Effects of Heart Control at Different Stages in Patients of Septic Shock With Tachycardia

Study Overview
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Brief Summary
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A sigle-center, randomized controlled trial will be do to investigate the effects of esomol on heart rate, clinical parameters, mortality, and safety in septic shock patients with tachycardia at different stages, compared with patients who received conventional therapy.

Detailed Description
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The incidence of septic shock complicated with tachycardia is high and the prognosis is poor. Enough attention should be paid to and appropriate treatment should be given. High heart rate and high cardiac output are beneficial compensatory reactions of sepsis and septic shock. However, excessive sympathetic activation and high heart rate also have adverse effects on the cardiovascular system. Sustained tachycardia is harmful to patients with sepsis and septic shock and needs to be controlled. At present, it is widely used in the treatment of cardiovascular diseases and β Receptor blockers have the functions of preventing and reversing sympathetic effects, anti arrhythmia, anti-inflammatory and balancing myocardial oxygen supply and demand. Therefore, they are recommended to control arrhythmias in patients with septic shock. The 2014 guidelines for sepsis / septic shock in China suggest that if cardiac output is not low and the heart rate is fast after adequate fluid resuscitation, short acting drugs（β Receptor blockers）can be considered. However, there are some differences in the current clinical research results, and it suggests that the timing of treatment may affect the hemodynamic results and clinical outcomes of patients. Therefore, this study intends to intervene with esmolol in patients with septic shock and tachycardia at different stages, and compare the hemodynamic parameters, clinical outcome, prognosis and adverse reactions with the conventional treatment group, in order to explore the appropriate time of esmolol in the treatment of patients with septic shock and tachycardia.

Official Title
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Effects of Heart Control at Different Stages on Hemodynamics Parameters and Clinical Prognosis in Patients of Septic Shock With Tachycardia

Conditions
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Septic Shock, Tachycardia

