Use of dexmedetomidine improved sedation among ventilated patients with sepsis, but did not significantly cut mortality rates or increase ventilator-free days in a multicenter, open-label randomized controlled trial.
Twenty-eight days after the start of mechanical ventilation, cumulative mortality rates were 23% among patients who received dexmedetomidine and 31% among those who did not (hazard ratio, 0.7; 95% confidence interval, 0.4 to 1.2; P = .2), Yu Kawazoe, MD, PhD, and his associates reported at the International Symposium on Intensive Care and Emergency Medicine. The report was simultaneously published in JAMA.
“The study may have identified a clinically important benefit of dexmedetomidine – an 8% reduction in 28-day mortality – that did not demonstrate statistical significance ... ” wrote Dr. Kawazoe of Tohoku University Graduate School of Medicine, Sendai, Japan. “Physicians may consider an 8% difference in 28-day mortality to be clinically significant, but this study was underpowered to detect this difference.”
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Dexmedetomidine often is used for sedation during ventilation, but its effects on mortality and ventilator weaning are poorly understood, the researchers noted. However, this highly selective alpha2-adrenergic agonist has been found to suppress inflammation and to protect organs, and “can improve patients’ ability to communicate pain compared with midazolam and propofol,” the researchers wrote. Therefore, they randomly assigned 201 patients with sepsis at eight intensive care units in Japan to receive sedation with or without dexmedetomidine. Both arms received fentanyl, propofol, and midazolam, dosed to achieve Richmond Agitation-Sedation Scale (RASS) scores of 0 (calm) during the day and –2 (lightly sedated) at night (JAMA. 2017 March 21. doi: 10.1001/jama.2017.2088).
The dexmedetomidine group spent a median of 20 days off the ventilator, compared with 18 days for controls (P = .20), the investigators reported. However, dexmedetomidine led to significantly higher rates of well-controlled sedation. The highest rate of well-controlled sedation (defined as having a RASS scores between –3 and 1 throughout 1 day in the ICU) in treated patients was 58%, while the highest rate of well-controlled sedation in the control group was 39% (P = .01).
Rates of adverse events did not significantly differ between groups. Bradycardia was most common, affecting 7% of the intervention group and 2% of controls (P = .1) the researchers said.
Hospira Japan provided partial funding with a grant to Wakayama Medical University, and helped design the study but was otherwise not involved in the research project. Dr. Kawazoe disclosed ties to Hospira Japan and Pfizer Japan. Three coinvestigators disclosed ties to Pfizer Japan, AbbVie, AstraZeneca, Daiichi Sankyo, and several other pharmaceutical companies. The other coinvestigators had no disclosures.