Dexmedetomidine vs. Propofol: Study Finds Similar Outcomes in Light Sedation of Ventilated Sepsis Patients

A new study finds patients with sepsis who are put on a mechanical ventilator under light sedation have similar outcomes regardless of whether they are sedated using dexmedetomidine or propofol.

The study, published in the New England Journal of Medicine, suggests that despite differences between the 2 agents, the relevant outcomes are similar.

Corresponding author Christopher G. Hughes, MD, MS, of Vanderbilt University Medical Center, and colleagues, noted that the two drugs have varying impacts on arousability, immunity, and inflammation. For instance, some evidence has suggested that the alpha2 receptor agonist dexmedetomidine has superior anti-inflammatory and bacterial clearance properties, and also reduces neuronal apoptosis and promotes biomimetic sleep.

Hughes and colleagues wanted to know whether the apparent immunomodulatory benefits of dexmedetomidine might lead to better outcomes in sepsis patients on ventilators. Their primary endpoint was days alive without delirium or coma over a 14-day intervention period. They also sought to measure the drug’s impact on ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status (TICS-I) questionnaire at 6 months.

The investigators recruited 432 patients, of whom 422 were randomized in the multicenter trial. The dexmedetomidine cohort of 214 patients received doses of 0.2 to 1.5 μg/kg of body weight per hour, with a median dose of 0.27 μg/kg. The 208 patients in the propofol group received 5 to 50 μg/kg per minute, with a median dose of 10.21 μg/kg. Doses were adjusted by bedside nurses based on target sedation goals set by clinicians. The median length of time patients received the drugs was 3.0 days, and the median score on the Richmond Agitation-Sedation Scale was -2.0. The scale ranges from -5 (unresponsive) to +4 (combative).

The data showed neither drug outperformed the other. Patients on dexmedetomidine had an adjusted median of 10.7 days without delirium of coma; those on propofol had an adjusted median of 10.8 days. Ventilator-free days over 28 days were 23.7 days and 24.0 days for dexmedetomidine and propofol, respectively, and the death rate at 90 days was 38% and 39%, respectively. TICS-T scores were also similar (40.9 for dexmedetomidine and 41.4 for propofol) after 6 months.

Hughes told Contagion Live that the findings, when combined with previous studies, amount to conclusive evidence that neither drug outperforms, at least with regard to the general intensive care population. However, he said further study is warranted to see if differences between the 2 agents emerge for more specific patient populations, such as those undergoing cardiac surgery or transplant, and possibly those with neurologic injury.

“Additional topics still needing evaluation are the potential inflammatory and secondary injury pathway differences between the two agents in case that lends to additional target populations that may benefit from one or the other,” he said.

After that, his team plans to look at some of the inflammatory profile differences and exploratory outcome differences between the groups, as well as newer sedation options.

In the meantime, Hughes said for most ICU patients, either agent would be acceptable.

“Some of that decision will come down to which of the two agents the team and ICU are more comfortable with, and have more experience with using, along with purchasing cost differences,” he said.

Some patients, such as those requiring deeper sedation or a neuromuscular block, would be better treated with propofol, he said. In cases of patients with tachycardia and/or those at risk for myocardial ischemia, the heart-rate reduction associated with dexmedetomidine would render that agent beneficial.

“The agents’ specific side effect profiles may have potential benefits to select patients and can be used to guide that decision for those patients,” he added, “but in general either agent seems appropriate for the majority of ICU patients.”