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 #
5R01HL092259-04
Application #
8293199
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Charette, Marc F
Project Start
2009-08-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$323,014
Indirect Cost
$66,654
Name
Johns Hopkins University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Laflam, Andrew; Joshi, Brijen; Brady, Kenneth et al. (2015) Shoulder surgery in the beach chair position is associated with diminished cerebral autoregulation but no differences in postoperative cognition or brain injury biomarker levels compared with supine positioning: the anesthesia patient safety foundation be Anesth Analg 120:176-85
Evans, Adam S; Yee, May-Sann; Hogue, Charles W (2014) Often overlooked problems with handoffs: from the intensive care unit to the operating room. Anesth Analg 118:687-9
Brown 4th, Charles H; Savage, William J; Masear, Courtney G et al. (2014) Odds of transfusion for older adults compared to younger adults undergoing surgery. Anesth Analg 118:1168-78
Brown 4th, Charles H; Grega, Maura; Selnes, Ola A et al. (2014) Length of red cell unit storage and risk for delirium after cardiac surgery. Anesth Analg 119:242-50
Hori, D; Brown, C; Ono, M et al. (2014) Arterial pressure above the upper cerebral autoregulation limit during cardiopulmonary bypass is associated with postoperative delirium. Br J Anaesth 113:1009-17
Salaria, Osman N; Barodka, Viachaslau M; Hogue, Charles W et al. (2014) Impaired red blood cell deformability after transfusion of stored allogeneic blood but not autologous salvaged blood in cardiac surgery patients. Anesth Analg 118:1179-87
Lee, Jennifer K; Brady, Ken M; Chung, Shang-En et al. (2014) A pilot study of cerebrovascular reactivity autoregulation after pediatric cardiac arrest. Resuscitation 85:1387-93
Steppan, Jochen; Hogue Jr, Charles W (2014) Cerebral and tissue oximetry. Best Pract Res Clin Anaesthesiol 28:429-39
Ono, Masahiro; Brady, Kenneth; Easley, R Blaine et al. (2014) Duration and magnitude of blood pressure below cerebral autoregulation threshold during cardiopulmonary bypass is associated with major morbidity and operative mortality. J Thorac Cardiovasc Surg 147:483-9
Frank, Steven M; Abazyan, Bagrat; Ono, Masahiro et al. (2013) Decreased erythrocyte deformability after transfusion and the effects of erythrocyte storage duration. Anesth Analg 116:975-81

Showing the most recent 10 out of 21 publications