Dexmedetomidine and Clonidine Offer No Advantage Over Propofol for Sedation in ICU Patients: A2B Trial

The study, published in JAMA, was led by Dr. Timothy S. Walsh and colleagues from the Usher Institute, University of Edinburgh, Edinburgh, Scotland. The researchers aimed to determine whether α2-adrenergic receptor agonists (dexmedetomidine or clonidine) could facilitate faster extubation compared to the standard propofol-based sedation in patients expected to require at least 48 hours of mechanical ventilation.

A total of 1404 adult patients, within 48 hours of initiating mechanical ventilation and already receiving propofol and an opioid for sedation and pain management, were randomized into three groups: dexmedetomidine (n=457), clonidine (n=476), or continued propofol sedation (n=471). The sedation protocols followed a targeted Richmond Agitation-Sedation Scale (RASS) score of −2 to +1, with adjustments based on clinical needs. Supplemental use of propofol was permitted in the dexmedetomidine and clonidine arms if needed.

The primary outcome assessed was the duration from randomization to successful extubation.

The following were the key findings of the study:

• The median time to successful extubation was 136 hours for dexmedetomidine, 146 hours for clonidine, and 162 hours for propofol.
• Statistical analysis revealed no significant difference in extubation times among the three groups.
• The subdistribution hazard ratio was 1.09 for dexmedetomidine and 1.05 for clonidine when compared to propofol, indicating no statistical superiority.
• Both dexmedetomidine and clonidine were linked to a more than 50% higher risk of agitation compared to propofol.
• The incidence of severe bradycardia (heart rate below 50 bpm) was also higher with dexmedetomidine and clonidine than with propofol.
• Mortality rates over 180 days were similar across all treatment groups.
• Subgroup analyses based on age, presence of sepsis, organ failure scores, and delirium risk did not show any significant variation in the outcomes.

In summary, the A2B trial concluded that dexmedetomidine and clonidine did not offer a clinical advantage over propofol in speeding up extubation in mechanically ventilated patients. Furthermore, the increased risk of adverse effects such as agitation and bradycardia with α2-agonists raises questions about their routine use as first-line sedatives in critical care settings.

"The findings showed that in critically ill patients anticipated to need mechanical ventilation for at least 48 hours, sedation using dexmedetomidine or clonidine did not demonstrate any advantage over propofol-based sedation," the researchers wrote.

Reference:

Walsh TS, Parker RA, Aitken LM, et al. Dexmedetomidine- or Clonidine-Based Sedation Compared With Propofol in Critically Ill Patients: The A2B Randomized Clinical Trial. JAMA. Published online May 19, 2025. doi:10.1001/jama.2025.7200