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Pro: Near-Infrared Spectroscopy Should Be Used for All Cardiopulmonary Bypass
PRO AND CON Lee A. Fleisher, MD Bonnie L. Milas, MD Section Editors
Pro: Near-Infrared Spectroscopy Should Be Used for All Cardiopulmonary Bypass George M. Hoffman, MD
Section Editors’ note: The issue of cerebral oxygenation during cardiopulmonary bypass is controversial. There is significant indication in favor of its use, not least of which is its potential for positive cost-to-benefit ratio. Yet, there remains compelling evidence that, although the technique is promising, the limitations must be acknowledged, including the potential for technical difficulties and the lack of evidence regarding long-term outcomes. With all of this in mind, the Section Editors decided to open the debate regarding the use of cerebral oxygenation monitoring during CPB to a lengthier, more detailed discussion. This Pro/Con will therefore continue the 2-part series begun in the June issue, so that the Journal might give this contentious topic the attention it deserves.
of which can be avoided by continuous delivery of oxygenated blood in sufficient quantity to the brain.3 The importance of neurologic injury has driven the development and application of monitors to enhance detection and direct treatment of conditions associated with brain injury. Because of the prominence of the potential for hypoxic-ischemic injury during CPB, brain oxygen monitoring has enjoyed persistent development efforts, in the form of intracranial oxygen electrodes, jugular venous saturation monitoring, and various forms of transcranial oximetry via near-infrared spectroscopy (NIRS). NIRS offers the advantages of noninvasive continuous regional tissue (organ) oxyhemoglobin saturation monitoring and is available in Food and Drug Administration– approved, commercially produced forms. TECHNICAL OVERVIEW OF NIRS
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EUROLOGIC OUTCOME has surpassed mortality as the primary distinguishing feature of cardiac surgery.1 As recently as the last decade, the incidence of neurologic abnormalities in children undergoing cardiopulmonary bypass (CPB) for congenital cardiac surgery has been at least 6%, and neurologic disability related to CPB in adults affects nearly half a million patients worldwide annually.2 Mechanisms of injury include ischemic, embolic, reperfusion, inflammatory, and excitotoxic. Episodes of global ischemia are frequent during CPB and have been related to both transient and permanent neurocognitive impairment, brain imaging abnormalities, and biochemical and histopathologic signs of injury. Hypoxic-ischemic injury causes both necrotic and apoptotic cell death, both
From the Department of Anesthesiology and Pediatrics, Medical College of Wisconsin, Pediatric Anesthesiology and Critical Care Medicine, Children’s Hospital of Wisconsin, Milwaukee, WI. The author has received an honorarium for speaking from Somanetics, Inc. Address reprint requests to George M. Hoffman, MD, Anesthesiology 735, Children’s Hospital of Wisconsin, 9000 W Wisconsin Ave, Milwaukee, WI 53226. E-mail: [email protected] © 2006 Elsevier Inc. All rights reserved. 1053-0770/00/2004-0024$32.00/0 doi:10.1053/j.jvca.2006.05.019 Key words: near-infrared spectroscopy, cardiopulmonary bypass, neurologic complications, cerebral blood flow, metabolism, cerebral hypoxia 606
NIRS techniques rely on applications of the Beer-Lambert law for measurement of the concentration of a substance according to its absorption of light. As in pulse oximetry, the oxygen saturation of hemoglobin is approximated by the differential absorption of 2 or more wavelengths of light.4 Early ear oximeters were NIRS devices that relied on local heating to enhance regional flow to allow the approximation of arterial saturation.5 NIRS devices measure the average oxyhemoglobin saturation in a field of tissue, rather than in arteries. Because most of the hemoglobin in tissue is on the venous side of the circulation, NIRS provides a venous-weighted oxyhemoglobin saturation index. Photons in the 680- to 800-nm range pass easily through bone, allowing noninvasive transcranial measures of hemoglobin in brain. Transmission spectroscopy, as first applied by Jobsis,6 is limited by the high light intensity required to achieve adequate photon recovery across the skull. Recent developments in brain NIRS have relied on a modified Beer’s law application of reflectance and absorption, with photons injected into the skull to be recovered after traversing an intracranial light path by detectors placed a few centimeters from the emitter.4,7 The average light path is approximately one half the source-detector distance, thus producing a tradeoff between photon recovery and monitored field depth. For brain monitoring, a source detector distance of at least 3 cm is necessary.8 These forms of spatially resolved NIRS make assumptions about the photon path length, which can be minimized but not eliminated by time- or frequency-resolved techniques9 or dual-path subtraction techniques.10 The NIRS-derived oxyhemoglobin relative saturation value
Journal of Cardiothoracic and Vascular Anesthesia, Vol 20, No 4 (August), 2006: pp 606-612
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is fairly robust with a precision of 3% in vitro and 6% in perfused phantom organ models,7,9 whereas the cytochrome oxidase signal is technically difficult and poorly validated in clinical studies.11 Validation in brain models has relied on measurement of carotid and jugular venous saturation, modeling the average field saturation as a mixture of arterial and venous blood and performing between-subjects and withinsubject regressions.10,12 Between-subject precision in these models has been approximately ⫾10 because of variations in optical path length and nonheme absorbers in tissue; however, as a within-subject trend monitor, NIRS devices have achieved precision of about ⫾3%.10 NIRS has been used as a clinical and laboratory aid for 30 years, and much of the knowledge of the cerebral circulation has been enhanced by NIRS applications. Various implementations of NIRS have been developed and reported in the literature. The Hamamatsu NIRO device (Hamamatsu USA, Bridgewater, NJ) measures oxy- and deoxyhemoglobin concentration with a source-detector distance of 4 or 5 cm but requires extensive calibration and exhibits a high failure rate in clinical application, which has limited its acceptance.13,14 The Somanetics INVOS device (Somanetics Corp, Troy, MI) uses a source-detector distance of 4 cm, reporting a relative oxyhemoglobin saturation in a cortical field about 2 cm deep into the skin.7 Thus, NIRS can provide an accurate trend of venousweighted regional brain saturation in a tissue volume of about 1 cm3.15 Comparison of the NIRO and INVOS devices generally shows good correlation for trends and group values but poor agreement for absolute data in an individual patient.13,14,16,17 The Somanetics device incorporates a dual pathlength subtraction algorithm to reject more extracranial signal.18-21 Currently, the only Food and Drug Administration– approved device for brain and somatic tissue oxygen trend monitoring is produced by Somanetics Inc, but other implementations can be expected to emerge. Major objections arise because there are no direct independent measurements to validate in vivo NIRS data. As a highly regional measure, NIRS may not reflect oxygenation status of quasi-hemispheric (jugular venous) or local (micropuncture) fields in all circumstances.22 However, the regional measure provided by NIRS is highly correlated with global and local measures of oxygenation during variations in global cerebral oxygen economy.23-25 NIRS has been used to monitor brain oxygenation during laboratory and clinical investigation for 30 years. During ischemia resulting from induced ventricular fibrillation in adult humans, the NIRS signal declined rapidly, with a progressive increase in ischemic electroencephalographic (EEG) changes at lower brain saturations, yielding an ischemic threshold of about 47%.26 In a neonatal piglet model of circulatory arrest, NIRS provided a graded signal of hypoxia, with lactate production occurring with NIRS signal in the mid-40%, EEG changes occurring in the high 30%, and biochemical failure occurring in the low 30% range.27 During deep hypothermic circulatory arrest (DHCA) in human neonates, the NIRS signal provided evidence of oxygen uptake until about 40 minutes,28 the approximate time threshold for increasing incidence of injury with DHCA.29 Thus, NIRS-derived measures of brain oxygenation provided a graded signal related to hypoxia and metabolic
