scholarly journals Estimation of the effect-site equilibration rate constant using the time-to-peak effect of muscle relaxants measured by train-of-four stimulation during general anesthesia induction

2018 ◽  
Vol 71 (2) ◽  
pp. 113-119
Author(s):  
Se Yeon Park ◽  
Hyun Jung Kim ◽  
Yun Suk Choi ◽  
So-hui Yun ◽  
Jong Cook Park
Keyword(s):  
General Anesthesia ◽  
Rate Constant ◽  
Peak Effect ◽  
Muscle Relaxants ◽  
Anesthesia Induction ◽  
Time To Peak ◽  
Effect Site ◽  
Train Of Four ◽  
Equilibration Rate

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.

Comparison of Plasma Compartment versus  Two Methods for Effect Compartment–controlled Target-controlled Infusion for Propofol

2000 ◽  
Vol 92 (2) ◽  
pp. 399-399 ◽  
Author(s):  
Michel M. R. F. Struys ◽  
Tom De Smet ◽  
Birgit Depoorter ◽  
Linda F. M. Versichelen ◽  
Eric P. Mortier ◽  
...  
Keyword(s):  
Time Course ◽  
Drug Effect ◽  
Peak Effect ◽  
Effect Compartment ◽  
Loss Of Consciousness ◽  
Group Iii ◽  
Time To Peak ◽  
Effect Site ◽  
Effect Site Concentration ◽  
Plasma Effect

Background Target-controlled infusion (TCI) systems can control the concentration in the plasma or at the site of drug effect. A TCI system that targets the effect site should be able to accurately predict the time course of drug effect. The authors tested this by comparing the performance of three control algorithms: plasmacontrol TCI versus two algorithms for effect-site control TCI. Methods One-hundred twenty healthy women patients received propofol via TCI for 12-min at a target concentration of 5.4 microg/ml. In all three groups, the plasma concentrations were computed using pharmacokinetics previously reported. In group I, the TCI device controlled the plasma concentration. In groups II and III, the TCI device controlled the effect-site concentration. In group II, the effect site was computed using a half-life for plasma effect-site equilibration (t1/2k(eo)) of 3.5 min. In group III, plasma effect-site equilibration rate constant (k(eo)) was computed to yield a time to peak effect of 1.6 min after bolus injection, yielding a t1/2keo of 34 s. the time course of propofol was measured using the bispectral index. Blood pressure, ventilation, and time of loss of consciousness were measured. Results The time course of propofol drug effect, as measured by the bispectral index, was best predicted in group III. Targeting the effect-site concentration shortened the time to loss of consciousness compared with the targeting plasma concentration without causing hypotension. The incidence of apnea was less in group III than in group II. Conclusion Effect compartment-controlled TCI can be safely applied in clinical practice. A biophase model combining the Marsh kinetics and a time to peak effect of 1.6 min accurately predicted the time course of propofol drug effect.

scholarly journals Pharmacokinetic-Pharmacodynamic Modeling of Propofol in Children

2010 ◽  
Vol 113 (2) ◽  
pp. 343-352 ◽  
Author(s):  
Agnes Rigouzzo ◽  
Frederique Servin ◽  
Isabelle Constant
Keyword(s):  
Peak Effect ◽  
Concentration Effect ◽  
Pharmacodynamic Modeling ◽  
Maximal Effect ◽  
Time To Peak ◽  
Effect Site ◽  
Mixed Effects Modeling ◽  
Effect Site Concentration ◽  
Relationship Of ◽  
The Relationship

