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Courtney A. Hardy, MD
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Co-Editors
Mark Twite, MD, BCh
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Stuart R. Hall, MD
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Call for CCAS Directors Nominations
Preview of the CCAS
Program at Pediatric Anesthesiology 2010
An Interesting Case
The Anesthetic and Cardiopulmonary Bypass Management of an 800g Premature Neonate for the Arterial Switch Operation
PRO vs. CON
Should NIRS Monitoring Be Considered Standard of Care on Every Case Involving CPB?
Literature Reviews
1. Perioperative stroke in infants undergoing open heart operations for congenital heart disease.
2.
Brain maturation is delayed in infants with complex congenital heart defects.
PRO: Cerebral Near-Infrared Spectroscopy SHOULD Become Standard of Care for Pediatric Cardiac Surgery with Cardiopulmonary Bypass
By Dean B. Andropoulos, MD, MHCM
Chief of Anesthesiology
Texas Children's Hospital
Professor, Anesthesiology and Pediatrics
Baylor College of Medicine
According to the American Society of Anesthesiologists, “Standards provide rules or minimum requirements for clinical practice. They are regarded as generally accepted principles of patient management. Standards may be modified only under unusual circumstances, e.g., extreme emergencies or unavailability of equipment.” (1) An example is the “Standards for Basic Anesthesia Monitoring,” mandating that oxygenation, ventilation, circulation, and temperature be monitored continuously by various methods. Should the monitoring of cerebral oxygenation during pediatric cardiac surgery with CPB become a standard of care, using this definition? In order to become a standard of care, a new monitoring technology must satisfy several requirements: 1. It should measure a real parameter with well established technology; 2. the parameter measured should be associated with an abnormal physiological state that will lead to organ injury and eventually death; 3. the parameter should be a unique value not measured by other monitors, and respond quickly to intervention; 4. the parameter should be reliable, real-time, and ideally either non-invasive, or if invasive the benefit of monitoring outweigh any risk; and 5. measuring and correcting the parameter should ideally lead to measurable improved outcomes in patients, i.e. reduced mortality, ICU stay, neurological injury. NIRS fulfills all of these criteria, and so in this author’s view SHOULD become a standard of care.
NIRS Measures a Real Physiological Parameter with Well Established Technology
Near-infrared spectroscopy (NIRS) is a non-invasive optical technique used to monitor brain tissue oxygenation (rSO2). Most devices utilize 2-4 wavelengths of infrared light at 700-1000 nm, where oxygenated and deoxygenated hemoglobin have distinct absorption spectra. (2-4). Commercially available devices measure the concentration of oxy- and de-oxyhemoglobin, using variants of the Beer-Lambert equation: 
where I0 is the intensity of light before passing through the tissue, I is the intensity of light after passing through the tissue, and the ratio of I/I0 is absorption. Absorption of the near-infrared light depends on the optical path length (L), the concentration of the chromophore in that path (C), and the molar absorptivity of the chromophore at the specific wavelength used (ελ).
Cerebral oximetry assumes that 75% of the cerebral blood volume in the light path is venous, and 25% is arterial. This 75:25 ratio is derived from theoretical anatomical models. Watzman et al.(5) attempted to verify this index in children with congenital heart disease by measuring jugular venous bulb saturation and arterial saturation, and comparing it to cerebral saturation measured with frequency-domain near infrared spectroscopy. The actual ratio in patients varied widely, but averaged 85:15. This well established technology firmly grounded in a physiologic basis first described in 1977 by Jobsis fulfills the first requirement for a new monitoring technology.(5)
Low NIRS Values are Associated with An Abnormal Physiological State that will Lead to Brain Injury and Eventually Death
There are now a number of elegant animal models that produce experimental conditions of graded cerebral hypoxemia that cannot be reproduced clinically, demonstrating that NIRS measures real cerebral hypoxemia that results in neuronal dysfunction, then oraganelle and cellular disruption, and acute neuronal death from necrosis. In a neonatal piglet study using frequency domain NIRS,(6) Kurth et al showed that cerebral lactate levels rose at rSO2 values of 44% or lower; major EEG changes occurred when the cerebral saturation declined to 37%, with reductions in cerebral ATP levels when oximetry readings were 33% or lower. This concept was confirmed in another neonatal piglet model using hypoxic gas mixtures for 30 minutes at normothermia demonstrating that rSO2 >40% did not change EEG or brain pathology obtained 72 hours later; rSO2 30-40% produced no EEG changes, but at 72 hours there were ischemic neuronal changes in the hippocampus, and mitochondrial injury occurred. At rSO2 <30%, there was circulatory failure, EEG amplitude decreased, and there was vacuolization of neurons and severe mitochondrial injury.(7) Finally in a similar piglet model, the hypoxic-ischemic cerebral saturation-time threshold for brain injury found rSO2 of 35% for 2 hours or more produced brain injury.(8) These studies demonstrate that NIRS fulfills the second requirement.
