Critically-ill patients receiving total parenteral nutrition show altered amikacin pharmacokinetics

The purpose of this clinical study was to characterise the kinetic behavior ofamikacin in the parenterally-fed critically-ill adult patient. 22 critically-ill adult patients treated with amikacin (15.5 ± 7.9 mg/kg/day) for severe gram-negative infections were enrolled into a nonrandomised control trial. Malnourished patients were administered total parenteral nutrition (TPN, n = 11), while well-nourished patients received fluid therapy (FT, n = 11). Amikacin pharmacokinetic parameters were estimated by non-linear regression analysis, assuming a one-compartment model and central first-order elimination. Patients receiving TPN showed an expanded amikacin distribution volume (0.403 ± 0.0961/kg vs. FT 0.298 ± 0.083 l/kg, p < 0.05), and a tendency towards increased total body clearance (0.089 ± 0.029 l/kg/h vs. FT 0.069 ± 0.0201/kg/h, p = 0.09). TPN produced lower peak concentrations (19.3 ± 3.1 mcg/ml vs. 23.1 ± 3.5 mcg/ml, p < 0.05), but had no significant influence on trough concentrations (p = 0.56). Patients on TPN also showed increased body temperature (p < 0.05) and fluid intake (p < 0.05), and decreased hematocrit (p < 0.05). Stress, malnutrition, parenteral nutrition itself, fluid and osmotic overload, and fever often occur concurrently in parenterally-fed patients and appear to produce lower amikacin serum levels. Consequently, critically-ill patients receiving TPN need higher amikacin doses and individualised treatment by monitoring serum concentrations, to ensure optimal therapeutic response.