[Infection-induced change in the pharmacokinetics of cefotaxime. Dose calculation in multiple organ failure and relevance of score systems].
The pharmacokinetics of cefotaxime were investigated in 14 patients suffering from multiple-organ failure requiring pump-assisted, continuous volume-constant hemofiltration (CVHF) for blood purification, whereby the filtration rate was 20 ml/min. Samples of blood and ultrafiltrate were evaluated by high-pressure liquid chromatography. For dose adjustment, three different algorithms of Dettli and Kroh were used. As compared with values obtained for anuric patients during the dialysis-free period, the mean serum half-life was nearly doubled (2.75 vs 4.48 h). This reduced elimination depended mainly on a diminished non-renal elimination ratio ranging from 0.085 to 0.366. The volume of distribution remained unchanged within a wide interindividual range (Vz, 0.35 l/kg, from 0.22 to 0.56 l/kg); the sieving coefficient increased to 0.89 as compared with 0.62 in healthy volunteers. Dose adjustment by algorithms showed varied degrees of over-dosage. The estimate closest to an optimal dose was reached by the application of a new algorithm of Kroh (mean dose deviation +19%; SD, +/- 27%) using an individual non-renal elimination ratio (QIND). QIND correlated significantly with the severity of disease according to the sepsis score of Elebute and Stoner (r = 0.763, P less than 0.005). Thus, it is possible to adjust reliably individual dosage in multiple-organ failure and to reduce the frequency of drug monitoring required.