Predictive Mini-bolus Fluid Responsiveness in Pediatric Septic Shock

Study Overview
=================
Brief Summary
-----------------
Severe sepsis and septic shock remain of particular gravity in children with a current mortality of about 20 % , despite the international prevention campaigns  survival sepsis campaign . Septic shock associates a macrocirculatory and a microcirculatory dysfunction. The volume expansion remains the treatment of severe sepsis at the initial phase supplemented by the use of vasopressors and / or inotropes. Nevertheless , it is essential to predict the fluid responsiveness after volemic expansion because fluid overload is associated with an increased morbidity in children. In studies , the volume expansion is considered effective if it allows an increase in cardiac output of more than 15 % compared to the basal level. However, their conditions of use remain very restrictive and not applicable to most of our patients ( tidal volume ≥ 7ml / kg , PEEP sufficient , absence of cardiac arrhythmia and effective sedation ) . To date , no index can be used for all patients with invasive mechanical ventilation. It therefore seems appropriate to develop new tests to predict the response to volume expansion in children with septic shock hospitalized in pediatric intensive care. A recent study has validated a test to predict the response to volume expansion in adults: injection of a mini-bolus of 50 ml of saline over 10s. The aim of the study is to evaluate the effect of mini bolus fluid to predict response to fluid expansion in pediatric septic shock.

Detailed Description
-----------------
Severe sepsis and septic shock remain of particular gravity in children with a current mortality of about 20 % , despite the international prevention campaigns  survival sepsis campaign  . Septic shock associates a macrocirculatory and a microcirculatory dysfunction. The volume expansion remains the treatment of severe sepsis at the initial phase supplemented by the use of vasopressors and / or inotropes . Nevertheless , it is essential to predict the fluid responsiveness after volemic expansion because fluid overload is associated with an increased morbidity in children . In studies , the volume expansion is considered effective if it allows an increase in cardiac output of more than 15 % compared to the basal level . However , their conditions of use remain very restrictive and not applicable to most of our patients ( tidal volume > 7ml / kg , PEEP sufficient, absence of cardiac arrhythmia and effective sedation ) . To date , no index can be used for all patients with invasive mechanical ventilation . It therefore seems appropriate to develop new tests to predict the response to volume expansion in children with septic shock hospitalized in pediatric intensive care. A recent study has validated a test to predict the response to volume expansion in adults : injection of a mini-bolus of 50 ml of saline over 10s. The aim of the study is to evaluate the effect of mini bolus fluid to predict response to fluid expansion in pediatric septic shock.

Official Title
-----------------
Predictive Mini-bolus Fluid Responsiveness in Pediatric Septic Shock

Conditions
-----------------
Severe Sepsis or Septic Shock in Pediatric Intensive Care Unit

Intervention / Treatment
-----------------
* Procedure: Mini-bolus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Baby (>28 days) or children < 15 years Hospitalisation in paediatric intensive Clinico-biological table compatible with severe sepsis or septic shock (likely or documented) Requiring the use of invasive mechanical ventilation Affiliate or beneficiary of a social security Legal guardians Consent Form or Emergency Procedure Exclusion Criteria: Any serious hemodynamic clinical situation that would be delayed by inclusion in the protocol Patient with shunt heart disease Patient in spontaneous or non-invasive ventilation or CPAP Patient with a contraindication to volemic/fluid expansion (major cardiac dysfunction, acute renal failure) Patient with cardiac arrest upper 5 min ECMO Postcardiotomia

Ages Eligible for Study
-----------------
Minimum Age: 28 Days
Maximum Age: 15 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mini-bolus<br>First injection of 2ml/kg (saline solution) Second injection of 18ml/kg (saline solution) | Procedure: Mini-bolus<br>* First injection of 2ml/kg (saline solution) Second injection of 18ml/kg (saline solution)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac output variability (ΔCO) | Cardiac output | 5 minutes | 
| Cardiac output variability (ΔCO) | Cardiac output : ΔCO (mL/min) = VES (ml)* heart rate and VES (cm3)= ITVA0(cm) * SA0 (cm2) | 15 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate variation (ΔHR) | Heart rate usual monitoring | 15 minutes | 
| Systolic, diastolic and mean arterial pressure variation (ΔSAP, ΔDAP, ΔMAP) | Arterial pressure invasive or not invasive monitoring according the care of patient | 5 minutes | 
| Systolic, diastolic and mean arterial pressure variation (ΔSAP, ΔDAP, ΔMAP) | Arterial pressure invasive or not invasive monitoring according the care of patient | 15 minutes | 
| Pulse pressure variation (ΔPP) | Pulse pressure invasive or not invasive monitoring according the care of patient | 5 minutes | 
| Pulse pressure variation (ΔPP) | Pulse pressure invasive or not invasive monitoring according the care of patient | 15 minutes | 
| Systolic ejection volume variation (ΔSEV) | Systolic ejection volume is measured by transthoracic echocardiography : VES (ml) =ITVa0*Sa0 | 5 minutes | 
| Systolic ejection volume variation (ΔSEV) | Systolic ejection volume is measured by transthoracic echocardiography : VES (ml) =ITVa0*Sa0 | 15 minutes | 
| Velocity time-index variation (ΔVTI) | ITVA0 is measured by transthoracic echocardiography with Doppler | 5 minutes | 
| Velocity time-index variation (ΔVTI) | ITVA0 is measured by transthoracic echocardiography with Doppler | 15 minutes | 
| Microvascular Flow Index variation (ΔMFI) | Microvascular Flow Index calculated by the Microscan software (Microvision) | 5 minutes | 
| Microvascular Flow Index variation (ΔMFI) | Microvascular Flow Index calculated by the Microscan software (Microvision) | 15 min | 
| Proportion Perfused Vessels variation (ΔPPV) | Proportion Perfused Vessels calculated by the Microscan software (Microvision) | 5 minutes | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mini-bolus challenge, fluid responsiveness, volemic expansion, pediatric septic shock, severe sepsis, microcirculation