Peripheral Perfusion Targeted Fluid Management

Study Overview
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Brief Summary
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Impaired peripheral perfusion is related to worse outcome in critically ill patients. Although this is known, these parameters have never been used as target for hemodynamic therapy. We hypothesize that targeting of fluid administration on parameters of peripheral perfusion might prevent excessive fluid administration, leading to less formation of tissue edema, less respiratory dysfunction and shorter duration of mechanical ventilation in critically ill patients.

Detailed Description
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Rationale: Currently, fluid administration of critically ill patients is aimed at optimizing conventional hemodynamic parameters such as stroke volume and cardiac output. Fluid is infused repeatedly until patients become non-responsive, i.e. cardiac output does not increase anymore. However, the ultimate goal of hemodynamic therapy should be to improve peripheral (i.e. tissue) perfusion. Recently we have shown that 1) increasing stroke volume does not always have an effect on peripheral perfusion and 2) that peripheral perfusion is not impaired when stroke volume can still be increased with fluid infusion. Furthermore, repeated administration of fluid in order to reach a maximum cardiac output can lead to an enormous accumulation of fluid in the patient. This leads to formation of lung edema and respiratory dysfunction and is associated with prolonged mechanical ventilation and ICU-stay. Recently, techniques have been developed which allow bedside assessment of peripheral perfusion. Although impaired peripheral perfusion was related to worse outcome, these parameters have never been used as target for hemodynamic therapy. Objective: To study whether peripheral perfusion targeted fluid management (PPTFM) leads to less fluid administration, improved respiratory function and shorter mechanical ventilation. Study design: The study is a pilot study and is designed as a randomized controlled trial. The study will be conducted as a single-center study at the Intensive Care of the Erasmus Medical Center. Study population: We aim to include 40 adult patients who are admitted to the Intensive Care with hemodynamic instability (defined as mean arterial pressure < 65 mmHg and an arterial lactate concentration > 3.0 mmol/l) due to severe sepsis and septic shock. Intervention: In the intervention group fluid management is targeted on peripheral perfusion parameters while in the control group fluid is administered in order to optimize cardiac output. Main study parameters/endpoints: The main study endpoints are daily fluid balance and duration of mechanical ventilation. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is a possible risk that in the treatment group the patients will remain hypovolemic. To ensure that this will not occur, fluids will be administrated in this group, irrespective of peripheral perfusion parameters, until cardiac index is 2,5 L/min/m2. Assessment of peripheral perfusion is performed with non-invasive optical techniques that impose no burden to the patient.

Official Title
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Peripheral Perfusion Targeted Fluid Management in Critically Ill Patients: a Pilot Study

Conditions
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Sepsis, Severe Sepsis

Intervention / Treatment
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* Other: PPTFM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All adult patients (>18 years) admitted to the intensive care with 1) hemodynamic instability due to severe sepsis, and 2) a mean arterial pressure < 65 mmHg and 3) an arterial lactate concentration > 3.0 mmol/L will be considered for participation Exclusion Criteria: moribund. severe coagulation disorder (contraindication for central venous catheter placement). severe peripheral vascular disease (interfering with peripheral perfusion measurement).

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>The fluid management algorithm of the control group is based on the standard care procedure of our ICU as recommended in guidelines: the patient's fluid status is assessed by performing a fluid challenge with a bolus of 250 ml colloids. When the patients is fluid responsive (i.e. showing an increase in stroke volume > 10% ) he will receive an additional bolus of 250 ml of colloids. After each fluid challenge, patients will be revaluated for fluid responsiveness to access need of further fluid administration. | |
| Experimental: PPTFM<br>The fluid management algorithm of the intervention group uses identical therapy (i.e. fluids) yet targeted at different endpoints (i.e. peripheral perfusion parameters). After evaluation of peripheral perfusion, only patients with a bad peripheral perfusion (i.e. 3 out of 4 criteria considered as bad) will receive a fluid challenge, the same way as in the standard care procedure (i.e. bolus of 250 ml of fluid). After each fluid challenge, patients will be re-evaluated for peripheral perfusion to access further need in fluid challenges. To ensure that no hypovolemia will occur in the intervention group, fluid will be administered irrespectively of peripheral perfusion parameters, if cardiac index falls below a value of 2,5 L/min/m2. | Other: PPTFM<br>* Peripheral Perfusion Targeted Fluid Management<br>* Other names: StO2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluid balance during Intensive Care Unit stay | Total and daily fuid balance for a maximal time period of 72 hours | untill 72 hours after admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRT (Capillary refill time) | Parameter of peripheral perfusion | Within 72 hours after admission | 
| Systemic hemodynamic variables | Heart Rate Mean Arterial Pressure Cardiac Index Cardiac output Stroke Volume Central Venous Pressure Systemic Vascular Resistance | Untill 72 hours after admission to the ICU | 
| Respiratory function | FiO2 PEEP Breathing Frequency pCO2 pO2 | Untill 72 hours after admission to the ICU | 
| PFI (Peripheral Flow Index) | Parameter of peripheral perfusion | Untill 72 hours after ICU admission | 
| Tskindiff (Forearm-to-Fingertip temperature skin difference) | Parameter of peripheral perfusion | Untill 72 hours after ICU admission | 
| StO2 (Peripheral tissue oxygenation) | Parameter of peripheral perfusion | Untill 72 hours after ICU admission | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral perfusion, critically ill patients, fluid administration