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Cerebral Autoregulation Monitoring During Cardiac Surgery

Continuous Cerebral Autoregulation Monitoring to Reduce Brain Injury From Cardiac Surgery

Status
Completed
Phases
Unknown
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00981474
Enrollment
460
Registered
2009-09-22
Start date
2009-09-01
Completion date
2020-02-28
Last updated
2026-06-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiopulmonary Bypass, Thoracic Surgery

Keywords

cardiac surgery; brain injury; cerebral autoregulation

Brief summary

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.

Detailed description

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.

Interventions

DRUGblood pressure maintenance based on cerebral blood flow autoregulation measurement

Blood pressure lowered or raised

DEVICEControl group

Institutional standard of care.

Sponsors

Northwestern University
Lead SponsorOTHER
National Heart, Lung, and Blood Institute (NHLBI)
CollaboratorNIH

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Male or female patients undergoing primary or re-operative Coronary Artery Bypass Graft (CABG) and/or valvular surgery or ascending aorta surgery that requires Cardio-pulmonary bypass (CPB) who are at high risk for neurologic complications (stroke or encephalopathy) as determined by a Johns Hopkins risk score of \>0.02

Exclusion criteria

* Contraindication to MRI imaging (e.g., permanent pacemaker, cerebral arterial vascular clips) * Liver function test before surgery more than twice the upper limit of institutional normal * Pre-existing renal dysfunction defined as an estimated glomerular filtration rate of ≤60 mL/min, or current renal dialysis * Emergency surgery * Inability to attend outpatient visits * Visual impairment or inability to speak and read English. The patient will be excluded from further study if an adequate temporal window for Transcranial Doppler (TCD) monitoring can not be identified before surgery.

Design outcomes

Primary

MeasureTime frameDescription
Composite Neurological Outcome of Clinical Stroke or New Ischemic Brain Lesion on Diffusion Weighted MRI or Neurocognitive Dysfunction 4 to 6 Weeks After Surgery.Up to 6 weeks post-operativeThe 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.

Secondary

MeasureTime frameDescription
Postoperative DeliriumPostoperative days 1-4Assessed with Confusion Assessment Method or Confusion Assessment Method-ICU along with adjudication by team of experts
Multiple Inotropic Drugs>24 Hours After Surgery7 days after surgeryUse of multiple inotropic drugs greater than 24 hours after the planned surgical procedure until discharge from the hospital.
Mechanical Lung Ventilation>24 Hours After SurgeryUp to 28 days after surgery.Subjects need for mechanical lung ventilation more than 24 hours after planned surgical procedure.
Insertion of Intra-aortic Balloon Pump7 days after surgeryProcedural insertion of intra-aortic balloon pump within 7 days after surgical procedure
Postoperative Atrial FibrillationUp to 28 days after surgery.Clinical diagnosis of postoperative atrial fibrillation from date of surgical procedure to discharge from the hospital.
SepsisUp to 28 days after surgery.Clinical diagnosis of sepsis from time of surgical procedure to discharge from the hospital.
Acute Kidney Injury Within 7 Days After Surgery.7 days after surgerySubject developed acute kidney injury within 7 days after surgical procedure. Based on Kidney disease: Improving Global Outcomes (KDIGO) classification system.
New Renal Replacement TherapyUp to 28 days after surgery.Subjects requiring new renal replacement therapy prior to discharge from hospital
Multisystem Organ Failure After SurgeryUp to 28 days after surgery.Subject diagnosis of multisystem organ failure after surgery.
Mortality28 daysSubject death within 28 days after surgical procedure

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORCharles Hogue, MD

Northwestern University

Participant flow

Pre-assignment details

After obtaining written informed consent, 468 were randomized to the two groups. 237 in the autoregulation group were randomized after consent and 5 subjects withdrew consent. 231 in the usual care group were randomized after consent and 3 subjects withdrew consent.