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change. The measure is not a diagnostic test for ischemic injury in isolation any more than a blood pressure or arterial saturation has definite diagnostic value; however, NIRS can readily be used to detect the individual autoregulatory threshold, making blood pressure management more rational.30 ALTERATIONS OF CEREBRAL BLOOD FLOW AND METABOLISM WITH CPB AND RELATED TECHNIQUES
The linkage between cerebral blood flow and metabolic demand is altered by a host of perioperative disease states, pharmacologic treatments, and perfusion strategies, such that assumptions about the adequacy of cerebral oxygen metabolism based on supply-side parameters are simplistic,31 and cerebral oxygenation cannot be adequately predicted by usual parameters in adults or children.32,33 Hypothermic CPB is associated with alterations in blood flow and metabolism that persist beyond the period of CPB.34,35 Hypothermia reduces cerebral metabolism, providing metabolic protection against global hypoxia36,37 and improving neuropsychologic outcome even with full-flow CPB.38 Hemodilution causes cerebral hyperemia39,40 and increased oxygen extraction if severe.41,42 Hypothermia and anemia cause opposite effects on cerebrovascular resistance, interfering with flowmetabolism coupling39; this impairment of autoregulation contributes to increased cerebrovascular resistance after CPB.43 The pH-stat strategies are generally associated with higher cerebral blood flow during perfusion but probably induce adaptation that results in higher cerebrovascular resistance at any given pCO2 postperfusion. Thus, the effects of any given perfusion strategy on cerebral hemodynamics will be complex, with periods of risk both during and after perfusion.44-48 The weight of the evidence strongly supports global hypoxic mechanisms as a significant cause of neurologic injury during CPB and related techniques. The duration of low-flow CPB or circulatory arrest remains an independent risk factor for neurologic morbidity and death in adults49 and children.29,50,51 DHCA is worse than low-flow CPB.52-55 Low-flow CPB is worse than high-flow CPB. Alpha-stat strategies are associated with more injury than pH-stat strategies,56 and even in adults, hypoxic-ischemic injury is attenuated by pH-stat perfusion around circulatory arrest.57,58 More severe hypercapnic acidosis may attenuate injury in deeper brain regions during low-flow perfusion even with pH-stat strategies.59 Severe hemodilution, even during hypothermia, is worse than moderate hemodilution in animals,60 children,61 and adults.62 Profound hypothermia provides greater protection than moderate hypothermia.63 Neonates may have a particular sensitivity to global hypoxic injury manifesting as periventricular leukomalacia.64 Circulatory arrest may occur as a planned or unavoidable consequence of perfusion strategy. The risk of neurologic injury increases with the duration of arrest, and oxygen availability during arrest is the limiting factor.65 Profound hypothermia causes significant protection against hypoxic injury.66 DHCA induces a dose-related reduction in cerebral metabolism during reperfusion, suggesting injury to cellular energy production mechanisms.67 After DHCA, cerebral oxygenation remains lower than with continuous perfusion techniques, suggesting a prolonged alteration in cerebral flow–metabolism coupling either measured by jugular bulb saturation34 or cerebral NIRS.68
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This delayed reflow can be partly but not completely ameliorated by alteration of pH strategy69 and alteration of inflammatory responses with aprotinin70,71 or thromboxane receptor blockade.72 In an animal model of multiple conditions of global hypoxia on CPB, the NIRS signal was a robust indicator of the development of injury.73,74 The degree of desaturation by NIRS is highly correlated with histologic injury, suggesting that the primary mechanism for posthypoxic injury is the hypoxic injury itself, not reperfusion injury.75 Although a case can be made that under optimal conditions brief circulatory arrest has a low morbidity,76 evidence to support the benefit of continuous oxygen delivery is overwhelming, resulting in use of specialized perfusion techniques to maintain organ oxygenation. All these data support the cerebral oxygen supply/demand ratio as a critical determinant of the susceptibility to hypoxic injury during CPB. Although whole-body oxygen supply-demand relationships can be measured and partially controlled during CPB, regional blood flow is still determined by perfusion pressure and regional resistance. Thus, blood pressure, more so than CPB flow rate, determines cerebral blood flow in adults on CPB,77,78 and management of CPB to avoid a low cerebral perfusion pressure can reduce the incidence of neurologic dysfunction in adults.79,80 However, targeting whole-body oxygen delivery and demand parameters does not adequately prevent the occurrence of ischemic complications of CPB because of undetected technical problems and individual variation in regional flow-metabolism relationships both related and unrelated to anesthetic, surgical, and perfusion techniques.32,33 Thus, organ-specific individualized monitoring has a role in reducing the occurrence of hypoxic conditions associated with injury.81 NIRS AND CLINICAL OUTCOMES
Preoperative brain oxygenation, as assessed by baseline NIRS, provides a marker for patient physiologic risk, both for adverse neurologic outcome and for mortality.82 Multiple periods during CPB are associated with hypoxic risk.44 In a study of infants and children on CPB for congenital cardiac repairs, Austin et al83 found significant changes in NIRS-derived indices of cerebral oxygenation in 70% of patients, which, if not reversed, were associated with a 3-fold increase of obvious postoperative neurologic findings; whereas effective interventions to reverse these changes, guided by NIRS, reduced the incidence of postoperative neurologic sequelae to the same rate as that in patients who did not experience NIRS changes. Failure to achieve full metabolic protection with hypothermia, as detected by brain NIRS, has been related to postoperative neurologic injury in human neonates.84 The occurrence of postoperative neurologic abnormalities in adults undergoing hypothermic CPB has been related to lower brain oxygenation by NIRS.85,86 Treatment of low brain NIRS readings on CPB reduced the incidence of postoperative stroke in adults.87 Thus, NIRS monitoring can identify conditions associated with neurologic risk, and treatment based on NIRS can reduce the occurrence of postoperative abnormalities. Frontal cerebral NIRS is a very close correlate of SvjO2 during hypothermic CPB and DHCA.88 In adults undergoing hypothermic arrest, NIRS nadirs of 35% were associated with high mortality.89 During stable antegrade cerebral perfusion,
