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

14 czerwca 2026 zaktualizowane przez: Qiancheng Xu, First Affiliated Hospital of Wannan Medical College

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

This prospective, multicenter, single-arm interventional pilot study aims to evaluate the short-term physiological effects of intravenous esmolol on sublingual microcirculation and vascular-waterfall parameters in adult patients with septic shock. Eligible patients will have septic shock according to Sepsis-3 criteria, persistent tachycardia after initial hemodynamic optimization, ongoing norepinephrine support, adequate volume status or absence of significant fluid responsiveness, and preserved or hyperdynamic cardiac function.

Approximately 20 patients will be enrolled from participating intensive care units. After baseline assessment, participants will receive continuous intravenous esmolol infusion according to the study protocol and clinical safety criteria. Sublingual microcirculatory variables, including microvascular flow index, perfused vessel density, proportion of perfused vessels, and heterogeneity index, as well as vascular-waterfall parameters, including estimated critical closing pressure, estimated mean systemic filling pressure, and the Pcc-Pmsf gradient, will be measured at baseline and at 3, and 6 hours after esmolol initiation. Additional systemic hemodynamic, perfusion, vasopressor, and safety variables will also be collected.

The primary objective is to characterize immediate changes in sublingual microcirculation and vascular-waterfall physiology after esmolol administration and to provide preliminary data for the design of future controlled studies.

Przegląd badań

Status

Jeszcze nie rekrutacja

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Szacowany)

20

Faza

  • Nie dotyczy

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

Lokalizacje studiów

  • Chiny
    • Anhu
      • Bengbu, Anhu, Chiny, 233000
        • The First Affiliated Hospital of Bengbu Medical University
        • Kontakt:
    • Anhui
      • Wuhu, Anhui, Chiny, 241000
        • The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College)
        • Kontakt:

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

  • Dorosły
  • Starszy dorosły

Akceptuje zdrowych ochotników

Nie

Opis

Inclusion Criteria:

Age 18-85 years. Diagnosis of septic shock according to Sepsis-3 criteria, requiring norepinephrine to maintain MAP ≥65 mmHg after adequate fluid resuscitation.

Persistent tachycardia after initial hemodynamic optimization, adequate analgesia/sedation, and correction of reversible causes, defined as heart rate ≥95 beats/min.

Continuous norepinephrine infusion for ≥6 hours, with norepinephrine dose ≥0.10 μg/kg/min at enrollment.

Adequate volume status or absence of fluid responsiveness assessed by dynamic indices, echocardiography, or advanced hemodynamic monitoring; if PiCCO is used, GEDVI >700 mL/m² and/or ITBVI >850 mL/m² may be used as supportive criteria.

Preserved or hyperdynamic cardiac function before esmolol initiation, defined as cardiac index >3.0 L/min/m² or absence of severe septic cardiomyopathy.

Ability to obtain sublingual microcirculatory images of acceptable quality at baseline.

Written informed consent obtained from the patient or legally authorized representative.

Exclusion Criteria:

Shock mainly caused by non-septic etiologies, including cardiogenic, hypovolemic, obstructive, hemorrhagic, or anaphylactic shock.

Severe cardiac dysfunction or severe septic cardiomyopathy, including cardiac index <2.2 L/min/m² despite adequate preload, severe ventricular dysfunction, or need for inotropic agents at enrollment.

Use of β-blockers before ICU admission or within 24 hours before enrollment. Contraindications to esmolol or β-blockade, including high-grade atrioventricular block without pacing, severe bradycardia, sick sinus syndrome, severe bronchospasm/asthma, or known allergy to esmolol.

Severe structural heart disease or major pulmonary conditions affecting hemodynamics or safety, including severe valvular disease, significant congenital heart disease, cardiomyopathy, severe pulmonary bullae, or untreated pneumothorax.

Acute coronary syndrome, life-threatening arrhythmia, or cardiac arrest before enrollment during the current ICU stay.

