New horizons in ICU sedation: exploring non-sedative effects of ICU sedation

Sedative drugs are widely used in intensive care, primarily in ventilated patients. The common actions and side-effects of these agents are widely recognised. However, recent evidence suggests that opiates and other sedative agents that are used in this situation also have important, but not widely appreciated, effects on metabolism, physiological signalling and disease mechanisms. Some of these effects are an extension of their expected therapeutic actions; these are being elucidated as the biological consequences of stress, and its suppression is now being clarified. An example is the central effects of benzodiazepines and opioids on metabolism and immune function. In other instances these drugs have important peripheral actions, with immunomodulatory or metabolic roles. Furthermore, some drugs may modify disease processes--an example being the antioxidant effect of propofol. Finally, basic cellular mechanisms, such as immediate early gene expression and transcription factor activation, may involve processes that may be susceptible to modification by sedative agents. Such secondary effects of sedative agents need to be investigated for three reasons. First, they provide explanations for some phenomena observed during their use. Second, some of the undesirable side-effects may be avoided by judicious use of drugs in certain clinical situations. Finally, there is the prospect that we may be able to harness some actions for novel therapeutic purposes.