Brain injury during cardiac surgery results primarily from cerebral embolism and/or reduced cerebral blood flow (CBF). The latter is of particular concern for the growing number of surgical patients who are aged and/or who have cerebral vascular disease. Normally, CBF is physiologically autoregulated (or kept constant) within a range of blood pressures allowing for stable cerebral O2 supply commensurate with metabolic demands. Cerebral autoregulation is impaired in patients undergoing cardiac surgery who have cerebral vascular disease and in many others due to other conditions. This could lead to brain injury since current practices of targeting low mean arterial blood pressure empirically (usually 50-70 mmHg) during cardiopulmonary bypass may expose patients with impaired cerebral autoregulation to cerebral hypoperfusion. The hypothesis of this proposal is that targeting mean arterial pressure during cardiopulmonary bypass to a level above an individual's lower autoregulatory threshold reduces the risk for brain injury in patients undergoing cardiac surgery. Monitoring of cerebral autoregulation will be performed in real time using software that continuously compares the relation between arterial blood pressure and CBF velocity of the middle cerebral artery measured with transcranial Doppler and with cerebral oximetry measured with near infrared spectroscopy. The primary end-point of the study will be a comprehensive composite outcome of clinical stroke, cognitive decline, and/or new ischemic brain lesions detected with diffusion weighted magnetic resonance (MR) imaging. Autoregulation is mediated by reactivity of cerebral resistance vessels. A secondary aim of this proposal is to evaluate whether near infrared reflectance spectroscopy can be used to trend changes in cerebral blood volume and provide a reliable monitor of vascular reactivity (the hemoglobin volume index). Assessments for extra-cranial and intra-cranial arterial stenosis will be performed using MR angiography to control for this potential confounding variable in the analysis. Finally, an additional aim of the study will be to assess whether preoperative transcranial Doppler examination of major cerebral arteries can identify patients who are prone to the composite neurological end-point. Near infrared oximetry is non-invasive, continuous, requires little care- giver intervention and, thus, could be widely used to individualize patient blood pressure management during surgery. Brain injury from cardiac surgery is an important source of operative mortality, prolonged hospitalization, increased health care expenditure, and impaired quality of life. Developing strategies to reduce the burden of this complication has wide public health implications and is within the mission of the NHLBI.

Public Health Relevance

Neurological complications from cardiac surgery are an important source of operative mortality, prolonged hospitalization, health care expenditure, and impaired quality of life. New strategies of care are needed to avoid rising complications for the growing number of aged patients undergoing cardiac surgery. This study will evaluate novel methods for reducing brain injury during surgery from inadequate brain blood flow using techniques that could be widely employed.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL092259-01A2
Application #
7714660
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Thrasher, Terry N
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
1
Fiscal Year
2009
Total Cost
$311,655
Indirect Cost
Name
Johns Hopkins University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Easley, Ronald B; Marino, Bradley S; Jennings, Jacky et al. (2018) Impaired cerebral autoregulation and elevation in plasma glial fibrillary acidic protein level during cardiopulmonary bypass surgery for CHD. Cardiol Young 28:55-65
Adatia, Krishma; Geocadin, Romergryko G; Healy, Ryan et al. (2018) Effect of Body Temperature on Cerebral Autoregulation in Acutely Comatose Neurocritically Ill Patients. Crit Care Med 46:e733-e741
Healy, Ryan J; Zorrilla-Vaca, Andres; Ziai, Wendy et al. (2018) Glasgow Coma Scale Score Fluctuations are Inversely Associated With a NIRS-based Index of Cerebral Autoregulation in Acutely Comatose Patients. J Neurosurg Anesthesiol :
Hori, Daijiro; Nomura, Yohei; Ono, Masahiro et al. (2017) Optimal blood pressure during cardiopulmonary bypass defined by cerebral autoregulation monitoring. J Thorac Cardiovasc Surg 154:1590-1598.e2
Chang, Aaron J; Nomura, Yohei; Barodka, Viachaslau M et al. (2017) Validation of a Real-Time Minute-to-Minute Urine Output Monitor and the Feasibility of Its Clinical Use for Patients Undergoing Cardiac Surgery. Anesth Analg 125:1883-1886
Rivera-Lara, Lucia; Geocadin, Romergryko; Zorrilla-Vaca, Andres et al. (2017) Validation of Near-Infrared Spectroscopy for Monitoring Cerebral Autoregulation in Comatose Patients. Neurocrit Care 27:362-369
Magruder, J Trent; Crawford, Todd C; Harness, Herbert Lynn et al. (2017) A pilot goal-directed perfusion initiative is associated with less acute kidney injury after cardiac surgery. J Thorac Cardiovasc Surg 153:118-125.e1
Brown 4th, Charles H; LaFlam, Andrew; Max, Laura et al. (2016) Delirium After Spine Surgery in Older Adults: Incidence, Risk Factors, and Outcomes. J Am Geriatr Soc 64:2101-2108
Subramanian, Balachundhar; Nyman, Charles; Fritock, Maria et al. (2016) A Multicenter Pilot Study Assessing Regional Cerebral Oxygen Desaturation Frequency During Cardiopulmonary Bypass and Responsiveness to an Intervention Algorithm. Anesth Analg 122:1786-93

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