G. Lugo et G. Castanedahernandez, RELATIONSHIP BETWEEN HEMODYNAMIC AND VITAL SUPPORT MEASURES AND PHARMACOKINETIC VARIABILITY OF AMIKACIN IN CRITICALLY ILL PATIENTS WITH SEPSIS, Critical care medicine, 25(5), 1997, pp. 806-811
Objective: To examine the relationship between aminoglycoside disposit
ion kinetics and hemodynamic response to sepsis, as well as vital supp
ort therapy, in critically ill patients with sepsis. Design: Cross sec
tional study of critically ill patients with sepsis undergoing physiol
ogic and aminoglycoside pharmacokinetic monitoring. Setting: Ten bed g
eneral intensive care unit in a tertiary care center. Patients: Thirty
consecutive critically ill patients who had Gramnegative sepsis treat
ed with amikacin and who were undergoing hemodynamic monitoring. Inter
ventions: Clinical, hemodynamic, oxygenation, and amikacin pharmacokin
etic data were obtained simultaneously in each patient during aminogly
coside therapy. Measurements and Main Results: Aminoglycoside pharmaco
kinetic values were estimated from serum amikacin concentration time
data using a nonlinear least squares regression computer program, assu
ming a one-compartment infusion pharmacokinetic model. Individual phar
macokinetic values were subjected to statistical analysis to explain t
heir variability. Selection of the subset of variables to be used in t
he final model was performed by combining principal component analysis
and multiple stepwise linear regression. The mean prediction error an
d the root mean square error, as expressions of bias and precision, we
re estimated. Mean volume of distribution was 0.47 L/kg, with a coeffi
cient of variation of 35%. Mean serum amikacin clearance was 60.2 mL/m
in, with a coefficient of variation of 34%. Seventy-six percent of the
variability in volume of distribution was explained by three covariat
es: body weight (p < .0001); oxygen extraction (p < .001); and serum a
lbumin (p < .001). For serum amikacin clearance, 70% of the variabilit
y was explained by three covariates: creatinine clearance (p < .001);
positive end-expiratory pressure (p < .01); and use of catecholamines
as vital support therapy (p < .05). Conclusions: Factors related to he
modynamic response and vital support measures have a significant influ
ence on the disposition kinetics of amikacin in severely ill patients
with sepsis. Consideration of hemodynamic response and vital support m
easures, in addition to other previously described covariates, can be
of great value in the design of initial dosing regimens.