Fluid Resuscitation in Early Septic Shock

• Status: Completed
• Trial end date: 2010-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Severe infection in the intensive care unit is common accounting for about 10% of admissions and has a death rate of approximately 40-50%. It is almost always associated with significant reductions in blood pressure. Administration of fluid often in large volumes is essential to normalize blood pressure and prevent failure of organs and death. Two common classes of fluid solutions are crystalloid fluids (salt based, normal saline) and colloid fluids (protein based, albumin). Due to its properties, the albumin fluid may remain in the vascular space better than the normal saline solution. Hence, there may be faster attainment of normal blood pressure as well as a reduction in failed organs and death. Preliminary clinical trial data suggests a potential for benefit with albumin in this setting but these findings require confirmation in a large clinical trial.

There are few data to explain how albumin may exert its protective effects and lead to better outcomes for patients with severe infections. We will conduct a clinical study that will examine potential biological mechanisms for albumin's protective effects in 50 patients across 6 Canadian academic hospitals. We will also examine our ability to successfully recruit patients into this trial.

This study will provide information that will help to understand the biological mechanisms of albumin in severe infection. The information gained will guide the investigative team for future fluid related mechanistic questions. The study will also provide essential information that will aid in the design and conduct of the future large clinical trial that will examine death as its primary outcome.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ottawa Hospital Research Institute
• Collaborators: Baxter Healthcare Corporation; Canadian Blood Services

Criteria

Inclusion Criteria:

Eligible patients will meet the following 2 inclusion criteria.

1. Refractory Hypotension: The patient has received at least 1 litre of normal saline or ringers lactate crystalloid fluid for hypotension (defined as a systolic blood pressure less than 90 mm Hg, or a systolic blood pressure more than 40 mm Hg below baseline, or a mean arterial blood pressure less than 65 mm Hg) within 8 hours of the first hypotensive event and has refractory hypotension defined by: a) Presence of hypotension OR b) Initiation of a vasopressor agent(s).

2. Two or more criteria for the systemic inflammatory response syndrome (SIRS): i) heart rate greater than 90 beats per minute; ii) respiratory rate greater than 20 breathes per minute, or a PaC02 less than 32 mm Hg, or mechanically ventilated; iii) temperature greater than 38 or less than 36 degrees Celsius; iv) or a white blood cell count greater than 12,000 x 109/L or less than 4,000 x 109/L, or more than 10% bands on the differential.

Exclusion Criteria:

1. Clinically apparent other forms of shock including cardiogenic, obstructive (massive pulmonary embolism, cardiac tamponade, tension pneumothorax) or hemorrhagic shock

2. Previous admission to ICU with severe sepsis or septic shock during the index hospitalization

3. More than 250 mls of colloid fluid (Pentaspan, Voluven, Hextend, or albumin) from the first episode of hypotension

4. A known previous severe reaction to albumin

5. Burns

6. Known cirrhosis

7. Traumatic brain injury

8. Religious objection to albumin use

9. Less than 18 years of age

10. Pregnant

11. Family or patient not committed to aggressive care

12. Currently enrolled in another related interventional study.