Dexmedetomidine improved renal function in patients with severe sepsis: an exploratory analysis of a randomized controlled trial

Abstract

Background: Dexmedetomidine has been reported to improve organ dysfunction in critically ill patients. In a recent randomized controlled trial (Dexmedetomidine for Sepsis in Intensive Care Unit (ICU) Randomized Evolution [DESIRE]), we demonstrated that dexmedetomidine was associated with reduced mortality risk among patients with severe sepsis. We performed this exploratory sub-analysis to examine the mechanism underlying improved survival in patients sedated with dexmedetomidine.

Methods: The DESIRE trial compared a sedation strategy with and without dexmedetomidine among 201 mechanically ventilated adult patients with sepsis across eight ICUs in Japan. In the present study, we included 104 patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of ≥ 23 (54 in the dexmedetomidine [DEX] group and 50 in the non-dexmedetomidine [non-DEX] group). Initially, we compared the changes in the sequential organ failure assessment (SOFA) scores from the baseline within 6 days after randomization between groups. Subsequently, we evaluated the variables comprising the organ component of the SOFA score that showed relevant improvement in the initial comparison.

Results: The mean patient age was 71.0 ± 14.1 years. There was no difference in the median APACHE II score between the two groups (29 [interquartile range (IQR), 25-31] vs. 30 [IQR, 25-33]; p = 0.35). The median SOFA score at the baseline was lower in the DEX group (9 [IQR, 7-11] vs. 11 [IQR, 9-13]; p = 0.01). While the renal SOFA subscore at the baseline was similar for both groups, it significantly decreased in the DEX group on day 4 (p = 0.02). During the first 6 days, the urinary output was not significantly different (p = 0.09), but serum creatinine levels were significantly lower (p = 0.04) in the DEX group. The 28-day and in-hospital mortality rates were significantly lower in the DEX group (22% vs. 42%; p = 0.03, 28% vs. 52%; p = 0.01, respectively).

Conclusion: A sedation strategy with dexmedetomidine is associated with improved renal function and decrease mortality rates among patients with severe sepsis.

Trial registration: This trial was registered on ClinicalTrials.gov (NCT01760967) on January 1, 2013.

Keywords: Acute kidney injury; Dexmedetomidine; Sedation; Septic shock; Sequential organ failure assessment score.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

© The Author(s). 2019.

Figures

Fig. 1

Flowchart of patients in this study. DESIRE, Dexmedetomidine for Sepsis in Intensive Care Unit Randomized Evaluation; APACHE, Acute Physiology and Chronic Health Evaluation; DEX, dexmedetomidine

Fig. 2

Comparison between the dexmedetomidine and non-dexmedetomidine groups regarding each component of the sequential organ failure assessment score. a Respiratory component. b Cardiovascular component. c Renal component. d Neurological component. e Hepatic component. f Coagulation component. g Total SOFA score. We compared continuous variables between both groups using Wilcoxon rank-sum test. DEX, dexmedetomidine

Fig. 3

Comparison between the dexmedetomidine and non-dexmedetomidine groups regarding urinary output within a week. A generalized linear model was used to examine the effect of dexmedetomidine on the natural logarithm of the daily urinary output. DEX, dexmedetomidine

Fig. 4

Comparison between the dexmedetomidine and non-dexmedetomidine groups regarding creatinine levels within a week. A generalized linear model was used to examine the effect of dexmedetomidine on the natural logarithm of the daily serum creatinine concentration. DEX, dexmedetomidine