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Anesth Analg 2008; 107:1566-1572
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e318181f013
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ANESTHETIC PHARMACOLOGY

The Influence of Age on the Dynamic Relationship Between End-Tidal Sevoflurane Concentrations and Bispectral Index

Luis I. Cortínez, MD*, Iñaki F. Trocóniz, PhD{dagger}, Ricardo Fuentes, MD*, Pedro Gambús, MD{ddagger}, Yung-Wei Hsu, MD§, Fernando Altermatt, MD*, and Hernán R. Muñoz, MD, MSc*

From the *Departamento de Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile. Santiago, Chile; {dagger}Department of Pharmacy; School of Pharmacy; University of Navarra; Pamplona, Spain; {ddagger}Department of Anesthesiology, Hospital CLINIC, Universidad de Barcelona, CIBERehd, IDIBAPS, Barcelona, Spain; and §Department of Anesthesiology, Mackay Memorial Hospital, Taiwan.

Address correspondence and reprint requests to Dr. Luis I. Cortínez, Departmento de Anestesiología, Hospital Clínico U.C., Marcoleta 367, Santiago, Chile. Address e-mail to licorti{at}med.puc.cl.

BACKGROUND: Age is an important determinant of the pharmacokinetic profile of inhaled anesthetics. The influence of age on the dynamic profile of sevoflurane’s effect has not been well described. We performed this study to characterize the influence of age and other covariates on the dynamic relationship between sevoflurane end-tidal concentration (CET) and its effect measured by bispectral index (BIS).

METHODS: Fifty patients, aged 3–71 yr, scheduled for minor surgery were prospectively studied. The BIS and sevoflurane CET were continuously measured during the study period. During maintenance of anesthesia and after stable BIS values of 60–65 were obtained, the inspired concentration of sevoflurane was increased to 5 vol % for 5 min or until BIS <40 and then decreased. The dynamic relationship between sevoflurane CET and its effect as measured by BIS during this transition period were modeled with an inhibitory Emax model using a population pharmacokinetic–pharmacodynamic approach with NONMEM V. A predictive check method was used to validate the final model.

RESULTS: The sensitivity to sevoflurane’s effect as measured by BIS expressed in the C50 [steady-state CET eliciting half of maximum response (Imax)] increased with age. The speed of change of sevoflurane’s effect, expressed as the effect–site equilibration half-life (t1/2 ke0), increased at older ages. The predictive check analysis confirmed the adequacy of the model.

CONCLUSIONS: Age significantly affects the dynamic relationship between sevoflurane CET and its effect measured with BIS.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2008 by the International Anesthesia Research Society.