NIRS rSO2 showed a very high correlation with oxygen delivery over variable perfusion flow rates.90 Antegrade selective cerebral perfusion reduced brain injury in experimental models compared with DHCA.55,91-93 Substantial controversy over optimal techniques for guiding selective perfusion techniques suggests that patient-specific factors are important.94,95 Management of blood flow and composition during antegrade cerebral perfusion (ACP) requires end-organ data because autoregulatory mechanisms are nearly inoperant, and canula placement is even more critical than during CPB.96,97 During ACP, a sustained drop in brain oxygen saturation is highly related to postoperative stroke.98 Targeting normal brain oxygen saturation values during ACP resulted in a low incidence of neurologic injury.93,99-101 The changes in cerebrovascular resistance with cold perfusion techniques may result in postoperative brain oxygenation deficiency.48 After hypothermic bypass and antegrade cerebral perfusion in neonates, the amount of time with cerebral NIRS less than 45% in the early postoperative period predicted the frequency of new ischemic lesions on magnetic resonance imaging.102 Unilateral stroke causes asymmetry in frontal NIRS values.103 NIRS values correlate with measures of cerebral blood flow during awake endarterectomy.104 More profound and prolonged changes in NIRS measures of brain oxygenation during neuroendovascular procedures occurred in patients who had intraoperative complications, allowing procedural modification to avoid new symptoms.105 The INVOS rSO2 change during internal carotid clamping for endarterectomy correlated well with ipsilateral jugular venous saturation106 and was greater in patients who had preexisting neurologic dysfunction than in those without (⫺18% v ⫺10%).107 EEG changes during clamping have been related to both the relative change and the absolute value of cerebral NIRS saturation.108 Changes in rSO2 are related to the occurrence of new ischemic injury, and predictive models using logistic regression allow selection of rSO2 thresholds for different sensitivity and specificity parameters.109,110 Elderly patients are at greater risk of perioperative stroke and have lower baseline cerebral rSO2.15 A randomized study of elderly patients undergoing major abdominal surgery found that cerebral desaturation was related to both postoperative delirium and prolonged postanesthesia care unit stay and that outcome was improved by targeting intraoperative NIRS at 75% of baseline or greater.111 NIRS AND PROGRAMMATIC IMPROVEMENTS
CPB is a widely used support strategy that can be applied with low incidence of neurologic complications in healthy children112 and can reduce the occurrence of neurologic injury resulting from circulatory failure when used as a rescue or support technique.113 However, the personal and social costs of neurologic injury are huge, and incremental reduction in risk through patient-specific monitoring is justifiable and, arguably, mandated if clinicians attempt to do no harm. NIRS is an old technology whose utility in monitoring brain blood flow and metabolism has been anticipated for more than a decade.114 The technology has achieved sufficient reliability and accuracy to allow clinically useful
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continuous monitoring of brain and other tissue oxygenation, with low enough cost to be a standard addition to the monitoring array for all patients during techniques that carry implicit risk such as CPB.115 Although embolic phenomena contribute to neurologic morbidity in adults,71,116,117 global hypoperfusion remains an important mechanism of injury even during straightforward CPB80; and for comparable physiologic risk, off-pump approaches may still have a lower incidence of neurologic morbidity.118 Thus, even routine CPB must be viewed as a support strategy that places the brain at risk. Because of profound changes in cerebral metabolism and cerebrovascular resistance with different perfusion strategies, the period of CPB-related risk is extensive, and consideration should be given for acute postoperative monitoring also.48,102 In the author’s experience, programmatic application of advanced monitoring has led to progressive improvement in the success of goal-directed strategies for oxygen delivery that parallel improved outcome.33,119 Supply-side variables do not adequately predict episodes of cerebral desaturation during or after CPB.33 Unexpected findings may be revealed by systematic application and analysis of the data.48 The use of advanced neurologic monitoring opens a window on brain oxygenation, thereby revealing the effects of known and unknown physiologic processes on brain metabolism, function, and injury, allowing interventions based on the
combination of treatment pathways and patient-specific factors.81,115,120-122 What are the consequences of implementing NIRS monitoring during CPB? If NIRS provides no consistently useful data, then treatments might be added or withheld from patients randomly, potentially resulting in a different distribution of morbidity but with no change in overall incidence. If NIRS provides largely helpful physiologic data, then a reduction but not elimination of hypoxic brain injury, with a net cost savings, would be expected.123 Only if NIRS provided consistently misleading information would outcomes be adversely affected; thus, the principles of measurement and physiology of cerebral blood flow must be understood when making clinical decisions. NIRS should be viewed not as a diagnostic test but as a physiologic trend monitor providing unique, organ-specific information. NIRS provides a physiologically based, noninvasive, continuous approximation of regional brain oxygen saturation that can identify dangerous conditions and drive interventions to improve outcome. From a variety of studies, brain oxygen saturation by NIRS less than 40% to 45% or a change of 20% from baseline are associated with neurologic injury. NIRS should be part of the standard monitoring array for routine use during CPB to help identify hypoxic conditions and drive both strategic improvements and individualized treatments to reduce neurologic injury.
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12. McCormick PW, Stewart M, Goetting MG, et al: Regional cerebrovascular oxygen saturation measured by optical spectroscopy in humans. Stroke 22:596-602, 1991 13. Gagnon RE, Macnab AJ, Gagnon FA, et al: Comparison of two spatially resolved NIRS oxygenation indices. J Clin Monit Comput 17:385-391, 2002 14. Dullenkopf A, Frey B, Baenziger O, et al: Measurement of cerebral oxygenation state in anaesthetized children using the INVOS 5100 cerebral oximeter. Paediatr Anaesth 13:384-391, 2003 15. Kishi K, Kawaguchi M, Yoshitani K, et al: Influence of patient variables and sensor location on regional cerebral oxygen saturation measured by INVOS 4100 near-infrared spectrophotometers. J Neurosurg Anesthesiol 15:302-306, 2003 16. Thavasothy M, Broadhead M, Elwell C, et al: A comparison of cerebral oxygenation as measured by the NIRO 300 and the INVOS 5100 near-infrared spectrophotometers. Anaesthesia 57:999-1006, 2002 17. Yoshitani K, Kawaguchi M, Tatsumi K, et al: A comparison of the INVOS 4100 and the NIRO 300 near-infrared spectrophotometers. Anesth Analg 94:586-590, 2002 18. Grubhofer G, Tonninger W, Keznickl P, et al: A comparison of the monitors INVOS 3100 and NIRO 500 in detecting changes in cerebral oxygenation. Acta Anaesthesiol Scand 43:470-475, 1999 19. Cho H, Nemoto EM, Sanders M, et al: Comparison of two commercially available near-infrared spectroscopy instruments for cerebral oximetry. Technical note. J Neurosurg 93:351-354, 2000 20. Cho H, Nemoto EM, Yonas H, et al: Cerebral monitoring by means of oximetry and somatosensory evoked potentials during carotid endarterectomy. J Neurosurg 89:533-538, 1998 21. Samra SK, Stanley JC, Zelenock GB, et al: An assessment of contributions made by extracranial tissues during cerebral oximetry. J Neurosurg Anesthesiol 11:1-5, 1999
