ROSE Trial

NEJM

May 23, 2019

Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome.

What was the research question?

Does the use of neuromuscular blockade in patients with moderate to severe adult respiratory distress syndrome improve outcomes in terms of 90-day mortality?


How did they do it?

  • Multicenter, unblinded, randomized trial in 48 ICUs in the United States.

  • 1006 patients with moderate to severe ARDS defined as PO2/FiO2 of <150.

  • Patients were randomized to the intervention group with 48-hour continuous infusion of cisatracurium with concomitant deep sedation, or to the control group with usual care without neuromuscular blockade and with lighter sedation.

  • Primary outcome was the 90-day ventilator-free days.

  • Secondary outcome included ICU-free days, ventilator-free days, in-hospital death at day 28, days free of organ dysfunction, and days not in the hospital at day 28.


What did they find?

  • 90-day mortality did not differ between the two groups (42.5% vs. 42.8, p=0.93)

  • Ventilator-free days was higher in the dexamethasone group than in the control group (mean

  • Patients in the intervention group were less physically active and had more adverse cardiovascular events (likely secondary to deeper sedation) than patients in the control group while in the hospital.

  • All secondary outcome measures were not different between the two groups at 3, 6, and 12 months.


Any limitation?

  • Possible bias as it is unblinded study

  • 13.5% of excluded patients was because receiving neuromuscular blockade as clinicians felt those patients may benefit from paralysis.

  • Did not measure effect of paralysis on ventilatory asynchrony.

  • Median enrollment time was 7.6 hours which may have allowed to enroll very sick patients who may have died before enrollment in other studies with longer enrollment time or patients with rapid improvement.


What does it mean?

  • The study results are different than the ACURASYS trial that showed benefit of neuromuscular blockade. The only difference is the level of sedation in the control group and the duration on the ventilator prior to enrollment.

  • Given the lack of benefit in the study, neuromuscular blockade may be given in selected patients only and on the as needed basis for ventilator synchrony and increased patient’s respiratory efforts (higher transpulmonary pressure) rather than routine neuromuscular blockade to all patients with PF ratio of less than 150.

ROSE Trial