Gentamicin volume of distribution in critically ill septic patients

Gentamicin intrapatient pharmacokinetics variations were studied in 40 critically ill medical patients, suffering gram-negative sepsis. These patients were studied in two phases throughout gentamicin treatment: firstly, on the second day of treatment, when aggressive fluid therapy was required, and secondly, five days later, when patients had achieved a more stable clinical condition. Pharmacokinetic parameters were determined using least squares linear regression analysis assuming a one-compartment model using the Sawchuk-Zaske method. The apparent volume of distribution (Vd) in the first phase of the study was 0.43±0.12 L/kg, while on the seventh day of treatment it was 0.29±0.17 L/kg (p<0.001). Statistically significant differences were also observed for peak serum concentration (p<0.001), total dosage recommended (p<0.001) and half-life (p<0.05), whilst differences were not found for trough levels. From the analysis of the results obtained, we recommend increasing the initial dosage and monitoring plasma levels within the first days of therapy in critically ill patients treated with gentamicin, since important variations in aminoglycoside Vd related to disease, fluid balance and renal function, commonly occur in these patients. © 1990 Springer-Verlag.