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22. Nemoto EM, Yonas H, Kassam A: Clinical experience with cerebral oximetry in stroke and cardiac arrest. Crit Care Med 28:10521054, 2000 23. Abdul-Khaliq H, Troitzsch D, Berger F, et al: [Regional transcranial oximetry with near-infrared spectroscopy (NIRS) in comparison with measuring oxygen saturation in the jugular bulb in infants and children for monitoring cerebral oxygenation]. Biomed Tech (Berl) 45:328-332, 2000 24. Rothoerl RD, Faltermeier R, Burger R, et al: Dynamic correlation between tissue PO2 and near-infrared spectroscopy. Acta Neurochir Suppl 81:311-313, 2002 25. Kim MB, Ward DS, Cartwright CR, et al: Estimation of jugular venous O2 saturation from cerebral oximetry or arterial O2 saturation during isocapnic hypoxia. J Clin Monit Comput 16:191-199, 2000 26. Levy WJ, Levin S, Chance B: Near-infrared measurement of cerebral oxygenation. Correlation with electroencephalographic ischemia during ventricular fibrillation. Anesthesiology 83:738-746, 1995 27. Kurth CD, Levy WJ, McCann J: Near-infrared spectroscopy cerebral oxygen saturation thresholds for hypoxia-ischemia in piglets. J Cereb Blood Flow Metab 22:335-341, 2002 28. Kurth CD, Steven JM, Nicolson SC, et al:Kinetics of cerebral deoxygenation during deep hypothermic circulatory arrest in neonates. Anesthesiology 77:656-661, 1992 29. Wypij D, Newburger JW, Rappaport LA, et al: The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment: The Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg 126:1397-1403, 2003 30. Dunham CM, Sosnowski C, Porter JM, et al: Correlation of noninvasive cerebral oximetry with cerebral perfusion in the severe head injured patient: A pilot study. J Trauma 52:40-46, 2002 31. Schell RM, Kern FH, Greeley WJ, et al: Cerebral blood flow and metabolism during cardiopulmonary bypass. Anesth Analg 76:849865, 1993 32. Ganushchak YM, Fransen EJ, Visser C, et al: Neurological complications after coronary artery bypass grafting related to the performance of cardiopulmonary bypass. Chest 125:2196-2205, 2004 33. Hoffman GM: Neurologic monitoring on cardiopulmonary bypass: What are we obligated to do? Ann Thorac Surg 81:S2373-S2380, 2006 34. Greeley WJ, Kern FH, Meliones JN, et al: Effect of deep hypothermia and circulatory arrest on cerebral blood flow and metabolism. Ann Thorac Surg 56:1464-1466, 1993 35. Mezrow CK, Sadeghi AM, Gandsas A, et al: Cerebral effects of low-flow cardiopulmonary bypass and hypothermic circulatory arrest. Ann Thorac Surg 57:532-539, 1994; discussion 539 36. Cook DJ, Oliver WC Jr, Orszulak TA, et al: A prospective, randomized comparison of cerebral venous oxygen saturation during normothermic and hypothermic cardiopulmonary bypass. J Thorac Cardiovasc Surg 107:1020-1028, 1994; discussion 1028-1029 37. Ehrlich MP, McCullough JN, Zhang N, et al: Effect of hypothermia on cerebral blood flow and metabolism in the pig. Ann Thorac Surg 73:191-197, 2002 38. Regragui I, Birdi I, Izzat MB, et al: The effects of cardiopulmonary bypass temperature on neuropsychologic outcome after coronary artery operations: A prospective randomized trial. J Thorac Cardiovasc Surg 112:1036-1045, 1996 39. Cook DJ, Oliver WC Jr, Orszulak TA, et al: Cardiopulmonary bypass temperature, hematocrit, and cerebral oxygen delivery in humans. Ann Thorac Surg 60:1671-1677, 1995 40. Floyd TF, McGarvey M, Ochroch EA, et al: Perioperative changes in cerebral blood flow after cardiac surgery: Influence of anemia and aging. Ann Thorac Surg 76:2037-2042, 2003 41. Hudak ML, Koehler RC, Rosenberg AA, et al: Effect of hematocrit on cerebral blood flow. Am J Physiol 251:H63-H70, 1986
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42. Todd MM, Wu B, Maktabi M, et al: Cerebral blood flow and oxygen delivery during hypoxemia and hemodilution: Role of arterial oxygen content. Am J Physiol 267:H2025-H2031, 1994 43. Abdul-Khaliq H, Uhlig R, Bottcher W, et al: Factors influencing the change in cerebral hemodynamics in pediatric patients during and after corrective cardiac surgery of congenital heart diseases by means of full-flow cardiopulmonary bypass. Perfusion 17:179-185, 2002 44. Daubeney PE, Smith DC, Pilkington SN, et al: Cerebral oxygenation during paediatric cardiac surgery: identification of vulnerable periods using near-infrared spectroscopy. Eur J Cardiothorac Surg 13:370-377, 1998 45. Abdul-Khaliq H, Schubert S, Troitzsch D, et al: Dynamic changes in cerebral oxygenation related to deep hypothermia and circulatory arrest evaluated by near-infrared spectroscopy. Acta Anaesthesiol Scand 45:696-701, 2001 46. Ali MS, Harmer M, Vaughan RS, et al: Changes in cerebral oxygenation during cold (28 degrees C) and warm (34 degrees C) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat) in patients undergoing coronary artery bypass graft surgery. Acta Anaesthesiol Scand 48:837-844, 2004 47. Halstead JC, Spielvogel D, Meier DM, et al: Optimal pH strategy for selective cerebral perfusion. Eur J Cardiothorac Surg 28:266273, 2005; discussion 273 48. Hoffman GM, Stuth EA, Jaquiss RD, et al: Changes in cerebral and somatic oxygenation during stage 1 palliation of hypoplastic left heart syndrome using continuous regional cerebral perfusion. J Thorac Cardiovasc Surg 127:223-233, 2004 49. Czerny M, Fleck T, Zimpfer D, et al: Risk factors of mortality and permanent neurologic injury in patients undergoing ascending aortic and arch repair. J Thorac Cardiovasc Surg 126:1296-1301, 2003 50. Gaynor JW, Nicolson SC, Jarvik GP, et al: Increasing duration of deep hypothermic circulatory arrest is associated with an increased incidence of postoperative electroencephalographic seizures. J Thorac Cardiovasc Surg 130:1278-1286, 2005 51. Limperopoulos C, Majnemer A, Shevell MI, et al: Predictors of developmental disabilities after open heart surgery in young children with congenital heart defects. J Pediatr 141:51-58, 2002 52. Newburger JW, Jonas RA, Wernovsky G, et al: A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery. N Engl J Med 329:1057-1064, 1993 53. Bellinger DC, Jonas RA, Rappaport LA, et al: Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med 332:549-555, 1995 54. Bellinger DC, Wypij D, du Plessis AJ, et al: Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: The Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg 126:1385-1396, 2003 55. Myung RJ, Petko M, Judkins AR, et al: Regional low-flow perfusion improves neurologic outcome compared with deep hypothermic circulatory arrest in neonatal piglets. J Thorac Cardiovasc Surg 127:1051-1056, 2004; discussion 1056-1057 56. Bellinger DC, Wypij D, du Plessis AJ, et al: Developmental and neurologic effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg 121:374-383, 2001 57. Dahlbacka S, Heikkinen J, Kaakinen T, et al: pH-stat versus alpha-stat acid-base management strategy during hypothermic circulatory arrest combined with embolic brain injury. Ann Thorac Surg 79:1316-1325, 2005 58. Pokela M, Dahlbacka S, Biancari F, et al: pH-stat versus alphastat perfusion strategy during experimental hypothermic circulatory arrest: a microdialysis study. Ann Thorac Surg 76:1215-1226, 2003
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59. Loepke AW, Golden JA, McCann JC, et al: Injury pattern of the neonatal brain after hypothermic low-flow cardiopulmonary bypass in a piglet model. Anesth Analg 101:340-348, 2005 60. Shin’oka T, Shum-Tim D, Jonas RA, et al: Higher hematocrit improves cerebral outcome after deep hypothermic circulatory arrest. J Thorac Cardiovasc Surg 112:1610-1620, 1996; discussion 1620-1621 61. Jonas RA, Wypij D, Roth SJ, et al: The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: Results of a randomized trial in infants. J Thorac Cardiovasc Surg 126:1765-1774, 2003 62. Karkouti K, Djaiani G, Borger MA, et al: Low hematocrit during cardiopulmonary bypass is associated with increased risk of perioperative stroke in cardiac surgery. Ann Thorac Surg 80:1381-1387, 2005 63. Kern FH, Ungerleider RM, Schulman SR, et al: Comparing two strategies of cardiopulmonary bypass cooling on jugular venous oxygen saturation in neonates and infants. Ann Thorac Surg 60:1198-1202, 1995 64. Kinney HC, Panigrahy A, Newburger JW, et al: Hypoxic-ischemic brain injury in infants with congenital heart disease dying after cardiac surgery. Acta Neuropathol (Berl) 110:563-578, 2005 65. Sakamoto T, Zurakowski D, Duebener LF, et al: Combination of alpha-stat strategy and hemodilution exacerbates neurologic injury in a survival piglet model with deep hypothermic circulatory arrest. Ann Thorac Surg 73:180-189, 2002; discussion 189-190 