[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Original Investigation
Caring for the Critically Ill Patient
April 4, 2017

Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation With Sepsis: A Randomized Clinical Trial

Author Affiliations
  • 1Division of Emergency and Critical Care Medicine, Tohoku University Graduate school of Medicine, Sendai, Japan
  • 2Department of Emergency and Critical Care Medicine, Wakayama Medical University, Wakayama, Japan
  • 3Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan
  • 4Department of Trauma and Critical Care Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
  • 5Emergency and Urgent Medical Care Center, Osaka City General Hospital, Osaka, Japan
  • 6Emergency and Critical Care Center, Hyogo College of Medicine, Nishinomiya, Japan
  • 7Advanced Emergency Care Center, Saga University Hospital, Saga, Japan
  • 8Department of Emergency Medicine and Critical Care Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
  • 9Department of Emergency Medicine, Sapporo Medical University, Sapporo, Japan
  • 10Department of Anesthesiology, Yamaguchi Grand Medical Center, Hofu, Japan
  • 11Division of General Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
  • 12Department of Disaster and Critical Care Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
JAMA. 2017;317(13):1321-1328. doi:10.1001/jama.2017.2088
Key Points

Question  Does a sedation strategy with dexmedetomidine compared with no dexmedetomidine improve ventilator-free days and mortality among patients with sepsis requiring ventilation?

Findings  In this randomized clinical trial that included 201 adults, treatment with dexmedetomidine compared with treatment without dexmedetomidine did not significantly improve ventilator-free days (20 days vs 18 days) or 28-day mortality (23% vs 31%; hazard ratio, 0.69).

Meaning  Treatment with dexmedetomidine in patients with sepsis did not improve either ventilator-free days or 28-day mortality.


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