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ORLANDO -- Ninety-day mortality was similar among mechanically ventilated patients in the ICU who received no sedation and those who received light sedation with daily interruption, according to the NON-SEDA trial.

In the multicenter, randomized, controlled trial, at 90 days, 42.4% of patients in the nonsedation group and 37.0% of patients in the sedation group had died (difference 5.4 percentage points, 95% CI -2.2 to 12.2, P=0.065), according to Palle Toft, MD, DMSc, of Odense University Hospital in Denmark, and colleagues.

Likewise, time on mechanical ventilation, length of ICU stay, and length of hospital stay were not significantly different between the two groups in the 700-patient study conducted at eight ICUs in Denmark, Norway, and Sweden, they reported in the .

Also, patients in the nonsedation group had 1 more day free from coma or delirium, had fewer major thrombolytic events, and researchers reported that there was a suggestion of better kidney function in the nonsedation group.

In a presentation at the Society of Critical Care Medicine (SCCM) congress, Toft noted that the multicenter study findings failed to confirm those from an by his group, which showed no sedation to be associated with significantly fewer days on mechanical ventilation and shorter hospital stays versus sedation with daily interruption.

He said while the study showed no mortality benefit for nonsedation, individual patients may still want to be awake while on mechanical ventilation instead of being lightly sedated or fully sedated.

"They are able to communicate and even watch television instead of being sedated," he said. "And they can even write their opinion to their doctor, so there is two-way communication."

Newly installed SCCM President Lewis J. Kaplan, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, told MedPage Today that studies like NON-SEDA are important because the optimal level of sedation for mechanically ventilated patients in the ICU is under debate.

"Years ago, patients on ventilators were deeply sedated and many were neuromuscularly blocked, and when they were better, we woke them up," he said. "We do things completely differently now, but the balance between no sedation, light sedation, and more sedation remains largely unresolved."

Toft told MedPage Today that technological improvements in mechanical ventilators make nonsedation feasible.

"Modern ventilators have much softer tubes, so in many cases you don't have to sedate patients," he said.

But patients who are fully awake on ventilators do require almost constant monitoring by an ICU nurse. "This was a Scandinavian study, and in most university hospitals we have a nurse-to-patient ratio of 1:1 in the ICU," he said.

Mechanically ventilated patients were assigned 1:1 to either no sedation or light sedation (arousable, score of -2 to -3 on the Richmond Agitation and Sedation Scale []) with daily interruption.

Mortality at 90 days was chosen as the primary study endpoint, and secondary endpoints included major thromboembolic events, days free from coma or delirium, acute kidney injury, number of ICU-free days, and number of ventilator-free days.

Patient characteristics at baseline were similar between the two intervention groups, with the exception of the score on the Acute Physiology and Chronic Health Evaluation II (), which was 1 point higher in the non-sedation group (indicative of greater risk for in-hospital death).

The median age of the patients in the nonsedation group was 72 versus 70 in the sedation group. A total of 42.1% and 67.0%, respectively, of those in the nonsedation and sedation groups were hospitalized with pneumonia or acute respiratory distress syndrome (ARDS) and 24.1% and 21.1%, respectively, had sepsis.

The mean RASS score in the nonsedation group increased from −1.3 on day 1 to −0.8 on day 7. The mean RASS in the sedation group increased from −2.3 on day 1 to −1.8 on day 7.

There was no significant difference between the two groups in ICU-free days and ventilator-free days, and median days free from coma or delirium was 27 and 26 in the non-sedation and sedation groups, respectively.

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 an , Claude Guerin, MD, PhD, of Hospital Edouard Herriot in Lyon, France, highlighted several issues with the multicenter study that could have contributed to the null finding for key endpoints.

"First, the patients were approximately 70 years of age on average, and the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen that mandated that sedation be used, and was therefore an exclusion criterion for participation, was 9 or lower (or ≤68 if the partial pressure of arterial oxygen was measured in millimeters of mercury), which is a low threshold to forego sedation in the view of many intensivists," Guerin wrote. "Taken together, these circumstances make the trial results specific to a somewhat circumscribed population."

Guerin noted that 14.6% of patients assessed for the study refused to participate -- much higher than similar trials -- possibly because patients or their family members did not want to be randomized to no sedation. And even though cross-over was discouraged, 27% of patients in the nonsedation group received some sedation in the first 24 hours.

But Guerin concluded that the trial findings 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," he stated.

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