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

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.

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Drug: Resuscitation (Voluven); Drug: Resuscitation (Saline)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1425
    • Clínica Bazterrica
  • Buenos Aires, Argentina, 1425
    • Clínica Santa Isabel
  • Buenos Aires, Argentina, 1425
    • Sanatorio Otamendi y Miroli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Voluven; Resuscitation fluid: Voluven (R)	Drug: Resuscitation (Voluven); Resuscitation aimed at venous oxygen saturation higher than 70%
Active Comparator: Saline; Resuscitation fluid: Saline solution	Drug: Resuscitation (Saline); Resuscitation aimed at venous oxygen saturation higher than 70%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sublingual microcirculation	24 hour

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Universidad Nacional de La Plata
• Collaborators: Clínica Bazterrica; National Agency for Scientific and Technological Promotion, Argentina; Sanatorio Otamendi y Miroli
• Investigators: Principal Investigator: Arnaldo Dubin, MD, Sanatorio Otamendi y Miroli

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: November 28, 2008
• First Submitted That Met QC Criteria: November 28, 2008
• First Posted (Estimate): December 1, 2008

Study Record Updates

• Last Update Posted (Estimate): September 15, 2009
• Last Update Submitted That Met QC Criteria: September 14, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Sepsis; Fluid resuscitation; Sublingual microcirculation; Voluven; Crystalloids; Saline solution; Colloids
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: GEM 001