Physiologic response of stress and aminoglycoside clearance in critically ill patients.

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.