Volemic Resuscitation in Sepsis and Septic Shock

Study Overview
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Brief Summary
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Severe sepsis and septic shock are among the leading causes of morbidity and mortality in patients admitted in the ICU, being responsible for approximately 200000 deaths/year in the USA and 150000 in Europe. Recognizing the early signs of sepsis and the different stages of this condition may lower the associated morbidity and mortality. The hemodynamic profile of the septic shock is characterized by the presence of the distributive shock, on which we can add elements from the hypovolemic and cardiogenic shocks. The objecive of this study is to optimize the volemic resuscitation of the severe septic and of the septic shock patient using two minimally invasive methods of hemdynamic monitoring which both use the same device (Edwards Lifescience). In the same time hemodinamic data will be colected by mesuring the inferior vena cava diameter.

Detailed Description
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Severe sepsis and septic shock are among the leading causes of morbidity and mortality in patients admitted in the ICU, being responsible for approximately 200000 deaths/year in the USA and 150000 in Europe . Recognizing the early signs of sepsis and the different stages of this condition may lower the associated morbidity and mortality. The hemodynamic profile of the septic shock is characterized by the presence of the distributive shock, on which we can add elements from the hypovolemic and cardiogenic shocks. The persistence of hypotension after adequate fluid load is the result of low vascular resistance and myocardial dysfunction and calls for certain specific correctional measures. The diffrent hemodynamic profiles which can be found in the different stages of the septic shock and their dificult clinical identification led to the development of varoius hemodynamic monitoring techniques and devices. These techniques can be classified into invasive and minimally invasive, calibrated and uncalibrated. The major diffrences among these tecniques is the easyness of utilisation and the acuracy of the data obtained. Inclusion Criteria: severe sepsis and septic shock (acording to the Sepsis Campaign 2013 crieria) patients with medical or surgical pathology which are admitted in the ICU unit in the first six hours after the onset of the severe sepsis/septic shock. The exclusion criteria of the patients are age less then 18 and more then 75, cardiac valvular pathology with hemodynamic importance, cardiac failure NYHA III și IV, primary or secondary pulmonary hypertension with hemodymanic impact with onset before the onset of the septic pathology,severe liver failure (Child-Pugh C), anuric renal failure, pregnant women, patient who refuse blood products adminitration, end-stage cancer. The objecive of this study is to optimize the volemic resuscitation of the severe septic and of the septic shock patient using two minimally invasive methods of hemdynamic monitoring which both use the same device (Edwards Lifescience). In the same time hemodinamic data will be colected by mesuring the inferior vena cava diameter. The primary outcome is the adecuacy of tissue perfusion at six hours (urinary output, blood pressure, lactate clearance, skin aspect). The secondary oucomes are duration of cardiovascular failure at the end of the 6 hours resuscitation period/ number of days, duration of respiratory failure (need of mechanical ventilation, number of days), duration of acute renal failure (need of dialysis) at ICU discharge/10/30/60 days, duration of ICU stay and in hospital stay, discharge status at 60 days (not discharged ,discharge to another acute care hospital, discharged to nursing home, discharged home ,other or unknown and all cause mortality at 60 days.

Official Title
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Volemic Resuscitation in Sepsis and Septic Shock

Conditions
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Hemodynamic Instability, Sepsis, Septic Shock

Intervention / Treatment
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* Device: Flotrac/Ev1000
* Device: Standard ICU monitorisation
* Device: VolumeView/Ev1000


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: sepsis and septic shock (acording to the Sepsis Campaign 2016 crieria) patients with medical or surgical pathology which are admitted in the ICU unit in the first 12 hours after the onset of the sepsis/septic shock Exclusion Criteria: age less then 18 and more then 85 cardiac valvular pathology with hemodynamic importance cardiac failure NYHA IV primary or secondary pulmonary hypertension with hemodymanic impact with onset before the onset of the septic pathology Severe liver failure (Child-Pugh C) Anuric renal failure Pregnant women Patient who refuse blood products adminitration End-stage cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sepsis grup 1<br>Flotrac/Ev1000 in the first 2 hours and VolumeView/Ev1000 monitoring during the next 4 hours | Device: Flotrac/Ev1000<br>* Hemodynamic resusucitation guided by the data obtained from the monitorisation with Flotrac/Ev1000 device in the first two hours<br>Device: VolumeView/Ev1000<br>* Hemodynamic resusucitation guided by the data obtained from the monitorisation with VolumeView/Ev1000 device in the next four hours<br>|
| Experimental: Sepsis grup 2<br>Hemodymanic resuscitation giuded by standard ICU monitorisation (BP, CVP) in the first 2 hours and VolumeView/Ev1000 monitoring during the next 4 hours | Device: Standard ICU monitorisation<br>* Hemodynamic resusucitation guided by the data obtained from ICU standard hemodynamic monitoring (BP, CVP) in the first 2 hours<br>Device: VolumeView/Ev1000<br>* Hemodynamic resusucitation guided by the data obtained from the monitorisation with VolumeView/Ev1000 device in the next four hours<br>|
| Experimental: Soc septic grup 1<br>Flotrac/Ev1000 in the first 2 hours and VolumeView/Ev1000 monitoring during the next 4 hours | Device: Flotrac/Ev1000<br>* Hemodynamic resusucitation guided by the data obtained from the monitorisation with Flotrac/Ev1000 device in the first two hours<br>Device: VolumeView/Ev1000<br>* Hemodynamic resusucitation guided by the data obtained from the monitorisation with VolumeView/Ev1000 device in the next four hours<br>|
| Experimental: Soc septic grup 2<br>Hemodymanic resuscitation giuded by standard ICU monitorisation (BP, CVP) in the first 2 hours andVolumeView/Ev1000 monitoring during the next 4 hours | Device: Standard ICU monitorisation<br>* Hemodynamic resusucitation guided by the data obtained from ICU standard hemodynamic monitoring (BP, CVP) in the first 2 hours<br>Device: VolumeView/Ev1000<br>* Hemodynamic resusucitation guided by the data obtained from the monitorisation with VolumeView/Ev1000 device in the next four hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tissue perfusion at six hours (composite) | Tissue perfusion at six hours: urinary output, blood pressure, lactate clearance, skin aspect | six hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of cardiovascular failure | need of vasopressor support: at the end of the 6 hours resuscitation period and one, two, six and twelve days | at the end of the 6 hours resuscitation period and one, two, six and twelve days | 
| Duration of respiratory failure | respiratory failure at oane day, two days, six days and twelve days | respiratory failure at oane day, two days, six days and twelve days | 
| Duration of acute renal failure | Duration of acute renal failure (need of dialysis) at 5 days, at 10 days, at 30 days and at 60 days | at 5 days, at 10 days, at 30 days and at 60 days | 
| Duration of ICU stay and in hospital stay | Duration of ICU stay and in hospital stay | status at 5 days, at 10 days, at 30 days and at 60 days | 
| Discharge status at 60 days | Discharge status at 60 days:Not discharged ,Discharge to another acute care hospital,Discharged to nursing home,Discharged home ,Other or unknown | at 60 days | 
| all cause mortality at 60 days | all cause mortality at 60 days | 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, hemodynamic monitoring, septic shock, volemic resuscitation, fluid resuscitation