The challenges of multiple organ dysfunction syndrome and extra-corporeal circuits for drug delivery in critically ill patients.

The multiple organ dysfunction syndrome (MODS) is characterized by more than one organ system failing, especially during critical illness. MODS is the leading cause of morbidity and mortality in current ICU practice; moreover, multiple organ dysfunction, especially liver and kidneys, may significantly affect the pharmacokinetics (PKs) of different drugs that are currently administered in critically ill patients. These PK alterations may either result in insufficient drug concentrations to achieve the desired effects or in blood and tissue accumulation, with the development of serious adverse events. The use of extra-corporeal circuits, such as extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), may further contribute to PKs changes in this patients' population. In this review, we have described the main PK changes occurring in all these conditions and how drug concentrations may potentially be affected. The lack of prospective studies on large cohorts of patients makes impossible any specific recommendation on drug regimen adjustment in ICU patients. Nevertheless, the clinicians should be aware of these abnormalities in order to better understand some unexpected therapeutic issues occurring in such patients.