ORLANDO – For critically ill, according to results of a multicenter, randomized trial.
Dr. Palle Toft
The lack of sedation did significantly improve certain secondary endpoints, including a reduced number of thromboembolic events and preservation of physical function, according to Palle Toft, PhD, DMSc, of Odense (Denmark) University Hospital.
However, the 90-day mortality rate was 42.4% in the no-sedation group versus 37.0% in the sedation group in the NONSEDA study, which was intended to test the hypothesis that mortality would be lower in the no-sedation group.
That 5.4 percentage point difference between arms in NONSEDA was not statistically significant (P = .65) in results of the study, presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine and concurrently published in the New England Journal of Medicine.
Yet that mortality trend is in the “opposite direction” of an earlier, single-center trial by Dr. Toft and colleagues, noted Claude Guérin, MD, PhD, in a related editorial that also appeared in the journal. In that earlier study, the reported hospital mortality rates were 36% for no sedation and 47% for sedation with daily interruption.
“The results from this trial [NONSEDA] 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,” Dr. Guérin wrote in his editorial.
That said, the earlier, single-center trial was not statistically powered to show between-group differences in mortality, Dr. Toft and coauthors wrote in their journal article.
In his presentation, Dr. Toft emphasized that light sedation with a wake-up trial was “comparable” with no sedation with regard to mortality.
“I think my main message is that we have to individualize patient treatment,” Dr. Toft told attendees at a late-breaking literature session. “Many patients would benefit from nonsedation, and some would benefit by light sedation with a daily wake-up trial. We have to respect patient autonomy, and try to establish a two-way communication with patients in 2020.”
Sandra L. Kane-Gill, PharmD, treasurer of SCCM and assistant professor of pharmacy and therapeutics at the University of Pittsburgh, said that current SCCM guidelines recommend using light sedation in critically ill, mechanically ventilated adults.
“I think we should stay consistent with what the guidelines are saying,” Dr. Kane-Gill said in an interview. “How you do that may vary, but targeting light sedation is consistent with what the evidence is suggesting in those guidelines.”
The depth of sedation between the no-sedation group in the light sedation group in the present study was not as great as the investigators had anticipated, which may explain the lack of statistically significant difference in mortality, according to Dr. Kane-Gill.
According to the report, 38.4% of patients in the no-sedation group received medication for sedation during their ICU stay, while Richmond Agitation and Sedation Scores increased in both groups, indicating a more alert state in both groups.
The multicenter NONSEDA trial included 700 mechanically ventilated ICU patients randomized either to no sedation or to light sedation, such that the patient was arousable, with daily interruption.
Previous studies have shown that daily interruption of sedation reduced mechanical ventilation duration, ICU stay length, and mortality in comparison with no interruption, the investigators noted.
While mortality at 90 days did not differ significantly between the no-sedation and light-sedation approaches, no sedation reduced thromboembolic events, Dr. Toft said at the meeting. The number of thrombolic events within 90 days was 10 (5%) in the sedation group and 1 (0.5%) in the no-sedation group (P less than .05), according to the reported data.
Likewise, several measures of physical function significantly improved in an a prior defined subgroup of 200 patients, he said. Those measures included hand grip at extubation and ICU discharge, as well as scores on the Barthel Index for Activities of Daily Living.
Nonsedation might improve kidney function, based on other reported outcomes of the study, Dr. Toft said. The number of coma- and delirium-free days was 3.0 in the no-sedation group versus 1.0 in the sedation group (P less than .01), he added.
The benefits of no sedation may extend beyond objective changes in health outcomes, according to Dr. Toft. “The patients are able to communicate with the staff, they might be able to enjoy food, in the evening they can look at the television instead of being sedated – and they can be mobilized and they can write their opinion about the treatments to the doctor, and in this way, you have two-way communication,” he explained in his presentation.
Dr. Toft reported that he had no financial relationships to disclose.
SOURCE: Toft P et al. N Engl J Med. 2019 Feb 16. doi: 10.1056/NEJMoa1906759.