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Douglas J Eleveld, Johannes H Proost, Hugo Vereecke, Anthony R Absalom, Erik Olofsen, Jaap Vuyk, Michel M R F Struys
BACKGROUND: Pharmacokinetic and pharmacodynamic models are used to predict and explore drug infusion schemes and their resulting concentration profiles for clinical application. Our aim was to develop a pharmacokinetic-pharmacodynamic model for remifentanil that is accurate in patients with a wide range of age and weight. METHODS: Remifentanil pharmacokinetic data were obtained from three previously published studies of adults and children, one of which also contained pharmacodynamic data from adults...
June 2017: Anesthesiology
Sumith K Mathew, Binu S Mathew, Michael N Neely, Girish S Naik, Ratna Prabha, Gijoe G Jacob, Subramani K, Denise H Fleming
BACKGROUND: Pharmacokinetics of meropenem differ widely in the critically ill population. It is imperative to maintain meropenem concentrations above the inhibitory concentrations for most of the interdose interval. A population pharmacokinetic/pharmacodynamic model was developed to determine the probability of target attainment for 3-hour and 30-minute infusion regimens in this population. METHODS: This study was performed in an intensive care setting among adult patients who were initiated on meropenem at a dose of 1000 mg...
October 2016: Therapeutic Drug Monitoring
Jian-Yan Chen, Ming Yi, Shang-Long Yao, Xue-Ping Zhang
This study aimed to establish a new propofol target-controlled infusion (TCI) model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol (10 mg/kg) was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using WinNonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend...
June 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
I Martín-Mateos, J A Méndez Pérez, J A Reboso Morales, J F Gómez-González
BACKGROUND AND OBJECTIVE: Propofol is widely used for hypnosis induction and maintenance of general anesthesia. Its effect can be assessed using the bispectral index (BIS). Many automatic infusion systems are based in pharmacokinetics (PK) and pharmacodynamics (PD) models to predict the response of the patient to the drug. However, all these models do not take into account intra and inter-patient variability. An adjusted intraoperative drug administration allows faster recovery and provides post-operative side-effect mitigation METHODS: BIS evolution and surgery-recorded propofol infusion data of a group of 60 adult patients (30 males/30 females) with ASA I/II physical status were used to test a real time PK/PD compartmental model...
August 1, 2016: Computers in Biology and Medicine
C Frederico Avendaño, L I Cortínez, C R Ramírez-Paesano
OBJECTIVE: To compare the Cortínez and Schnider models in effect-site TCI mode (3 mcg/ml) in healthy volunteers. METHODS: Ten healthy volunteers were prospectively studied on 2 occasions. Propofol was administered with the Cortínez or the Schnider models, as randomly assigned. Times and predicted concentrations at the time of loss and recovery of consciousness (LOC and ROC), mass of drug administered, BIS, and haemodynamic variables were compared. Statistical analysis was with paired Wilcoxon test...
December 2016: Revista Española de Anestesiología y Reanimación
N Simon, F Viallet, A Boulamery, A Eusebio, D Gayraud, J-P Azulay
PURPOSE: Levodopa is the reference treatment for Parkinson's disease. However, after several years of treatment, dyskinesia may occur and strategies to overcome this side effect still need to be explored. We identified a unique population pharmacokinetic/pharmacodynamic model in Parkinson's disease to investigate the relationship and dissociability of motor response and dyskinesia. METHODS: Thirty parkinsonian patients (Hoehn and Yahr stages 3-4), treated with levodopa and suffering from peak-dose dyskinesia, were included in a prospective open-label study...
April 2016: European Journal of Clinical Pharmacology
J B Glen, F H M Engbers
One advantage of effect-site target-controlled infusion is the administration of a larger initial dose of propofol to speed up the induction of anaesthesia. This dose is determined by the combination of the pharmacokinetic model parameters, the target setting and the blood-effect time-constant, ke0 . With the help of computer simulation, we determined the ke0 values required to deliver a range of initial doses with three pharmacokinetic models for propofol. With an effect site target of 4 μ , in a 35-year-old, 170-cm tall, 70-kg male subject, the ke0 values delivering a dose of 1...
