Statins in the critically ill

Abstract

The use or misuse of statins in critically ill patients recently attracted the attention of intensive care clinicians. Indeed, statins are probably the most common chronic treatment before critical illness and some recent experimental and clinical data demonstrated their beneficial effects during sepsis, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), or after aneurismal subarachnoidal hemorrhage (aSAH). Due to the heterogeneity of current studies and the lack of well-designed prospective studies, definitive conclusions for systematic and large-scale utilization in intensive care units cannot be drawn from the published evidence. Furthermore, the extent of statins side effects in critically ill patients is still unknown. For the intensive care clinician, it is a matter of individually identifying the patient who can benefit from this therapy according to the current literature. The purpose of this review is to describe the mechanisms of actions of statins and to synthesize the clinical data that underline the relevant effects of statins in the particular setting of critical care, in an attempt to guide the clinician through his daily practice.

Figure 1

Effects of statins on the cholesterol biosynthesis pathway. HMG-CoA reductase inhibition by statins reduces intracellular mevalonate levels. Consequently, not only cholesterol levels are reduced but also the intermediary products farnesylpyrophosphate and geranylgeranylpyrophosphate. These latter two provide binding sites for protein isoprenylation, and activation.

Figure 2

Pleiotropic effects of statins. Statins have anti-inflammatory, immunomodulatory, antithrombotic, and antioxidant properties found independently of their lipid-lowering properties. Because statins do not target individual inflammatory mediators, they could modulate the overall magnitude of the inflammatory response.