Impact of Early Goal-directed Fluid Therapy in Septic Patients Undergoing Emergency Surgery

Study Overview
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Brief Summary
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This study wants to compared the safety and efficacy of GDTs using standard pressure-related parameters vs. dynamic hemodynamic indices associated with fluid compartment monitoring, in septic patients requiring emergency surgery.

Official Title
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Impact of Early Goal-directed Fluid Therapy in Septic Patients Undergoing Emergency Surgery. A Prospective, Randomised, Open Trial

Conditions
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Severe Sepsis, Emergency, Surgery

Intervention / Treatment
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* Other: CONTROL
* Other: OPTIMIZED


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults > 18 years Severe sepsis* as defined by the ACCCP/SCCM consensus conference Need for emergent interventional procedure under general anesthesia with an expected duration > 120 min (in and out patients). Exclusion Criteria: Patients responding to early fluid resuscitation (20ml/kg) who don't require a CVC Neurotrauma (Glasgow Coma Score < 12) and/ or medullar trauma Known pregnancy or diagnosed by US or Ct-scan (> 14 weeks) Sustained cardiac arrhythmia (see Logbook P8) Known or diagnosed severe cardiac valvular dysfunction (stenosis, insufficiency) (see Logbook P8) Known or diagnosed intracardiac shunt: interventricular or atrial defect (see Logbook P8) Burn injury > 10% Needed emergency thoracotomy or ABC resuscitation protocol Pre-existing severe liver dysfunction(Child-Pugh class C) Do-not-resuscitate order, died within 48h of admission

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CONTROL<br>In the CONTROL group, the administration of fluid (250-500ml crystalloids or colloids) and cardiovascular supportive drugs will be guided to maintain standard pressure-related parameters within a normal range: MAP > 65mmHg, HR < 90/min, CVP >8-12< cm H20, urinary output > 0.5 ml/kg/h. In line with the conventional approach, other physiological parameters will also be targeted: T° > 35.5°C, Sp02 > 95%, lactate < 2.5 mmol/L, normalisation of the BE. The maximal infused volume of hydroxyethyl starch (Voluven®) will be 33 ml/kg. At the discretion of the attending anaesthesiologist with the FMH level, a pulmonary artery catheter, a transoesophageal Doppler flow probe or the PiCCO monitor will be inserted to complement the standard hemodynamic monitoring if deemed necessary. | Other: CONTROL<br>* In the CONTROL group, the administration of fluid (250-500ml crystalloids or colloids) and cardiovascular supportive drugs will be guided to maintain standard pressure-related parameters within a normal range: MAP > 65mmHg, HR < 90/min, CVP >8-12< cm H20, urinary output > 0.5 ml/kg/h. In line with the conventional approach, other physiological parameters will also be targeted: T° > 35.5°C, Sp02 > 95%, lactate < 2.5 mmol/L, normalisation of the BE. The maximal infused volume of hydroxyethyl starch (Voluven®) will be 33 ml/kg.<br>* Other names: sepsis;|
| Active Comparator: OPTIMIZED<br>In the OPTIMIZED group, the central venous catheter and the 4-French artery catheter (femoral or humeral access site) will be connected to a dedicated haemodynamic monitor (Pulsiocath, PV2024L; Pulsion Medical Systems AG, Munich, Germany). The administration of fluid (250-500ml crystalloids or colloids) and cardiovascular supportive drugs will be guided by an algorithm taking into account standard parameters (HR, MAP, lactate, Hb), as well as static and dynamic volumetric parameters (SVI, CI, GEDVI, EVLWI, SVV, PPV, PVI). | Other: OPTIMIZED<br>* In the OPTIMIZED group, the haemodynamic monitor (Pulsiocath)will help to a goal-directed administration of fluid (250-500ml crystalloids or colloids).The cardiovascular supportive drugs will be guided by an algorithm taking into account standard parameters (HR, MAP, lactate, Hb), as well as static and dynamic volumetric parameters (SVI, CI, GEDVI, EVLWI, SVV, PPV, PVI).<br>* Other names: Picco;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta lactate | The primary study endpoint will be the difference between the baseline arterial blood lactate at the time of randomization and the value of the arterial blood lactate at the time of transfer from the emergency operating room (∆ lactate). | From randomization, for the duration of surgery and up to transfer from the operating room to the ICU or recovery room, an expected average of 6 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular complications: myocardial infarct or congestive heart failure | Clinical outcome and surrogate biomarkers (Troponin-I and pro-BNP: day 1-2-3) will be recorded by extracting this specific data from the electronic medical file, until discharge, death or up to 28 days, whichever comes first. | Day 1, day 2, day 3 after randomization until hospital discharge or up to 28 days or death, whichever comes first | 
| Cerebral complications: stroke | Clinical outcomes at day 1-2-3 will be recorded by extracting this specific data from the electronic medical file, and until discharge, death or up to 28 days, whichever comes first. | Day 1, day 2, day 3 after randomization until hospital discharge or up to 28 days or death, whichever comes first. | 
| Pulmonary complications: ALI/ARDS, bronchopneumonia | Clinical outcomes at day 1-2-3 will be recorded by extracting this specific data from the electronic medical file, and until discharge, death or up to 28 days, whichever comes first. | Day 1, day 2, day 3 after randomization until hospital discharge or up to 28 days or death, whichever comes first. | 
| Pulmonary complications: respiratory insufficiency necessitating re-intubation | Clinical outcomes at day 1-2-3 will be recorded by extracting this specific data from the electronic medical file, and until discharge, death or up to 28 days, whichever comes first. | Day 1, day 2, day 3 after randomization until hospital discharge or up to 28 days or death, whichever comes first. | 
| Surgical complications: re-operation for bleeding or infection | Clinical outcomes at day 1-2-3 will be recorded by extracting this specific data from the electronic medical file, and until discharge, death or up to 28 days, whichever comes first. | Day 1, day 2, day 3 after randomization until hospital discharge or up to 28 days or death, whichever comes first. | 
| Renal complications: infection, urosepsis or renal insufficiency | Clinical outcome and surrogate biomarkers (Riffle score, creatinine: day 1-2-3) will be recorded by extracting this specific data from the electronic medical file, until discharge, death or up to 28 days, whichever comes first. | Day 1, day 2, day 3 after randomization until hospital discharge or up to 28 days or death, whichever comes first | 
| Duration of post-operative mechanical ventilation: in hours | Clinical outcomes at day 1-2-3 will be recorded by extracting this specific data from the electronic medical file, and until discharge, death or up to 28 days, whichever comes first. | Day 1, day 2, day 3 after randomization until hospital discharge or up to 28 days or death, whichever comes first. | 
| Total duration of ventilation : days | Clinical outcomes (ventilation free days) will be recorded by extracting this specific data from the electronic medical file, and until discharge, death or up to 28 days, whichever comes first. | Day 1, day 2, day 3 after randomization until hospital discharge or up to 28 days or death, whichever comes first | 
| Length of stay in the ICU: in days |  | Day 1, day 2, day 3 after randomization until hospital discharge or up to 28 days or death, whichever comes first. | 
| Length of stay in hospital: in days |  | Day 1, day 2, day 3 after randomization until hospital discharge or up to 28 days or death, whichever comes first. | 
| Mortality |  | From randomization up to 28 days | 
| SOFA score measurement |  | From randomization : day 1, day 2, day 3 | 
| Death |  | Day 1, day 2, day 3 after randomization until hospital discharge or up to 28 days or death, whichever comes first | 
| Number of unexpected ICU admission |  | From randomization up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Goal-directed therapy, severe sepsis, emergency surgery, vasopressor, dynamic flow-related parameters