66. O’Connor JV, Wilding T, Farmer P, et al: The protective effect of profound hypothermia on the canine central nervous system during one hour of circulatory arrest. Ann Thorac Surg 41:255-259, 1986 67. Mault JR, Ohtake S, Klingensmith ME, et al: Cerebral metabolism and circulatory arrest: Effects of duration and strategies for protection. Ann Thorac Surg 55:57-63, 1993 68. Wardle SP, Yoxall CW, Weindling AM: Cerebral oxygenation during cardiopulmonary bypass. Arch Dis Child 78:26-32, 1998 69. Aoki M, Nomura F, Stromski ME, et al: Effects of pH on brain energetics after hypothermic circulatory arrest. Ann Thorac Surg 55: 1093-1103, 1993 70. Aoki M, Jonas RA, Nomura F, et al: Effects of aprotinin on acute recovery of cerebral metabolism in piglets after hypothermic circulatory arrest. Ann Thorac Surg 58:146-153, 1994 71. Murkin JM: Attenuation of neurologic injury during cardiac surgery. Ann Thorac Surg 72:S1838-S1844, 2001 72. Tsui SS, Kirshbom PM, Davies MJ, et al: Thromboxane A2receptor blockade improves cerebral protection for deep hypothermic circulatory arrest. Eur J Cardiothorac Surg 12:228-235, 1997 73. Hagino I, Anttila V, Zurakowski D, et al: Tissue oxygenation index is a useful monitor of histologic and neurologic outcome after cardiopulmonary bypass in piglets. J Thorac Cardiovasc Surg 130:384392, 2005 74. Anttila V, Hagino I, Zurakowski D, et al: Specific bypass conditions determine safe minimum flow rate. Ann Thorac Surg 80: 1460-1467, 2005 75. Nollert G, Nagashima M, Bucerius J, et al: Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest. II. hypoxic versus free radical injury. J Thorac Cardiovasc Surg 117:11721179, 1999 76. Kunihara T, Grun T, Aicher D, et al: Hypothermic circulatory arrest is not a risk factor for neurologic morbidity in aortic surgery: A propensity score analysis. J Thorac Cardiovasc Surg 130:712-718, 2005 77. Schwartz AE, Sandhu AA, Kaplon RJ, et al: Cerebral blood flow is determined by arterial pressure and not cardiopulmonary bypass flow rate. Ann Thorac Surg 60:165-169, 1995; discussion 169-170 78. Schwartz AE, Minanov O, Stone JG, et al: Phenylephrine increases cerebral blood flow during low-flow hypothermic cardiopulmonary bypass in baboons. Anesthesiology 85:380-384, 1996
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79. Gold JP, Charlson ME, Williams-Russo P, et al: Improvement of outcomes after coronary artery bypass. A randomized trial comparing intraoperative high versus low mean arterial pressure. J Thorac Cardiovasc Surg 110:1302-1311, 1995; discussion 1311-1314 80. van Wermeskerken GK, Lardenoye JW, Hill SE, et al: Intraoperative physiologic variables and outcome in cardiac surgery: Part II. Neurologic outcome. Ann Thorac Surg 69:1077-1083, 2000 81. Saidi N, Murkin JM: Applied neuromonitoring in cardiac surgery: Patient-specific management. Semin Cardiothorac Vasc Anesth 9:17-23, 2005 82. Fenton KN, Freeman K, Glogowski K, et al: The significance of baseline cerebral oxygen saturation in children undergoing congenital heart surgery. Am J Surg 190:260-263, 2005 83. Austin EH 3rd, Edmonds HL Jr, Auden SM, et al: Benefit of neurophysiologic monitoring for pediatric cardiac surgery. J Thorac Cardiovasc Surg 114:707-715, 1997; discussion 715-716 84. Kurth CD, Steven JM, Nicolson SC: Cerebral oxygenation during pediatric cardiac surgery using deep hypothermic circulatory arrest. Anesthesiology 82:74-82, 1995 85. Nollert G, Mohnle P, Tassani-Prell P, et al: Postoperative neuropsychological dysfunction and cerebral oxygenation during cardiac surgery. Thorac Cardiovasc Surg 43:260-264, 1995 86. Yao FS, Tseng CC, Ho CY, et al: Cerebral oxygen desaturation is associated with early postoperative neuropsychological dysfunction in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth 18:552-558, 2004 87. Goldman S, Sutter F, Ferdinand F, et al: Optimizing intraoperative cerebral oxygen delivery using noninvasive cerebral oximetry decreases the incidence of stroke for cardiac surgical patients. Heart Surg Forum 7:E376-E381, 2004 88. Abdul-Khaliq H, Troitzsch D, Schubert S, et al: Cerebral oxygen monitoring during neonatal cardiopulmonary bypass and deep hypothermic circulatory arrest. Thorac Cardiovasc Surg 50:77-81, 2002 89. Ausman JI, McCormick PW, Stewart M, et al: Cerebral oxygen metabolism during hypothermic circulatory arrest in humans. J Neurosurg 79:810-815, 1993 90. Yu Q, Sun L, Chang Q, et al: Monitoring of antegrade selective cerebral perfusion for aortic arch surgery with transcranial Doppler ultrasonography and near-infrared spectroscopy. Chin Med J (Engl) 114:257-261, 2001 91. Ye J, Yang L, Del Bigio MR, et al: Neuronal damage after hypothermic circulatory arrest and retrograde cerebral perfusion in the pig. Ann Thorac Surg 61:1316-1322, 1996 92. Hagl C, Khaladj N, Peterss S, et al: Hypothermic circulatory arrest with and without cold selective antegrade cerebral perfusion: impact on neurological recovery and tissue metabolism in an acute porcine model. Eur J Cardiothorac Surg 26:73-80, 2004 93. Kilpack VD, Stayer SA, McKenzie ED, et al: Limiting circulatory arrest using regional low-flow perfusion. J Extra Corpor Technol 36:133-138, 2004 94. Ueno K, Takamoto S, Miyairi T, et al: Arterial blood gas management in retrograde cerebral perfusion: The importance of carbon dioxide. Eur J Cardiothorac Surg 20:979-985, 2001 95. Andropoulos DB, Stayer SA, McKenzie ED, et al: Novel cerebral physiologic monitoring to guide low-flow cerebral perfusion during neonatal aortic arch reconstruction. J Thorac Cardiovasc Surg 125:491-499, 2003 96. Hofer A, Haizinger B, Geiselseder G, et al: Monitoring of selective antegrade cerebral perfusion using near-infrared spectroscopy in neonatal aortic arch surgery. Eur J Anaesthesiol 22:293-298, 2005 97. Orihashi K, Sueda T, Okada K, et al: Malposition of selective cerebral perfusion catheter is not a rare event. Eur J Cardiothorac Surg 27:644-648, 2005
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98. Orihashi K, Sueda T, Okada K, et al: Near-infrared spectroscopy for monitoring cerebral ischemia during selective cerebral perfusion. Eur J Cardiothorac Surg 26:907-911, 2004 99. Yamashita K, Kazui T, Terada H, et al: Cerebral oxygenation monitoring for total arch replacement using selective cerebral perfusion. Ann Thorac Surg 72:503-508, 2001 100. Andropoulos DB, Diaz LK, Fraser CD Jr, et al: Is bilateral monitoring of cerebral oxygen saturation necessary during neonatal aortic arch reconstruction? Anesth Analg 98:1267-1272, 2004 101. Olsson C, Thelin S: Regional cerebral saturation monitoring with near-infrared spectroscopy during selective antegrade cerebral perfusion: Diagnostic performance and relationship to postoperative stroke. J Thorac Cardiovasc Surg 131:371-379, 2006 102. Dent CL, Spaeth JP, Jones BV, et al: Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion. J Thorac Cardiovasc Surg 131:190-197, 2006 103. Demet G, Talip A, Nevzat U, et al: The evaluation of cerebral oxygenation by oximetry in patients with ischaemic stroke. J Postgrad Med 46:70-74, 2000 104. Carlin RE, McGraw DJ, Calimlim JR, et al: The use of nearinfrared cerebral oximetry in awake carotid endarterectomy. J Clin Anesth 10:109-113, 1998 105. Hernandez-Avila G, Dujovny M, Slavin KV, et al: Use of transcranial cerebral oximetry to monitor regional cerebral oxygen saturation during neuroendovascular procedures. AJNR Am J Neuroradiol 16:1618-1625, 1995 106. Schindler E, Zickmann B, Muller M, et al: Cerebral oximetry by infrared spectroscopy in comparison with continuous measurement of oxygen saturation of the jugular vein bulb in interventions of the internal carotid artery. Vasa 24:168-175, 1995 107. Cuadra SA, Zwerling JS, Feuerman M, et al: Cerebral oximetry monitoring during carotid endarterectomy: Effect of carotid clamping and shunting. Vasc Endovascular Surg 37:407-413, 2003 108. Hirofumi O, Otone E, Hiroshi I, et al: The effectiveness of regional cerebral oxygen saturation monitoring using near-infrared spectroscopy in carotid endarterectomy. J Clin Neurosci 10:79-83, 2003 109. Samra SK, Dy EA, Welch K, et al: Evaluation of a cerebral oximeter as a monitor of cerebral ischemia during carotid endarterectomy. Anesthesiology 93:964 –370, 2000 110. Mille T, Tachimiri ME, Klersy C, et al: Near-infrared spectroscopy monitoring during carotid endarterectomy: Which threshold value is critical? Eur J Vasc Endovasc Surg 2004;27:646-650, 2004
