Effect of Altered Volume of Distribution on Aminoglycoside Levels in Patients in Surgical Intensive Care

The apparent volume of distribution (Vd) of aminoglycosides was found to be increased in 100 patients in a surgical intensive care unit who had gram-negative pneumonia or intraabdominal sepsis and acute physiologic scores greater than 12. Following loading or maintenance doses, carefully timed blood samples were collected for measurements of serum concentrations by fluorescence polarization immunoassay. The Vd, determined by linear regression analysis of a one-compartment model using the Sawchuk-Zaske method, was 0.34 +/- 0.121 L/kg and was larger than the normal Vd of 0.20 to 0.25 L/kg, suggesting a 36% to 70% increase in extracellular fluid volume. Since there is a predictable increase in aminoglycoside Vd in the septic surgical patient, a proportionately larger aminoglycoside dosage is required initially to achieve desirable peak serum levels. Close monitoring of blood levels during maintenance dosing is suggested since dynamic changes in renal function and aminoglycoside Vd occur in the critically ill.