Cerebral Autoregulation Monitoring During Cardiac Surgery

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00981474
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 460
• Location: 1
• Arms: 2
• Actual Duration (Months): 125.9
• Patients Per Site Per Month: 3.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Thoracic Surgery; Cardiopulmonary Bypass	Drug: blood pressure maintenance based on cerebral blood flow autoregulation measurement; Device: Control group	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 460 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Continuous Cerebral Autoregulation Monitoring to Reduce Brain Injury From Cardiac Surgery
• Actual Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Feb 4, 2020
• Actual Study Completion Date: Feb 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management.	Device: Control group; Institutional standard of care.; Other Names: Usual (Control Group)
Experimental: Intervention Blood pressure management based on cerebral autoregulation data.	Drug: blood pressure maintenance based on cerebral blood flow autoregulation measurement; Blood pressure lowered or raised; Other Names: Autoregulation

Outcome Measures

Primary Outcome Measures

1. 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-operative]

   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.

Secondary Outcome Measures

1. Postoperative Delirium [Postoperative days 1-4]

   Assessed with Confusion Assessment Method or Confusion Assessment Method-ICU along with adjudication by team of experts

2. Multiple Inotropic Drugs>24 Hours After Surgery [7 days after surgery]

   Use of multiple inotropic drugs greater than 24 hours after the planned surgical procedure until discharge from the hospital.

3. Mechanical Lung Ventilation>24 Hours After Surgery [Up to 28 days after surgery.]

   Subjects need for mechanical lung ventilation more than 24 hours after planned surgical procedure.

4. Insertion of Intra-aortic Balloon Pump [7 days after surgery]

   Procedural insertion of intra-aortic balloon pump within 7 days after surgical procedure

5. Postoperative Atrial Fibrillation [Up to 28 days after surgery.]

   Clinical diagnosis of postoperative atrial fibrillation from date of surgical procedure to discharge from the hospital.

6. Sepsis [Up to 28 days after surgery.]

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

7. Acute Kidney Injury Within 7 Days After Surgery. [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.

8. New Renal Replacement Therapy [Up to 28 days after surgery.]

   Subjects requiring new renal replacement therapy prior to discharge from hospital

9. Multisystem Organ Failure After Surgery [Up to 28 days after surgery.]

   Subject diagnosis of multisystem organ failure after surgery.

10. Mortality [28 days]

    Subject death within 28 days after surgical procedure

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Charles Hogue, MD, Northwestern University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 15, 2019