Participants by arm

ArmCount
Usual Care Group
Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.
228
Autoregulation Group
Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
232
Total460

Baseline characteristics

CharacteristicUsual Care GroupTotalAutoregulation Group
Age, Continuous70.8 years
STANDARD_DEVIATION 8
70.4 years
STANDARD_DEVIATION 7.6
70.0 years
STANDARD_DEVIATION 7.3
Aortic cross-clamp (time in minutes)73 Minutes71 Minutes69 Minutes
Cardiopulmonary bypass duration107 Minutes105 Minutes103 Minutes
Current tobacco use22 Participants46 Participants24 Participants
Duration of hospitalization (days)8 Days7 Days7 Days
Duration of ICU admission (hours)44.1 Hours44 Hours44 Hours
Highest Grade of Formal Education (median,[inter-quartile range])14.0 Years14 Years14.5 Years
History of anemia101 Participants209 Participants108 Participants
History of a prior stroke25 Participants44 Participants19 Participants
History of atrial fibrillation53 Participants102 Participants49 Participants
History of chronic obstructive lung disease31 Participants52 Participants21 Participants
History of diabetes101 Participants209 Participants108 Participants
History of hypertension213 Participants420 Participants207 Participants
History of myocardial infarction65 Participants139 Participants74 Participants
Logistic EuroSCORE (median,[interquartile range])5.3 score on a scale 0-2 good >=5 high risk5.19 score on a scale 0-2 good >=5 high risk5.08 score on a scale 0-2 good >=5 high risk
Mini-Mental State Exam28 score on a scale (30 good- 0 poor)28 score on a scale (30 good- 0 poor)28 score on a scale (30 good- 0 poor)
Obstructive sleep apnea41 Participants77 Participants36 Participants
Race/Ethnicity, Customized
African American
24 participants52 participants28 participants
Race/Ethnicity, Customized
Asian
0 participants4 participants4 participants
Race/Ethnicity, Customized
Caucasian
189 participants273 participants184 participants
Race/Ethnicity, Customized
Hispanic
3 participants5 participants2 participants
Race/Ethnicity, Customized
Multiple
0 participants2 participants2 participants
Race/Ethnicity, Customized
Native American
1 participants4 participants3 participants
Race/Ethnicity, Customized
Other
10 participants19 participants9 participants
Region of Enrollment
United States
228 Participants460 Participants232 Participants
Sex/Gender, Customized
Female
67 participants129 participants62 participants
Sex/Gender, Customized
Male
160 participants330 participants170 participants
Sex/Gender, Customized
Missing designation
1 participants1 participants0 participants
Type of surgery
Aortic Root Replacement
2 Participants4 Participants2 Participants
Type of surgery
Aortic Valve Replacement (AVR)
41 Participants89 Participants48 Participants
Type of surgery
Aortic Valve Replacement, Mitral Valve Replacement (AVR/MVR)
9 Participants14 Participants5 Participants
Type of surgery
Coronary Aertery Bypass Graft, Aortic Valve Replacement (CABG/AVR)
35 Participants61 Participants26 Participants
Type of surgery
Coronary Artery Bypass Graft, Aortic Valve Replacement, Mitral Valve Replacement (CABG/AVR/MVR)
3 Participants6 Participants3 Participants
Type of surgery
Coronary Artery Bypass Graft (CABG)
109 Participants226 Participants117 Participants
Type of surgery
Coronary Artery Bypass Graft, (CABG) / Aortic Root Replacement
1 Participants1 Participants0 Participants
Type of surgery
Coronary Artery Bypass Graft, Mitral Valve Replacement CABG/MVR)
6 Participants15 Participants9 Participants
Type of surgery
Mitral Valve Replacement (MVR)
19 Participants41 Participants22 Participants
Type of surgery
Transcatheter Aortic Valve Replacement (TAVR)
3 Participants3 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
12 / 2285 / 232
other
Total, other adverse events
34 / 22819 / 232
serious
Total, serious adverse events
133 / 228121 / 232

