Effect of Red Blood Cell Transfusion on Brain Metabolism in Patients With Subarachnoid Hemorrhage
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.
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.
Study Design
Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Subarachnoid Hemorrhage
Intervention
Red blood cell transfusion
Location
Washington University Medical Center
St Louis
Missouri
United States
63110
Status
Recruiting
Source
Washington University School of Medicine
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00968227
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Subarachnoid Hemorrhage
Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.
Subarachnoid Hemorrhage, Traumatic
Bleeding into the SUBARACHNOID SPACE due to CRANIOCEREBRAL TRAUMA. Minor hemorrhages may be asymptomatic; moderate to severe hemorrhages may be associated with INTRACRANIAL HYPERTENSION and VASOSPASM, INTRACRANIAL.
Hemodilution
Reduction of blood viscosity usually by the addition of cell free solutions. Used clinically (1) in states of impaired microcirculation, (2) for replacement of intraoperative blood loss without homologous blood transfusion, and (3) in cardiopulmonary bypass and hypothermia.
Exchange Transfusion, Whole Blood
Repetitive withdrawal of small amounts of blood and replacement with donor blood until a large proportion of the blood volume has been exchanged. Used in treatment of fetal erythroblastosis, hepatic coma, sickle cell anemia, disseminated intravascular coagulation, septicemia, burns, thrombotic thrombopenic purpura, and fulminant malaria.
Blood Transfusion, Intrauterine
In utero transfusion of BLOOD into the FETUS for the treatment of FETAL DISEASES, such as fetal erythroblastosis (ERYTHROBLASTOSIS, FETAL).
Clinical Trials
The Factors Cause Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Extensive research has shown that the big event that leads to the initiation of vasospasm is the release of oxyhemoglobin (blood breakdown product).Depletion of NO synthase (19,20,21) was...
Well Being of Obstetric Patients on Minimal Blood Transfusions
Postpartum haemorrhage (PPH) is one of the top five causes of maternal mortality in developed and developing countries. The most important treatment of PPH is red blood cell (RBC) transfus...
To determine whether HMG-CoA reductase inhibitor simvastatin prevents or ameliorates subarachnoid hemorrhage-induced delayed vasospasm and its ischemic consequences.
Atorvastatin After Aneurysmal Subarachnoid Hemorrhage
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have recently been demonstrated to improve endothelial function. Additionally, numerous studies...
Evaluation of Cerebral Spinal Fluid and Blood in Patients With Subarachnoid Hemorrhage
In this project we are collecting cerebrospinal fluid and blood from patients at Vanderbilt Medical Center who have a subarachnoid hemorrhage which has followed the rupture of a brain aneu...
PubMed Articles
Diagnostic imaging of subarachnoid hemorrhage.
Subarachnoid hemorrhage is characterized by the extravasation of blood into the spaces covering the central nervous system which are filled with cerebrospinal fluid. The leading cause of non-traumatic...
Predictors of hemorrhage volume and disability after perimesencephalic subarachnoid hemorrhage.
The determinants of subarachnoid hemorrhage (SAH) volume and an atypical pattern of blood are not clear. Our objective was to determine if reduced platelet activity on admission and abnormal venous dr...
Progesterone attenuates early brain injury after subarachnoid hemorrhage in rats.
Although the neuroprotective effects of progesterone against early brain injury (EBI) after trauma have been demonstrated in several studies, whether progesterone reduces EBI after subarachnoid hemorr...
The Risks of Blood Transfusion in Patients with Subarachnoid Hemorrhage.
