We have evaluated the effectiveness of a technique of blended anaesthesia (epidural-general) in 31 patients undergoing major surgery. Thoracic epidural blockade with lidocaina CO2, adrenalin 1/200000, ensures analgesia while induction and hypnosis maintenance were obtained with midazolam, alfentanil, atracurium and N2O/O2. This technique seems able to protect the patients from endotracheal intubation and surgical stress and also to enable a rapid, quiet awakening. The dose of midazolam necessary to maintain hypnosis was inversely proportional to the patient's age. The reversal of hypnosis was necessary in 4 patients only.
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CPT Pharmacometrics Syst Pharmacol
January 2025
Bayer AG, Pharmacometrics/Modeling and Simulation, Systems Pharmacology & Medicine - PBPK, Leverkusen, Germany.
Gastrointestinal first-pass metabolism plays an important role in bioavailability and in drug-drug interactions. Physiologically-based pharmacokinetic (PBPK) modeling is a powerful tool to integrate these processes mechanistically. However, a correct bottom-up prediction of GI first-pass metabolism is challenging and depends on various model parameters like the level of enzyme expression and the basolateral intestinal mucosa permeability (P).
View Article and Find Full Text PDFClin Pharmacokinet
August 2024
Department of Anesthesiology, University of Washington, Seattle, WA, USA.
Background And Objectives: Clearances and the area under the plasma concentration-time curve extrapolated to infinity (AUC) of intravenous (IV) and oral midazolam and alfentanil are probes for hepatic and first-pass cytochrome P450 3A (CYP3A) activity, drug interactions, and phenotyping. Single-time plasma concentrations are also used as a proxy for clearance and AUC. Pupil diameter change is a noninvasive surrogate for plasma alfentanil.
View Article and Find Full Text PDFBMC Anesthesiol
May 2024
Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, 300100, China.
Background: Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP).
Methods: A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.
J Clin Pharmacol
September 2024
Certara Predictive Technologies Division, Certara UK Limited, Sheffield, UK.
The rapid growth in the use of pediatric physiologically based pharmacokinetic (PBPK) models, particularly for regulatory applications, has focused emphasis on model verification and ensuring system parameters are robust, including how these change with age. Uncertainty remains regarding the ontogeny of some enzymes and transporters, in this study 2 published ontogeny profiles for hepatic CYP3A4 were compared. Clinical pharmacokinetic data on 4 intravenously administered CYP3A4 substrates (alfentanil, fentanyl, midazolam, and sildenafil) used across the pediatric age range was collected from the literature.
View Article and Find Full Text PDFBMC Gastroenterol
April 2024
Department of Anesthesiology, Cheeloo College of Medicine, Shandong Provincial Third Hospital, Shandong University, No.12 Wuyingshan Middle Road, Jinan, Shandong, 250000, China.
Background: Proper sedation of patients, particularly elderly individuals, who are more susceptible to sedation-related complications, is of significant importance in endoscopic retrograde cholangiopancreatography (ERCP). This study aims to assess the safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for deep sedation in elderly patients undergoing ERCP, compared to a group of middle-aged patients.
Methods: The medical records of 610 patients with common bile duct stones who underwent elective ERCP under deep sedation with a three-drug regimen, including midazolam, alfentanil, and propofol at Shandong Provincial Third Hospital from January 2023 to September 2023 were retrospectively reviewed in this study.
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