Impact of altered aminoglycoside volume of distribution on the adequacy of a three milligram per kilogram loading dose. Critical Care Research Group

Abstract

Background: Sepsis is associated with an increased volume of distribution for aminoglycoside antibiotics. As a result of this increased volume of distribution, 2 mg/kg loading doses have previously been shown to be ineffective in producing adequate aminoglycoside peak plasma levels in critically ill patients. The main objective of this pharmacokinetic observational study was to determine the adequacy of a 3 mg/kg loading dose of gentamicin or tobramycin in attaining an initial peak level of 8 micrograms/ml or greater.

Methods: Fifty-three consecutive patients given gentamicin or tobramycin for documented or suspected life-threatening gram-negative infections were enrolled. Loading doses of either aminoglycoside were administered during 30 minutes, and a peak level was obtained 1 hour after completed infusion.

Results: The patient's mean age was 61 +/- 2 years, with a male/female ratio of 33:20. The loading dose of 3 mg/kg produced 1-hour peak aminoglycoside levels greater than 8 micrograms/ml in only 50% of the patients studied. The calculated aminoglycoside volume of distribution was increased by 34%.

Conclusions: An aminoglycoside loading dose of 3 mg/kg is inadequate in critically ill patients undergoing operation. The documented increase in volume of distribution is principally responsible for the inadequacy of this dose. Future studies should use a 4 mg/kg loading dose to maximize aminoglycoside bactericidal activity.