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

14 de junho de 2026 atualizado por: 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.

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Intervenção / Tratamento

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Estimado)

20

Estágio

  • Não aplicável

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

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.

Plano de estudo

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Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Ciência básica
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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.
Medicamento: 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.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Change From Baseline in Sublingual Microvascular Flow Index
Prazo: 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
Prazo: 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

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Change From Baseline in Perfused Vessel Density
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 28 days after enrollment.
All-cause mortality within 28 days after enrollment.
28 days after enrollment.
Incidence of Prespecified Adverse Events
Prazo: 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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

First Affiliated Hospital of Wannan Medical College

Colaboradores

The First Affiliated Hospital of Bengbu Medical University

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

1 de agosto de 2026

Conclusão Primária (Estimado)

1 de dezembro de 2027

Conclusão do estudo (Estimado)

30 de dezembro de 2027

Datas de inscrição no estudo

Enviado pela primeira vez

14 de junho de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

14 de junho de 2026

Primeira postagem (Real)

18 de junho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

18 de junho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

14 de junho de 2026

Última verificação

1 de junho de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • 2026-ICU05

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Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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