March 2016: Anaesthesia
Jacqueline A Hannam, Xavier Borrat, Iñaki F Trocóniz, José F Valencia, Erik W Jensen, Angela Pedroso, Jenifer Muñoz, Sergi Castellví-Bel, Antoni Castells, Pedro L Gambús
Respiratory depression is a common adverse effect of propofol and remifentanil. We aimed to develop a model for respiratory depressant effects of propofol with remifentanil in patients undergoing endoscopy with sedation. Data were available for 136 patients undergoing endoscopy with sedation. Participants randomly received infusions of propofol and remifentanil. Predicted plasma concentrations, outputted by infusion pumps, were available. Transcutaneous arterial pressure of carbon dioxide (pCO2) was measured...
March 2016: Journal of Pharmacology and Experimental Therapeutics
In-Kyung Song, Ji-Hyun Lee, SungAe Jung, Jin-Tae Kim, Hee-Soo Kim
OBJECTIVES: Although targeting the effect site concentration may offer advantages over the traditional forms of administering intravenous anesthetics, it is not applicable for sufentanil in children because its plasma effect site equilibration rate constant (ke0) is not known yet. We estimated ke0 of sufentanil in children using the time to peak effect (t peak) method. MATERIALS AND METHODS: Under general anesthesia, sufentanil t peak was measured after administration of a submaximal bolus dose by means of the decrease in heart rate, blood pressure and calculated approximate entropy (ApEn) of electroencephalogram in 105 children (age range: 3-11 years)...
July 2015: Indian Journal of Pharmacology
Marcus A Björnsson, Åke Norberg, Sigridur Kalman, Ulrika S H Simonsson
BACKGROUND: AZD3043 is a positive allosteric modulator of the γ-aminobutyric acid type A receptor, with sedative and anesthetic properties. We describe a population pharmacokinetic (PK) model of arterial and venous concentrations of AZD3043 and the pharmacodynamic effects on bispectral index (BIS) in healthy volunteers. METHODS: Arterial and venous plasma concentrations of AZD3043 and BIS were measured in 2 clinical studies in 125 healthy volunteers, where AZD3043 was given as a 1-minute bolus (1-6 mg/kg), a 30-minute infusion (1-81 mg/kg/h), or 0...
October 2015: Anesthesia and Analgesia
François Gaudreault, Pierre Drolet, Michel Fallaha, France Varin
BACKGROUND: Even though ropivacaine is frequently used during orthopedic surgery, the relationship between plasma concentrations and degree of sensory anesthesia after a peripheral nerve block is currently unknown. The aim of this study was to characterize this relation using population pharmacokinetic-pharmacodynamic modeling. METHODS: Femoral nerve block was performed by the anterior approach using a single injection (20 ml) of 0.5% ropivacaine hydrochloride in 20 patients scheduled for total knee arthroplasty under spinal anesthesia...
May 2015: Anesthesiology
Ricardo Francisco Simoni, Luiz Eduardo de Paula Gomes Miziara, Luis Otávio Esteves, Diógenes de Oliveira Silva, Cristina Alves Ribeiro, Mariana Oki Smith, Leonardo Ferreira de Paula, Luis Henrique Cangiani
BACKGROUND AND OBJECTIVE: studies have shown that rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26min(-1)) in loss of consciousness during fast or slow induction. METHOD: the study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0...
March 2015: Revista Brasileira de Anestesiologia
Ricardo Francisco Simoni, Luiz Eduardo de Paula Gomes Miziara, Luis Otávio Esteves, Diógenes de Oliveira Silva, Cristina Alves Ribeiro, Mariana Oki Smith, Leonardo Ferreira de Paula, Luis Henrique Cangiani
BACKGROUND AND OBJECTIVE: Studies have shown that the rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26min(-1)) in loss of consciousness during fast or slow induction. METHOD: The study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0...
