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.
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. Delirium assessed using a validated procedure that includes validated tools is a secondary outcome measure. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
460
Blood pressure lowered or raised
Institutional standard of care.
Northwestern Memorial Hospital
Chicago, Illinois, United States
Composite Neurological Outcome of Clinical Stroke or New Ischemic Brain Lesion on Diffusion Weighted MRI or Neurocognitive Dysfunction 4 to 6 Weeks After Surgery.
The composite neurological outcome was composed of clinical stroke, or new ischemic lesions detected on postoperative brain diffusion weighted magnetic resonance imaging(DWI), or cognitive decline from baseline to 4-6 weeks after surgery.
Time frame: Up to 6 weeks post-operative
Postoperative Delirium
Assessed with Confusion Assessment Method or Confusion Assessment Method-ICU along with adjudication by team of experts
Time frame: Postoperative days 1-4
Multiple Inotropic Drugs>24 Hours After Surgery
Use of multiple inotropic drugs greater than 24 hours after the planned surgical procedure until discharge from the hospital.
Time frame: 7 days after surgery
Mechanical Lung Ventilation>24 Hours After Surgery
Subjects need for mechanical lung ventilation more than 24 hours after planned surgical procedure.
Time frame: Up to 28 days after surgery.
Insertion of Intra-aortic Balloon Pump
Procedural insertion of intra-aortic balloon pump within 7 days after surgical procedure
Time frame: 7 days after surgery
Postoperative Atrial Fibrillation
Clinical diagnosis of postoperative atrial fibrillation from date of surgical procedure to discharge from the hospital.
Time frame: Up to 28 days after surgery.
Sepsis
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Clinical diagnosis of sepsis from time of surgical procedure to discharge from the hospital.
Time frame: Up to 28 days after surgery.
Acute Kidney Injury Within 7 Days After Surgery.
Subject developed acute kidney injury within 7 days after surgical procedure. Based on Kidney disease: Improving Global Outcomes (KDIGO) classification system.
Time frame: 7 days after surgery
New Renal Replacement Therapy
Subjects requiring new renal replacement therapy prior to discharge from hospital
Time frame: Up to 28 days after surgery.
Multisystem Organ Failure After Surgery
Subject diagnosis of multisystem organ failure after surgery.
Time frame: Up to 28 days after surgery.
Mortality
Subject death within 28 days after surgical procedure
Time frame: 28 days