Samu Save Sepsis: Early Goal Directed Therapy in Pre Hospital Care of Patients With Severe Sepsis and/or Septic Shock

Study Overview
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Brief Summary
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The purpose of this study is to determine whether an aggressive strategy of severe sepsis patients since pre hospital care, including early antibiotics administration, hemodynamic optimization, and opotherapy when indicated, could reduce mortality

Detailed Description
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Major prognostic factor in sepsis management is rapidity of treatments implementation. In 2001, Rivers observed a reduction in mortality through early hemodynamic optimization. In 2009, Arnold emphasizes that establishing more early antibiotic therapy allowed a further reduction of mortality. In France, pre hospital care is based on mobile intensive care unit (MICU) called SMUR. SMUR is consisting of a driver, a nurse and an emergency physician. Actually in France, management of severe septic syndrome (severe sepsis and septic shock) are not standardized and based on a conventional strategy at the discretion of the emergency physician. Antibiotics are given in only two cases: fulminans purpura and meningitis. Hemodynamic optimization is not a standard of care and no recommendation exist for hemodynamic targets. An aggressive strategy based on early antibiotics administration, hemodynamic optimization and opotherapy when required could be initiated by SMUR since first contact with the patient before hospital admission. We assume that an aggressive strategy initiated during the first 60 minutes of prehospital stage compared to conventional strategy could allow to reduce mortality in severe sepsis patients.

Official Title
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Samu Save Sepsis: Early Goal Directed Therapy in Pre Hospital Care of Patients With Severe Sepsis and/or Septic Shock

Conditions
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Severe Septic Syndrome (Severe Sepsis and Septic Shock) Diagnosed and Treated by Mobile Intensive Care Unit

Intervention / Treatment
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* Drug: Ceftriaxone
* Drug: Piperacillin tazobactam
* Drug: Norepinephrine
* Drug: Hydrocortisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients fulfilling the following criteria: Age ≥ 18 years Patient with suspected severe infection defined by the existence of a suspected infection AND Hypotension before vascular fluid loading AND/OR Lactataemia greater than 4 mmol/l AND/OR Glasgow scale lower than 13 AND/OR Mottling score greater than 2 Patient with a septic shock Exclusion Criteria: Age <18 years or Unable Pregnant Severe concomitant pathology requiring urgent care(i.e.epilepsy) Status not to be reanimated life expectancy less than 6 months with no indication of reanimation support ( prior decision on care limitation). Fulminans purpura True allergy to beta-lactam defined by an angioedema or by an anaphylactic shock during a prior exposure to beta-lactam. Patient who have already received hemodynamic optimization or antibiotic treatment before the MICU's (Mobile Intensive Care Unit) care.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conventional<br>No antibiotic administration and no hemodynamic target are required | |
| Active Comparator: Aggressive<br>Antibiotics (Ceftriaxone or piperacillin tazobactam) administration, hemodynamic optimization and opotherapy (norepinephrine, hydrocortisone) when required should be performed in the first 60 minutes after contact with the patient | Drug: Ceftriaxone<br>* Ceftriaxone 2g IV will be infused in the first 60 minutes, for non nosocomial severe septic syndrome<br>Drug: Piperacillin tazobactam<br>* Piperacillin/tazobactam 4g IV will be infused in the first 60 minutes, for nosocomial severe septic syndrome<br>Drug: Norepinephrine<br>* Norepinephrine will be infused after failure of hemodynamic optimization using vascular fluid loading<br>Drug: Hydrocortisone<br>* Hydrocortisone 100mg IV will be infused after failure of hemodynamic optimization using norepinephrine with at least 1.5mg/h<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of death |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of death |  | 90 days | 
| Number of death |  | at hospital discharge time, estimated at 90 days | 
| Number of days of stay in intensive care unit |  | at Intensive Care Unit discharge time, estimated at 90 days | 
| Number of days of stay at hospital |  | at hospital discharge time, estimated at 90 days | 
| Number of days of vasopressor support |  | at Intensive Care Unit discharge time, estimated at 90 days | 
| Number of days of mechanical ventilation support |  | at Intensive Care Unit discharge time, estimated at 90 days | 
| Number of days of renal replacement therapy |  | at Intensive Care Unit discharge time, estimated at 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe septic syndrome, mobile intensive care unit, strategy, antibiotics, hemodynamic optimization