediatrics patients undergoing cardiac surgery.MEASUREMENTS AND MAIN RESULTSThe patients were randomly assigned to either the intravenous group (n = 58) or the inhalational group (n = 58). The inhalational group received anesthesia induction with 4% to 6% sevoflurane and a bolus of pipecuronium 0.2 mg/kg, whereas the intravenous group received anesthesia induction with intravenous midazolam 0.2 mg/kg, pipecuronium 0.2 mg/kg, and sufentanil 1 μg/kg. Ten minutes after tracheal intubation, the following parameters were measured: spectral edge frequency, burst suppression event, patient state index, middle cerebral artery blood flow velocity, cerebral oxygen saturation, and hemodynamic parameters. In comparison with the intravenous group, the inhalational group exhibited significant increases in 95% spectral edge frequency, ratio of burst suppression event, blood flow velocity in the middle cerebral artery, and cerebral oxygen saturation (p < 0.05 for all), as well as decreases in systolic pressure, diastolic pressure, cardiac index, and the maximal slope of systolic upstroke (p < 0.05 for all).CONCLUSIONSThe administration of sevoflurane for anesthesia induction results in more burst suppression, while also demonstrating superior cerebral perfusion when compared with the use of intravenous medications for anesthesia induction.TRIAL REGISTRATIONChinese Clinical Trial Registry (ChiCTR1800015946).

01 Jan 2022·Computational and Structural Biotechnology Journal

Targeting non-structural proteins of Hepatitis C virus for predicting repurposed drugs using QSAR and machine learning approaches

Article

Author: Rajput, Akanksha ; Kumar, Manoj ; Kamboj, Sakshi ; Thakur, Anamika ; Rastogi, Amber

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.

01 Dec 2021·BMC AnesthesiologyQ4 · MEDICINE

Carboxymethyl-γ-cyclodextrin, a novel selective relaxant binding agent for the reversal of neuromuscular block induced by aminosteroid neuromuscular blockers: an ex vivo laboratory study

Q4 · MEDICINE

ArticleOA

Author: Sohajda, Tamás ; Csernoch, Vera ; Fedor, Marianna ; Tassonyi, Edömér ; Szente, Lajos ; Fábián, Ákos I ; Fülesdi, Béla

AbstractBackgroundResidual neuromuscular block at the end of surgery may compromise the patient’s safety. The risk of airway complications can be minimized through monitoring of neuromuscular function and reversal of neuromuscular block if needed. Effective reversal can be achieved with selective relaxant binding agents, however, sugammadex is the only clinically approved drug in this group.We investigated the concentration–response properties of a novel selective relaxant binding agent, carboxymethyl-γ-cyclodextrin for the reversal of neuromuscular block. We evaluated the hypothesis that it is equally potent for reversing neuromuscular block as sugammadex.MethodsPhrenic nerve – hemidiaphragm tissue preparations were isolated from male Wistar rats and suspended in a tissue holder allowing electrical stimulation of the nerve and monitoring of muscle contraction force. Concentration–response relationships were constructed for the neuromuscular blocking agents rocuronium, pipecuronium, and vecuronium. The half-effective concentrations of sugammadex and carboxymethyl-γ-cyclodextrin for reversal of neuromuscular block were determined.ResultsThe half effective concentrations (95% confidence interval, CI) were 7.50 (6.93–8.12) μM for rocuronium, 1.38 (1.33–1.42) μM for pipecuronium, and 3.69 (3.59–3.80) μM for vecuronium. The half effective concentrations (95% CI) of carboxymethyl-γ-cyclodextrin and sugammadex were 35.89 (32.67–39.41) μM and 3.67 (3.43–3.92) μM, respectively, for the reversal of rocuronium-induced block; 10.14 (9.61–10.70) μM and 0.67 (0.62–0.74) μM, respectively, for the reversal of pipecuronium-induced block; and 376.1 (341.9–413.8) μM and 1.45 (1.35–1.56) μM, respectively, for the reversal of vecuronium-induced block.ConclusionsCarboxymethyl-γ-cyclodextrin is an effective, but less potent agent for reversal of neuromuscular block than sugammadex.

100 Deals associated with Pipecuronium Bromide

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KEGG	Wiki	ATC	Drug Bank
D00764	Pipecuronium Bromide	M03AC06	DB01338

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