Saline Solution Versus Voluven®: A Controlled Study of Fluid Resuscitation in Severe Sepsis

Study Overview
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Brief Summary
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Fluid resuscitation of severe sepsis may consist of natural or artificial colloids or crystalloids. There is no evidence-based support for one type of fluid over another. The investigators hypothesis is that fluid resuscitation with Voluven® is advantageous to normal saline solution to improve sublingual microcirculation.

Detailed Description
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Shock is the failure of circulatory system to maintain adequate cellular perfusion. Septic shock is primarily a form of distributive shock and is characterized by ineffective tissue oxygen delivery and extraction associated with inappropriate peripheral vasodilation despite preserved or increased cardiac output. In sepsis, a complex interaction between pathologic vasodilation, relative and absolute hypovolemia, myocardial dysfunction, and altered blood flow distribution occurs due to the inflammatory response to infection. Even after the restoration of intravascular volume, microcirculatory abnormalities may persist and lead to maldistribution of cardiac output. Notwithstanding the complexity of its pathophysiology and treatment, to maintain adequate organ perfusion is a main goal in the management of severe sepsis and septic shock. For this purpose, optimization of intravascular volume and preload is the more important step. Fluid challenge is a term used to describe the initial volume expansion period in which the response of the patient to fluid administration is carefully evaluated. During this process, large amounts of fluids may be administered over a short period of time under close monitoring to evaluate the patient's response and avoid the development of pulmonary edema. Fluid challenge should be given in all patients suspected of hypovolemia. Fluid resuscitation may consist of natural or artificial colloids or crystalloids. There is no evidence-based support for one type of fluid over another. As the volume of distribution is much larger for crystalloids than for colloids, resuscitation with crystalloids requires more fluid to achieve the same end points and might result in more edema. In addition, post-hoc analysis and experimental studies suggest that colloids might be superior to crystalloids, in terms of physiologic end-points, recruitment of the microcirculation and mortality.

Official Title
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Saline Solution Versus Voluven®: A Controlled Study of Fluid Resuscitation in Severe Sepsis

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Resuscitation (Voluven)
* Drug: Resuscitation (Saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe sepsis Exclusion Criteria: Age of less than 18 years Pregnancy, or the presence of an acute cerebral vascular event, acute coronary syndrome, acute pulmonary edema, status asthmatics Cardiac dysrhythmias (as a primary diagnosis), contraindication to central venous catheterization, active gastrointestinal hemorrhage, seizure Drug overdose, burn injury, trauma, a requirement for immediate surgery, uncured cancer (during chemotherapy Immunosuppression (because of organ transplantation or systemic disease), do-not-resuscitate status, advanced directives restricting implementation of the protocol Delayed admission to ICU from emergency department (more than 4 hours), or fluid resuscitation previous to ICU with more than 1,500 cc

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 |
| --- | --- |
| Active Comparator: Voluven<br>Resuscitation fluid: Voluven (R) | Drug: Resuscitation (Voluven)<br>* Resuscitation aimed at venous oxygen saturation higher than 70%<br>|
| Active Comparator: Saline<br>Resuscitation fluid: Saline solution | Drug: Resuscitation (Saline)<br>* Resuscitation aimed at venous oxygen saturation higher than 70%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sublingual microcirculation |  | 24 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gases, hemoglobin and oxygen saturations |  | 24 hours | 
| Electrolytes and lactate |  | 24 hours | 
| Anion gap corrected to albumin |  | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Voluven, Colloids, Saline solution, Crystalloids, Sublingual microcirculation, Fluid resuscitation