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111. Casati A, Fanelli G, Pietropaoli P, et al: Continuous monitoring of cerebral oxygen saturation in elderly patients undergoing major abdominal surgery minimizes brain exposure to potential hypoxia. Anesth Analg 101:740-747, 2005 112. Mahle WT, Lundine K, Kanter KR, et al: The short-term effects of cardiopulmonary bypass on neurologic function in children and young adults. Eur J Cardiothorac Surg 26:920-925, 2004 113. Ungerleider RM, Shen I, Yeh T, et al: Routine mechanical ventricular assist following the Norwood procedure—Improved neurologic outcome and excellent hospital survival. Ann Thorac Surg 77: 18-22, 2004 114. Kern FH, Schell RM, Greeley WJ: Cerebral monitoring during cardiopulmonary bypass in children. J Neurosurg Anesthesiol 5:213217, 1993 115. Edmonds HL Jr, Ganzel BL, Austin EH 3rd: Cerebral oximetry for cardiac and vascular surgery. Semin Cardiothorac Vasc Anesth 8:147-166, 2004 116. Murkin JM: Etiology and incidence of brain dysfunction after cardiac surgery. J Cardiothorac Vasc Anesth 13:12-17, 1999; discussion 36-37 117. Nussmeier NA: A review of risk factors for adverse neurologic outcome after cardiac surgery. J Extra Corpor Technol 34:4-10, 2002 118. Zangrillo A, Crescenzi G, Landoni G, et al: Off-pump coronary artery bypass grafting reduces postoperative neurologic complications. J Cardiothorac Vasc Anesth 19:193-196, 2005 119. Tweddell JS, Hoffman GM, Mussatto KA, et al: Improved survival of patients undergoing palliation of hypoplastic left heart syndrome: Lessons learned from 115 consecutive patients. Circulation 106:I82-I89, 2002 120. Stump DA, Jones TJ, Rorie KD: Neurophysiologic monitoring and outcomes in cardiovascular surgery. J Cardiothorac Vasc Anesth 13:600-613, 1999 121. Murkin JM: Applied neuromonitoring and improving CNS outcomes. Semin Cardiothorac Vasc Anesth 9:139-142, 2005 122. Nugent WC: Building and supporting sustainable improvement in cardiac surgery: The Northern New England experience. Semin Cardiothorac Vasc Anesth 9:115-118, 2005 123. Taillefer MC, Denault AY: Cerebral near-infrared spectroscopy in adult heart surgery: Systematic review of its clinical efficacy. Can J Anaesth 52:79-87, 2005
Pro: Near-Infrared Spectroscopy Should Be Used for All Cardiopulmonary Bypass George M. Hoffman, MD
Section Editors’ note: The issue of cerebral oxygenation during cardiopulmonary bypass is controversial. There is significant indication in favor of its use, not least of which is its potential for positive cost-to-benefit ratio. Yet, there remains compelling evidence that, although the technique is promising, the limitations must be acknowledged, including the potential for technical difficulties and the lack of evidence regarding long-term outcomes. With all of this in mind, the Section Editors decided to open the debate regarding the use of cerebral oxygenation monitoring during CPB to a lengthier, more detailed discussion. This Pro/Con will therefore continue the 2-part series begun in the June issue, so that the Journal might give this contentious topic the attention it deserves.
of which can be avoided by continuous delivery of oxygenated blood in sufficient quantity to the brain.3 The importance of neurologic injury has driven the development and application of monitors to enhance detection and direct treatment of conditions associated with brain injury. Because of the prominence of the potential for hypoxic-ischemic injury during CPB, brain oxygen monitoring has enjoyed persistent development efforts, in the form of intracranial oxygen electrodes, jugular venous saturation monitoring, and various forms of transcranial oximetry via near-infrared spectroscopy (NIRS). NIRS offers the advantages of noninvasive continuous regional tissue (organ) oxyhemoglobin saturation monitoring and is available in Food and Drug Administration– approved, commercially produced forms. TECHNICAL OVERVIEW OF NIRS
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EUROLOGIC OUTCOME has surpassed mortality as the primary distinguishing feature of cardiac surgery.1 As recently as the last decade, the incidence of neurologic abnormalities in children undergoing cardiopulmonary bypass (CPB) for congenital cardiac surgery has been at least 6%, and neurologic disability related to CPB in adults affects nearly half a million patients worldwide annually.2 Mechanisms of injury include ischemic, embolic, reperfusion, inflammatory, and excitotoxic. Episodes of global ischemia are frequent during CPB and have been related to both transient and permanent neurocognitive impairment, brain imaging abnormalities, and biochemical and histopathologic signs of injury. Hypoxic-ischemic injury causes both necrotic and apoptotic cell death, both
From the Department of Anesthesiology and Pediatrics, Medical College of Wisconsin, Pediatric Anesthesiology and Critical Care Medicine, Children’s Hospital of Wisconsin, Milwaukee, WI. The author has received an honorarium for speaking from Somanetics, Inc. Address reprint requests to George M. Hoffman, MD, Anesthesiology 735, Children’s Hospital of Wisconsin, 9000 W Wisconsin Ave, Milwaukee, WI 53226. E-mail: [email protected] © 2006 Elsevier Inc. All rights reserved. 1053-0770/00/2004-0024$32.00/0 doi:10.1053/j.jvca.2006.05.019 Key words: near-infrared spectroscopy, cardiopulmonary bypass, neurologic complications, cerebral blood flow, metabolism, cerebral hypoxia 606
NIRS techniques rely on applications of the Beer-Lambert law for measurement of the concentration of a substance according to its absorption of light. As in pulse oximetry, the oxygen saturation of hemoglobin is approximated by the differential absorption of 2 or more wavelengths of light.4 Early ear oximeters were NIRS devices that relied on local heating to enhance regional flow to allow the approximation of arterial saturation.5 NIRS devices measure the average oxyhemoglobin saturation in a field of tissue, rather than in arteries. Because most of the hemoglobin in tissue is on the venous side of the circulation, NIRS provides a venous-weighted oxyhemoglobin saturation index. Photons in the 680- to 800-nm range pass easily through bone, allowing noninvasive transcranial measures of hemoglobin in brain. Transmission spectroscopy, as first applied by Jobsis,6 is limited by the high light intensity required to achieve adequate photon recovery across the skull. Recent developments in brain NIRS have relied on a modified Beer’s law application of reflectance and absorption, with photons injected into the skull to be recovered after traversing an intracranial light path by detectors placed a few centimeters from the emitter.4,7 The average light path is approximately one half the source-detector distance, thus producing a tradeoff between photon recovery and monitored field depth. For brain monitoring, a source detector distance of at least 3 cm is necessary.8 These forms of spatially resolved NIRS make assumptions about the photon path length, which can be minimized but not eliminated by time- or frequency-resolved techniques9 or dual-path subtraction techniques.10 The NIRS-derived oxyhemoglobin relative saturation value
Journal of Cardiothoracic and Vascular Anesthesia, Vol 20, No 4 (August), 2006: pp 606-612
PRO AND CON
