scholarly journals Influence of a modified propofol equilibration rate constant (ke0) on the effect-site concentration at loss and recovery of consciousness with the Marsh model

Anaesthesia ◽  
2013 ◽  
Vol 68 (12) ◽  
pp. 1232-1238 ◽  
Author(s):  
J. H. Seo ◽  
E. K. Goo ◽  
I. A. Song ◽  
S. H. Park ◽  
H. P. Park ◽  
...  
Keyword(s):  
Rate Constant ◽  
Effect Site ◽  
Effect Site Concentration ◽  
Equilibration Rate ◽  
Recovery Of Consciousness

Estimation of the Plasma Effect Site Equilibration Rate Constant (ke0) of Propofol in Children Using the Time to Peak Effect

2004 ◽  
Vol 101 (6) ◽  
pp. 1269-1274 ◽  
Author(s):  
Hernán R. Muñoz ◽  
Luis I. Cortínez ◽  
Mauricio E. Ibacache ◽  
Fernando R. Altermatt
Keyword(s):  
Rate Constant ◽  
Peak Effect ◽  
Auditory Evoked Potential ◽  
Pharmacokinetic Parameters ◽  
Time To Peak ◽  
Effect Site ◽  
Effect Site Concentration ◽  
Target Effect ◽  
Equilibration Rate ◽  
Plasma Effect

Background Targeting the effect site concentration may offer advantages over the traditional forms of administrating intravenous anesthetics. Because the lack of the plasma effect site equilibration rate constant (ke0) for propofol in children precludes the use of this technique in this population, the authors estimated the value of ke0 for propofol in children using the time to peak effect (tpeak) method and two pharmacokinetic models of propofol for children. Methods : The tpeak after a submaximal bolus dose of propofol was measured by means of the Alaris A-Line auditory evoked potential monitor (Danmeter A/S, Odense, Denmark) in 25 children (aged 3-11 yr) and 25 adults (aged 35-48 yr). Using tpeak and two previously validated sets of pharmacokinetic parameters for propofol in children, Kataria's and that used in the Paedfusor (Graseby Medical Ltd., Hertfordshire, United Kingdom), the ke0 was estimated according to a method recently published. Results The mean tpeak was 80 +/- 20 s in adults and 132 +/- 49 s in children (P < 0.001). The median ke0 in children was 0.41 min(-1) with the model of Kataria and 0.91 min(-1) with the Paedfusor model (P < 0.01). The corresponding t1/2 ke0 values, in minutes, were 1.7 and 0.8, respectively (P < 0.01). Conclusions : Children have a significantly longer tpeak of propofol than adults. The values of ke0 of propofol calculated for children depend on the pharmacokinetic model used and also can only be used with the appropriate set of pharmacokinetic parameters to target effect site in this population.

The Influence of Age on Propofol Pharmacodynamics

1999 ◽  
Vol 90 (6) ◽  
pp. 1502-1516. ◽  
Author(s):  
Thomas W. Schnider ◽  
Charles F. Minto ◽  
Steven L. Shafer ◽  
Pedro L. Gambus ◽  
Corina Andresen ◽  
...  
Keyword(s):  
Rate Constant ◽  
Canonical Correlation ◽  
Drug Effect ◽  
Peak Effect ◽  
Pharmacodynamic Model ◽  
Time To Peak ◽  
Effect Site ◽  
Effect Site Concentration ◽  
Equilibration Rate ◽  
Plasma Effect

Background The authors studied the influence of age on the pharmacodynamics of propofol, including characterization of the relation between plasma concentration and the time course of drug effect. Methods The authors evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 mg/kg in persons older than 65 yr) and an infusion (25, 50, 100, or 200 microg x kg(-1) x min(-1)) of the older or the new (containing EDTA) formulation of propofol were given on each of two different study days. The propofol concentration was determined in frequent arterial samples. The electroencephalogram (EEG) was used to measure drug effect. A statistical technique called semilinear canonical correlation was used to select components of the EEG power spectrum that correlated optimally with the effect-site concentration. The effect-site concentration was related to drug effect with a biphasic pharmacodynamic model. The plasma effect-site equilibration rate constant was estimated parametrically. Estimates of this rate constant were validated by comparing the predicted time of peak effect with the time of peak EEG effect. The probability of being asleep, as a function of age, was determined from steady state concentrations after 60 min of propofol infusion. Results Twenty-four volunteers completed the study. Three parameters of the biphasic pharmacodynamic model were correlated linearly with age. The plasma effect-site equilibration rate constant was 0.456 min(-1). The predicted time to peak effect after bolus injection ranging was 1.7 min. The time to peak effect assessed visually was 1.6 min (range, 1-2.4 min). The steady state observations showed increasing sensitivity to propofol in elderly patients, with C50 values for loss of consciousness of 2.35, 1.8, and 1.25 microg/ml in volunteers who were 25, 50, and 75 yr old, respectively. Conclusions Semilinear canonical correlation defined a new measure of propofol effect on the EEG, the canonical univariate parameter for propofol. Using this parameter, propofol plasma effect-site equilibration is faster than previously reported. This fast onset was confirmed by inspection of the EEG data. Elderly patients are more sensitive to the hypnotic and EEG effects of propofol than are younger persons.

Maximizing Prediction Probability PK as an Alternative Semiparametric Approach to Estimate the Plasma Effect-Site Equilibration Rate Constant ke0

2009 ◽  
Vol 109 (5) ◽  
pp. 1470-1478 ◽  
Author(s):  
Richard K. Ellerkmann ◽  
Joergen Bruhn ◽  
Martin Soehle ◽  
Michael Kehrer ◽  
Andreas Hoeft ◽  
...  
Keyword(s):  
Rate Constant ◽  
Effect Site ◽  
Semiparametric Approach ◽  
Prediction Probability ◽  
Equilibration Rate ◽  
Plasma Effect
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