Designing drug regimens for special intensive care unit populations

Table 7 Considerations with therapeutic drug monitoring

Blood concentration measurements are not available for the majority of drugs used in critically ill patients

So-called therapeutic ranges for therapeutic drug monitoring (TDM) are typically derived from studies involving small numbers of patients

Most therapeutic ranges are based on steady-state drug concentrations, so non–steady-state concentrations can be very difficult to interpret (and often meaningless)

Disease states that affect a drug’s volume of distribution or clearance often negate the presumption of steady-state conditions necessary for proper interpretation of concentrations

The minimum and maximum concentrations used to define a therapeutic range are often quite arbitrary and not necessarily applicable to a specific patient

The free or unbound form of a drug is the active form, but the total drug concentration is most commonly measured by clinical laboratories

Total drug concentrations for a drug with high protein binding (e.g., > 90%) can be difficult to interpret when protein concentrations are decreased or when other drugs or diseases displace drug

Clinical response, not a TDM measurement, should be the primary driver of dosing decisions

The administration and timing of drug doses prior to TDM measurement should be verified, not presumed, because these affect the proper interpretation of the measurement

TDM is most useful when clinical indicators are misleading or not available or when the clinical indicator is a problem that the clinician is trying to prevent (e.g., aminoglycoside nephrotoxicity)

Unnecessary TDM should be avoided (e.g., ordering daily measurements of drug concentrations for a drug with a long half-life) because it may lead to inappropriate changes and unnecessary TDM costs

Reprinted with permission from Erstad[56].