Effect of Red Blood Cell Transfusion on Brain Metabolism in Patients With Subarachnoid Hemorrhage

NCT ID: NCT00968227

Last Updated: 2017-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2015-08-31

Brief Summary

The purpose of this study is to determine if giving blood transfusions to anemic patients with subarachnoid hemorrhage will reduce their chances of having a stroke from vasospasm.

Detailed Description

Each year, approximately 30,000 people suffer aneurysmal subarachnoid hemorrhage (SAH) in the United States. The most common and potentially treatable cause of secondary neurological injury in this population is delayed ischemic deficit (DID). As the name implies, this phenomenon is fundamentally a reduction of cerebral blood flow (CBF) and oxygen delivery below critical ischemic thresholds, occurring days after the onset of hemorrhage. Three inter-related physiological processes appear to be involved in the reduced oxygen delivery: severe narrowing of intracranial arteries (arterial vasospasm), intravascular volume depletion and a loss of normal autoregulatory function in the distal circulation. DID occurs in up to 40% of patients surviving SAH. One third of these patients will die from this phenomenon and another third will be left with permanent and severe disability.

The optimal treatment of vasospasm is not known. Medical management involves a number of hemodynamic manipulations and is usually referred to as hypervolemic, hypertensive, hemodilution (or Triple-H) therapy. Our knowledge of the physiological impact of the individual components or a combination of them is limited and clinical efficacy has not been established. The information gained in this study has great potential to advance our knowledge regarding the role of hematocrit in the optimal treatment of this often-devastating condition.

Changes in hematocrit can potentially impact brain oxygen delivery in two ways. First, there is a linear relationship between hemoglobin and arterial oxygen content, lower hematocrit less oxygen. Thus at a given CBF lowering hematocrit reduces brain oxygen delivery. Fortunately, the brain responds to this by increasing blood flow to restore oxygen delivery to baseline levels. Additionally, lowering hematocrit has another effect, it reduces viscosity which in and of itself can raise CBF, but in a non-linear way. It is the relative contribution of these two effects that will determine if oxygen delivery improves.

It has been proposed by largely on theoretical consideration that the "optimal" hematocrit that achieves this balance is 30-35%. Yet no study to date has assessed the relationship between hematocrit and oxygen delivery in SAH patients. Other observations, however, suggest that higher hemoglobin levels in SAH patients was associated with better outcomes. Finally another retrospective review suggested that receiving transfusions increased risk for vasospasm and poor outcome after subarachnoid hemorrhage.

We are proposing to begin a series of studies to determine the appropriate management of hematocrit in SAH patients. The first is to define the appropriate physiologic response (cerebral oxygen delivery and metabolism) to a change in hematocrit. Then the "optimal" hematocrit can be defined. Only then will we be able to properly design clinical outcome trials.

Conditions

Subarachnoid Hemorrhage; Vasospasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Transfusion

Group Type: EXPERIMENTAL

Red blood cell transfusion

Intervention Type: BIOLOGICAL

Transfusion of 1 unit of packed red blood cells over 1 hour.

Interventions

Red blood cell transfusion

Transfusion of 1 unit of packed red blood cells over 1 hour.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Aneurysmal SAH confirmed by angiography

2. Hemoglobin < 12.5 gm/dl

3. One of the following:

• Considered at increased risk for vasospasm by care team
• Angiographic vasospasm
• Delayed ischemic deficit

4. Able to be studied within 2 weeks after subarachnoid hemorrhage

Exclusion Criteria

1. Active Coronary Artery Disease

2. Severe congestive heart failure

3. Jehovah's witness

4. Unable to obtain appropriately matched blood

5. Other contraindications for transfusion

6. Pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Diringer, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University Medical Center

St Louis, Missouri, United States

Countries

United States

References

Dhar R, Zazulia AR, Videen TO, Zipfel GJ, Derdeyn CP, Diringer MN. Red blood cell transfusion increases cerebral oxygen delivery in anemic patients with subarachnoid hemorrhage. Stroke. 2009 Sep;40(9):3039-44. doi: 10.1161/STROKEAHA.109.556159. Epub 2009 Jul 23.

Reference Type: RESULT

PMID: 19628806 (View on PubMed)

Other Identifiers

NIH 5P50NS035966-10

Identifier Type: -

Identifier Source: secondary_id

07-0733

Identifier Type: -

Identifier Source: org_study_id