Cerebral Autoregulation Monitoring During Cardiac Surgery

Thoracic Surgery Clinical Trial

Official title:

Continuous Cerebral Autoregulation Monitoring to Reduce Brain Injury From Cardiac Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00981474
• Other study ID #: 680
• Secondary ID: 1R01HL092259
• Status: Completed
• Phase: N/A
• Start date: September 1, 2009
• Est. completion date: February 28, 2020

Study information

• Verified date: January 2021
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 460
• Est. completion date: February 28, 2020
• Est. primary completion date: February 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Injuries
• Cardiopulmonary Bypass
• Thoracic Surgery

Intervention

Drug:
• blood pressure maintenance based on cerebral blood flow autoregulation measurement
Blood pressure lowered or raised

Device:
• Control group
Institutional standard of care.

Locations

Country	Name	City	State
United States	Northwestern Memorial Hospital	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (25)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Goldstein LB, Bertels C, Davis JN. Interrater reliability of the NIH stroke scale. Arch Neurol. 1989 Jun;46(6):660-2. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Up to 6 weeks post-operative
Secondary	Postoperative Delirium	Assessed with Confusion Assessment Method or Confusion Assessment Method-ICU along with adjudication by team of experts	Postoperative days 1-4
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.	7 days after surgery
Secondary	Mechanical Lung Ventilation>24 Hours After Surgery	Subjects need for mechanical lung ventilation more than 24 hours after planned surgical procedure.	Up to 28 days after surgery.
Secondary	Insertion of Intra-aortic Balloon Pump	Procedural insertion of intra-aortic balloon pump within 7 days after surgical procedure	7 days after surgery
Secondary	Postoperative Atrial Fibrillation	Clinical diagnosis of postoperative atrial fibrillation from date of surgical procedure to discharge from the hospital.	Up to 28 days after surgery.
Secondary	Sepsis	Clinical diagnosis of sepsis from time of surgical procedure to discharge from the hospital.	Up to 28 days after surgery.
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.	7 days after surgery
Secondary	New Renal Replacement Therapy	Subjects requiring new renal replacement therapy prior to discharge from hospital	Up to 28 days after surgery.
Secondary	Multisystem Organ Failure After Surgery	Subject diagnosis of multisystem organ failure after surgery.	Up to 28 days after surgery.
Secondary	Mortality	Subject death within 28 days after surgical procedure	28 days