More Information

Publications

• Brady K, Joshi B, Zweifel C, Smielewski P, Czosnyka M, Easley RB, Hogue CW Jr. Real-time continuous monitoring of cerebral blood flow autoregulation using near-infrared spectroscopy in patients undergoing cardiopulmonary bypass. Stroke. 2010 Sep;41(9):1951-6. doi: 10.1161/STROKEAHA.109.575159. Epub 2010 Jul 22.
• Brady KM, Lee JK, Kibler KK, Smielewski P, Czosnyka M, Easley RB, Koehler RC, Shaffner DH. Continuous time-domain analysis of cerebrovascular autoregulation using near-infrared spectroscopy. Stroke. 2007 Oct;38(10):2818-25. Epub 2007 Aug 30.
• Brown CH 4th, Laflam A, Max L, Lymar D, Neufeld KJ, Tian J, Shah AS, Whitman GJ, Hogue CW. The Impact of Delirium After Cardiac Surgical Procedures on Postoperative Resource Use. Ann Thorac Surg. 2016 May;101(5):1663-9. doi: 10.1016/j.athoracsur.2015.12.074. Epub 2016 Mar 31.
• Brown CH 4th, Neufeld KJ, Tian J, Probert J, LaFlam A, Max L, Hori D, Nomura Y, Mandal K, Brady K, Hogue CW; Cerebral Autoregulation Study Group, Shah A, Zehr K, Cameron D, Conte J, Bienvenu OJ, Gottesman R, Yamaguchi A, Kraut M. Effect of Targeting Mean Arterial Pressure During Cardiopulmonary Bypass by Monitoring Cerebral Autoregulation on Postsurgical Delirium Among Older Patients: A Nested Randomized Clinical Trial. JAMA Surg. 2019 Sep 1;154(9):819-826. doi: 10.1001/jamasurg.2019.1163.
• Brown CH 4th, Probert J, Healy R, Parish M, Nomura Y, Yamaguchi A, Tian J, Zehr K, Mandal K, Kamath V, Neufeld KJ, Hogue CW. Cognitive Decline after Delirium in Patients Undergoing Cardiac Surgery. Anesthesiology. 2018 Sep;129(3):406-416. doi: 10.1097/ALN.0000000000002253.
• Cook DJ, Huston J 3rd, Trenerry MR, Brown RD Jr, Zehr KJ, Sundt TM 3rd. Postcardiac surgical cognitive impairment in the aged using diffusion-weighted magnetic resonance imaging. Ann Thorac Surg. 2007 Apr;83(4):1389-95.
• Czosnyka M, Brady K, Reinhard M, Smielewski P, Steiner LA. Monitoring of cerebrovascular autoregulation: facts, myths, and missing links. Neurocrit Care. 2009;10(3):373-86. doi: 10.1007/s12028-008-9175-7. Epub 2009 Jan 6. Review.
• Evered L, Eckenhoff RG; International Perioperative Cognition Nomenclature Working Group. Perioperative cognitive disorders. Response to: Postoperative delirium portends descent to dementia. Br J Anaesth. 2017 Dec 1;119(6):1241. doi: 10.1093/bja/aex404.
• Gold JP, Charlson ME, Williams-Russo P, Szatrowski TP, Peterson JC, Pirraglia PA, Hartman GS, Yao FS, Hollenberg JP, Barbut D, et al. Improvement of outcomes after coronary artery bypass. A randomized trial comparing intraoperative high versus low mean arterial pressure. J Thorac Cardiovasc Surg. 1995 Nov;110(5):1302-11; discussion 1311-4.
• Goldstein LB, Bertels C, Davis JN. Interrater reliability of the NIH stroke scale. Arch Neurol. 1989 Jun;46(6):660-2.
• Gottesman RF, Grega MA, Bailey MM, Pham LD, Zeger SL, Baumgartner WA, Selnes OA, McKhann GM. Delirium after coronary artery bypass graft surgery and late mortality. Ann Neurol. 2010 Mar;67(3):338-44. doi: 10.1002/ana.21899.
• Gottesman RF, Hillis AE, Grega MA, Borowicz LM Jr, Selnes OA, Baumgartner WA, McKhann GM. Early postoperative cognitive dysfunction and blood pressure during coronary artery bypass graft operation. Arch Neurol. 2007 Aug;64(8):1111-4. Epub 2007 Jun 11.