is fairly robust with a precision of 3% in vitro and 6% in perfused phantom organ models,7,9 whereas the cytochrome oxidase signal is technically difficult and poorly validated in clinical studies.11 Validation in brain models has relied on measurement of carotid and jugular venous saturation, modeling the average field saturation as a mixture of arterial and venous blood and performing between-subjects and withinsubject regressions.10,12 Between-subject precision in these models has been approximately ⫾10 because of variations in optical path length and nonheme absorbers in tissue; however, as a within-subject trend monitor, NIRS devices have achieved precision of about ⫾3%.10 NIRS has been used as a clinical and laboratory aid for 30 years, and much of the knowledge of the cerebral circulation has been enhanced by NIRS applications. Various implementations of NIRS have been developed and reported in the literature. The Hamamatsu NIRO device (Hamamatsu USA, Bridgewater, NJ) measures oxy- and deoxyhemoglobin concentration with a source-detector distance of 4 or 5 cm but requires extensive calibration and exhibits a high failure rate in clinical application, which has limited its acceptance.13,14 The Somanetics INVOS device (Somanetics Corp, Troy, MI) uses a source-detector distance of 4 cm, reporting a relative oxyhemoglobin saturation in a cortical field about 2 cm deep into the skin.7 Thus, NIRS can provide an accurate trend of venousweighted regional brain saturation in a tissue volume of about 1 cm3.15 Comparison of the NIRO and INVOS devices generally shows good correlation for trends and group values but poor agreement for absolute data in an individual patient.13,14,16,17 The Somanetics device incorporates a dual pathlength subtraction algorithm to reject more extracranial signal.18-21 Currently, the only Food and Drug Administration– approved device for brain and somatic tissue oxygen trend monitoring is produced by Somanetics Inc, but other implementations can be expected to emerge. Major objections arise because there are no direct independent measurements to validate in vivo NIRS data. As a highly regional measure, NIRS may not reflect oxygenation status of quasi-hemispheric (jugular venous) or local (micropuncture) fields in all circumstances.22 However, the regional measure provided by NIRS is highly correlated with global and local measures of oxygenation during variations in global cerebral oxygen economy.23-25 NIRS has been used to monitor brain oxygenation during laboratory and clinical investigation for 30 years. During ischemia resulting from induced ventricular fibrillation in adult humans, the NIRS signal declined rapidly, with a progressive increase in ischemic electroencephalographic (EEG) changes at lower brain saturations, yielding an ischemic threshold of about 47%.26 In a neonatal piglet model of circulatory arrest, NIRS provided a graded signal of hypoxia, with lactate production occurring with NIRS signal in the mid-40%, EEG changes occurring in the high 30%, and biochemical failure occurring in the low 30% range.27 During deep hypothermic circulatory arrest (DHCA) in human neonates, the NIRS signal provided evidence of oxygen uptake until about 40 minutes,28 the approximate time threshold for increasing incidence of injury with DHCA.29 Thus, NIRS-derived measures of brain oxygenation provided a graded signal related to hypoxia and metabolic
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change. The measure is not a diagnostic test for ischemic injury in isolation any more than a blood pressure or arterial saturation has definite diagnostic value; however, NIRS can readily be used to detect the individual autoregulatory threshold, making blood pressure management more rational.30 ALTERATIONS OF CEREBRAL BLOOD FLOW AND METABOLISM WITH CPB AND RELATED TECHNIQUES
The linkage between cerebral blood flow and metabolic demand is altered by a host of perioperative disease states, pharmacologic treatments, and perfusion strategies, such that assumptions about the adequacy of cerebral oxygen metabolism based on supply-side parameters are simplistic,31 and cerebral oxygenation cannot be adequately predicted by usual parameters in adults or children.32,33 Hypothermic CPB is associated with alterations in blood flow and metabolism that persist beyond the period of CPB.34,35 Hypothermia reduces cerebral metabolism, providing metabolic protection against global hypoxia36,37 and improving neuropsychologic outcome even with full-flow CPB.38 Hemodilution causes cerebral hyperemia39,40 and increased oxygen extraction if severe.41,42 Hypothermia and anemia cause opposite effects on cerebrovascular resistance, interfering with flowmetabolism coupling39; this impairment of autoregulation contributes to increased cerebrovascular resistance after CPB.43 The pH-stat strategies are generally associated with higher cerebral blood flow during perfusion but probably induce adaptation that results in higher cerebrovascular resistance at any given pCO2 postperfusion. Thus, the effects of any given perfusion strategy on cerebral hemodynamics will be complex, with periods of risk both during and after perfusion.44-48 The weight of the evidence strongly supports global hypoxic mechanisms as a significant cause of neurologic injury during CPB and related techniques. The duration of low-flow CPB or circulatory arrest remains an independent risk factor for neurologic morbidity and death in adults49 and children.29,50,51 DHCA is worse than low-flow CPB.52-55 Low-flow CPB is worse than high-flow CPB. Alpha-stat strategies are associated with more injury than pH-stat strategies,56 and even in adults, hypoxic-ischemic injury is attenuated by pH-stat perfusion around circulatory arrest.57,58 More severe hypercapnic acidosis may attenuate injury in deeper brain regions during low-flow perfusion even with pH-stat strategies.59 Severe hemodilution, even during hypothermia, is worse than moderate hemodilution in animals,60 children,61 and adults.62 Profound hypothermia provides greater protection than moderate hypothermia.63 Neonates may have a particular sensitivity to global hypoxic injury manifesting as periventricular leukomalacia.64 Circulatory arrest may occur as a planned or unavoidable consequence of perfusion strategy. The risk of neurologic injury increases with the duration of arrest, and oxygen availability during arrest is the limiting factor.65 Profound hypothermia causes significant protection against hypoxic injury.66 DHCA induces a dose-related reduction in cerebral metabolism during reperfusion, suggesting injury to cellular energy production mechanisms.67 After DHCA, cerebral oxygenation remains lower than with continuous perfusion techniques, suggesting a prolonged alteration in cerebral flow–metabolism coupling either measured by jugular bulb saturation34 or cerebral NIRS.68
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This delayed reflow can be partly but not completely ameliorated by alteration of pH strategy69 and alteration of inflammatory responses with aprotinin70,71 or thromboxane receptor blockade.72 In an animal model of multiple conditions of global hypoxia on CPB, the NIRS signal was a robust indicator of the development of injury.73,74 The degree of desaturation by NIRS is highly correlated with histologic injury, suggesting that the primary mechanism for posthypoxic injury is the hypoxic injury itself, not reperfusion injury.75 Although a case can be made that under optimal conditions brief circulatory arrest has a low morbidity,76 evidence to support the benefit of continuous oxygen delivery is overwhelming, resulting in use of specialized perfusion techniques to maintain organ oxygenation. All these data support the cerebral oxygen supply/demand ratio as a critical determinant of the susceptibility to hypoxic injury during CPB. Although whole-body oxygen supply-demand relationships can be measured and partially controlled during CPB, regional blood flow is still determined by perfusion pressure and regional resistance. Thus, blood pressure, more so than CPB flow rate, determines cerebral blood flow in adults on CPB,77,78 and management of CPB to avoid a low cerebral perfusion pressure can reduce the incidence of neurologic dysfunction in adults.79,80 However, targeting whole-body oxygen delivery and demand parameters does not adequately prevent the occurrence of ischemic complications of CPB because of undetected technical problems and individual variation in regional flow-metabolism relationships both related and unrelated to anesthetic, surgical, and perfusion techniques.32,33 Thus, organ-specific individualized monitoring has a role in reducing the occurrence of hypoxic conditions associated with injury.81 NIRS AND CLINICAL OUTCOMES
