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



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



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.



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.



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.



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.



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.



clinicaltrials.gov Identifier: NCT01760967.
Division of Emergency and Critical Care Medicine, Tohoku University Graduate school of Medicine, Sendai, Japan.
Yu
Y
Kawazoe
Department of Emergency and Critical Care Medicine, Wakayama Medical University, Wakayama, Japan.
Kyohei
K
Miyamoto
Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan.
Takeshi
T
Morimoto
Department of Trauma and Critical Care Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
Tomonori
T
Yamamoto
Emergency and Urgent Medical Care Center, Osaka City General Hospital, Osaka, Japan.
Akihiro
A
Fuke
Emergency and Critical Care Center, Hyogo College of Medicine, Nishinomiya, Japan.
Atsunori
A
Hashimoto
Advanced Emergency Care Center, Saga University Hospital, Saga, Japan.
Hiroyuki
H
Koami
Department of Emergency Medicine and Critical Care Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
Satoru
S
Beppu
Department of Emergency Medicine, Sapporo Medical University, Sapporo, Japan.
Yoichi
Y
Katayama
Department of Anesthesiology, Yamaguchi Grand Medical Center, Hofu, Japan.
Makoto
M
Itoh
Division of General Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Yoshinori
Y
Ohta
Department of Disaster and Critical Care Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Hitoshi
H
Yamamura
D000368:Aged; D000369:Aged, 80 and over; D020927:Dexmedetomidine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D012121:Respiration, Artificial; D018805:Sepsis / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D015300:Ventilator Weaning
D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine