Rethinking dosing in critically ill patients:on altered renal drug clearance and inflammation

In this thesis we showed that drug clearance and metabolism in critically ill patients are highly variable and dynamic, influenced by severity of disease (inflammation), CRRT- and patient-related factors (residual diuresis). All this can contribute to variable and prolonged pharmacodynamic effects. In dose adjustment strategies, CRRT is typically considered as either present or absent. We have shown that this binary approach does not resemble the far more complex reality in which CRRT technique, CRRT dosing, downtime of CRRT, f ilter patency and residual clearance play an important role. Furthermore, by reviewing all potential factors that may influence PK during CRRT has resulted in a checklist that is widely applicable in both clinical care and future research. Next, by explaining ARC and discussing knowledge gaps, we directly contribute to clinical practice and follow-up research. Finally, using scavenged syringes from arterial blood gas tests may serve as an example of sustainable practice. Overall, we added new insights to the field of optimizing drug therapy in critically ill patients.