The pharmacodynamics of isoflurane in children using Bispectral index and composite auditory evoked potentials HJ Bluss

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The pharmacodynamics of isoflurane in children
using Bispectral index and composite auditory
evoked potentialsHJ Blussé van Oud-Alblas (1),
MYM Peeters (3), MJE Brill (4), CAJ Knibbe
(2,3,4), J Klein (1), D Tibboel (2), M Danhof
(4), F Weber (1)1 Department of Anesthesiology,
Erasmus Medical Center Sophia Childrens
Hospital, Rotterdam, The Netherlands2 Department
of Pediatric Intensive Care, Erasmus Medical
Center - Sophia Childrens Hospital, Rotterdam,
The Netherlands3 Department of Clinical
Pharmacy, St. Antonius Hospital, Nieuwegein, The
Netherlands4 Division of Pharmacology,
Leiden/Amsterdam Center for Drug Research, Leiden
University, Leiden, The Netherlands
OBJECTIVES Bispectral index (BIS), derived from
the electroencephalography (EEG), and the
composite A-line autoregressive index (cAAI),
derived from both the EEG and auditory evoked
potentials, have been promoted as monitors of
depth of anaesthesia. The aim of the study was to
characterize the relationship between isoflurane
end-tidal concentrations and its effect measured
by BIS and cAAI in children.
METHODS Twenty children, aged 3-16 years,
undergoing standardized isoflurane anaesthesia
for cardiac catherization, were enrolled.
Population pharmacodynamic modelling and
covariate analysis was performed using NONMEM VI.

RESULTS The relationship between isoflurane and
effect was best described for the BIS by an
indirect sigmoid Emax model and a direct opposite
Emax model for the cAAI. The pharmacodynamic
parameters are shown in Table 1. For the BIS, the
EC50 was higher (1.31 versus 0.38) and the Hill
coefficient lower (2.63 versus 7.88). The EC50
using the BIS as endpoint decreased linearly with
age (-2LL decrease of 7.77). No covariates were
found for the cAAI.
CONCLUSIONS Compared to the BIS, the cAAI is
more sensitive to isoflurane and is associated
with an on-off response with no time delay in
response calculation, which is reflected by the
lower EC50, the steeper Hill coefficient and the
direct model. Higher end-tidals isoflurane
concentrations are needed in younger children, as
age is a covariate using the BIS as an endpoint.
At this stage there is little evidence to suggest
superiority for cAAI over BIS.