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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00968227
Recruitment Status : Completed
First Posted : August 28, 2009
Results First Posted : April 17, 2017
Last Update Posted : April 17, 2017
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Subarachnoid Hemorrhage Vasospasm Biological: Red blood cell transfusion Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Red Blood Cell Transfusion on Brain Metabolism in Patients With Subarachnoid Hemorrhage
Study Start Date : November 2007
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Transfusion Biological: Red blood cell transfusion
Transfusion of 1 unit of packed red blood cells over 1 hour.

Primary Outcome Measures :
  1. Change in Oxygen Delivery in Vulnerable Brain Regions [ Time Frame: 1 hour ]
    Change in oxygen delivery after transfusion in brain regions with low baseline delivery.

Secondary Outcome Measures :
  1. Change in Oxygen Extraction Fraction in Regions With Low Baseline Delivery. [ Time Frame: 1 hour ]
    Change in oxygen extraction fraction after transfusion of 1 unit of RBC in regions with low baseline delivery (DO2 < 4.5 ml/100g/min.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00968227

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United States, Missouri
Washington University Medical Center
St Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
National Institute of Neurological Disorders and Stroke (NINDS)
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Principal Investigator: Michael Diringer, MD Washington University School of Medicine

Publications of Results:
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Responsible Party: Washington University School of Medicine Identifier: NCT00968227     History of Changes
Other Study ID Numbers: 07-0733
NIH 5P50NS035966-10
First Posted: August 28, 2009    Key Record Dates
Results First Posted: April 17, 2017
Last Update Posted: April 17, 2017
Last Verified: March 2017
Keywords provided by Washington University School of Medicine:
subarachnoid hemorrhage
cerebral oxygen delivery
Additional relevant MeSH terms:
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Subarachnoid Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases