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      Non-invasive Assessment of Cerebral Blood Flow and Oxygen Metabolism in Neonates during Hypothermic Cardiopulmonary Bypass: Feasibility and Clinical Implications

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          Abstract

          The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO 2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO 2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO 2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.

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          Arterial and venous contributions to near-infrared cerebral oximetry.

          Cerebral oximetry is a noninvasive bedside technology using near-infrared light to monitor cerebral oxygen saturation (Sco2) in an uncertain mixture of arteries, capillaries, and veins. The present study used frequency domain near-infrared spectroscopy to determine the ratio of arterial and venous blood monitored by cerebral oximetry during normoxia, hypoxia, and hypocapnia. Twenty anesthetized children aged < 8 yr with congenital heart disease of varying arterial oxygen saturation (Sao2) were studied during cardiac catheterization. Sco2, Sao2, and jugular bulb oxygen saturation (Sjo2) were measured by frequency domain near-infrared spectroscopy and blood oximetry at normocapnia room air, normocapnia 100% inspired O2, and hypocapnia room air. Among subject conditions, Sao2 ranged from 68% to 100%, Sjo2 from 27% to 96%, and Sco2 from 29% to 92%. Sco2 was significantly related to Sao2 (y = 0. 85 x -17, r = 0.47), Sjo2 (y = 0.77 x +13, r = 0.70), and the combination (Sco2 = 0.46 Sao2 + 0.56 Sjo2 - 17, R = 0.71). The arterial and venous contribution to cerebral oximetry was 16 +/- 21% and 84 +/- 21%, respectively (where Sco2 = alpha Sao2 + beta Sjo2 with alpha and beta being arterial and venous contributions). The contribution was similar among conditions but differed significantly among subjects (range, approximately 40:60 to approximately 0:100, arterial:venous). Cerebral oximetry monitors an arterial/venous ratio of 16:84, similar in normoxia, hypoxia, and hypocapnia. Because of biologic variation in cerebral arterial/venous ratios, use of a fixed ratio is not a good method to validate the technology.
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            Temporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects.

            Brain injury is common in newborns with congenital heart disease (CHD) requiring neonatal surgery. The purpose of this study is to define the risk factors for preoperative and postoperative brain injuries and their association with functional cardiac anatomic groups. Sixty-two neonates with CHD were studied with preoperative MRI, and 53 received postoperative scans. Clinical and therapeutic characteristics were compared in newborns with and without newly acquired brain injuries. A subset of 16 consecutive patients was monitored with intraoperative cerebral near-infrared spectroscopy. Brain injury was observed in 56% of patients. Preoperative brain injury, seen in 39%, was most commonly stroke and was associated with balloon atrial septostomy (P=0.002). Postoperative brain injury, seen in 35%, was most commonly white matter injury and was particularly common in neonates with single-ventricle physiology and aortic arch obstruction (P=0.001). Risk factors associated with acquired postoperative brain injury included cardiopulmonary bypass (CPB) with regional cerebral perfusion (P=0.01) and lower intraoperative cerebral hemoglobin oxygen saturation during the myocardial ischemic period of CPB (P=0.008). In a multivariable model, new postoperative white matter injury was specifically associated with low mean blood pressure during the first postoperative day (P=0.04). Specific modifiable risk factors can be identified for preoperative and postoperative white matter injury and stroke associated with neonatal surgery for CHD. The high incidence of postoperative injury observed despite new methodologies of CPB indicates the need for ongoing evaluation to optimize neurological outcome.
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              Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high-flow bypass and cerebral oxygenation monitoring.

              New intraparenchymal brain injury on magnetic resonance imaging is observed in 36% to 73% of neonates after cardiac surgery with cardiopulmonary bypass. Brain immaturity in this population is common. We performed brain magnetic resonance imaging before and after neonatal cardiac surgery, using a high-flow cardiopulmonary bypass protocol, hypothesizing that brain injury on magnetic resonance imaging would be associated with brain immaturity. Cardiopulmonary bypass protocol included 150 mL . kg(-1) . min(-1) flows, pH stat management, hematocrit > 30%, and high-flow antegrade cerebral perfusion. Regional brain oxygen saturation was monitored, with a treatment protocol for regional brain oxygen saturation < 50%. Brain magnetic resonance imaging, consisting of T1-, T2-, and diffusion-weighted imaging, and magnetic resonance spectroscopy were performed preoperatively, 7 days postoperatively, and at age 3 to 6 months. Twenty-four of 67 patients (36%) had new postoperative white matter injury, infarction, or hemorrhage, and 16% had new white matter injury. Associations with preoperative brain injury included low brain maturity score (P = .002). Postoperative white matter injury was associated with single-ventricle diagnosis (P = .02), preoperative white matter injury (P < .001), and low brain maturity score (P = .05). Low brain maturity score was also associated with more severe postoperative brain injury (P = .01). Forty-five patients had a third scan, with a 27% incidence of new minor lesions, but 58% of previous lesions had partially or completely resolved. We observed a significant incidence of both pre- and postoperative magnetic resonance imaging abnormality and an association with brain immaturity. Many lesions resolved in the first 6 months after surgery. Timing of delivery and surgery with bypass could affect the risk of brain injury. Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                09 March 2017
                2017
                : 7
                : 44117
                Affiliations
                [1 ]Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children’s Hospital, Harvard Medical School , Boston, Massachusetts, USA
                [2 ]Department of Anesthesiology, Perioperative & Pain Medicine, Boston Children’s Hospital, Harvard Medical School , Boston, Massachusetts, USA
                [3 ]Department of Cardiology, Boston Children’s Hospital, Harvard Medical School , Boston, Massachusetts, USA
                [4 ]Department of Cardiovascular Surgery, Boston Children’s Hospital, Harvard Medical School , Boston, Massachusetts, USA
                [5 ]Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, Massachusetts, USA
                Author notes
                [*]

                These authors contributed equally to this work.

                [†]

                These authors jointly supervised this work.

                Article
                srep44117
                10.1038/srep44117
                5343476
                28276534
                d6aa85de-b16e-4507-82c9-cbc2c5a3fb21
                Copyright © 2017, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 23 June 2016
                : 02 February 2017
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