NONSEDA: Some mechanically ventilated ICU patients need not be sedated

Among critically ill adults receiving mechanical ventilation in the intensive care unit (ICU), a protocol of no sedation is comparable to light sedation with daily interruption in terms of mortality, as shown in the NONSEDA trial.

In a cohort of 700 patients, mortality at 90 days was 42.4 percent in the nonsedation group and 37.0 percent in the sedated group (difference, 5.4 percentage points, 95 percent confidence interval [CI], −2.2 to 12.2; p=0.65), said Dr Palle Toft, from Odense University Hospital in Denmark in a virtual presentation at the Critical Care Reviews Meeting 2021 (eCCR21).

Moreover, there were no important between-group differences in the number of ventilator-free days (20 vs 19 days; p=0.99), ICU-free days (12.0 vs 12.1 days; p=0.9), and hospital-free days (6.3 vs 5.4 days; p=0.15) within a 28-day period.

However, compared with the sedation group, the nonsedation group appeared to have fewer major thromboembolic events at day 90 (0.3 percent vs 2.8 percent), more coma- and delirium-free days during the ICU stay (3.0 vs 1.0 day), better kidney function (days with highest RIFLE* score, 6 vs 7.5 days; proportion of haemodialysis-dependent patients at discharge, 5 percent vs 10 percent), and significantly preserved physical function (at ICU discharge: handgrip strength, 20.4 vs 15.2; Barthel Index, 9 vs 4).

An accidental extubation that led to reintubation within 1 hour occurred in four patients in the nonsedation group and in one patient in the sedation group (1.1 percent vs 0.3 percent; p=0.20). There were no cases of accidental removal of a central venous catheter that led to reinsertion within 4 hours.

The median age of the patients was 72 years in the nonsedation group versus 70 years in the sedation group. Baseline characteristics were similar between the two groups, with the exception of the score on the Acute Physiology and Chronic Health Evaluation II (APACHE II), which was 1 point higher in the nonsedation group (indicative of higher risk of in-hospital death).

To be or not to be sedated

Many patients in the ICU, especially those who are on a ventilator, are sedated at the time of intubation. Maintained for hours or even days, sedation aims to adapt patients to the mechanical ventilator and help them remain comfortably connected to it. [Crit Care 2013;17:322]

On the other hand, Toft asserted that there must be a medical indication to sedate. Furthermore, technological improvements in mechanical ventilators have made omission of sedation feasible. “Modern ventilators have much softer tubes, which the patients can tolerate even in a nonsedated state.”

He also pointed out that while the trial showed no survival benefit for sedation omission, some patients may still prefer to be awake while on mechanical ventilation instead of being lightly or fully sedated.

“Being awake allows patients to communicate with the staff and express what they want, enjoy food, and entertain visitors,” he said. “In the evening, they can look at the television instead of being sedated.”

As such, the sedation strategy should be individualized according to the patients’ needs or issue, as some may want to be awake at daytime to interact with their environment, and others may also choose to be lightly sedated at night-time, according to Toft.

Is nonsedation feasible in other countries?

Delivering an editorial on NONSEDA, Dr Murali Shyamsundar from Queen's University Belfast in Northern Ireland pointed to the fact that the study was conducted in Nordic countries, where the staff is well-trained and an ICU nurse constantly monitors a patient who is fully awake on ventilator.

“Having [that kind of resources] makes such a clinical trial successful and feasible. This also makes us wonder whether the [findings are] generalizable to low- and middle-income countries where the staff and infrastructure may not be available, which is relevant [with regard] to the outcome measures,” Shyamsundar said.

In closing, he enumerated several questions needed to be explored further. Some of them were ‘Why does sedation increase mortality?’, ‘Is mortality the right endpoint for sedation studies in the era where the harms of deep sedation is well established?’, and ‘Should sedation or no sedation be the research question or the level of sedation?’