xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06013319</url>
    </required_header>
    <id_info>
      <org_study_id>QFSKYLLTZH-2023-043</org_study_id>
      <nct_id>NCT06013319</nct_id>
    </id_info>
    <brief_title>Effect of Esmolol on Oxygenation Index in Patients With Acute Respiratory Distress Syndrome</brief_title>
    <official_title>Effects of Esmolol on Oxygenation Index by Controlling Heart Rate in Patients With Acute Respiratory Distress Syndrome</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zhiming Jiang</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Qianfoshan Hospital</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Acute respiratory distress syndrome (ARDS) is a clinical syndrome caused by intrapulmonary&#xD;
        and/or extrapulmonary causes, characterized by intractable hypoxemia. Studies have shown that&#xD;
        the sympathetic nervous system is over-activated in patients with acute respiratory distress&#xD;
        syndrome. A large retrospective study showed a reduction in mortality in ARDS patients&#xD;
        treated with oral β1 blockers before admission, and this beneficial effect of β1 blockers&#xD;
        applies to ARDS patients with or without cardiac disease. Esmolol is an ultra-short-acting&#xD;
        selective β1 receptor blocker. Previous studies have shown that esmolol can improve&#xD;
        oxygenation and reduce the levels of inflammatory cytokines and exudate proteins in&#xD;
        bronchoalveolar lavage fluid, thereby alleviating pulmonary injury. According to the&#xD;
        literature and our previous clinical observations, we made the following hypothesis: When&#xD;
        Estolol is applied to various ARDS patients undergoing mechanical ventilation in ICU, it can&#xD;
        control the heart rate by inhibiting β-adrenergic receptor, which can ultimately improve the&#xD;
        oxygenation index of patients and shorten the mechanical ventilation time. This project&#xD;
        intends to include ARDS patients with optimal hemodynamic treatment for 24 hours, whose heart&#xD;
        rate is still ≥95 beats/min after conventional treatment, but ≤120 beats/min. They are&#xD;
        randomly divided into control group and Esmolol treatment group to study the effects of&#xD;
        esmolol on patients' oxygenation index, mechanical ventilation time, hemodynamics, function&#xD;
        of various organs and inflammation level. The aim of this study is to optimize the treatment&#xD;
        of ARDS patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        At present, there are few studies on Esmolol in acute respiratory distress syndrome. However,&#xD;
        previous studies have shown that Esmolol can improve oxygenation and reduce the levels of&#xD;
        inflammatory cytokines and exudate proteins in bronchoalveolar lavage fluid, thus alleviating&#xD;
        pulmonary injury. Considering that a considerable number of ARDS patients in the intensive&#xD;
        care unit suffer from sepsis, we conducted this study to explore the application timing of&#xD;
        esmolol therapy and whether esmolol can improve the symptoms and prognosis of ARDS patients.&#xD;
        Based on the literature and our previous clinical observations, we make the following&#xD;
        assumptions: Esmolol is applied to various ARDS patients receiving mechanical ventilation in&#xD;
        ICU. By inhibiting the β-adrenergic receptor to control the heart rate, it can ultimately&#xD;
        improve the oxygenation index of patients, shorten the mechanical ventilation time, achieve&#xD;
        tracheal intubation extraction as soon as possible, and reduce the 28-day mortality. At the&#xD;
        same time, esmolol can also improve the function of various organs of patients and reduce the&#xD;
        level of inflammatory factors. This project intends to include ARDS patients with optimal&#xD;
        hemodynamic treatment for 24 hours, whose heart rate is still ≥95 beats/min after&#xD;
        conventional treatment, but ≤120 beats/min. They are randomly divided into control group and&#xD;
        Esmolol treatment group to study the effects of esmolol on patients' oxygenation index,&#xD;
        mechanical ventilation time, hemodynamics, function of various organs and inflammation level.&#xD;
        To optimize the treatment of ARDS patients.&#xD;
  &#xD;
        Acute respiratory distress syndrome (ARDS) is a clinical syndrome caused by intrapulmonary&#xD;
        and/or extrapulmonary causes, characterized by intractable hypoxemia. ARDS is the most common&#xD;
        cause of respiratory failure in severe patients, and also the main factor leading to poor&#xD;
        prognosis in severe patients. In recent years, although the research on ARDS has continued to&#xD;
        go deeper, clinical treatment still remains in the stage of lung protective ventilation and&#xD;
        restricted fluid management, and there is still a lack of specific drug therapy, and the&#xD;
        fatality rate is still as high as 40%.&#xD;
