Early Sedation With Dexmedetomidine vs. Placebo in Older Ventilated Critically Ill Patients

Sedation remains a ubiquitous and crucial component of intensive care treatments in critically ill mechanically ventilated patients. Sedation relieves anxiety, reduces distress, and promotes tolerance of endotracheal intubation and associated life-sustaining interventions such as mechanical ventilation, cardiovascular assistance, and renal support. Thus, choosing the optimal sedative agent is vital to patient comfort, safety, and survival. Despite more than 20 years of intensive care sedation research, there is still no consensus on what constitutes best sedation practice. The Society of Critical Care Medicine, the premier critical care organisation in North America, published the 2018 Clinical Practice Guidelines on the management of Pain, Agitation/Sedation, Delirium, Immobility and Sleep (PADIS) disruption (chaired by our primary applicant W.A.) and issued weak recommendations to provide analgesia before sedation, to target light sedation whenever clinically feasible, and to use either dexmedetomidine or propofol over midazolam for the sedation of mechanically ventilated critically ill patients. Similarly, the American Thoracic Society produced a set of Clinical Practice Guidelines to promote liberation and weaning from mechanical ventilation in critically ill patients, with weak recommendations for the use of non-benzodiazepines as primary sedatives and to target light sedation when clinically possible. A weak recommendation was issued in an Intensive Care Medicine Rapid Practice Guideline published in 2022 to use dexmedetomidine over propofol for sedation of critically ill adults, if the desired outcome is a reduction in delirium. These guidelines, however, do not consider age-dependent pharmacokinetics and pharmacodynamics, illness severity, timing of sedative administration, operative vs medical reason for admission, or the changing dynamics of sedation practice at different phases of critical illness. The lack of high-level evidence to inform sedation practice in the critically ill has led to approaches that are mainly opinion-based and lack the support of evidence from large multicentre, international randomised clinical trials.