What is a major factor affecting pharmacokinetics in critical illness?

The major factor affecting pharmacokinetics in critical illness is altered protein binding. In critically ill patients, the levels of plasma proteins, such as albumin, can be different from those in healthy individuals. This alteration affects the binding of drugs to these proteins, which in turn influences the free drug concentration in the bloodstream.

When protein binding is reduced, a higher proportion of the drug remains unbound and can exert its therapeutic effect, but it can also lead to potential toxicity if the unbound fraction becomes excessively high. This is particularly important for medications with a narrow therapeutic index, where small changes in drug concentration can lead to significant clinical consequences.

In contrast, stable capillary permeability would not significantly influence pharmacokinetics, as it implies an unchanged barrier to drug distribution. Decreased cardiac output, while impactful in critical care settings, primarily affects drug delivery rather than bulk pharmacokinetics. Fixed drug absorption does not adequately represent the variability seen in critically ill patients, as they often experience significant changes in gastrointestinal function and drug absorption rates due to their illness.