The Influence of Method of Administration and Covariates on the Pharmacokinetics of Propofol in Adult Volunteers

Schnider, Thomas W.; Minto, Charles F.; Gambús, Pedro L.; Andresen, Corina; Goodale, David; Shafer, Steven L.; Youngs, Elizabeth J.

doi:10.1097/00000542-199805000-00006

Cited by 988 publications

(771 citation statements)

References 29 publications

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“…The study drugs were given using a volumetric infusion pump (Infusomat s ; Braun Medical SA, Sempach, Switzerland) for 15 min before induction of anaesthesia. At the end of the study drug administration, the intravenous line was flushed, and anaesthesia was induced with sufentanil 0.2 mg/kg and propofol using a target-controlled infusion system (Base Primea, Fresenius-Vial, Brezins, France) using the pharmacokinetic model of Schnider et al 9 The targeted effect-site concentration of propofol for induction was 4 AE 1 mg/ml. As soon as the patient lost consciousness, the lungs were normo-ventilated (endtidal partial pressure of carbon dioxide, 4.6-6.0 kPa) with a 50% oxygen-air mixture.…”

Section: Methodsmentioning

confidence: 99%

Time course of rocuronium‐induced neuromuscular block after pre‐treatment with magnesium sulphate: a randomised study

Czarnetzki

Lysakowski

Elia

et al. 2010

Acta Anaesthesiol Scand

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Background: A previously published study suggested that pre-treatment with magnesium sulphate (MgSO 4 ) had no impact on the speed of onset of rocuroniuminduced neuromuscular block. We set out to verify this assumption. Methods: Eighty patients (18-60 years) were randomly allocated to MgSO 4 60 mg/kg or placebo (saline). Study drugs were given intravenously for 15 min before induction of anaesthesia with propofol, sufentanil and rocuronium 0.6 mg/kg. Anaesthesia was maintained with a target-controlled propofol infusion. Neuromuscular transmission was measured using train-of-four (TOF)-Watch SX s acceleromyography. M AGNESIUM is widely used in peri-operative medicine, for instance, to treat arrhythmia in cardiac patients or to control blood pressure and to prevent seizures in parturients with pre-eclampsia.Magnesium has an impact on neuromuscular transmission. It reduces the amount of acetylcholine that is released at the motor nerve terminal 1,2 by decreasing the calcium conductance of presynaptic voltage-dependent calcium channels. 3 After pre-treatment with magnesium sulphate (MgSO 4 ), an increased speed of onset and a prolongation of the recovery period of neuromuscular blockade have been observed with atracurium and vecuronium. 4,5 However, in a similar study, rapid administration of an intravenous bolus of MgSO 4 , 60 mg/kg, injected immediately before rocuronium, significantly prolonged recovery of the neuromuscular block but curiously had no influence on the speed of onset. 6 The authors of that MgSO 4 -rocuronium interaction study speculated that differences in the efficacy of magnesium pretreatment in reducing the onset time of different non-depolarising neuromuscular blocking agents (NMBA) reflected differences in the pharmacodynamic properties of the NMBAs; the shorter the baseline onset time of the NMBA (as with rocuronium), the less effect MgSO 4 pre-treatment would have. However, it may be assumed that the effect of the magnesium ion on the neuromuscular endplate is both concentration and time dependent. Therefore, an alternative hypothesis would be that, after a rapid bolus injection immediately before the administration of rocuronium, the magnesium ions have no scope to reach the motor nerve These data were presented in part at the annual scientific meeting of the Swiss Society of Anaesthesiology and Resuscitation, Fribourg, Switzerland, November 2008. 299 Acta Anaesthesiol Scand 2010; 54: 299-306 : 10.1111/j.1399-6576.2009.02160.x terminal in a concentration that is high enough to interfere with rocuronium. In an in vitro study on mammalian motor nerve endings, 4-6 min were necessary to establish a new frequency of miniature end-plate potentials after administration of increasing magnesium concentrations. 7 Consequently, a magnesium infusion, rather than a bolus injection immediately before the injection of the NMBA, should have an impact on neuromuscular blockade. In theory, MgSO 4 pre-treatment should reduce the onset time of a rocuronium-induced block to an extent that makes it an ...

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Section: Methodsmentioning

confidence: 99%

Time course of rocuronium‐induced neuromuscular block after pre‐treatment with magnesium sulphate: a randomised study

Czarnetzki

Lysakowski

Elia

et al. 2010

Acta Anaesthesiol Scand

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“…They have a reliable pharmacological profile, with fast onset and recovery times, making them suitable candidates for closed loop control of depth of anesthesia. Propofol is a hypnotic agent, whose pharmacological properties have been well described and studied in different kind of patients [11,12]. Remifentanil is an opioid with a unique pharmacological profile, best characterized by its high metabolic clearance, independent of the most common metabolic pathways which are usually known to metabolize anesthetic drugs [13,14].…”

Section: Patient Modelmentioning

confidence: 99%

“…The amount of drug in this compartment is represented by C e . The parameters k ij of the PK models depend on age, weight, height and gender and the relations can be found for propofol in [11,12] and for remifentanil in [13,14]. This hypothetical effect compartment makes the link to the drug effect, i.e.…”

Section: Patient Modelmentioning

confidence: 99%

Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

Ionescu

Machado

Keyser

et al. 2015

Communications in Nonlinear Science and Numerical Simulation

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a b s t r a c tIn today's healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time-frequency analysis is used to extract useful infor-mation from the clinical signals, since they are time-varying and mark important changes in patient's response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identifi-cation from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

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“…The GALENO-TCI is a heuristic predictive TCI algorithm that uses the compartment PK/PD models in [6], [7], [8], [9] for propofol, remifentanil and sufentanil, as predictive models. Figure 3 shows a general scheme of these tri-compartmental models, being its mathematical representation [10] given by…”

Section: ) Neuromuscular Blockadementioning

confidence: 99%

Automated total intravenous anesthesia (amTIVA) from induction to recovery

Paz

Silva

Esteves

et al. 2014

2014 IEEE International Symposium on Medical Measurements and Applications (MeMeA)

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Abstract-This paper presents a multi-functional automatic control approach for total intravenous anesthesia (TIVA) administration, valid for several drug combinations and able to run autonomously during the three main phases of general anesthesia: induction, maintenance and recovery. While using this standalone TIVA module, named as amTIVA, the anesthesiologist has the crucial role of system supervisor. Bolus administration, openloop target controlled infusion (TCI) and closed-loop controlled infusion modes are implemented and available for the control of the two main components of anesthesia: the neuromuscular blockade and the depth of anesthesia. This multi-functional module is implemented in the GALENO Platform and was successfully tested in more than thirty clinical cases.

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The Influence of Method of Administration and Covariates on the Pharmacokinetics of Propofol in Adult Volunteers

Abstract: These results demonstrate that method of administration (bolus vs. infusion), but not EDTA, influences the pharmacokinetics of propofol. Within the clinically relevant range, the kinetics of propofol during infusions are linear regarding infusion rate.

Cited by 988 publications

References 29 publications

Time course of rocuronium‐induced neuromuscular block after pre‐treatment with magnesium sulphate: a randomised study

Time course of rocuronium‐induced neuromuscular block after pre‐treatment with magnesium sulphate: a randomised study

Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

Automated total intravenous anesthesia (amTIVA) from induction to recovery

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