Dexmedetomidine for Reducing Mortality in Patients With Septic Shock: A Randomized Controlled Trial (DecatSepsis)

Abstract

Background: Sepsis, especially septic shock, and its complications have been linked to the hyperadrenergic stress response.

Research question: Does decatecholaminization with dexmedetomidine lower the in-hospital mortality in patients with septic shock?

Study design and methods: This open-label randomized controlled trial assessed the effects of a heart rate (HR)-calibrated dexmedetomidine infusion on in-hospital mortality in patients with septic shock and HR of > 90 beats/min, regardless of whether they are receiving mechanical ventilation. Dexmedetomidine was infused for 48 h to maintain the HR at 60 to 90 beats/min. Mechanically ventilated patients received conventional sedation in both groups. Other outcomes were the norepinephrine equivalent dose, the need for additional vasopressor, Acute Physiology and Chronic Health Evaluation (APACHE) II score, persistent atrial fibrillation (AF), and C-reactive protein (CRP) level.

Results: In 90 patients of either sex, dexmedetomidine reduced the mean HR over the first 3 days in the ICU by 11.2 beats/min (95% CI, -17 to -5 beats/min; P < .001). The in-hospital mortality risk ratio (RR) was 0.68 (95% CI, 0.43-1.07; P = .091). The dexmedetomidine group received a norepinephrine equivalent dose of 0.55 μm/kg/min (interquartile range [IQR], 0.37-0.82 μm/kg/min) vs 0.61 μm/kg/min (IQR, 0.47-0.89 μm/kg/min; P = .121). Dexmedetomidine reduced the epinephrine infusion rescue (relative risk reduction, 0.6; 95% CI, 0.06-0.93; P = .025). The RR of persistent AF was 0.47 (95% CI, 0.21-0.99; P = .05). Dexmedetomidine reduced the median APACHE II score on the third day by -6 (95% CI, -10 to -2; P = .003) and the mean CRP concentration by -40 mg/dL (95% CI, -78 to -3.4 mg/dL; P = .033).

Interpretation: The study was underpowered to detect a reduction in in-hospital mortality or norepinephrine equivalent dose in patients with septic shock with dexmedetomidine. However, dexmedetomidine may reduce epinephrine infusion rescue, persistent AF, APACHE II score, and CRP.

Clinical trial registry: ClinicalTrials.gov; No.: NCT05283083; URL: www.

Clinicaltrials: gov.

Keywords: dexmedetomidine; mortality; randomized controlled trial; sepsis; septic shock.