Pharmacokinetics and pharmacodynamics in critically ill patients.

Abstract

AbstractThe rapidly changing physiology of critically ill patients causes variations in the absorption, distribution, metabolism, excretion, and pharmacodynamic effect of drugs used to treat these patients. Alterations in fluid status, cardiac, renal and hepatic function, and circulating serum proteins necessitate increased attention to drug selection and dosage modification. Cardiac failure results in decreased absorption, metabolism, and excretion of drugs while renal failure results in parent drug and metabolite accumulation, increases in unbound drug, and changes in distribution volume. The changes in hepatic blood flow and protein binding, and decreases in hepatocellular mass and enzyme function that occur in hepatic failure may alter the clearance of several drugs. Serum drug concentrations are helpful in defining the pharmacokinetics and ultimately the pharmacodynamic effect of the drugs used in critically ill patients. The serum drug concentrations must be interpreted in association with their pharmacodynamic effect and the clinical situation. Adjusting drug therapy based on pharmacokinetic principles is discussed in detail with specific suggestions for dosage modifications in renal and hepatic failure.