Preoperative brain oxygenation, as assessed by baseline NIRS, provides a marker for patient physiologic risk, both for adverse neurologic outcome and for mortality.82 Multiple periods during CPB are associated with hypoxic risk.44 In a study of infants and children on CPB for congenital cardiac repairs, Austin et al83 found significant changes in NIRS-derived indices of cerebral oxygenation in 70% of patients, which, if not reversed, were associated with a 3-fold increase of obvious postoperative neurologic findings; whereas effective interventions to reverse these changes, guided by NIRS, reduced the incidence of postoperative neurologic sequelae to the same rate as that in patients who did not experience NIRS changes. Failure to achieve full metabolic protection with hypothermia, as detected by brain NIRS, has been related to postoperative neurologic injury in human neonates.84 The occurrence of postoperative neurologic abnormalities in adults undergoing hypothermic CPB has been related to lower brain oxygenation by NIRS.85,86 Treatment of low brain NIRS readings on CPB reduced the incidence of postoperative stroke in adults.87 Thus, NIRS monitoring can identify conditions associated with neurologic risk, and treatment based on NIRS can reduce the occurrence of postoperative abnormalities. Frontal cerebral NIRS is a very close correlate of SvjO2 during hypothermic CPB and DHCA.88 In adults undergoing hypothermic arrest, NIRS nadirs of 35% were associated with high mortality.89 During stable antegrade cerebral perfusion,
NIRS rSO2 showed a very high correlation with oxygen delivery over variable perfusion flow rates.90 Antegrade selective cerebral perfusion reduced brain injury in experimental models compared with DHCA.55,91-93 Substantial controversy over optimal techniques for guiding selective perfusion techniques suggests that patient-specific factors are important.94,95 Management of blood flow and composition during antegrade cerebral perfusion (ACP) requires end-organ data because autoregulatory mechanisms are nearly inoperant, and canula placement is even more critical than during CPB.96,97 During ACP, a sustained drop in brain oxygen saturation is highly related to postoperative stroke.98 Targeting normal brain oxygen saturation values during ACP resulted in a low incidence of neurologic injury.93,99-101 The changes in cerebrovascular resistance with cold perfusion techniques may result in postoperative brain oxygenation deficiency.48 After hypothermic bypass and antegrade cerebral perfusion in neonates, the amount of time with cerebral NIRS less than 45% in the early postoperative period predicted the frequency of new ischemic lesions on magnetic resonance imaging.102 Unilateral stroke causes asymmetry in frontal NIRS values.103 NIRS values correlate with measures of cerebral blood flow during awake endarterectomy.104 More profound and prolonged changes in NIRS measures of brain oxygenation during neuroendovascular procedures occurred in patients who had intraoperative complications, allowing procedural modification to avoid new symptoms.105 The INVOS rSO2 change during internal carotid clamping for endarterectomy correlated well with ipsilateral jugular venous saturation106 and was greater in patients who had preexisting neurologic dysfunction than in those without (⫺18% v ⫺10%).107 EEG changes during clamping have been related to both the relative change and the absolute value of cerebral NIRS saturation.108 Changes in rSO2 are related to the occurrence of new ischemic injury, and predictive models using logistic regression allow selection of rSO2 thresholds for different sensitivity and specificity parameters.109,110 Elderly patients are at greater risk of perioperative stroke and have lower baseline cerebral rSO2.15 A randomized study of elderly patients undergoing major abdominal surgery found that cerebral desaturation was related to both postoperative delirium and prolonged postanesthesia care unit stay and that outcome was improved by targeting intraoperative NIRS at 75% of baseline or greater.111 NIRS AND PROGRAMMATIC IMPROVEMENTS
CPB is a widely used support strategy that can be applied with low incidence of neurologic complications in healthy children112 and can reduce the occurrence of neurologic injury resulting from circulatory failure when used as a rescue or support technique.113 However, the personal and social costs of neurologic injury are huge, and incremental reduction in risk through patient-specific monitoring is justifiable and, arguably, mandated if clinicians attempt to do no harm. NIRS is an old technology whose utility in monitoring brain blood flow and metabolism has been anticipated for more than a decade.114 The technology has achieved sufficient reliability and accuracy to allow clinically useful
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continuous monitoring of brain and other tissue oxygenation, with low enough cost to be a standard addition to the monitoring array for all patients during techniques that carry implicit risk such as CPB.115 Although embolic phenomena contribute to neurologic morbidity in adults,71,116,117 global hypoperfusion remains an important mechanism of injury even during straightforward CPB80; and for comparable physiologic risk, off-pump approaches may still have a lower incidence of neurologic morbidity.118 Thus, even routine CPB must be viewed as a support strategy that places the brain at risk. Because of profound changes in cerebral metabolism and cerebrovascular resistance with different perfusion strategies, the period of CPB-related risk is extensive, and consideration should be given for acute postoperative monitoring also.48,102 In the author’s experience, programmatic application of advanced monitoring has led to progressive improvement in the success of goal-directed strategies for oxygen delivery that parallel improved outcome.33,119 Supply-side variables do not adequately predict episodes of cerebral desaturation during or after CPB.33 Unexpected findings may be revealed by systematic application and analysis of the data.48 The use of advanced neurologic monitoring opens a window on brain oxygenation, thereby revealing the effects of known and unknown physiologic processes on brain metabolism, function, and injury, allowing interventions based on the
combination of treatment pathways and patient-specific factors.81,115,120-122 What are the consequences of implementing NIRS monitoring during CPB? If NIRS provides no consistently useful data, then treatments might be added or withheld from patients randomly, potentially resulting in a different distribution of morbidity but with no change in overall incidence. If NIRS provides largely helpful physiologic data, then a reduction but not elimination of hypoxic brain injury, with a net cost savings, would be expected.123 Only if NIRS provided consistently misleading information would outcomes be adversely affected; thus, the principles of measurement and physiology of cerebral blood flow must be understood when making clinical decisions. NIRS should be viewed not as a diagnostic test but as a physiologic trend monitor providing unique, organ-specific information. NIRS provides a physiologically based, noninvasive, continuous approximation of regional brain oxygen saturation that can identify dangerous conditions and drive interventions to improve outcome. From a variety of studies, brain oxygen saturation by NIRS less than 40% to 45% or a change of 20% from baseline are associated with neurologic injury. NIRS should be part of the standard monitoring array for routine use during CPB to help identify hypoxic conditions and drive both strategic improvements and individualized treatments to reduce neurologic injury.
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