  &#xD;
        Studies have shown that the sympathetic nervous system is over-activated in patients with&#xD;
        acute respiratory distress syndrome. Because 75 to 80 percent of myocardial adrenergic&#xD;
        receptors are β1 type, and adrenergic stress is primarily mediated by beta receptors, the&#xD;
        heart is a prime target for sympathetic overstimulation. Elevated heart rate is associated&#xD;
        with adverse outcomes in patients with severe infection and represents the severity of the&#xD;
        disease.Another large retrospective study showed a reduction in mortality in ARDS patients&#xD;
        treated with oral β1 blockers before admission, and this beneficial effect of β1 blockers&#xD;
        applies to ARDS patients with or without cardiac disease.&#xD;
  &#xD;
        Esmolol is an ultra-short-acting selective β1 receptor blocker, which mainly inhibits β1&#xD;
        receptor by competing for catecholamine binding sites in myocaroma, and has the effect of&#xD;
        slowing resting and exercise heart rate, lowering blood pressure, and reducing myocardial&#xD;
        oxygen consumption. Esmolol is a metabolite coupled with enzyme, so its distribution&#xD;
        half-life is very short, intravenous injection begins to take effect 1-2 min, elimination&#xD;
        half-life is only 9min, easy to control, high safety, and remarkable effect. There have been&#xD;
        numerous studies on esmolol in sepsis. For patients with septic shock, the use of esmolol can&#xD;
        reduce heart rate to the target level, but does not increase the incidence of adverse events,&#xD;
        and does not reduce microcirculation perfusion, and can improve the hemodynamics and 28-day&#xD;
        mortality of patients. In addition, both animal and human experiments have proved that&#xD;
        Esmolol can reduce the release of inflammatory factors in sepsis, improve inflammatory&#xD;
        response, and protect cardiac and renal function.&#xD;
  &#xD;
        At present, there are few studies on Esmolol in acute respiratory distress syndrome. However,&#xD;
        previous studies have shown that Esmolol can improve oxygenation and reduce the levels of&#xD;
        inflammatory cytokines and exudate proteins in bronchoalveolar lavage fluid, thus alleviating&#xD;
        pulmonary injury. Considering that a considerable number of ARDS patients in the intensive&#xD;
        care unit suffer from sepsis, we conducted this study to explore the application timing of&#xD;
        esmolol therapy and whether esmolol can improve the symptoms and prognosis of ARDS patients.&#xD;
        Based on the literature and our previous clinical observations, we make the following&#xD;
        assumptions: Esmolol is applied to various ARDS patients receiving mechanical ventilation in&#xD;
        ICU. By inhibiting the β-adrenergic receptor to control the heart rate, it can ultimately&#xD;
        improve the oxygenation index of patients, shorten the mechanical ventilation time, achieve&#xD;
        tracheal intubation extraction as soon as possible, and reduce the 28-day mortality. At the&#xD;
        same time, esmolol can also improve the function of various organs of patients and reduce the&#xD;
        level of inflammatory factors. This project intends to include ARDS patients with optimal&#xD;
        hemodynamic treatment for 24 hours, whose heart rate is still ≥95 beats/min after&#xD;
        conventional treatment, but ≤120 beats/min. They are randomly divided into control group and&#xD;
        Esmolol treatment group to study the effects of esmolol on patients' oxygenation index,&#xD;
        mechanical ventilation time, hemodynamics, function of various organs and inflammation level.&#xD;
        To optimize the treatment of ARDS patients.&#xD;
  &#xD;
        To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory&#xD;
        distress syndrome (ARDS) on oxygenation index. A total of 187 patients aged 18-65 years who&#xD;
        met the 2012 Berlin diagnostic criteria for acute respiratory distress syndrome will be&#xD;
        included in our study. Hemodynamic optimization was performed within 24 hours after&#xD;
        diagnosis. After treatment, the patient's heart rate continued to be ≥95 beats/min but ≤120&#xD;
        beats/min for at least 10 minutes, with or without esmolol pumping. The improvement of&#xD;
        oxygenation index in different treatment groups was observed.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 1, 2023</start_date>
    <completion_date type="Anticipated">October 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2026</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Participant)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Oxygenation index improved or not</measure>
      <time_frame>From the start of the trial to 12 hours after administering the drug</time_frame>
      <description>To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Oxygenation index improved or not</measure>
