Sedatives recommended in intensive care are just as safe and effective, study finds

Sedative drugs used in intensive care are associated with an increase in delirium, which in turn is linked to higher medical costs and an increased risk of death and dementia associated with intensive care.

A study published today in the New England Journal of Medicine provides the most definitive evidence to date that, of the two drugs recommended for mild sedation of mechanically ventilated ICU patients, one is as effective and safe as the other.

Mechanical ventilation is a life-saving procedure often involving a breathing tube inserted into the patient’s trachea, usually resulting in mild sedation to soothe the resulting discomfort, anxiety, and psychological stress. Several studies have looked for evidence of which sedative is best for this purpose. Two sedatives are currently recommended, dexmedetomidine or propofol.

The new study, a double-blind randomized controlled trial led by researchers at Vanderbilt University Medical Center, recruited 422 mechanically ventilated adults at 13 US medical centers. While the patients were placed on ventilators, approximately half were lightly sedated with dexmedetomidine, the other half with propofol. The patients all had sepsis, an extreme and dangerous body reaction to the infection.

“We found very similar results for patients with the two drugs for brain function, ventilation times and death. From an intensive care outcome perspective, our results show that these two sedatives are equally effective in of the critical care update, “said Christopher Hughes, MD, professor of anesthesiology, who led the study with Pratik Pandharipande, MD, MSCI, professor of anesthesiology.

• During the 14 days after the start of mechanical ventilation, the median total number of days alive without delirium and coma was 10.7 in the dexmedetomidine group, 10.8 in the propofol group.
• During the 28 days from the start of ventilation, the median number of ventilator-free days was 23.7 in the dexmedetomidine group, 24.0 in the propofol group.
• Death occurred within 90 days for 38% of those who received dexmedetomidine and 39% of those who received propofol.
• The median cognitive status score at six months was 40.9 in the dexmedetomidine group, 41.4 in the propofol group. (In both groups of drugs, six months after their illness, about one in four patients appeared to have clinically important cognitive dysfunction, with cognitive scores two standard deviations below population norms.)

“For this critical care application, statistically speaking, there is nothing in our results to distinguish the safety and patient outcome profiles of these two drugs,” Pandharipande said.

One would have expected that dexmedetomidine, which is a newer sedative drug, would promote better patient outcomes because, compared to some other sedatives used in critically ill patients, it is known to provide benefits. such as better sleep and better anti-inflammatory properties. The new results, however, confirm less rigorous trials that found no major benefit to the results with the new drug.

“Our discoveries […] strongly reinforce current guidelines recommending the use of dexmedetomidine or propofol for mild sedation when continuous sedation is required for adults requiring mechanical ventilation, with or without sepsis, ”the authors write.

“This multicentre randomized clinical trial answers an important clinical question in critical care,” said Lora Reineck, MD, MS, program director of the Acute Lung Injury and Critical Care Program at National Heart, Lung, and Blood Institute. “We now know that the choice of dexmedetomidine over propofol does not alter the outcome for patients with sepsis on ventilators in an intensive care setting.”

Pandharipande and Hughes were joined in the study by 24 other researchers from VUMC and 38 researchers from other institutions. The study was funded by a grant from the National Institutes of Health (HL111111).

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