Author: Christina Frangou
“The times are changing, and I think we have to move towards individualized medicine on sedation,” said Palle Toft, MD, a professor in the Department of Anesthesiology and Intensive Care at Denmark’s Odense University Hospital, in an emailed interview.
Dr. Toft, one of the study authors, presented the results at the 2020 annual meeting of the Society of Critical Care Medicine. It was published in The New England Journal of Medicine (2020 Feb 16. [Epub ahead of print]. doi: 10.1056/NEJMoa1906759).
“Today we do not need sedation in most of our ICU patients, as long as there is an educated nurse bedside,” he said.
The trial follows on a single-center study from Toft et al that showed a strategy of no sedation for mechanically ventilated ICU patients was associated with significantly fewer days on mechanical ventilation and shorter hospital stays compared with sedation with daily interruption (Lancet 2010;375:475-480).
In the new trial, 700 patients at eight European centers were randomized to receive a plan of no sedation or light sedation with daily interruption within 24 hours of intubation. The mean Richmond Agitation-Sedation Score in the sedation group increased from –2.3 on day 1 to –1.8 on day 7, and, in the nonsedation group, from –1.3 to –0.8.
Mortality at 90 days was 37% in the sedation group and 42% in the nonsedation group (relative risk, 1.10; 95% CI, 0.90-1.35)—a trend contrary to what investigators hypothesized.
But the depth of sedation did not differ between the groups as much as investigators intended, and this may explain some of the outcomes, the authors said. Patients in the nonsedation group could receive bolus doses of morphine for analgesia and, if needed, medications similar to those in the sedation group.
Twenty-seven percent of patients in the nonsedation group received medication for sedation on the first day and 38.4% at some time during their ICU stay. The main reason for sedation was delirium.
One patient in the nonsedation group (0.3%) and 10 in the sedation group (2.8%) experienced a major thromboembolic event (difference, –2.5 percentage points; 95% CI, –4.8 to –0.7).
In most of the participating ICUs, the nurse-to-patient ratio was 1:1. The ICU teams sought to individualize sedation according to a patient’s need, based on two-way communication with the patient. “At the moment, we have, for example, a patient who wants to be sedated at night but prefers nonsedation in the daytime and evening,” Dr. Toft said.
In an accompanying editorial in The New England Journal of Medicine, Claude GuÉrin, MD, PhD, of the HÔpital Edouard Herriot in Lyon, France, pointed out several notable concerns with the trial findings. The results are specific to a somewhat circumscribed population; a high percentage of patients (14.6%) declined to participate, raising questions about patients’ comfort with forgoing sedation; and it may have been underpowered, he said.
But the results 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.”