title: Challenges in Individualizing Drug Dosage for Intensive Care Unit Patients: Is Augmented Renal Clearance What We Really Want to Know? Some Suggested Management Approaches and Clinical Software Tools.
abstract: Acutely ill intensive care unit (ICU) patients often have large apparent volumes of distribution of drugs and, because of this, their drug clearance (CL) is usually also increased. 'Augmented renal Cl' is a current issue in the management of drug therapy for acutely ill and unstable ICU patients; however, Cl, the product of volume and the rate constant for excretion, describes only a theoretical volume of drug cleared per unit of time. Information of the actual rate of movement of the drug itself is obscured. It is suggested that the most useful clinical information is given by describing drug volume and elimination rate constant separately. This also permits better understanding of the patient's separate issues of fluid balance and drug elimination, especially when dialysis, renal replacement therapy, or extracorporeal membrane oxygenation (ECMO) may be used, and facilitates management of these two important separate clinical issues. Optimal management of drug therapy also requires optimal methods embodied in clinical software to describe drug behavior in these highly unstable patients, and considerably more data than for ordinary patients. The interacting multiple model (IMM) clinical software facilitates management of both fluid balance and drug therapy in these unstable patients. Illustrative cases are discussed, and new monitoring and management strategies are suggested. Like other ICU skills, physicians need to learn optimal tools for managing drug therapy in the ICU. Further work should help evaluate these new approaches.
authors.affiliation: Laboratory of Applied Pharmacokinetics and Bioinformatics, Children's Hospital of Los Angeles, 4640 Hollywood Blvd, Los Angeles, CA, 90027, USA. jelliffe@usc.edu.
authors.forename: Roger
authors.initials: R
authors.lastname: Jelliffe
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016638:Critical Illness / Q000628:therapy*; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D017582:Renal Replacement Therapy / Q000009:adverse effects / Q000379:methods; D012984:Software
chemical_list: D000900:Anti-Bacterial Agents