Influence of renal replacement therapy on pharmacokinetics in critically ill patients

Critical illness has a great impact on many pharmacokinetic parameters. An increased volume of distribution often results in drug underdosing, whereas organ impairment may lead to drug accumulation and overdosing. Renal replacement therapy (RRT) in critically ill patients with renal failure may significantly increase drug clearance, requiring drug-dosing adjustments. Drugs significantly eliminated by the kidney are likely to experience substantial removal during RRT, and a supplemental dose--corresponding to the amount of drug removed by RRT--should be administered. Mechanisms of drug removal during RRT are reviewed together with methods for measuring or estimating RRT drug clearances. Approaches for drug-dosing adjustments are suggested and, at the end, the pharmacological principles for antibiotic prescription in the critically ill are discussed.