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Physiologic response of stress and aminoglycoside clearance in critically ill patients
D A Tholl1, L R Shikuma, T Q Miller
1Section of Clinical Pharmacy, St. Paul-Ramsey Medical Center, MN 55101.
Objective:
To examine the relationships between aminoglycoside clearance and physiologic parameters associated with the physiologic response to injury.
Design:
Cross-sectional study of surgical patients receiving aminoglycoside pharmacokinetic monitoring and parenteral nutritional support.
Setting:
An adult surgical ICU.
Patients:
Fifty-four surgical/trauma patients who had Gram-negative sepsis.
Interventions:
Measurements of the physiologic stress response to injury were associated with aminoglycoside clearance in 54 surgical/trauma patients who had Gram-negative sepsis. Measurements used to estimate the magnitude of the stress response included a 24-hr urinary urea nitrogen excretion, blood urea nitrogen, peak temperature, serum albumin, bilirubin, and transferrin concentrations.
Measurements And Main Results:
Mean drug clearance rate (4.4 +/- 2.5 [SD] L/hr) was related to the physiologic measurements using correlation and regression techniques. Collectively, all physiologic indices (utilized) explained 59% of the variance in drug clearance (p < .001), an amount similar to the variance explained by creatinine clearance alone (53%). When all six physiologic measurements were included into a multiple regression model that included creatinine clearance, the total variance explained increased to 73%.
Conclusions:
Along with renal function estimates, the physiologic response to stress should be considered when treating critically ill patients with aminoglycosides and other, similar, renally eliminated drugs.