• Gottesman RF, Sherman PM, Grega MA, Yousem DM, Borowicz LM Jr, Selnes OA, Baumgartner WA, McKhann GM. Watershed strokes after cardiac surgery: diagnosis, etiology, and outcome. Stroke. 2006 Sep;37(9):2306-11. Epub 2006 Jul 20.
• Hogue CW Jr, Palin CA, Arrowsmith JE. Cardiopulmonary bypass management and neurologic outcomes: an evidence-based appraisal of current practices. Anesth Analg. 2006 Jul;103(1):21-37. Review.
• Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. Review. Erratum in: N Engl J Med. 2006 Apr 13;354(15):1655.
• Joshi B, Ono M, Brown C, Brady K, Easley RB, Yenokyan G, Gottesman RF, Hogue CW. Predicting the limits of cerebral autoregulation during cardiopulmonary bypass. Anesth Analg. 2012 Mar;114(3):503-10. doi: 10.1213/ANE.0b013e31823d292a. Epub 2011 Nov 21.
• Kellum JA, Lameire N; KDIGO AKI Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care. 2013 Feb 4;17(1):204. doi: 10.1186/cc11454. Review.
• Kneebone AC, Andrew MJ, Baker RA, Knight JL. Neuropsychologic changes after coronary artery bypass grafting: use of reliable change indices. Ann Thorac Surg. 1998 May;65(5):1320-5.
• Lameire N, Kellum JA; KDIGO AKI Guideline Work Group. Contrast-induced acute kidney injury and renal support for acute kidney injury: a KDIGO summary (Part 2). Crit Care. 2013 Feb 4;17(1):205. doi: 10.1186/cc11455. Review.
• Mathew JP, Mackensen GB, Phillips-Bute B, Grocott HP, Glower DD, Laskowitz DT, Blumenthal JA, Newman MF; Neurologic Outcome Research Group (NORG) of the Duke Heart Center. Randomized, double-blinded, placebo controlled study of neuroprotection with lidocaine in cardiac surgery. Stroke. 2009 Mar;40(3):880-7. doi: 10.1161/STROKEAHA.108.531236. Epub 2009 Jan 22.
• Nomura Y, Faegle R, Hori D, Al-Qamari A, Nemeth AJ, Gottesman R, Yenokyan G, Brown C, Hogue CW. Cerebral Small Vessel, But Not Large Vessel Disease, Is Associated With Impaired Cerebral Autoregulation During Cardiopulmonary Bypass: A Retrospective Cohort Study. Anesth Analg. 2018 Dec;127(6):1314-1322. doi: 10.1213/ANE.0000000000003384.
• Piechnik SK, Yang X, Czosnyka M, Smielewski P, Fletcher SH, Jones AL, Pickard JD. The continuous assessment of cerebrovascular reactivity: a validation of the method in healthy volunteers. Anesth Analg. 1999 Oct;89(4):944-9.
• Siepe M, Pfeiffer T, Gieringer A, Zemann S, Benk C, Schlensak C, Beyersdorf F. Increased systemic perfusion pressure during cardiopulmonary bypass is associated with less early postoperative cognitive dysfunction and delirium. Eur J Cardiothorac Surg. 2011 Jul;40(1):200-7. doi: 10.1016/j.ejcts.2010.11.024. Epub 2010 Dec 18.
• Vedel AG, Holmgaard F, Rasmussen LS, Langkilde A, Paulson OB, Lange T, Thomsen C, Olsen PS, Ravn HB, Nilsson JC. High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial. Circulation. 2018 Apr 24;137(17):1770-1780. doi: 10.1161/CIRCULATIONAHA.117.030308. Epub 2018 Jan 16.
• Vedel AG, Holmgaard F, Siersma V, Langkilde A, Paulson OB, Ravn HB, Nilsson JC, Rasmussen LS. Domain-specific cognitive dysfunction after cardiac surgery. A secondary analysis of a randomized trial. Acta Anaesthesiol Scand. 2019 Jul;63(6):730-738. doi: 10.1111/aas.13343. Epub 2019 Mar 19.