Conditions interfering with sublingual microcirculatory assessment, including major oral/sublingual lesions, active oral bleeding, inability to access the sublingual area, or poor baseline image quality.

Pregnancy or lactation, expected death or withdrawal of life-sustaining treatment within 24 hours, expected ICU stay <48 hours, or inability to obtain informed consent.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Podstawowa nauka
  • Przydział: Nie dotyczy
  • Model interwencyjny: Zadanie dla jednej grupy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Esmolol arm
Adult patients with septic shock and persistent tachycardia after initial hemodynamic optimization will receive continuous intravenous esmolol infusion. Sublingual microcirculatory, vascular-waterfall, macrocirculatory, perfusion, and safety variables will be assessed at baseline and at 3, and 6 hours after esmolol initiation.
Lek: Esmolol intravenous infusion
Esmolol will be administered as a continuous intravenous infusion after initial hemodynamic optimization. The suggested initial infusion rate is 25-50 μg/kg/min and may be titrated according to heart rate, blood pressure, cardiac output, and clinical judgment. The target heart rate is generally 80-94 beats/min, unless individualized by the treating physician. Dose adjustment, temporary interruption, or discontinuation is permitted for safety reasons, including hypotension, bradycardia, reduced cardiac output, or other clinically significant adverse events. The actual dose and reasons for dose changes will be recorded at each study time point.

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Change From Baseline in Sublingual Microvascular Flow Index
Ramy czasowe: Baseline, 3 hours, and 6 hours after initiation of esmolol
Microvascular flow index will be assessed using sublingual microcirculatory imaging. Three to five sublingual video fields will be recorded at each time point, and MFI will be calculated according to standard microcirculatory scoring methods. The outcome is the change in MFI from baseline to each post-esmolol time point.
Baseline, 3 hours, and 6 hours after initiation of esmolol
Change From Baseline in Pcc-Pmsf Gradient
Ramy czasowe: Baseline, 3 hours, and 6 hours after initiation of esmolol
The vascular-waterfall pressure gradient will be calculated as the difference between estimated critical closing pressure and estimated mean systemic filling pressure. The outcome is the change in Pcc-Pmsf from baseline to each post-esmolol time point.
Baseline, 3 hours, and 6 hours after initiation of esmolol

