Clinical trial NCT00799916: Saline Solution Versus Voluven®: A Controlled Study of Fluid Resuscitation in Severe Sepsis
Official title: Saline Solution Versus Voluven®: A Controlled Study of Fluid Resuscitation in Severe Sepsis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sepsis
Keywords: Sepsis
Fluid resuscitation
Voluven
Colloids
Saline solution
Crystalloids
Sublingual microcirculation
Lead sponsor: Universidad Nacional de La Plata
Sponsor class: OTHER
Collaborators: name: Clínica Bazterrica
name: Sanatorio Otamendi y Miroli
name: National Agency for Scientific and Technological Promotion, Argentina
First posted: 2008-12-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Sublingual microcirculation
timeFrame: 24 hour
Secondary outcomes:
measure: Gases, hemoglobin and oxygen saturations
timeFrame: 24 hours
measure: Electrolytes and lactate
timeFrame: 24 hours
measure: Anion gap corrected to albumin
timeFrame: 24 hours
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Clinica Bazterrica
city: Buenos Aires
country: Argentina
facility: Clínica Santa Isabel
city: Buenos Aires
country: Argentina
facility: Sanatorio Otamendi y Miroli
Study officials:
affiliation: Sanatorio Otamendi y Miroli
name: Arnaldo Dubin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dubin A, Pozo MO, Casabella CA, Murias G, Palizas F Jr, Moseinco MC, Kanoore Edul VS, Palizas F, Estenssoro E, Ince C. Comparison of 6% hydroxyethyl starch 130/0.4 and saline solution for resuscitation of the microcirculation during the early goal-directed therapy of septic patients. J Crit Care. 2010 Dec;25(4):659.e1-8. doi: 10.1016/j.jcrc.2010.04.007. Epub 2010 Sep 1.