Mechanically ventilated adults with sepsis who received light sedation had similar outcomes whether they received dexmedetomidine or propofol, according to results from a multicenter, randomized trial.

The findings from the MENDS2 (Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure) trial were presented at the 2021 virtual Clinical Congress of the Society of Critical Care Medicine and published simultaneously in The New England Journal of Medicine (2021, Feb 2; [Epub ahead of print]).

Dexmedetomidine, an alpha-2 receptor agonist, did not improve days alive without acute brain dysfunction, ventilator-free days, deaths at 90 days or global cognition at six months in patients with sepsis, compared with propofol.

Previous trials indicated that dexmedetomidine may be superior to benzodiazepines in improving outcomes such as delirium, coma and time receiving mechanical ventilation.

The findings from MENDS2 reinforce current guidelines recommending the use of dexmedetomidine or propofol for light sedation when continuous sedation is needed.

“The choice between dexmedetomidine and propofol alone does not appear to substantially affect patient outcomes in the complex milieu of critical illness with sepsis,” lead investigator Christopher Hughes, MD, a professor of anesthesiology at Vanderbilt University Medical Center, in Nashville, Tenn., and his colleagues wrote in their journal publication.

Safety end points were similar in the two groups.

At 13 centers across the United States, researchers randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2-1.5 mcg/kg per hour) or propofol (5-50 mcg/kg per minute), with doses adjusted by bedside nurses to achieve the target sedation goals set by clinicians according to the Richmond Agitation Sedation Scale (RAss). The IV fluid bags and tubing were hidden under opaque coverings to conceal the sedative medication, and unblinded bedside nurses administered the sedation to meet clinical targets.

Of the 422 patients included in the analysis, 214 patients received dexmedetomidine at a median dose of 0.27 mcg/kg per hour, and 208 received propofol at a median dose of 10.21 mcg/kg per minute. The median duration of treatment with the trial drugs was three days and the median RAss score was –2.0.

For more than 90% of patients, the care team adhered to the ABCDE bundle, performing regular interventions of trial awakening and breathing, nondrug delirium interventions and early mobilization.

Six months after randomization, researchers assessed patients’ cognition with the Telephone Interview for Cognitive Status questionnaire and other validated tests for cognition, functional status and quality of life.

About 25% of patients had clinically important cognitive dysfunction after sepsis, with no difference between dexmedetomidine and propofol in terms of long-term impairment.

“It appears that sedation choice does not affect survivorship outcomes when currently recommended sedation approaches are used,” the authors wrote.

Salman Ahmad, MD, an associate professor of surgery and the medical director of the surgical ICU at the University of Missouri, in Columbia, said the study findings are especially critical now, given limited resources and medication shortages across the country.

“Many patients respond differently to each medication at different time points in their care, and I am more confident in switching between these medications if necessary,” Dr. Ahmad said.

The study’s limitations include unmasking episodes in 14% of patients and crossover in 10%. In addition, the trial drug was started a median of 22 hours after patients met the inclusion criteria, which may have limited the ability to affect outcomes. Investigators decreased the planned sample size due to slow enrollment, but said the study remains adequately powered.

One-third of patients in the trial were surgical ICU patients. All were enrolled within one day of ICU admission and had a high severity of illness, a greater risk for acute respiratory distress syndrome and a higher requirement for continuous sedation.