A Randomized Clinical Trial

Yu Kawazoe, MD, PhD1; Kyohei Miyamoto, MD2; Takeshi Morimoto, MD, PhD, MPH3; et al

Abstract

Importance  Dexmedetomidine provides sedation for patients undergoing ventilation; however, its effects on mortality and ventilator-free days have not been well studied among patients with sepsis.

Objectives  To examine whether a sedation strategy with dexmedetomidine can improve clinical outcomes in patients with sepsis undergoing ventilation.

Design, Setting, and Participants  Open-label, multicenter randomized clinical trial conducted at 8 intensive care units in Japan from February 2013 until January 2016 among 201 consecutive adult patients with sepsis requiring mechanical ventilation for at least 24 hours.

Interventions  Patients were randomized to receive either sedation with dexmedetomidine (n = 100) or sedation without dexmedetomidine (control group; n = 101). Other agents used in both groups were fentanyl, propofol, and midazolam.

Main Outcomes and Measures  The co–primary outcomes were mortality and ventilator-free days (over a 28-day duration). Sequential Organ Failure Assessment score (days 1, 2, 4, 6, 8), sedation control, occurrence of delirium and coma, intensive care unit stay duration, renal function, inflammation, and nutrition state were assessed as secondary outcomes.

Results  Of the 203 screened patients, 201 were randomized. The mean age was 69 years (SD, 14 years); 63% were male. Mortality at 28 days was not significantly different in the dexmedetomidine group vs the control group (19 patients [22.8%] vs 28 patients [30.8%]; hazard ratio, 0.69; 95% CI, 0.38-1.22; P = .20). Ventilator-free days over 28 days were not significantly different between groups (dexmedetomidine group: median, 20 [interquartile range, 5-24] days; control group: median, 18 [interquartile range, 0.5-23] days; P = .20). The dexmedetomidine group had a significantly higher rate of well-controlled sedation during mechanical ventilation (range, 17%-58% vs 20%-39%; P = .01); other outcomes were not significantly different between groups. Adverse events occurred in 8 (8%) and 3 (3%) patients in the dexmedetomidine and control groups, respectively.

Conclusions and Relevance  Among patients requiring mechanical ventilation, the use of dexmedetomidine compared with no dexmedetomidine did not result in statistically significant improvement in mortality or ventilator-free days. However, the study may have been underpowered for mortality, and additional research may be needed to evaluate this further.

Trial Registration  clinicaltrials.gov Identifier: NCT01760967

JAMA