Therapeutic study, level IV.

After decades of research in drug development, PDE4Is are a welcomed addition to the COPD therapeutic armamentarium. In its current clinical role, the salubrious clinical effects of PDE4I in reducing exacerbations and stabilizing the frequent exacerbator phenotype have to be cautiously balanced with numerous adverse effects. Developing drugs may provide similar or better clinical benefits while minimizing adverse effects by changing the mode of drug delivery to inhaled formulations, combining dual PDE isoenzyme inhibitors (PDE1/4I and PDE3/4I) and by forming hybrid molecules with other bronchodilators (muscarinic receptor antagonist/PDE4I and β2-agonist/PDE4I).

Critically ill patients with single or multiple organ failure require lower therapeutic argatroban dosages compared with noncritically ill patients. Because of an inverse relationship with SOFA score, initial argatroban dosage in critically ill patients should be based on the presence and magnitude of organ failure.