Population pharmacokinetic and pharmacodynamic model of propofol externally validated in children

Choi, Byung‐Moon; Lee, Hyun Gu; Byon, Hyo-Jin; Lee, Soo Han; Lee, Eun Kyung; Kim, Hee Soo; Noh, Gyu Jeong

doi:10.1007/s10928-015-9408-2

Cited by 34 publications

(39 citation statements)

References 51 publications

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“…The covariates analyzed included age, sex (0 = female, 1 = male), body weight, height, body surface area [13], lean body mass [14], ideal body weight [15], body mass index, cardiac output, cardiac index, stroke volume, SVV, stroke volume index, heart rate, systolic arterial pressure, diastolic arterial pressure, and mean arterial pressure. A non-parametric bootstrap analysis served to internally validate the models (fit4NM 3.3.3, Eun-Kyung Lee and Gyu-Jeong Noh; http:// cran.r-project.org/web/packages/fit4NM/index.html; last accessed 16 March 2011) [16]. Predictive checks were also performed using fit4NM 3.3.3 [7].…”

Section: Administration Of Ringer's Lactate Solutionmentioning

confidence: 99%

Population-based volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomy

Lee¹,

Choo

Lee

et al. 2018

Acta Pharmacol Sin

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In order to maintain stable blood pressure and heart rate during surgery, anesthesiologists need to administer the appropriate amount of fluid with appropriate fluid type to the patient, then quantifying how fluid is distributed and eliminated from the body is useful for establishing a fluid administration strategy. In this study we characterized the volume kinetics of Ringer's lactate solution in patients undergoing open gastrectomy. When propofol and remifentanil reached a pseudosteady state at the target concentration and blood pressure was stabilized following surgical stimulation, enrolled patients were administered 1000 mL of Ringer's lactate solution for 20 min, followed by continuous infusion at a rate of 6 mL/kg/h until the time of the last blood collection for volume kinetic analysis. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. The change in hemoglobin-derived plasma dilution induced by the administration of Ringer's lactate solution was evaluated by nonlinear mixed effects modeling. Three hundred and twenty-three plasma dilution data points from 27 patients were used to determine the pharmacokinetic characteristics of Ringer's lactate solution. A two-volume model best described the pharmacokinetics of Ringer's lactate solution. The mean arterial pressure (MAP) and body weight (WT) were significant covariates for the elimination clearance (k r ) and central volume of distribution at baseline (V c0 ), respectively. The parameter estimates were as follows: k r (mL/min) = 124 + (MAP/70) 14.2 , V c0 (mL) = 0.95 + 3440 × (WT/63), V t0 (mL) = 2730, and k t (mL/min) = 181. A higher MAP was associated with a greater elimination clearance and, consequently, less water accumulation in the interstitium. As body weight increases, volume expansion in the blood vessels increases.

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Section: Administration Of Ringer's Lactate Solutionmentioning

confidence: 99%

Population-based volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomy

Lee¹,

Choo

Lee

et al. 2018

Acta Pharmacol Sin

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“…The covariates analysed were age, sex (0 = male, 1 = female), weight, height, body surface area [38], body mass index, ideal body weight [39], and lean body mass [29]. Nonparametric bootstrap analysis served to validate the models internally (fit4NM 3.5.1, Eun-Kyung Lee and Gyu-Jeong Noh, http://cran.r-project.org/web/packages/fit4NM/index.html, last access: Oct 11, 2011) [40]. …”

Section: Methodsmentioning

confidence: 99%

Spectral Gini Index for Quantifying the Depth of Consciousness

You

Noh

Shin

2016

Computational Intelligence and Neuroscience

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We propose indices that describe the depth of consciousness (DOC) based on electroencephalograms (EEGs) acquired during anesthesia. The spectral Gini index (SpG) is a novel index utilizing the inequality in the powers of the EEG spectral components; a similar index is the binarized spectral Gini index (BSpG), which has low computational complexity. A set of EEG data from 15 subjects was obtained during the induction and recovery periods of general anesthesia with propofol. The efficacy of the indices as indicators of the DOC was demonstrated by examining Spearman's correlation coefficients between the indices and the effect-site concentration of propofol. A higher correlation was observed for SpG and BSpG (0.633 and 0.770, resp., p < 0.001) compared to the conventional indices. These results show that the proposed indices can achieve a reliable quantification of the DOC with simplified calculations.