• Responsible Party: Charles W Hogue, Professor, Northwestern University
• ClinicalTrials.gov Identifier: NCT00981474
• Other Study ID Numbers: 680; 1R01HL092259
• First Posted: Sep 22, 2009
• Last Update Posted: Mar 2, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Charles W Hogue, Professor, Northwestern University: cardiac surgery; brain injury; cerebral autoregulation
• Additional relevant MeSH terms: Brain Injuries

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Usual Care Group (Control)	Autoregulation Group
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Period Title: Overall Study
STARTED	228	232
COMPLETED	228	232
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Usual Care Group	Autoregulation Group	Total
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised	Total of all reporting groups
Overall Participants	228	232	460
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.8 (8.0)	70.0 (7.3)	70.4 (7.6)
Sex/Gender, Customized (participants) [Number]
Female	67 29.4%	62 26.7%	129 28%
Male	160 70.2%	170 73.3%	330 71.7%
Missing designation	1 0.4%	0 0%	1 0.2%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	189 82.9%	184 79.3%	273 59.3%
African American	24 10.5%	28 12.1%	52 11.3%
Hispanic	3 1.3%	2 0.9%	5 1.1%
Native American	1 0.4%	3 1.3%	4 0.9%
Asian	0 0%	4 1.7%	4 0.9%
Multiple	0 0%	2 0.9%	2 0.4%
Other	10 4.4%	9 3.9%	19 4.1%
Region of Enrollment (Count of Participants)
United States	228 100%	232 100%	460 100%
Highest Grade of Formal Education (median,[inter-quartile range]) (Years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Years]	14.0	14.5	14
Mini-Mental State Exam (score on a scale (30 good- 0 poor)) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [score on a scale (30 good- 0 poor)]	28	28	28
History of a prior stroke (Count of Participants)
Count of Participants [Participants]	25 11%	19 8.2%	44 9.6%
History of hypertension (Count of Participants)
Count of Participants [Participants]	213 93.4%	207 89.2%	420 91.3%
History of atrial fibrillation (Count of Participants)
Count of Participants [Participants]	53 23.2%	49 21.1%	102 22.2%
History of myocardial infarction (Count of Participants)
Count of Participants [Participants]	65 28.5%	74 31.9%	139 30.2%
History of chronic obstructive lung disease (Count of Participants)
Count of Participants [Participants]	31 13.6%	21 9.1%	52 11.3%
Obstructive sleep apnea (Count of Participants)
Count of Participants [Participants]	41 18%	36 15.5%	77 16.7%
Current tobacco use (Count of Participants)
Count of Participants [Participants]	22 9.6%	24 10.3%	46 10%
History of diabetes (Count of Participants)
Count of Participants [Participants]	101 44.3%	108 46.6%	209 45.4%
History of anemia (Count of Participants)
Count of Participants [Participants]	101 44.3%	108 46.6%	209 45.4%
Logistic EuroSCORE (median,[interquartile range]) (score on a scale 0-2 good >=5 high risk) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [score on a scale 0-2 good >=5 high risk]	5.3	5.08	5.19
Cardiopulmonary bypass duration (Minutes) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Minutes]	107	103	105
Type of surgery (Count of Participants)
Coronary Artery Bypass Graft (CABG)	109 47.8%	117 50.4%	226 49.1%
Coronary Aertery Bypass Graft, Aortic Valve Replacement (CABG/AVR)	35 15.4%	26 11.2%	61 13.3%
Coronary Artery Bypass Graft, Mitral Valve Replacement CABG/MVR)	6 2.6%	9 3.9%	15 3.3%
Coronary Artery Bypass Graft, Aortic Valve Replacement, Mitral Valve Replacement (CABG/AVR/MVR)	3 1.3%	3 1.3%	6 1.3%
Aortic Valve Replacement (AVR)	41 18%	48 20.7%	89 19.3%
Mitral Valve Replacement (MVR)	19 8.3%	22 9.5%	41 8.9%
Aortic Valve Replacement, Mitral Valve Replacement (AVR/MVR)	9 3.9%	5 2.2%	14 3%
Aortic Root Replacement	2 0.9%	2 0.9%	4 0.9%
Coronary Artery Bypass Graft, (CABG) / Aortic Root Replacement	1 0.4%	0 0%	1 0.2%
Transcatheter Aortic Valve Replacement (TAVR)	3 1.3%	0 0%	3 0.7%
Aortic cross-clamp (time in minutes) (Minutes) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Minutes]	73	69	71
Duration of ICU admission (hours) (Hours) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Hours]	44.1	44	44
Duration of hospitalization (days) (Days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Days]	8	7	7
Cardiopulmonary bypass duration (Minutes) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Minutes]	107	103	105

Outcome Measures

1. Primary Outcome

Title	Composite Neurological Outcome of Clinical Stroke or New Ischemic Brain Lesion on Diffusion Weighted MRI or Neurocognitive Dysfunction 4 to 6 Weeks After Surgery.
Description	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