      <time_frame>From the start of the trial to 24 hours after administering the drug</time_frame>
      <description>To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Oxygenation index improved or not</measure>
      <time_frame>From the start of the trial to 48 hours after administering the drug</time_frame>
      <description>To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Oxygenation index improved or not</measure>
      <time_frame>From the start of the trial to 72 hours after administering the drug</time_frame>
      <description>To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Oxygenation index improved or not</measure>
      <time_frame>From the start of the trial to 120 hours after administering the drug</time_frame>
      <description>To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>the difference of mechanical ventilation duration</measure>
      <time_frame>from the start of the trial to removal of the endotracheal tube and cessation of mechanical ventilation，up to 28 days</time_frame>
      <description>The duration of mechanical ventilation was compared between the two groups with or without esmolol treatment</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">178</enrollment>
    <condition>Acute Respiratory Distress Syndrome</condition>
    <arm_group>
      <arm_group_label>Esmolol group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients with ARDS who require mechanical ventilation after adequate disease assessment and whose heart rate continues to be ≥95 beats/min, but ≤120 beats/min within 24 hours after diagnosis, for at least 10 minutes without changing the dosage of catecholamine, were diagnosed as atrial fibrillation, atrial flutter or sinus tachycardia. The primary treatment is maintained while the esmolol load dose is administered and the maintenance dose is pumped continuously until the patient's heart rate is maintained between 80 and 94 beats per minute.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Patients with ARDS who need mechanical ventilation after adequate condition assessment and whose heart rate continues to be ≥95 beats /min but ≤120 beats /min after optimal hemodynamic treatment within 24 hours after diagnosis were randomly included in the control group. Routine mechanical ventilation, full sedation and analgesia, maintain RASS score 0-2 points; The target tidal volume is 6ml/kg, and the ventilator parameters should be adjusted in time according to the blood gas analysis. Hypotensive patients with sufficient blood volume should be pumped with pressor drugs. Timely sputum suction, airway management, eliminate fever, asthma, pain and other stimulation caused by the heart rate is too fast.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Esmolol</intervention_name>
      <description>The load dose of esmolol was first injected intravenously: 0.5mg/kg.min, for about 1 minute; then the maintenance dose was pumped intravenously: from 0.05mg/kg/min, and continued after 4 minutes if the efficacy was ideal; if the efficacy was poor, the load dose could be repeated and the maintenance dose increased by 0.05mg/kg/min. The maintenance dose should not exceed 0.3mg/kg/min.</description>
      <arm_group_label>Esmolol group</arm_group_label>
      <other_name>Esmolol hydrochloride injection</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Meeting the 2012 Berlin diagnostic criteria for acute respiratory distress syndrome;&#xD;
  &#xD;
            -  Aged between 18-65 years (inclusive);&#xD;
  &#xD;
            -  95 times/min ≤ heart rate ≤120 times/min;&#xD;
  &#xD;
            -  The patient needs to undergo endotracheal intubation mechanical ventilation after&#xD;
               condition assessment;&#xD;
  &#xD;
            -  Obtain the informed consent of the patient or his legal representative.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Bradycardia and second degree or more atrioventricular block;&#xD;
  &#xD;
            -  Long-term use of beta-blockers;&#xD;
  &#xD;
            -  Combined with emphysema, asthma and other β-blocker contraindicated diseases;&#xD;
  &#xD;
            -  Cardiac insufficiency (NYHA grade Ⅲ or Ⅳ);&#xD;
  &#xD;
            -  Pregnancy&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>zhiming Jiang, doctor</last_name>
      <role>Study Director</role>
      <affiliation>Qianfo Mountain Hospital, Shandong Province</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Quanzhen Wang, doctor</last_name>
      <phone>15562570205</phone>
      <email>wangquanzhen1986@163.com</email>
    </overall_contact>
    <reference>
      <citation>Meyer NJ, Gattinoni L, Calfee CS. Acute respiratory distress syndrome. Lancet. 2021 Aug 14;398(10300):622-637. doi: 10.1016/S0140-6736(21)00439-6. Epub 2021 Jul 1.</citation>
      <PMID>34217425</PMID>
    </reference>
    <reference>
      <citation>van der Jagt M, Miranda DR. Beta-blockers in intensive care medicine: potential benefit in acute brain injury and acute respiratory distress syndrome. Recent Pat Cardiovasc Drug Discov. 2012 Aug;7(2):141-51. doi: 10.2174/157489012801227274.</citation>
