Pharmacological Management of Sedation and Delirium in Mechanically Ventilated ICU Patients: Remaining Evidence Gaps and Controversies

Although pharmacotherapy remains the mainstay for the prevention and treatment of pain, anxiety, and delirium (PAD) in the intensive care unit (ICU), many of the PAD-related medications currently used may lead to unintended consequences, particularly when these agents are administered at excessive doses for prolonged periods. The method by which these medications are administered and titrated is increasingly being recognized as potentially affecting patient outcomes as much as the drug itself. Drugs once thought to have a pharmacologically desirable profile in reducing PAD have been shown to have either little benefit, the potential for significant risk associated with any benefit, or in some cases, the potential to worsen patient outcome. The recently published American College of Critical Care Medicine (ACCM) Pain, Agitation, and Delirium Clinical Practice Guidelines provide 12 medication-related recommendations surrounding the prevention and treatment of PAD. This paper (1) provides the ICU bedside clinician with more background on the most important, and in some cases most contentious and challenging areas, of sedation and delirium pharmacotherapy in the critical care setting; (2) provides an update on the most recent evidence surrounding the prevention and treatment of agitation and delirium in ICU; and (3) highlights areas that require further investigation and provide practical strategies by which to apply current evidence in this area to daily ICU practice.