NONSEDA Trial

NEJM

March 19, 2020

Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients.

What was the research question?

  • ·Does a plan of no sedation in mechanically ventilated patients have an effect on mortality compared to a plan of light sedation?


How did they do it?

  • A multicenter, non-blinded, randomized, controlled trial, with a 1:1 ratio assignment.

  • Control group: light sedation: RASS score -2 to -3

  • Intervention group: no sedation, PRN if needed.

  • The primary outcome was mortality at 90 days.

  • Secondary outcomes were the number of major thromboembolic events, the number of days free from coma or delirium, acute kidney injury according to severity, the number of ICU-free days, and the number of ventilator-free days.


What did they find?

  • 90-day mortality was not different between non-sedation group and light sedation group (42.4% vs. 37.0%, P=0.65).

  • No significant difference in the days until death (13 vs. 12), number of ICU-free days (13 vs. 14), ventilator-free days (20 vs. 19), highest RIFLE score (2 vs. 2), days free from coma or delirium (27 vs. 26), and accidental extubation requiring reintubation in the first 1 hour (1.1% vs. 0.3%) between the two groups.

  • Higher rate of major thromboembolic events occurred in sedation group (2.8%) compared to 0.3% in the non-sedation group.

  • Higher rate of accidental extubation requiring reintubation <24 hours occurred in the non-sedation group (8.9%) compared to 4% in the sedation group (p=0.01).

  • Higher rate of accidental removal of other      equipment (NGT, art line) in the non-sedation group (15%) compared to 9%      in the sedation group (p= 0.01).

  • Confidence intervals was not adjusted for multiple comparisons, therefore, cannot infer treatment effects.


Any limitations?

  • Cross over rate was 27% of no sedation patients to receive sedation during the first 24hours after randomization

  • Non-blinded trial.

  • RASS score differed by only 1 on day 1 (-1.3 vs -2.3) and 7 (-1.8 vs 2.8), too little to test the hypothesis.

  • 14% of patients declined and [potential for selection bias.

  • 1:1 nursing ratio, cannot be generalized.


What does it mean?

  • No significant difference in 90-day mortality with the use of no sedation compared to light sedation strategies. Less cases of major embolic events but more accidental extubations and removal of other equipment.

  • The study supports the practice to continue targeting light sedation (ie RASS -2 to 1) combined with daily sedation interruptions.

NONSEDA Trial