      <PMID>22642505</PMID>
    </reference>
    <reference>
      <citation>Morelli A, Donati A, Ertmer C, Rehberg S, Kampmeier T, Orecchioni A, D'Egidio A, Cecchini V, Landoni G, Pietropaoli P, Westphal M, Venditti M, Mebazaa A, Singer M. Microvascular effects of heart rate control with esmolol in patients with septic shock: a pilot study. Crit Care Med. 2013 Sep;41(9):2162-8. doi: 10.1097/CCM.0b013e31828a678d.</citation>
      <PMID>23873274</PMID>
    </reference>
    <reference>
      <citation>Levy B, Fritz C, Piona C, Duarte K, Morelli A, Guerci P, Kimmoun A, Girerd N. Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study. Crit Care. 2021 Jan 7;25(1):21. doi: 10.1186/s13054-020-03445-w.</citation>
      <PMID>33413583</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Qianfoshan Hospital</investigator_affiliation>
      <investigator_full_name>Zhiming Jiang</investigator_full_name>
      <investigator_title>Chief Physician</investigator_title>
    </responsible_party>
    <keyword>esmolol</keyword>
    <keyword>ARDS</keyword>
    <keyword>heart rate</keyword>
    <keyword>oxygenation index</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Respiratory Distress Syndrome</mesh_term>
      <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
      <mesh_term>Acute Lung Injury</mesh_term>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Esmolol</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06013319
  org study id: QFSKYLLTZH-2023-043
  nct id: NCT06013319
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Acute respiratory distress syndrome (ARDS) is a clinical syndrome caused by intrapulmonary
        and/or extrapulmonary causes, characterized by intractable hypoxemia. Studies have shown that
        the sympathetic nervous system is over-activated in patients with acute respiratory distress
        syndrome. A large retrospective study showed a reduction in mortality in ARDS patients
        treated with oral β1 blockers before admission, and this beneficial effect of β1 blockers
        applies to ARDS patients with or without cardiac disease. Esmolol is an ultra-short-acting
        selective β1 receptor blocker. Previous studies have shown that esmolol can improve
        oxygenation and reduce the levels of inflammatory cytokines and exudate proteins in
        bronchoalveolar lavage fluid, thereby alleviating pulmonary injury. According to the
        literature and our previous clinical observations, we made the following hypothesis: When
        Estolol is applied to various ARDS patients undergoing mechanical ventilation in ICU, it can
        control the heart rate by inhibiting β-adrenergic receptor, which can ultimately improve the
        oxygenation index of patients and shorten the mechanical ventilation time. This project
        intends to include ARDS patients with optimal hemodynamic treatment for 24 hours, whose heart
        rate is still ≥95 beats/min after conventional treatment, but ≤120 beats/min. They are
        randomly divided into control group and Esmolol treatment group to study the effects of
        esmolol on patients' oxygenation index, mechanical ventilation time, hemodynamics, function
        of various organs and inflammation level. The aim of this study is to optimize the treatment
        of ARDS patients.
  At present, there are few studies on Esmolol in acute respiratory distress syndrome. However,
        previous studies have shown that Esmolol can improve oxygenation and reduce the levels of
        inflammatory cytokines and exudate proteins in bronchoalveolar lavage fluid, thus alleviating
        pulmonary injury. Considering that a considerable number of ARDS patients in the intensive
        care unit suffer from sepsis, we conducted this study to explore the application timing of
        esmolol therapy and whether esmolol can improve the symptoms and prognosis of ARDS patients.
        Based on the literature and our previous clinical observations, we make the following
        assumptions: Esmolol is applied to various ARDS patients receiving mechanical ventilation in
        ICU. By inhibiting the β-adrenergic receptor to control the heart rate, it can ultimately
        improve the oxygenation index of patients, shorten the mechanical ventilation time, achieve
        tracheal intubation extraction as soon as possible, and reduce the 28-day mortality. At the
        same time, esmolol can also improve the function of various organs of patients and reduce the
        level of inflammatory factors. This project intends to include ARDS patients with optimal
        hemodynamic treatment for 24 hours, whose heart rate is still ≥95 beats/min after
        conventional treatment, but ≤120 beats/min. They are randomly divided into control group and
        Esmolol treatment group to study the effects of esmolol on patients' oxygenation index,
        mechanical ventilation time, hemodynamics, function of various organs and inflammation level.
