Drug administration in critically ill patients with acute renal failure

Patients with acute renal failure are commonly treated by continuous renal replacement therapies. To understand drug disposition in multiple organ failure patients, the pharmacokinetics of 18 drugs were evaluated in 243 patients. Continuous hemofiltration served as a model for constant elimination rates. In addition, the elimination of drugs was investigated during extracorporeal lung support. The dosage of 11 of 15 drugs had to be reduced as a result of these kinetic studies. Wide variability in volumes of distribution, clearances, and the extrarenal fractions of elimination were detected. There was a close correlation of the latter with Acute Physiology and Chronic Health Evaluation II scores of illness severity. A new algorithm was developed for primary estimates of drug dosage during hemofiltration and other organ support systems. Two in vitro studies confirmed the clinical results on drug sieving and provided important information on adsorption to membranes. A clinical validation study of the algorithm improved drug dosage. A simplified therapeutic drug monitoring approach is given.