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Nonsedation fails to lower mortality in mechanically ventilated patients
A strategy of no sedation failed to reduce mortality when compared with a strategy of light sedation with daily interruption among critically ill, mechanically ventilated patients, according to results from the NONSEDA trial.
In the multicenter, randomized controlled trial, which was published in The New England Journal of Medicine, the researchers assigned mechanically ventilated adults in the ICU to no sedation or light sedation, defined as sedation to a level at which the patient was arousable, based on a score of –2 to –3 on the Richmond Agitation-Sedation Scale (RASS), with daily interruption.
Overall, baseline characteristics were similar among the 700 patients included in the modified intention-to-treat analysis, with the exception of a 1-point higher score on the Acute Physiology and Chronic Health Evaluation II among patients assigned nonsedation (n = 349) vs. light sedation (n = 351). From day 1 to day 7, the mean RASS sore increased from –1.3 to –0.8 in the sedation group and from –2.3 to –1.8 in the light sedation group.
Ninety-day mortality — the primary endpoint — did not differ significantly between the nonsedation and light sedation groups (42.4% vs. 37%). Similarly, there were no significant differences between study groups for most secondary outcomes, including the number of ICU days or ventilator-free days. Patients in the nonsedation group had 1 more day free from coma or delirium than those in the light sedation group (median, 27 vs. 26 days), and the nonsedation group had fewer major thromboembolic events (0.3% vs. 2.8%). However, lack of a prespecified plan for adjustment for multiple comparisons prevented the researchers from drawing firm conclusions about these data.
In an accompanying editorial, Claude Guérin, MD, PhD, from Médecine Intensive Réanimation, Hospices Civils de Lyon, Groupement Hospitalier Centre, Hôpital Edouard Herriot, Lyon, France, discussed several important findings from the study.
For instance, the average age of patients in the study was approximately 70 years and the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen that mandated that sedation be used was nine or lower, which is a low threshold to forgo sedation, according to Guérin.
“Taken together, these circumstances make the trial results specific to a somewhat circumscribed population,” he wrote.
Additionally, Guérin highlighted the higher percentage of patients who declined trial participation — 14.6% — in this study than in other similar studies; the fact that the 1-day difference in coma- or delirium-free days between study groups could include any time period between 1 and 24 hours due to daily data collection; and the proportion of patients — 27% — in the nonsedation group who received sedation during the first 24 hours after sedation despite discouragement of crossover between study arms. He also noted that the trial may have been underpowered due to its reliance on outcomes from a preliminary trial to calculate the power to detect a mortality difference.
“The results from this trial are important because they arouse concern about omitting sedation in mechanically ventilated patients and reinforce the need to monitor sedation clinically with the aim of discontinuing it as early as possible or at least interrupting it daily. Such monitoring should be performed continuously (24 hours per day, every day), on the basis of standardized criteria that can be applied uniformly in an ICU,” Guérin wrote. – by Melissa Foster
Disclosures: Olsen reports receiving grants from the Aase og Ejnar Danielsens Fond, the Danish Council for Strategic Research and the Scandinavian Society of Anaesthesiology and Intensive Care Medicine. Please see the study for all other authors’ relevant financial disclosures. Guérin reports no relevant financial disclosures.