Effects of Dexmedetomidine on Sublingual Microcirculation and Vascular Waterfall Phenomenon in Patients With Septic Shock: A Prospective, Multicenter, Single-arm, Open-label, Pilot Physiological Study

Septic shock is characterized by profound circulatory dysfunction involving both the macrocirculation and the microcirculation. Although conventional resuscitation targets such as mean arterial pressure, cardiac output, and serum lactate are widely used, microcirculatory alterations may persist despite apparent stabilization of systemic hemodynamics. Direct evaluation of sublingual microcirculation may therefore provide additional physiological information in patients with septic shock.

Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist commonly used for sedation in critically ill patients. Compared with traditional sedatives, dexmedetomidine provides cooperative sedation with limited respiratory depression and may modulate sympathetic tone, inflammation, endothelial function, and regional perfusion. However, dexmedetomidine may also cause bradycardia, hypotension, and changes in vascular tone, which may influence systemic hemodynamics and microcirculatory perfusion. Its immediate effects on directly visualized sublingual microcirculation and vascular-waterfall physiology in patients with septic shock remain insufficiently characterized.

The vascular-waterfall phenomenon refers to the concept that tissue perfusion is influenced not only by arterial and venous pressures but also by the relationship between upstream pressure, critical closing pressure, and mean systemic filling pressure. In septic shock, changes in vascular tone, vasopressor exposure, stressed blood volume, venous return, and cardiac output may alter the effective pressure gradient for tissue perfusion. Evaluation of vascular-waterfall variables together with direct sublingual microcirculatory imaging may provide mechanistic insight into the physiological effects of dexmedetomidine beyond conventional macrocirculatory variables.

This is a prospective, multicenter, single-arm, open-label, interventional pilot physiological study conducted in adult intensive care unit patients with septic shock. Patients will be screened after initial hemodynamic optimization. Eligible patients must have septic shock according to Sepsis-3 criteria, ongoing norepinephrine support, invasive mechanical ventilation with a clinical need for sedation, and PiCCO-based hemodynamic monitoring available before dexmedetomidine initiation. Patients with contraindications to dexmedetomidine, severe bradycardia, high-grade atrioventricular block without a pacemaker, severe uncontrolled arrhythmia, severe hemodynamic instability judged unsuitable for dexmedetomidine, or conditions interfering with sublingual microcirculatory imaging will be excluded.

After informed consent is obtained, baseline measurements will be performed immediately before dexmedetomidine administration. Dexmedetomidine will be administered as a continuous intravenous infusion at 0.2-0.7 µg/kg/hour without a loading dose. The dose may be titrated by the treating physician according to the target sedation level, hemodynamic status, heart rate, vasopressor requirement, and adverse effects. The target sedation level will generally be light-to-moderate sedation according to local ICU practice, such as a Richmond Agitation-Sedation Scale score between -2 and 0, unless otherwise clinically indicated. Dose reduction, temporary interruption, or discontinuation will be permitted for safety reasons, including clinically significant hypotension, bradycardia, new-onset or worsening arrhythmia, high-grade atrioventricular block, increased vasopressor requirement, suspected myocardial ischemia, or other clinically significant adverse events.