Background The aim of this study was to identify the best model to describe pharmacokinetics and pharmacodynamics in prepubertal children and therefore to calculate the corresponding pharmacodynamic parameters. In addition, and to confirm our method, a group of postpubertal subjects was also studied. Methods Sixteen children (9.5 yr, range 6-12) and 13 adults (22 yr, range 13-35) were included. Induction was performed by plasma target-controlled infusion of propofol (6 microg/ml) based on the Kataria model in children and on the Schnider model in adults. The relationship of bispectral index to predicted concentrations was studied during induction using the Kataria, pediatric Marsh, Schüttler, and Schnider models in children. Because the best performance was obtained, strangely enough, with the Schnider model, the two groups were pooled to investigate influence of puberty on pharmacodynamic parameters (kE0 [plasma effect-site equilibration rate constant] and Ce50 [effect-site concentration corresponding with 50% of the maximal effect]). The time-to-peak effect was calculated, and the kE0 was determined for the Kataria model (nonlinear mixed-effects modeling; pkpdtools). Results In children, the predicted concentration/effect relationship was best described using the Schnider model. When the whole population was considered, a significant improvement in this model was obtained using puberty as a covariate for kE0 and Ce50. The time to peak effect, Tpeak (median, 0.71 [range, 0.37-1.64] and 1.73 [1.4-2.68] min), and the Ce50 (3.71 [1.88-4.4] and 3.07 [2.95-5.21] microg/ml) were shorter and higher, respectively, in children than in adults. The kE0 linked to the Kataria model was 4.6 [1.4-11] min. Conclusions In children, the predicted concentration/effect relationships were best described using the Schnider model described for adults compared with classic pediatric models. The study suggests that the Schnider model might be useful for propofol target-control infusion in children.

Prospective evaluation of the time to peak effect of propofol to target the effect site in children

2009 ◽  
Vol 53 (7) ◽  
pp. 883-890 ◽  
Author(s):  
H. R. MUÑOZ ◽  
P. J. LEÓN ◽  
R. S. FUENTES ◽  
G. C. ECHEVARRÍA ◽  
L. I. CORTÍNEZ
Keyword(s):  
Peak Effect ◽  
Prospective Evaluation ◽  
Time To Peak ◽  
Effect Site

Mivacurium Neuromuscular Block at the Adductor Muscles of the Larynx and Adductor Pollicis in Humans

1996 ◽  
Vol 85 (1) ◽  
pp. 77-81 ◽  
Author(s):  
Benoit Plaud ◽  
Bertrand Debaene ◽  
Frank Lequeau ◽  
Claude Meistelman ◽  
Francois Donati
Keyword(s):  
Neuromuscular Block ◽  
Onset Time ◽  
Pressure Change ◽  
Peak Effect ◽  
Adductor Pollicis ◽  
Vocal Cords ◽  
Laryngeal Muscles ◽  
Time To Peak ◽  
Adductor Muscles ◽  
Train Of Four

Background Laryngeal muscles must be paralyzed for tracheal intubation. Time to peak effect (onset time) is shorter and intensity of blockade is less at laryngeal muscles compared with the adductor pollicis. The authors' aim in this study was to determine the neuromuscular effects of mivacurium at the laryngeal adductor muscles and the adductor pollicis. Methods In 22 adults, anesthesia was induced and maintained with propofol and alfentanil. The force of contraction of the adductor pollicis was recorded, and the laryngeal response was evaluated by measuring the pressure change in the cuff of a tracheal tube positioned between the vocal cords after train-of-four stimulation. Mivacurium (0.07 mg.kg-1 or 0.14 mg.kg-1) was given intravenously (10s). Results With 0.07 mg.kg-1 mivacurium, onset time was 151 +/- 40 s(mean +/- SD) at the larynx and 241 +/- 79 s at the adductor pollicis, respectively (P < 0.005). Maximum block was 78 +/- 18% and 95 +/- 8%, respectively (P < 0.002), and time to 90% recovery was 11.1 +/- 2.9 min and 23.3 +/- 7.6 min, respectively (P < 0.001). With 0.14 mg.kg-1 mivacurium, onset time also was more rapid at the vocal cords (137 +/- 20 s) than at the adductor pollicis (201 +/- 59 s, P < 0.01). Maximum block was 90 +/- 7% and 99 +/- 1% (P < 0.005), and time to 90% recovery was 16.4 +/- 4.9 min and 27.4 +/- 7.8 min, respectively (P < 0.01). Conclusions With mivacurium, onset and recovery are faster at the laryngeal muscles, but block is less intense than at the adductor pollicis. A dose greater than 0.14 mg.kg-1 mivacurium is necessary to ensure complete relaxation at the vocal cords.

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