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

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.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Kawazoe reports receipt of lecture fees from Hospira Japan and Pfizer Japan and a scholarship from Hospira Japan. Dr Miyamoto reports receipt of lecture fees from Pfizer Japan. Dr Morimoto reports receipt of lecture fees from AbbVie, AstraZeneca, Daiichi-Sankyo, Kowa, Kyorin, and Pfizer Japan and educational consulting fees from Boston Scientific. Dr Yamamura reports receipt of lecture fees from Hospira Japan, Nipro, and Asahi Kasei and educational consulting fees from Toray Industries, CSL Behring, Teijin Pharma, and Nihon Pharmaceutical. No other disclosures were reported.

Figures

Figure 1.. Flow of Participants in the Dexmedetomidine for Sepsis in Intensive Care Unit Randomized Evaluation Trial

Figure 2.. 28-Day Mortality Among the Dexmedetomidine and Control Groups

Day 1 is defined as the first day of randomization into the trial.

Figure 3.. Percentage of Patients With Well-Controlled Sedation and Delirium- and Coma-Free Days During ICU Stay Among the Dexmedetomidine and Control Groups

To examine the effect of dexmedetomidine on sedation control and the occurrence of delirium and coma, a generalized linear model was used accounting for repeated measurements in the same patient. Well-controlled sedation was defined as a Richmond Agitation-Sedation Scale (RASS) score between −3 and +1 throughout 1 day spent in the intensive care unit (ICU) and was defined as (rate of controlled sedation) = (patient’s number of days with well-controlled sedation)/(total number of patients in the ICU), calculated for each day. Coma was defined as an RASS score between −4 and −5 throughout 1 day in the ICU. Day 1 is defined as the first day of randomization into the trial.