RCT

A2B

Dexmedetomidine- or Clonidine-Based Sedation Compared With Propofol in Critically Ill Patients

JAMA, 2025 · Pragmatic multicenter randomized clinical trial across 41 UK ICUs (n=1404)

Clinical question

Does primary alpha-2 agonist sedation shorten time to successful extubation compared with propofol-based sedation?

Population: Mechanically ventilated adults expected to require ventilation for at least 48 hours
Intervention: Dexmedetomidine-based or clonidine-based sedation
Comparator: Propofol-based sedation
Primary outcome: Time from randomization to successful extubation
Result: Neither dexmedetomidine (HR 1.09, 95% CI 0.96–1.25) nor clonidine (HR 1.05, 95% CI 0.95–1.17) significantly shortened time to successful extubation versus propofol. Agitation and severe bradycardia were more frequent with both alpha-2 agonists; 180-day mortality was similar.

What the trial found

Alpha-2 agonist–based sedation was not superior to propofol for time to successful extubation.

Current guideline position

Maintain light, protocolized, analgesia-first sedation and avoid unnecessary benzodiazepine exposure; select the non-benzodiazepine sedative according to patient goals and hemodynamics.

Clinical interpretation

Choice among propofol and dexmedetomidine should be phenotype- and adverse-effect-driven; dexmedetomidine should not be taught as universally superior for ventilator liberation or delirium prevention.

Clinical Context & Relevant Topics (1)

Disease Reference

ICU Sedation, Analgesia, Delirium & Liberation

Analgesia-first sedation, light sedation targets, ABCDEF bundle, spontaneous breathing trials, and non-pharmacologic delirium mitigation.

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