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TOPLINE:

In critically ill patients, sedation with alpha-2 adrenergic receptor agonists such as dexmedetomidine and clonidine, introduced within 48 hours of initiating mechanical ventilation, was not superior to propofol-based sedation in decreasing the time to successful extubation.

METHODOLOGY:

• Researchers conducted a pragmatic randomized clinical trial was conducted across 41 ICUs in the United Kingdom between December 2018 and October 2023 to compare the effectiveness of dexmedetomidine- and clonidine-based sedation with propofol-based sedation in critically ill patients receiving mechanical ventilation.
• Patients (mean age, 59.2 years; 64% men) sedated with propofol, who were expected to require ventilation for at least 48 hours were randomly assigned to receive sedation with dexmedetomidine (n = 457), clonidine (n = 476), or propofol (n = 471) within 48 hours of starting mechanical ventilation, with propofol allowed as an adjunct if needed.
• The primary outcome was the time from randomization to successful extubation, which was defined as extubation followed by 48 hours of spontaneous breathing without mechanical ventilation.
• Secondary outcomes included all-cause mortality at 180 days; length of stay in the ICU; quality of sedation; and rates of delirium, coma, cardiovascular adverse events, and other complications.

TAKEAWAY:

• The median time to successful extubation was 136 hours for dexmedetomidine, 146 hours for clonidine, and 162 hours for propofol, with no significance noted for superiority of clonidine vs propofol or dexmedetomidine vs propofol.
• Over 7 days postrandomization, the rates of agitation were higher with dexmedetomidine (risk ratio [RR], 1.54; 95% CI, 1.21-1.97) and clonidine (RR, 1.55; 95% CI, 1.22-1.97) than with propofol. Rescue medication for agitation was required by 31% of patients on dexmedetomidine, 34% on clonidine, and 38% on propofol.
• Mortality and the rates of delirium or coma did not differ between patients receiving dexmedetomidine and propofol or between those given clonidine and propofol.
• A higher prevalence of severe bradycardia was observed with dexmedetomidine (33%) and clonidine (33%) than with propofol (20%). Higher rates of cardiac arrhythmia were associated with dexmedetomidine than with propofol (RR, 1.27; 95% CI, 1.15-1.40), with more adverse events in the group receiving dexmedetomidine.

IN PRACTICE:

“Our findings do not support the routine early use of either a dexmedetomidine- or a clonidine-based sedation strategy as an alternative to propofol,” the researchers reported.

The new study “suggests that dexmedetomidine, enteral clonidine, and propofol sedation strategies result in similar clinical outcomes without obvious differences across easily clinically identified subgroups. In the spectrum of sedatives, these results confirm previous results suggesting that no one sedative is best for all critically ill patients,” experts wrote in an editorial accompanying the journal article.

SOURCE:

The study was led by Timothy S. Walsh, MD, of the Usher Institute at the University of Edinburgh in Edinburgh, Scotland. It was published online on May 19, 2025, in JAMA.

LIMITATIONS:

The trial was unblinded, which may have introduced bias in outcome assessment. The continual use of low-dose propofol in the dexmedetomidine and clonidine groups might have affected the results. The findings may not be generalizable to all critically ill patients, including those with less severe illness or those with specific conditions like cardiac surgery or brain injury.

DISCLOSURES:

The study was supported by the National Institute for Health and Care Research. Some authors disclosed receiving personal fees and/or grants or research reward and serving as consultants. One author reported being the director of research and the intensive care society chair; another author reported having a patent, serving as codirector of research for the Intensive Care Society, and serving as program director for the National Institute for Health and Care Research/Medical Research Council.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.