Pharmacokinetics/Pharmacodynamics

variables using scales arranged such that one variable can be determined if the other variables are known. A

classic drug-dosing example is the once-daily aminoglycoside nomogram (Antimicrob Agents Chemother

1995;39:650-5). The nomogram allows the user to determine only one variable (usually, the dosing interval)

using other variables (time from infusion to drug concentration and the measured drug concentration).

Many institutions incorporate nomograms into drug-dosing protocols or pathways and routinely refer to

them as drug-dosing nomograms. Of note, many of these nomograms (e.g., Hartford) were not developed

in critically ill patients and likely do not consider the potential for alterations in PK. One of the most

commonly used drug-dosing nomograms was developed for continuous infusions of unfractionated heparin.

As previously noted, a heparin nomogram can improve time to therapeutic activated partial thromboplastin

time when developed specifically for critically ill patients. However, the patient population used to develop a

nomogram should be considered because the variables may not apply to all patient populations. An example

of this occurs with protocols for insulin infusions in critically ill patients. As previously noted, patients with

AKI are at a greater risk of hypoglycemia if treated with an insulin infusion protocol developed in critically

ill patients without kidney impairment.

There are marked differences in the ways in which critically ill patients respond to drugs. Research in this

area has noted significant changes in the PK and PD of certain medications in select critically ill populations.

Although these studies have highlighted important issues, considerable work is still needed to better define these

changes in different critically ill populations. As research continues to advance, together with our knowledge of

how patients respond to drugs differently, critical care clinicians must stay abreast of new information and the

ways in which it will affect the care of their patients.