Outcome Measure Data

Analysis Population Description

Subjects who completed neurological testing and MRI testing

Arm/Group Title	Usual Care Group (Control)	Autoregulation Group
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Measure Participants	101	93
Count of Participants [Participants]	79 34.6%	70 30.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care Group (Control), Autoregulation Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.752
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	.96
	Confidence Interval	(2-Sided) 95%; .82 to 1.121
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Postoperative Delirium
Description	Assessed with Confusion Assessment Method or Confusion Assessment Method-ICU along with adjudication by team of experts
Time Frame	Postoperative days 1-4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Usual Care Group (Control)	Autoregulation Group
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Measure Participants	228	232
Count of Participants [Participants]	34 14.9%	19 8.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care Group (Control), Autoregulation Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.053
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	.55
	Confidence Interval	(2-Sided) 95%; .32 to .93
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Multiple Inotropic Drugs>24 Hours After Surgery
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Usual Care Group (Control)	Autoregulation Group
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Measure Participants	228	232
Number [participants]	13 5.7%	6 2.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care Group (Control), Autoregulation Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.149
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	.454
	Confidence Interval	(2-Sided) 95%; .18 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Mechanical Lung Ventilation>24 Hours After Surgery
Description	Subjects need for mechanical lung ventilation more than 24 hours after planned surgical procedure.
Time Frame	Up to 28 days after surgery.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Measure Participants	228	232
Count of Participants [Participants]	22 9.6%	13 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care Group (Control), Autoregulation Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.144
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	.581
	Confidence Interval	(2-Sided) 95%; .30 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Insertion of Intra-aortic Balloon Pump
Description	Procedural insertion of intra-aortic balloon pump within 7 days after surgical procedure
Time Frame	7 days after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Measure Participants	228	232
Count of Participants [Participants]	19 8.3%	14 6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care Group (Control), Autoregulation Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.439
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	.724
	Confidence Interval	(2-Sided) 95%; .37 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Postoperative Atrial Fibrillation
Description	Clinical diagnosis of postoperative atrial fibrillation from date of surgical procedure to discharge from the hospital.
Time Frame	Up to 28 days after surgery.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Measure Participants	228	232
Count of Participants [Participants]	89 39%	79 34.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care Group (Control), Autoregulation Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.311
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	.872
	Confidence Interval	(2-Sided) 95%; .69 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Sepsis
Description	Clinical diagnosis of sepsis from time of surgical procedure to discharge from the hospital.
Time Frame	Up to 28 days after surgery.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Measure Participants	228	232
Count of Participants [Participants]	7 3.1%	2 0.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care Group (Control), Autoregulation Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.103
	Comments
	Method	Fisher Exact
	Comments	Fisher exact test used due to the small number of events.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	.247
	Confidence Interval	(2-Sided) 95%; .005 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Acute Kidney Injury Within 7 Days After Surgery.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Measure Participants	228	232
Count of Participants [Participants]	56 24.6%	62 26.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care Group (Control), Autoregulation Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.608
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.102
	Confidence Interval	(2-Sided) 95%; .81 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	New Renal Replacement Therapy
Description	Subjects requiring new renal replacement therapy prior to discharge from hospital
Time Frame	Up to 28 days after surgery.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Measure Participants	228	232
Count of Participants [Participants]	6 2.6%	4 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care Group (Control), Autoregulation Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.541
	Comments
	Method	Fisher Exact
	Comments	Fisher exact test used due to the small number of events.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	.564
	Confidence Interval	(2-Sided) 95%; .16 to 1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Multisystem Organ Failure After Surgery
Description	Subject diagnosis of multisystem organ failure after surgery.
Time Frame	Up to 28 days after surgery.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Measure Participants	228	232
Count of Participants [Participants]	7 3.1%	2 0.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care Group (Control), Autoregulation Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.103
	Comments
	Method	Fisher Exact
	Comments	Fisher exact test used due to small number of events.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	.247
	Confidence Interval	(2-Sided) 95%; .05 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Mortality
Description	Subject death within 28 days after surgical procedure
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.	Blood pressure management based on cerebral autoregulation data. blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
Measure Participants	228	232
Count of Participants [Participants]	12 5.3%	5 2.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care Group (Control), Autoregulation Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.129
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	.409
	Confidence Interval	(2-Sided) 95%; .15 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Data were collected over a period of 1 year.
Adverse Event Reporting Description	Postoperative complications were based on the Society of Thoracic Surgery National Cardiac Surgery Database definitions (www.sts.org) as safety outcomes.
Arm/Group Title	Usual Care Group (Control)		Autoregulation Group
Arm/Group Description	Blood pressure targets during cardiopulmonary bypass based on institutional standards of empiric management. Control group: Institutional standard of care.		Blood pressure management based on cerebral autoregulation data. Blood pressure maintenance based on cerebral blood flow autoregulation measurement: Blood pressure lowered or raised
All Cause Mortality
	Usual Care Group (Control)		Autoregulation Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/228 (5.3%)		5/232 (2.2%)
Serious Adverse Events
	Usual Care Group (Control)		Autoregulation Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	133/228 (58.3%)		121/232 (52.2%)
Blood and lymphatic system disorders
Sepsis	7/228 (3.1%)	7	2/232 (0.9%)	2
General disorders
Multisystem Organ Failure after Surgery	6/228 (2.6%)	6	4/232 (1.7%)	4
Delayed Neurocognitive Recovery	35/164 (21.3%)	35	27/172 (15.7%)	27
Nervous system disorders
Clinical Stroke	9/228 (3.9%)	9	13/232 (5.6%)	13
New Ischemic Lesions in Brian	47/85 (55.3%)	47	48/79 (60.8%)	48
Renal and urinary disorders
Acute Kidney Injury	56/228 (24.6%)	56	62/232 (26.7%)	62
Other (Not Including Serious) Adverse Events
	Usual Care Group (Control)		Autoregulation Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/228 (14.9%)		19/232 (8.2%)
Psychiatric disorders
Clinically detected delirium	34/228 (14.9%)	34	19/232 (8.2%)	19

Limitations/Caveats

Limitations include missing data including unavoidable missing MRI data (retained temporary cardiac pacemaker leads, patient refusal and discharge prior to scheduled MRI. Patient refusal of completing cognitive tests. Enrollment period of 9 years.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.