Study shows potential alternative sedation drugs show no benefit over usual care in patients receiving mechanical ventilation

A new pragmatic, multicentre randomised clinical trial has found that neither dexmedetomidine nor clonidine-based sedation shortened ventilation time compared to standard propofol-based sedation among critically ill patients.

Researchers from the Usher Institute including lead author, Tim Walsh, along with collaborators from institutions across the UK, enrolled over 1400 mechanically ventilated patients across more than 40 intensive care units between December 2018 and October 2023.

The trial involved critically ill adults in UK intensive care units who were expected to need mechanical ventilation for at least 48 hours. Participants were randomly assigned to receive one of three sedatives - dexmedetomidine, clonidine, or the usual care drug, propofol. Researchers aimed to see if the newer drugs could shorten the time patients needed breathing support. 

Sedation was carefully monitored and adjusted based on patient condition, and the study also tracked side effects like low heart rate and agitation. Patients and families helped shape the study design and goals. COVID-19 briefly interrupted recruitment, but the trial was adjusted and successfully completed.

Neither dexmedetomidine nor clonidine significantly shortened the time to extubation compared to propofol. Mortality over 180 days, ICU length of stay, and long-term outcomes (such as quality of life and mental health) were also similar across all groups.

Although sedation targets were achieved similarly, patients in the dexmedetomidine and clonidine groups experienced more agitation and required more rescue medication. Serious safety concerns were more common in the dexmedetomidine group, including higher rates of bradycardia and cardiac arrhythmias. There were no notable differences in delirium or coma rates between groups, despite these complications being one of the reasons clinicians have previously used these drugs. Subgroup analyses suggested the age and illness severity of patients, and their risk of delirium when admitted to the ICU, did not influence the effects seen with the different sedative drugs. Overall, dexmedetomidine and clonidine did not provide significant clinical advantages over propofol and were associated with higher rates of some adverse events.

This large trial found that dexmedetomidine and clonidine did not help critically ill patients come off a ventilator any faster than the commonly used sedative, propofol. This study suggests there’s no clear advantage to using dexmedetomidine or clonidine early on instead of propofol, and in some cases, they may carry additional risks.

Cite as

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

Further information

Read the full JAMA article