• Luis Ignacio Cortínez and Brian J Anderson.
• Division Anestesiologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, de Chile.
• Paediatr Anaesth. 2018 Oct 1; 28 (10): 834-840.

BackgroundSevoflurane pharmacokinetics have been traditionally described using physiological models, while pharmacodynamics employed the use of minimal alveolar concentration.AimsThe integrated pharmacokinetic-pharmacodynamic relationship of sevoflurane in both adults and children was reviewed using compartment models. We wished to delineate age-related changes in both pharmacokinetics and pharmacodynamics.MethodsThe bispectral index and sevoflurane endtidal concentration were continuously measured in 50 patients, aged 3-71 years, scheduled for minor surgery. During maintenance of anesthesia and after stable bispectral index values of 60-65 were obtained, the inspired concentration of sevoflurane was increased to 5 vol % for 5 minutes or until BIS 40 and then decreased. Data were analyzed using mammillary compartments with nonlinear mixed effects population modeling. The covariate effects of age and size were investigated.ResultsA three-compartment PK model adequately described sevoflurane pharmacokinetics. Size standardization using allometry explained clearance and volume changes with age. The equilibration half-time (1.48 minutes) increased with age, but could be predicted using allometry in those under 40 years. The effect site concentration eliciting half the maximum response at age 40 years was 1.3% (95%CI 1.22, 1.42) decreased with age from 1.6% at 3 years to 1.1% at 70 years.ConclusionPharmacokinetic compartment models offer an alternative method to describe inhalation anesthetic drug disposition and effects.© 2018 John Wiley & Sons Ltd.

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