J Clin Monit Comput - Pharmacodynamic modeling of propofol-induced tidal volume depression in children.


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JECTIVE: This investigation aimed to develop a pediatric pharmacodynamic model of propofol-induced tidal volume depression towards an ultimate goal of developing a dosing schedule that would preserve spontaneous breathing following a loading dose of propofol.METHODS: Fifty two ASA 1 and 2 children aged 6-15?year presenting for gastrointestinal endoscopy were enrolled. Subjects were administered a loading dose of 4?mg/kg of propofol intravenously at a constant infusion rate determined by a randomization schedule. Respiratory parameters including tidal volume, respiratory rate, minute volume, and end-tidal CO(2) were recorded at 5?s intervals. Using the predicted plasma concentration, based on the Paedfusor pharmacokinetic model, propofol-induced tidal volume depression was modeled by 3 different approaches (2-stage, pooled, and mixed effects) and results were compared using prediction residual, median percentage errors, median absolute percentage errors, and root-mean-squared normalized errors. The effects of age and body weight as covariates were examined.RESULTS: Respiratory rate and end-tidal CO(2) did not show clear dependence on the predicted plasma concentration. The pharmacodynamic models for tidal volume derived from different modeling approaches were highly consistent. The 2-stage, pooled, and mixed effects approaches yielded k(e0) of 1.06, 1.24, and 0.72?min(-1); of 1.10, 0.83, and 0.93; EC50 of 3.18, 3.44, and 3.00?mcg/ml. Including age and body weight as covariates did not significantly improve the predictive performance of the models.CONCLUSIONS: A pediatric pharmacodynamic model of propofol-induced tidal volume depression was developed. Models derived from 3 different approaches were shown to be consistent with each other; however, the individual pharmacodynamic parameters exhibited significant inter-individual variability without strong dependence on age and body weight. This would suggest the desirability of adapting the pharmacodynamic model to each subject in real time.

Resumo Limpo

jectiv investig aim develop pediatr pharmacodynam model propofolinduc tidal volum depress toward ultim goal develop dose schedul preserv spontan breath follow load dose propofolmethod fifti two asa children age year present gastrointestin endoscopi enrol subject administ load dose mgkg propofol intraven constant infus rate determin random schedul respiratori paramet includ tidal volum respiratori rate minut volum endtid co record s interv use predict plasma concentr base paedfusor pharmacokinet model propofolinduc tidal volum depress model differ approach stage pool mix effect result compar use predict residu median percentag error median absolut percentag error rootmeansquar normal error effect age bodi weight covari examinedresult respiratori rate endtid co show clear depend predict plasma concentr pharmacodynam model tidal volum deriv differ model approach high consist stage pool mix effect approach yield ke min ec mcgml includ age bodi weight covari signific improv predict perform modelsconclus pediatr pharmacodynam model propofolinduc tidal volum depress develop model deriv differ approach shown consist howev individu pharmacodynam paramet exhibit signific interindividu variabl without strong depend age bodi weight suggest desir adapt pharmacodynam model subject real time

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