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“…The Akaike Information‐theoretic Criterion (AIC) was used to compare non‐nested models instead of the likelihood ratio criterion as follows: AIC = −2 LL + 2 P , where −2 LL is the minimum value of the objective function produced by NONMEM, and P denotes the number of parameters. The relative standard error was calculated as the standard error divided by the estimate for evaluating the precision of the parameter estimated . R software (version 3.1.2; R Foundation for Statistical Computing, Vienna, Austria) was used for graphical model diagnoses.…”

Section: Methodsmentioning

confidence: 99%

“…The median weighted residuals and median absolute weighted residuals were calculated to examine the quality of the predictions from the pharmacodynamic models for TLMC and ApEn. A nonparametric bootstrap analysis was used to internally validate the models (fit4NM 3.7.9, Eun‐Kyung Lee and Gyu‐Jeong Noh, http://www.fit4nm.org/download, last accessed: October 17, 2011) . Briefly, 2000 bootstrap replicates were generated via random sampling from the original dataset, with replacement.…”

Section: Methodsmentioning

confidence: 99%

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Response surface modelling of the pharmacodynamic interaction between propofol and remifentanil in patients undergoing anaesthesia

Choe

Choi

Lee

et al. 2016

Clin Exp Pharma Physio

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This study describes the pharmacodynamic interaction between propofol and remifentanil. Sixty patients who were scheduled for elective surgery under general anaesthesia (30 males/30 females) were enrolled. Patients were randomly allocated to receive one of 15 combinations of drug levels. Baseline electroencephalograms (EEGs) were recorded for 5 minutes prior to administering the drugs. Patients received a target-controlled infusion at one of four predefined doses of propofol (high, 3 μg/mL; medium, 1.5 μg/mL; low, 0.5 μg/mL; or no drug) and of remifentanil (high, 6 or 8 ng/mL; medium, 4 ng/mL; low, 2 ng/mL; or no drug). The occurrence of muscle rigidity, apnoea, and loss of consciousness (LOC) was monitored, and EEGs were recorded during the drug administration phase. Electroencephalographic approximate entropy (ApEn) and temporal linear mode complexity (TLMC) parameters at baseline and under steady state conditions were calculated off-line. Response surfaces were developed to map the interaction between propofol and remifentanil to the probability of occurrence for quantal responses (muscle rigidity, apnoea, LOC) and ApEn and TLMC measurements. Model parameters were estimated using non-linear mixed effects modelling. The response surface revealed infra-additive and synergistic effects for muscle rigidity and apnoea, respectively. The effects of the combined drugs on LOC and EEG parameters (eg, ApEn and TLMC) were additive. The C estimates of remifentanil (ng/mL) and propofol (μg/mL) were 9.11 and 130 000 for muscle rigidity, 8.99 and 6.26 for apnoea, 13.9 and 3.04 for LOC, 23.4 and 10.4 for ApEn, and 14.8 and 6.51 for TLMC, respectively. The probability of occurrence for muscle rigidity declined when propofol was combined with remifentanil.

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Population pharmacokinetic and pharmacodynamic model of propofol externally validated in children

Cited by 34 publications

References 51 publications

Population-based volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomy

Population-based volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomy

Spectral Gini Index for Quantifying the Depth of Consciousness

Response surface modelling of the pharmacodynamic interaction between propofol and remifentanil in patients undergoing anaesthesia

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