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.


METHODS
Cross-sectional study of surgical patients receiving aminoglycoside pharmacokinetic monitoring and parenteral nutritional support.


METHODS
An adult surgical ICU.


METHODS
Fifty-four surgical/trauma patients who had Gram-negative sepsis.


METHODS
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.


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.
Tholl
D A
DA
Section of Clinical Pharmacy, St. Paul-Ramsey Medical Center, MN 55101.
Shikuma
L R
LR
Miller
T Q
TQ
Woodward
J M
JM
Cerra
F B
FB
Zaske
D E
DE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000493:pharmacokinetics*; D001806:Blood Urea Nitrogen; D003430:Cross-Sectional Studies; D005260:Female; D005839:Gentamicins / Q000493:pharmacokinetics / Q000627:therapeutic use; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007362:Intensive Care Units; D007668:Kidney / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010288:Parenteral Nutrition; D013312:Stress, Physiological / Q000378:metabolism*; D014947:Wounds and Injuries / Q000378:metabolism* / Q000503:physiopathology
D000617:Aminoglycosides; D005839:Gentamicins