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

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.

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