Intervention / Treatment
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* Drug: Esmolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:  ≥ 18 years old;  New septic shock within 24 hours, meeting the diagnostic criteria in 2012;  Septic shock lasts for more than 6 hours, and after fluid optimization using dynamic parameters, vasoactive drugs are still needed to maintain blood pressure;  the heart rate is greater than 100 beats / min for ≥ 1 hour，not caused by agitation, fever, and other factors;  informed consents are signed. Exclusion Criteria:  Shock caused by sepsis;  Septic cardiomyopathy or decreased myocardial contractility, requiring the use of positive inotropic drugs or significant cardiac insufficiency, such as CI ≤ 2.2l/min m2, PAWP>18mmHg, EF<40%;  Severe bronchial asthma or COPD;  Pregnant or lactating women;  Sinus bradycardia, degree II and degree III heart block;  β-receptor blockers were used before enrollment or have the history of sinus tachycardia;  Severe valvular heart disease;  Allergic to esmolol;  Tachycardia due to elevated body temperature, agitation, insufficient capacity and other reasons;  Have participated in other clinical studies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Esmolol is used 6 to 24 hours after onset of septic shock in patients with fluid optimization to control heart beats between 70-100bpm. | Drug: Esmolol<br>* a continuous esmolol infusion titrated to maintain heart rate between 70/min and 100/min<br>* Other names: β-receptor blockers;|
| Experimental: Group B<br>Esmolol is used 24 hours after onset of septic shock in patients to control heart beats between 70-100bpm. | Drug: Esmolol<br>* a continuous esmolol infusion titrated to maintain heart rate between 70/min and 100/min<br>* Other names: β-receptor blockers;|
| No Intervention: Group C<br>patients received conventional therapy in accordance with septic shock guidelines 2021 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the proportion of patients with heart rate of 70-100 bpm | the proportion of patients with heart rate of 70-100 bpm | at 24-hour after randomization | 
| the proportion of patients with heart rate of 70-100 bpm | the proportion of patients with heart rate of 70-100 bpm | at 48-hour after randomization | 
| the proportion of patients with heart rate of 70-100 bpm | the proportion of patients with heart rate of 70-100 bpm | at 72-hour after randomization | 
| the proportion of patients with heart rate of 70-100 bpm | the proportion of patients with heart rate of 70-100 bpm | at 96-hour after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiac index | PiCCO monitoring parameters | at 24-hour after randomization | 
| cardiac index | PiCCO monitoring parameters | at 48-hour after randomization | 
| cardiac index | PiCCO monitoring parameters | at 72-hour after randomization | 
| cardiac index | PiCCO monitoring parameters | at 96-hour after randomization | 
| ejection fraction | cardiac measurement by cardiac ultrasound | at 24-hour after randomization | 
| ejection fraction | cardiac measurement by cardiac ultrasound | at 48-hour after randomization | 
| ejection fraction | cardiac measurement by cardiac ultrasound | at 72-hour after randomization | 
| ejection fraction | cardiac measurement by cardiac ultrasound | at 96-hour after randomization | 
| Arterial blood PH value | Arterial blood PH value by arterial blood gas analysis | at 24-hour after randomization | 
| Arterial blood PH value | Arterial blood PH value by arterial blood gas analysis | at 48-hour after randomization | 
| Arterial blood PH value | Arterial blood PH value by arterial blood gas analysis | at 72-hour after randomization | 
| Arterial blood PH value | Arterial blood PH value by arterial blood gas analysis | at 96-hour after randomization | 
| Arterial blood lactate | Arterial blood lactate by arterial blood gas analysis | at 24-hour after randomization | 
| Arterial blood lactate | Arterial blood lactate by arterial blood gas analysis | at 48-hour after randomization | 
| Arterial blood lactate | Arterial blood lactate by arterial blood gas analysis | at 72-hour after randomization | 
| Arterial blood lactate | Arterial blood lactate by arterial blood gas analysis | at 96-hour after randomization | 
| APACHEII scores | the Acute Physiology and Chronic Health Evaluation II scores，value 0～60, the higher score means worse outcome. | at 24-hour after randomization | 
| APACHEII scores | the Acute Physiology and Chronic Health Evaluation II scores，value 0 60, the higher score means worse outcome. | at 48-hour after randomization | 
| APACHEII scores | the Acute Physiology and Chronic Health Evaluation II scores，value 0 60, the higher score means worse outcome. | at 72-hour after randomization | 
| APACHEII scores | the Acute Physiology and Chronic Health Evaluation II scores，value 0 60, the higher score means worse outcome. | at 96-hour after randomization | 
| SOFA scores | sepsis-related organ failure assessment score，value 4 24, the higher score means worse outcome. | at 24-hour after randomization | 
| SOFA scores | sepsis-related organ failure assessment score，value 4 24, the higher score means worse outcome. | at 48-hour after randomization | 
| SOFA scores | sepsis-related organ failure assessment score，value 4 24, the higher score means worse outcome. | at 72-hour after randomization | 
| SOFA scores | sepsis-related organ failure assessment score，value 4 24, the higher score means worse outcome. | at 96-hour after randomization | 
| norepinephrine dose | norepinephrine dose (ug/kg.min) | at 24-hour after randomization | 
| norepinephrine dose | norepinephrine dose (ug/kg.min) | at 48-hour after randomization | 
| norepinephrine dose | norepinephrine dose (ug/kg.min) | at 72-hour after randomization | 
| norepinephrine dose | norepinephrine dose (ug/kg.min) | at 96-hour after randomization | 
| ICU- free days (by 28 days) | days free of ICU | from randomization until 28 days | 
| 28-day mortality | 28-day mortality | from randomization until 28 days | 
| days of mechanical ventilation | days of mechanical ventilation | from randomization until 28 days | 
| the incidence of hypotension deteriorated | the incidence of hypotension deteriorated | by 96-hour after randomization | 
| the incidence of heart arrest | the incidence of heart arrest | by 96-hour after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Septic Shock, Tachycardia, β receptor blockers