Outcome results

Primary

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

Population: Subjects who completed neurological testing and MRI testing

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Usual Care Group (Control)Composite Neurological Outcome of Clinical Stroke or New Ischemic Brain Lesion on Diffusion Weighted MRI or Neurocognitive Dysfunction 4 to 6 Weeks After Surgery.79 Participants
Autoregulation GroupComposite Neurological Outcome of Clinical Stroke or New Ischemic Brain Lesion on Diffusion Weighted MRI or Neurocognitive Dysfunction 4 to 6 Weeks After Surgery.70 Participants
p-value: 0.75295% CI: [0.82, 1.121]Chi-squared
Secondary

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

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Usual Care Group (Control)Acute Kidney Injury Within 7 Days After Surgery.56 Participants
Autoregulation GroupAcute Kidney Injury Within 7 Days After Surgery.62 Participants
p-value: 0.60895% CI: [0.81, 1.5]Chi-squared
Secondary

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

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Usual Care Group (Control)Insertion of Intra-aortic Balloon Pump19 Participants
Autoregulation GroupInsertion of Intra-aortic Balloon Pump14 Participants
p-value: 0.43995% CI: [0.37, 1.41]Chi-squared
Secondary

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.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Usual Care Group (Control)Mechanical Lung Ventilation>24 Hours After Surgery22 Participants
Autoregulation GroupMechanical Lung Ventilation>24 Hours After Surgery13 Participants
p-value: 0.14495% CI: [0.3, 1.13]Chi-squared
Secondary

Mortality

Subject death within 28 days after surgical procedure

Time frame: 28 days

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Usual Care Group (Control)Mortality12 Participants
Autoregulation GroupMortality5 Participants
p-value: 0.12995% CI: [0.15, 1.14]Chi-squared
Secondary

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

Population: 228 in the usual care group and 232 in the autoregulation group were analyzed.

ArmMeasureValue (NUMBER)
Usual Care Group (Control)Multiple Inotropic Drugs>24 Hours After Surgery13 participants
Autoregulation GroupMultiple Inotropic Drugs>24 Hours After Surgery6 participants
p-value: 0.14995% CI: [0.18, 1.17]Chi-squared
Secondary

Multisystem Organ Failure After Surgery

Subject diagnosis of multisystem organ failure after surgery.

Time frame: Up to 28 days after surgery.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Usual Care Group (Control)Multisystem Organ Failure After Surgery7 Participants
Autoregulation GroupMultisystem Organ Failure After Surgery2 Participants
p-value: 0.10395% CI: [0.05, 1.18]Fisher Exact
Secondary

New Renal Replacement Therapy

Subjects requiring new renal replacement therapy prior to discharge from hospital

Time frame: Up to 28 days after surgery.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Usual Care Group (Control)New Renal Replacement Therapy6 Participants
Autoregulation GroupNew Renal Replacement Therapy4 Participants
p-value: 0.54195% CI: [0.16, 1.97]Fisher Exact
Secondary

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.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Usual Care Group (Control)Postoperative Atrial Fibrillation89 Participants
Autoregulation GroupPostoperative Atrial Fibrillation79 Participants
p-value: 0.31195% CI: [0.69, 1.11]Chi-squared
Secondary

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

Population: Delirium was measured day 1-4. 232 in the autoregulation group were assessed and 228 were assessed in the usual care group.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Usual Care Group (Control)Postoperative Delirium34 Participants
Autoregulation GroupPostoperative Delirium19 Participants
p-value: 0.05395% CI: [0.32, 0.93]Chi-squared
Secondary

Sepsis

Clinical diagnosis of sepsis from time of surgical procedure to discharge from the hospital.

Time frame: Up to 28 days after surgery.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Usual Care Group (Control)Sepsis7 Participants
Autoregulation GroupSepsis2 Participants
p-value: 0.10395% CI: [0.005, 1.18]Fisher Exact

Source: ClinicalTrials.gov · Data processed: Jun 6, 2026