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DALLAS -- Early neuromuscular blockade delivered with heavy sedation did not result in improved 30-day mortality versus no blockade and a light sedation strategy in patients with acute respiratory distress syndrome (ARDS), researchers reported here.

In the ROSE trial at 90-day follow-up in patients with moderate-to-severe ARDS, 42.5% of the intervention group and 42.8% of the control group died before hospital discharge (between group difference -0.3%, 95% CI -6.4 to 5, P=0.93), reported Derek Angus, MD, MPH, of the University of Pittsburgh, and colleagues in the .

The trial was stopped early short of the target enrollment after it became clear that the medically-induced paralysis and heavy sedation approach did not improve death outcomes, explained Angus at the American Thoracic Society annual meeting.

"We intended to enroll 1,400 patients, but at the second interim analysis, with roughly 1,000 patients enrolled, we had our answer, which was that neuromuscular blockade was not superior to managing patients with light sedation," Angus told MedPage Today.

He explained that the trial was designed to expand on findings from the 2010 French study that showed a survival benefit for medically-induced controlled paralysis in patients with severe ARDS.

"The idea is that paralyzing patients keeps them from fighting against the ventilator, which can result in lung injury," he said. "But of course, paralyzed patients must be heavily sedated, and in North America and much of the rest of the world, the focus is now on managing patients with as little sedation as possible."

ROSE was designed to compare early neuromuscular blockade and heavy sedation to no blockade and light sedation. The control cohort in ACURASYS received heavy sedation.

A total of 1,006 patients with moderate-to-severe ARDS were enrolled in ROSE before the trial was stopped, and 488 of 501 patients (97.4%) in the intervention group received a continuous infusion of cisatracurium for 48 hours (median duration of infusion 47.8 hours; median dose 1,807 mg).

Just 86 of the 505 patients (17%) in the control group received treatment with a neuromuscular blocking agent (median dose 38 mg).

"The intervention group got 2 days of continuous blockade," Angus said. "In the control arm, just 14% of patients had any blockade and they received individual boluses."

At 28 days, no between-group differences were seen in the secondary endpoints of in-hospital mortality, days free of ventilation, days out of the ICU, or days out of the hospital.

The researchers also reported that while in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events versus control patients. There also were no consistent between-group differences in the 3-, 6-, and 12-month endpoints.

The researchers noted that several factors may explain the very different results in the ROSE and ACURASYS trials, including the use of higher positive end-expiratory pressure (PEEP) in both groups in ROSE, the reliance on mostly light sedation; and the enrollment of patients earlier in the onset of ARDS.

The ROSE trial is the first of a series of NIH-sponsored studies examining strategies for improving ARDS treatments and outcomes in the Prevention & Early Treatment of Acute Lung Injury () Network.

In an , Arthur Slutsky, MD, and Jesús Villar, MD, PhD, of St. Michael's Hospital in Toronto, noted that ROSE was larger and more current than ACURASYS, and it showed a signal of cardiovascular harm with cisatracurium use.

Given these differences, "we recommend that neuromuscular blocking agents not be used routinely in patients with moderate-to-severe ARDS," they wrote.

But they added that controlled paralysis remains an appropriate treatment for carefully selected ARDS patients.

"Therapeutic strategies in ARDS should ideally be tailored to the specific underlying disease or injury mechanism at any given point in time, rather than being applied uniformly to all patients," they wrote. "Early paralytic agents for ARDS? Given their long-term neuromuscular safety profile in the ROSE trial, we suggest that paralytic agents can sometimes be used, when physiologically and clinically indicated."