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Change From Baseline in Perfused Vessel Density
Ramy czasowe: Baseline, 3 hours, and 6 hours after initiation of esmolol
Perfused vessel density will be measured from sublingual microcirculatory images. The outcome is the change in PVD from baseline to each post-esmolol time point.
Baseline, 3 hours, and 6 hours after initiation of esmolol
Change From Baseline in Proportion of Perfused Vessels
Ramy czasowe: Baseline, 3 hours, and 6 hours after initiation of esmolol
Proportion of perfused vessels will be measured from sublingual microcirculatory images. The outcome is the change in PPV from baseline to each post-esmolol time point.
Baseline, 3 hours, and 6 hours after initiation of esmolol
Change From Baseline in Microcirculatory Heterogeneity Index
Ramy czasowe: Baseline, 3 hours, and 6 hours after initiation of esmolol
Microcirculatory heterogeneity index will be calculated from sublingual microcirculatory measurements. The outcome is the change in HI from baseline to each post-esmolol time point.
Baseline, 3 hours, and 6 hours after initiation of esmolol
Change From Baseline in Estimated Critical Closing Pressure
Ramy czasowe: Baseline, 3 hours, and 6 hours after initiation of esmolol
Estimated critical closing pressure will be calculated using predefined hemodynamic methods. The outcome is the change in Pcc from baseline to each post-esmolol time point.
Baseline, 3 hours, and 6 hours after initiation of esmolol
Change From Baseline in Estimated Mean Systemic Filling Pressure
Ramy czasowe: Baseline, 3 hours, and 6 hours after initiation of esmolol
Estimated mean systemic filling pressure will be calculated using predefined hemodynamic methods. The outcome is the change in Pmsf from baseline to each post-esmolol time point.
Baseline, 3 hours, and 6 hours after initiation of esmolol
Change From Baseline in Heart Rate
Ramy czasowe: Baseline, 3 hours, and 6 hours after initiation of esmolol
Heart rate will be recorded at each study time point. The outcome is the change in heart rate from baseline to each post-esmolol time point.
Baseline, 3 hours, and 6 hours after initiation of esmolol
Change From Baseline in Mean Arterial Pressure
Ramy czasowe: Baseline, 3 hours, and 6 hours after initiation of esmolol
Mean arterial pressure will be recorded from invasive arterial monitoring at each study time point. The outcome is the change in MAP from baseline to each post-esmolol time point.
Baseline, 3 hours, and 6 hours after initiation of esmolol
Change From Baseline in Cardiac Index
Ramy czasowe: Baseline, 3 hours, and 6 hours after initiation of esmolol
Cardiac index will be measured using echocardiography, pulse contour analysis, transpulmonary thermodilution, or other clinically available hemodynamic monitoring methods. The outcome is the change in cardiac index from baseline to each post-esmolol time point.
Baseline, 3 hours, and 6 hours after initiation of esmolol
Change From Baseline in Norepinephrine Dose
Ramy czasowe: Baseline, 3 hours, and 6 hours after initiation of esmolol.
Norepinephrine dose will be recorded in μg/kg/min at each study time point. The outcome is the change in norepinephrine dose from baseline to each post-esmolol time point.
Baseline, 3 hours, and 6 hours after initiation of esmolol.
Change From Baseline in Arterial Lactate
Ramy czasowe: Baseline and 6 hours after initiation of esmolol.
Arterial lactate concentration will be measured according to routine clinical practice. The outcome is the change in lactate from baseline to 6 hours after initiation of esmolol.
Baseline and 6 hours after initiation of esmolol.
ICU Length of Stay
Ramy czasowe: From ICU admission to ICU discharge, assessed up to 28 days after enrollment
Number of days from ICU admission to ICU discharge.
From ICU admission to ICU discharge, assessed up to 28 days after enrollment
Ventilator-Free Days at Day 28
Ramy czasowe: 28 days after enrollment.
Number of days alive and free from invasive mechanical ventilation within 28 days after enrollment.
28 days after enrollment.
28-Day Mortality
Ramy czasowe: 28 days after enrollment.
All-cause mortality within 28 days after enrollment.
28 days after enrollment.
Incidence of Prespecified Adverse Events
Ramy czasowe: From initiation of esmolol to 6 hours after initiation
Prespecified adverse events include clinically significant hypotension, bradycardia, new-onset or worsening arrhythmia, reduction in cardiac index requiring treatment modification, escalation of vasopressor or inotropic support, interruption or discontinuation of esmolol for safety reasons, cardiac arrest, or other clinically significant events during the observation period.
From initiation of esmolol to 6 hours after initiation

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

First Affiliated Hospital of Wannan Medical College

Współpracownicy

The First Affiliated Hospital of Bengbu Medical University

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Szacowany)

1 sierpnia 2026

Zakończenie podstawowe (Szacowany)

1 grudnia 2027

Ukończenie studiów (Szacowany)

30 grudnia 2027

Daty rejestracji na studia

Pierwszy przesłany

14 czerwca 2026

Pierwszy przesłany, który spełnia kryteria kontroli jakości

14 czerwca 2026

Pierwszy wysłany (Rzeczywisty)

18 czerwca 2026

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

18 czerwca 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

14 czerwca 2026

Ostatnia weryfikacja

1 czerwca 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • 2026-ICU05

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIEZDECYDOWANY

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

Badania kliniczne na Posocznica

Badania kliniczne na Esmolol intravenous infusion

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