March 2015: Brazilian Journal of Anesthesiology
B Morel, M Clémençon, S Rota, G Y Millet, D J Bishop, O Brosseau, D M Rouffet, C A Hautier
This study aimed to compare the magnitude and etiology of neuromuscular fatigue during maximal repeated contractions performed in two contraction modes (concentric vs isometric) and at two contraction velocities (30/s vs 240°/s). Eleven lower limb-trained males performed 20 sets of maximal contractions at three different angular velocities: 0°/s (KE0), 30/s (KE30), and 240°/s (KE240). Cumulated work, number of contraction, duty cycle, and contraction time were controlled. Torque, superimposed and resting twitches, as well as gas exchange, were analyzed...
October 2015: Scandinavian Journal of Medicine & Science in Sports
Luis I Cortínez, Natalia De la Fuente, Douglas J Eleveld, Ana Oliveros, Fernando Crovari, Pablo Sepulveda, Mauricio Ibacache, Sandra Solari
BACKGROUND: Obesity is associated with important physiologic changes that can potentially affect the pharmacokinetic (PK) and pharmacodynamic (PD) profile of anesthetic drugs. We designed this study to assess the predictive performance of 5 currently available propofol PK models in morbidly obese patients and to characterize the Bispectral Index (BIS) response in this population. METHODS: Twenty obese patients (body mass index >35 kg/m), aged 20 to 60 years, scheduled for laparoscopic bariatric surgery, were studied...
August 2014: Anesthesia and Analgesia
A R Hedges, B H Pypendop, Y Shilo-Benjamini, S D Stanley, J E Ilkiw
This study reports the pharmacokinetics of buprenorphine, following i.v. and buccal administration, and the relationship between buprenorphine concentration and its effect on thermal threshold. Buprenorphine (20 μg/kg) was administered intravenously or buccally to six cats. Thermal threshold was determined, and arterial blood sampled prior to, and at various times up to 24 h following drug administration. Plasma buprenorphine concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to the time-concentration data...
June 2014: Journal of Veterinary Pharmacology and Therapeutics
A J Thomson, G Morrison, E Thomson, C Beattie, A F Nimmo, J B Glen
We studied the use of a new ke0 value (0.6 min(-1)) for the Marsh pharmacokinetic model for propofol. Speed of induction and side-effects produced were compared with three other target-controlled infusion systems. Eighty patients of ASA physical status 1-2 were studied in four groups in a prospective, randomised study. Median (IQR [range]) induction times were shorter with the Marsh model in effect-site control mode with a ke0 of either 0.6 min(-1) (81 (61-101 [49-302])s, p < 0.01), or 1.2 min(-1) (78 (68-208 [51-325])s, p < 0...
May 2014: Anaesthesia
A J Thomson, A F Nimmo, F H M Engbers, J B Glen
Debate continues over the most appropriate blood-brain equilibration rate constant (ke0) for use with the Marsh pharmacokinetic model for propofol. We aimed to define the optimal ke0 value. Sixty-four patients were sedated with incremental increases in effect-site target concentration of propofol while using six different ke0 values within the range 0.2-1.2 min(-1). Depth of sedation was assessed by measuring visual reaction time. A median 'apparent ke0' value of 0.61 min(-1) (95% CI 0.37-0.78 min(-1)) led to the greatest probability of achieving a stable clinical effect when the effect-site target was fixed at the effect-site concentration displayed by the target-controlled infusion system, at the time when a desired depth of sedation had been reached...
May 2014: Anaesthesia
L I Cortínez
No abstract text is available yet for this article.
May 2014: Anaesthesia
Byung-Moon Choi, Eun-Hyo Koh, Mun-Gyu Kim, Sang-Ho Kim, Si-Young Ok, Gyu-Jeong Noh
BACKGROUND: The aims of this study were to compare the stability, correlation with end-tidal sevoflurane, and area below the effect (AUCeffect) vs. time curves of temporal linear mode complexity (TLMC) and approximate entropy (ApEn) during sevoflurane anesthesia. Another study goal was to characterize the time course of the effects of sevoflurane. METHODS: Electroencephalogram (EEG) parame1ter stability was evaluated using the coefficients of variation (CV) of the median baseline (E0 ), maximal (Emax ), and individual median E0 - Emax values...
November 2013: Korean Journal of Anesthesiology
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