        To optimize the treatment of ARDS patients.
  
        Acute respiratory distress syndrome (ARDS) is a clinical syndrome caused by intrapulmonary
        and/or extrapulmonary causes, characterized by intractable hypoxemia. ARDS is the most common
        cause of respiratory failure in severe patients, and also the main factor leading to poor
        prognosis in severe patients. In recent years, although the research on ARDS has continued to
        go deeper, clinical treatment still remains in the stage of lung protective ventilation and
        restricted fluid management, and there is still a lack of specific drug therapy, and the
        fatality rate is still as high as 40%.
  
        Studies have shown that the sympathetic nervous system is over-activated in patients with
        acute respiratory distress syndrome. Because 75 to 80 percent of myocardial adrenergic
        receptors are β1 type, and adrenergic stress is primarily mediated by beta receptors, the
        heart is a prime target for sympathetic overstimulation. Elevated heart rate is associated
        with adverse outcomes in patients with severe infection and represents the severity of the
        disease.Another large retrospective study showed a reduction in mortality in ARDS patients
        treated with oral β1 blockers before admission, and this beneficial effect of β1 blockers
        applies to ARDS patients with or without cardiac disease.
  
        Esmolol is an ultra-short-acting selective β1 receptor blocker, which mainly inhibits β1
        receptor by competing for catecholamine binding sites in myocaroma, and has the effect of
        slowing resting and exercise heart rate, lowering blood pressure, and reducing myocardial
        oxygen consumption. Esmolol is a metabolite coupled with enzyme, so its distribution
        half-life is very short, intravenous injection begins to take effect 1-2 min, elimination
        half-life is only 9min, easy to control, high safety, and remarkable effect. There have been
        numerous studies on esmolol in sepsis. For patients with septic shock, the use of esmolol can
        reduce heart rate to the target level, but does not increase the incidence of adverse events,
        and does not reduce microcirculation perfusion, and can improve the hemodynamics and 28-day
        mortality of patients. In addition, both animal and human experiments have proved that
        Esmolol can reduce the release of inflammatory factors in sepsis, improve inflammatory
        response, and protect cardiac and renal function.
  
        At present, there are few studies on Esmolol in acute respiratory distress syndrome. However,
        previous studies have shown that Esmolol can improve oxygenation and reduce the levels of
        inflammatory cytokines and exudate proteins in bronchoalveolar lavage fluid, thus alleviating
        pulmonary injury. Considering that a considerable number of ARDS patients in the intensive
        care unit suffer from sepsis, we conducted this study to explore the application timing of
        esmolol therapy and whether esmolol can improve the symptoms and prognosis of ARDS patients.
        Based on the literature and our previous clinical observations, we make the following
        assumptions: Esmolol is applied to various ARDS patients receiving mechanical ventilation in
        ICU. By inhibiting the β-adrenergic receptor to control the heart rate, it can ultimately
        improve the oxygenation index of patients, shorten the mechanical ventilation time, achieve
        tracheal intubation extraction as soon as possible, and reduce the 28-day mortality. At the
        same time, esmolol can also improve the function of various organs of patients and reduce the
        level of inflammatory factors. This project intends to include ARDS patients with optimal
        hemodynamic treatment for 24 hours, whose heart rate is still ≥95 beats/min after
        conventional treatment, but ≤120 beats/min. They are randomly divided into control group and
        Esmolol treatment group to study the effects of esmolol on patients' oxygenation index,
        mechanical ventilation time, hemodynamics, function of various organs and inflammation level.
        To optimize the treatment of ARDS patients.
  
        To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory
        distress syndrome (ARDS) on oxygenation index. A total of 187 patients aged 18-65 years who
        met the 2012 Berlin diagnostic criteria for acute respiratory distress syndrome will be
        included in our study. Hemodynamic optimization was performed within 24 hours after
        diagnosis. After treatment, the patient's heart rate continued to be ≥95 beats/min but ≤120
        beats/min for at least 10 minutes, with or without esmolol pumping. The improvement of
        oxygenation index in different treatment groups was observed.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Single (Participant)
  measure: Oxygenation index improved or not
  time frame: From the start of the trial to 12 hours after administering the drug
  description: To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.
  measure: Oxygenation index improved or not
  time frame: From the start of the trial to 24 hours after administering the drug
  description: To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.
  measure: Oxygenation index improved or not
  time frame: From the start of the trial to 48 hours after administering the drug
  description: To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.
