IMPACT OF ALTERED AMINOGLYCOSIDE VOLUME OF DISTRIBUTION ON THE ADEQUACY OF A 3 MILLIGRAM PER KILOGRAM LOADING DOSE

Background. Sepsis is associated with an increased volume of distribut ion for aminoglycoside antibiotics. As a result of this increased volu me of distribution, 2 mg/kg loading doses have previously been shown t o be ineffective in producing adequate aminoglycoside peak plasma leve ls in critically ill patients. The main objective of this pharmacokine tic observational study was to determine the adequacy of a 3 mg/kg loa ding dose of gentamicin or tobramycin in attaining an initial peak lev el of 8 mu g/ml or greater. Methods. Fifty-three consecutive patients given gentamicin or tobramycin for documented or suspected life-threat ening gram-negative infections were enrolled. Loading doses of either aminoglycoside were administered during 30 minutes, and a peak level w as obtained 1 hour after completed infusion. Results. The patient's me an age was 61 +/- 2 years, with a male/female ratio of 33:20. The load ing dose of 3 mg/kg produced 1-hour peak aminoglycoside levels greater than 8 mu g/ml in only 50% of the patients studied. The calculated am inoglycoside 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 ami noglycoside bactericidal activity.