Pharmacokinetic and Pharmacodynamic Modeling of Sedation in the ICU: Future Perspectives

Abstract

In the intensive care unit (ICU) environment sedation is often an integral component of critical care therapy. Patients who are being mechanically ventilated frequently require sedation because the endotracheal tube is extremely irritating and the ICU is an anxiety-provoking environment. In addition to alleviating anxiety, sedation may prevent sleep deprivation [1], a common problem for mechanically ventilated patients. Sleep deprivation may lead to disorientation and agitation (so-called “ICU psychosis”), as well as results in a decreased ventilatory response to hypoxia and hypercapnia [2], both of which may interfere with weaning from ventilatory support [3]. Furthermore, there is anecdotal evidence to suggest that restoration of a normal sleep-wake cycle can improve patient outcome in the ICU, and reduce the need for additional medications [4]. Thus, a sedation technique which would allow patients to rest comfortably (or sleep) may be of benefit in weaning patients from mechanical ventilation. Finally, effective sedation can decrease stress hormone levels in healthy patients and might produce similar effects in ICU patients. Since stress hormones can significantly increase both metabolic rate and protein catabolism, sedation may have the added benefit of decreasing ventilatory requirements.