The New England Journal of Medicine. 2019.

- Clinical Question
Does the use of dexmedetomidine as the primary sedative agent in mechanically ventilated ICU patients reduce mortality rates compared to usual sedation care?

- Bottom Line
Early use of dexmedetomidine as the primary sedative in mechanically ventilated ICU patients did not result in a lower 90-day mortality compared to other sedatives and was associated with more adverse events.

- Major Points


- Guidelines
Not available.

- Design
Open-label, randomized, controlled trial.
N=4000 mechanically ventilated ICU patients.
Intervention: Dexmedetomidine as sole/primary sedative (n=2001).
Control: Usual sedation care - propofol, midazolam, or other sedatives (n=1999).
Setting: 74 ICUs in eight countries.
Enrollment: 2013-2018.
Mean follow-up: 90 days.
Primary outcome: Death from any cause at 90 days.

- Population
Inclusion Criteria: Adults in ICU, requiring mechanical ventilation for more than the next calendar day, receiving sedatives for safety and comfort.
Exclusion Criteria: Age <18 years, mechanical ventilation for over 12 hours before enrollment, suspected/confirmed acute primary brain injury.
Median age: 63.7 years.

- Interventions
Dexmedetomidine aiming to be the primary sedative, supplemented with propofol, midazolam, or both when required.
Usual care consisting of propofol, midazolam, or other sedatives, excluding dexmedetomidine.

- Outcomes
Primary Outcome: At 90 days, death from any cause occurred in 29.1% of both dexmedetomidine and usual-care groups (adjusted risk difference, 0.0 percentage points).
Secondary Outcomes: No significant differences in 180-day mortality, institution dependency at 180 days, cognitive function, health-related quality of life, days free from coma/delirium, or ventilator-free days at day 28.
Additional Findings: Dexmedetomidine group required additional sedatives to maintain target sedation, more target sedation scores achieved in the dexmedetomidine group, deep sedation for clinical reasons frequent in both groups.

- Criticisms
The trial was open-label, and the use of supplemental sedation might have affected sedation levels and outcomes.

- Funding
Supported by the National Health and Medical Research Council of Australia, Health Research Council of New Zealand, National Heart Institute Foundation of Malaysia. Pfizer and Orion Pharma provided dexmedetomidine.

- Further Reading