Objectives: Impaired oxygen delivery due to reduced cerebral blood flow is the hallmark of delayed cerebral ischemia following subarachnoid hemorrhage. Since anemia reduces arterial oxygen content, it further threatens oxygen delivery increasing the risk of cerebral infarction. Thus, subarachnoid hemorrhage may constitute an important exception to current restrictive transfusion practices, wherein raising hemoglobin could reduce the risk of ischemia in a critically hypoperfused organ. In this physiologic proof-of-principle study, we determined whether transfusion could augment cerebral oxygen delivery, particularly in vulnerable brain regions, across a broad range of hemoglobin values.
Design: Prospective study measuring cerebral blood flow and oxygen extraction fraction using 15O-PET. Vulnerable brain regions were defined as those with baseline oxygen delivery less than 4.5 mL/100 g/min.
Setting: PET facility located within the Neurology/Neurosurgery ICU.
Patients: Fifty-two patients at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage with hemoglobin 7–13 g/dL.
Interventions: Transfusion of one unit of RBCs over 1 hour.
Measurements and Main Results: Baseline hemoglobin was 9.7 g/dL (range, 6.9–12.9), and cerebral blood flow was 43 ± 11 mL/100 g/min. After transfusion, hemoglobin rose from 9.6 ± 1.4 to 10.8 ± 1.4 g/dL (12%; p < 0.001) and oxygen delivery from 5.0 (interquartile range, 4.4–6.6) to 5.5 mL/100 g/min (interquartile range, 4.8–7.0) (10%; p = 0.001); the response was comparable across the range of hemoglobin values. In vulnerable brain regions, transfusion resulted in a greater (16%) rise in oxygen delivery associated with reduction in oxygen extraction fraction, independent of Hgb level (p = 0.002 vs normal regions).
Conclusions: This study demonstrates that RBC transfusion improves cerebral oxygen delivery globally and particularly to vulnerable regions in subarachnoid hemorrhage patients at risk for delayed cerebral ischemia across a wide range of hemoglobin values and suggests that restrictive transfusion practices may not be appropriate in this population. Large prospective trials are necessary to determine if these physiologic benefits translate into clinical improvement and outweigh the risk of transfusion.
1Department of Neurology, Washington University School of Medicine, St. Louis, MO.
2Department of Radiology, Washington University School of Medicine, St. Louis, MO.
3Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO.
ClinicalTrials.gov registration: Effect of Red Blood Cell Transfusion on Brain Metabolism in Patients With Subarachnoid Hemorrhage; Identifier: NCT00968227.
Supported, in part, by AHA Scientist Development Grant SDG3440008 (to Dr. Dhar), National Institutes of Health/National Institute of Neurological Disorders and Stroke 5P01NS035966 (to Dr. Diringer), and Barnes-Jewish Hospital Foundation grant 00956-0807-01 (to Dr. Dhar).
Dr. Dhar’s institution received funding from the Barnes-Jewish Hospital Foundation and the American Heart Association (AHA). He received support for article research from the AHA. Dr. Derdeyn received support for article research from the National Institutes of Health (NIH). He also disclosed support from Pulse Therapeutics (stock options; acute stroke treatment device). Dr. Diringer’s institution received funding from the NIH/National Institute of Neurological Disorders and Stroke, the AHA, Barnes-Jewish Hospital Foundation, and Prolong Pharmaceuticals. He received funding from Remedy Pharmaceuticals and Pfizer. He received support for article research from the NIH. Dr. Zazulia has disclosed that she does not have any potential conflicts of interest.
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