Cardiac surgery, ICU sedation, and delirium: is dexmedetomidine the silver bullet?

Delirium is a marker of acute brain insufficiency and a harbinger of poor outcomes and increased healthcare costs. Despite success preventing delirium by nonpharmacologic measures, the incidence in the postcardiac surgical ICU population remains high. Dexmedetomidine, a selective alpha-2 agonist, is a plausible preventive agent with sedative, anxiolytic, analgesic, sympatholytic and anti-inflammatory properties, and is the subject of very active study in cardiac surgery populations.

Recent trials, including DEXACET (2019), DECADE (2020), LOWDEXDEL (2021), and DIRECT (2022) individually, failed to show a benefit for dexmedetomidine and highlighted associated risks. Meta-analyses have offered conflicting results, highlighting the complexity of delirium, and likely interaction of multiple etiological pathways; those that concluded benefit often were driven by trials at high risk of bias. Meta-analyses excluding biased trials currently suggest no benefit for dexmedetomidine over control in unselected cardiac surgical populations.

Although using dexmedetomidine to prevent delirium in unselected cardiac surgical patients is not supported by current evidence, there remains hope that it may offer benefits in highly selected populations, and further trials are ongoing.