  measure: Oxygenation index improved or not
  time frame: From the start of the trial to 72 hours after administering the drug
  description: To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.
  measure: Oxygenation index improved or not
  time frame: From the start of the trial to 120 hours after administering the drug
  description: To evaluate the effect of Esmolol control on heart rate in patients with acute respiratory distress syndrome (ARDS) on oxygenation index.
  measure: the difference of mechanical ventilation duration
  time frame: from the start of the trial to removal of the endotracheal tube and cessation of mechanical ventilation，up to 28 days
  description: The duration of mechanical ventilation was compared between the two groups with or without esmolol treatment
  arm group label: Esmolol group
  arm group type: Experimental
  description: Patients with ARDS who require mechanical ventilation after adequate disease assessment and whose heart rate continues to be ≥95 beats/min, but ≤120 beats/min within 24 hours after diagnosis, for at least 10 minutes without changing the dosage of catecholamine, were diagnosed as atrial fibrillation, atrial flutter or sinus tachycardia. The primary treatment is maintained while the esmolol load dose is administered and the maintenance dose is pumped continuously until the patient's heart rate is maintained between 80 and 94 beats per minute.
  arm group label: Control group
  arm group type: No Intervention
  description: Patients with ARDS who need mechanical ventilation after adequate condition assessment and whose heart rate continues to be ≥95 beats /min but ≤120 beats /min after optimal hemodynamic treatment within 24 hours after diagnosis were randomly included in the control group. Routine mechanical ventilation, full sedation and analgesia, maintain RASS score 0-2 points; The target tidal volume is 6ml/kg, and the ventilator parameters should be adjusted in time according to the blood gas analysis. Hypotensive patients with sufficient blood volume should be pumped with pressor drugs. Timely sputum suction, airway management, eliminate fever, asthma, pain and other stimulation caused by the heart rate is too fast.
  intervention type: Drug
  intervention name: Esmolol
  description: The load dose of esmolol was first injected intravenously: 0.5mg/kg.min, for about 1 minute; then the maintenance dose was pumped intravenously: from 0.05mg/kg/min, and continued after 4 minutes if the efficacy was ideal; if the efficacy was poor, the load dose could be repeated and the maintenance dose increased by 0.05mg/kg/min. The maintenance dose should not exceed 0.3mg/kg/min.
  arm group label: Esmolol group
  other name: Esmolol hydrochloride injection
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: zhiming Jiang, doctor
  role: Study Director
  affiliation: Qianfo Mountain Hospital, Shandong Province
  last name: Quanzhen Wang, doctor
  phone: 15562570205
  email: wangquanzhen1986@163.com
  citation: Meyer NJ, Gattinoni L, Calfee CS. Acute respiratory distress syndrome. Lancet. 2021 Aug 14;398(10300):622-637. doi: 10.1016/S0140-6736(21)00439-6. Epub 2021 Jul 1.
  PMID: 34217425
  citation: van der Jagt M, Miranda DR. Beta-blockers in intensive care medicine: potential benefit in acute brain injury and acute respiratory distress syndrome. Recent Pat Cardiovasc Drug Discov. 2012 Aug;7(2):141-51. doi: 10.2174/157489012801227274.
  PMID: 22642505
  citation: Morelli A, Donati A, Ertmer C, Rehberg S, Kampmeier T, Orecchioni A, D'Egidio A, Cecchini V, Landoni G, Pietropaoli P, Westphal M, Venditti M, Mebazaa A, Singer M. Microvascular effects of heart rate control with esmolol in patients with septic shock: a pilot study. Crit Care Med. 2013 Sep;41(9):2162-8. doi: 10.1097/CCM.0b013e31828a678d.
  PMID: 23873274
  citation: Levy B, Fritz C, Piona C, Duarte K, Morelli A, Guerci P, Kimmoun A, Girerd N. Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study. Crit Care. 2021 Jan 7;25(1):21. doi: 10.1186/s13054-020-03445-w.
  PMID: 33413583
  responsible party type: Sponsor-Investigator
  investigator affiliation: Qianfoshan Hospital
  investigator full name: Zhiming Jiang
  investigator title: Chief Physician
  mesh term: Respiratory Distress Syndrome
  mesh term: Respiratory Distress Syndrome, Newborn
  mesh term: Acute Lung Injury
  mesh term: Syndrome
  mesh term: Esmolol
  sharing ipd: No