Effects of Esmolol on Sublingual Microcirculation and Vascular Waterfall Phenomenon in Patients With Septic Shock

Septic shock is characterized by profound circulatory dysfunction involving both systemic hemodynamics and the microcirculation. Persistent tachycardia is common in septic shock and may reflect sympathetic overactivation, high catecholamine exposure, fever, pain, hypovolemia, or ongoing circulatory stress. After adequate fluid resuscitation, vasopressor support, analgesia and sedation, and correction of reversible causes, persistent tachycardia may contribute to increased myocardial oxygen consumption, impaired diastolic filling, reduced ventriculo-arterial coupling, and altered tissue perfusion.

Esmolol is an ultra-short-acting β1-selective adrenergic blocker that can be titrated rapidly and discontinued promptly if adverse hemodynamic effects occur. Previous studies suggest that heart rate control with esmolol in selected patients with septic shock may reduce catecholamine requirements and improve cardiovascular efficiency. However, its immediate effects on sublingual microcirculation and vascular-waterfall physiology remain insufficiently characterized.

The vascular-waterfall phenomenon refers to the concept that tissue perfusion may depend not only on arterial and venous pressures but also on the relationship between upstream pressure, critical closing pressure, and mean systemic filling pressure. In septic shock, changes in vascular tone, vasopressor exposure, and microvascular regulation may alter critical closing pressure and the effective pressure gradient for tissue perfusion. Evaluating these parameters together with direct sublingual microcirculatory imaging may provide mechanistic insight into the physiological effects of esmolol beyond conventional macrocirculatory variables.

This is a prospective, multicenter, single-arm interventional pilot 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, persistent tachycardia, ongoing norepinephrine support, adequate volume status or no significant fluid responsiveness, and preserved or hyperdynamic cardiac function before esmolol initiation. Patients with shock predominantly due to non-septic causes, severe cardiac dysfunction, contraindications to β-blockade, or inability to obtain acceptable sublingual microcirculatory images will be excluded.

After informed consent is obtained, baseline measurements will be performed immediately before esmolol initiation. Participants will then receive continuous intravenous esmolol infusion. The infusion may be started at a low dose and titrated according to heart rate, mean arterial pressure, cardiac output or cardiac index, vasopressor requirement, and clinical safety criteria. Temporary dose reduction, interruption, or discontinuation of esmolol will be permitted for safety reasons, including clinically significant hypotension, bradycardia, reduced cardiac output, worsening shock, new or worsening arrhythmia, or other adverse events judged by the treating physician or investigator.

Study assessments will be performed at baseline and at 3, and 6 hours after initiation of esmolol. Sublingual microcirculatory imaging will be used to assess microvascular flow index, perfused vessel density, proportion of perfused vessels, and microcirculatory heterogeneity index. Vascular-waterfall related variables will include estimated critical closing pressure, estimated mean systemic filling pressure, and the Pcc-Pmsf gradient. Systemic hemodynamic and perfusion variables, including heart rate, mean arterial pressure, cardiac index, norepinephrine dose, arterial lactate, urine output, and predefined adverse events, will also be recorded.

Approximately 20 patients will be enrolled to assess feasibility and generate preliminary estimates of physiological changes after esmolol administration. The main analyses will describe changes from baseline in sublingual microcirculatory and vascular-waterfall parameters over the 6-hour observation period. Safety events and exploratory clinical outcomes may be summarized descriptively to inform the design of subsequent controlled trials.