Low Cerebral NIRS Values are Not Measured by Other Monitors, and Respond Quickly to Intervention
Low NIRS values, often defined as cerebral oxygen saturation (rSO2) <50%, or >20% relative change below a baseline established under normal physiologic conditions, i.e. pre-induction of anesthesia, respond rapidly and reliably to a number of maneuvers before, during, or after cardiopulmonary bypass. Manipulation of PaCO2 is one of the most common maneuvers to affect rSO2, and Hoskote et al (9) demonstrated rapid increases in rSO2 in infants after bidirectional cavopulmonary anastomosis with changing of PaCO2 from 35 to 45 to 55 mm Hg, then back to 40 mm Hg. Andropoulos et al documented several examples of rapid decline or increase in rSO2 in response to cooling or warming on CPB, onset of DHCA, onset of sudden anemia with initiation of CPB and increasing rSO2 with hemofiltration. (10) Cerebral NIRS, especially during CPB, measures a parameter not addressed by other monitors, i.e. mixed venous oxygen saturation on the CPB circuit. Redlin et al (11) studied 20 infants <10 kg undergoing surgery with CPB and found no correlation with brain rSO2 and SvO2 from the CPB circuit in 55 paired measurements.
NIRS is Reliable, Real-Time, and Non-Invasive
NIRS is non-invasive, self calibrating, has minimal warm up time, and continuously refreshes the rSO2 values every 4 seconds. Commercially available monitors are FDA approved (Somanetics, Cas Med, Nonin Medical), and display a signal strength indication and will not display an rSO2 value with inadequate signal strength. The non-invasive nature of the sensor applied to the forehead, and the lack of any reports of skin injury from the probe placement are important advantages of NIRS. The unique absorption spectrum of hemoglobin minimizes any spurious data, with the main interference with the signal being hyperbilirubinemia (11) and excessive ambient light. The device does not depend on pulsatility and so will function in any circulatory state, including low cardiac output, low flow, non pulsatile flow, i.e. axial ventricular assist device, and cardiac arrest. Although rSO2 is not identical to jugular venous bulb saturation (SjvO2) because rSO2 has an arterial component, the correlation between rSO2 and SjvO2 is strong, and the r value was 0.93 in 30 patients with congenital heart disease undergoing cardiac catheterization. (12)
Low NIRS Values are Associated with Adverse Outcomes, and Measuring and Correcting Low rSO2 Leads to Measurable Improved Outcomes in Patients
The true measure of any new monitoring technology is whether adverse outcomes are reduced, or desired outcomes enhanced, with the use of the new monitor. An example of a monitor with great theoretical appeal that was widely adopted is percutaneous pulmonary artery catheterization in adult cardiac surgery and critical illness. After many years of use and debate over its value, the frequency of use of this technology has declined significantly because of it often does not benefit the patient, and may cause more complications because of its invasive nature. (13) There is increasing evidence that low rSO2 values are associated with adverse neurological outcomes and death in congenital heart surgery. In a retrospective review of 50 HLHS patients undergoing Norwood Stage I palliation, Phelps et al (14) determined the relationship between mean rSO2 in the 48 hours postoperatively, with death, need for ECMO, and prolonged ICU stay >30 days. They found that in patients with adverse outcomes the mean rSO2 was 52.8%, vs. 60.8% with good outcomes (p<0.001), and a mean rSO2 <56% had a sensitivity of 75% and specificity of 79% for adverse outcomes. Dent et al (15) studied 15 neonates undergoing the Norwood operation who underwent preoperative, intra- and postoperative rSO2 monitoring. A prolonged low rSO2 (>180 minutes with< rSO2 45%) was associated with a higher risk of new ischemic lesions on postoperative MRI when compared to the pre-surgical study, with a sensitivity of 82% specificity of 75% , positive predictive value of 90%, and negative predictive value of 60% . In a study of 16 patients undergoing neonatal cardiac surgery, with NIRS monitoring and pre and postoperative brain MRI, 6 of 16 patients developed a new postoperative brain injury; these patients had a lower rSO2 during aortic crossclamp period vs. those without new brain injury. (48% vs. 57%, p=0.008).(16)
The gold standard for accepting a monitoring modality as a standard of care is outcome: does using the monitor, and treating abnormal values lead to improved outcomes? The first, and still one of the very best studies of NIRS and outcomes in congenital heart surgery was by Austin et al published in 1997. (17) In this retrospective study of prospectively collected NIRS data in 250 infants and children undergoing cardiac surgery with bypass, (21) the historical control group had a 26% incidence of acute postoperative neurological events defined as seizure, coma, or hemiparesis. Low rSO2, defined as more than 20% below prebypass baseline, was treated in the active intervention phase of the study, and this resulted in a reduction of acute neurological events to 7%, the same incidence observed when no low rSO2 occurred. In a recent study of 44 neonates undergoing the Norwood operation, who were tested at age 4-5 using a visual-motor integration test, the first 34 patients did not have NIRS monitoring, and the last 10 did have NIRS monitoring with a strict treatment protocol for low rSO2 values <50%. No patients with NIRS monitoring had a VMI score <85 (normal is 100), versus 6% without NIRS monitoring. Mean rSO2 in the perioperative period was associated with VMI score, with not patient with mean rSO2 ≥55 having VMI less than 96.(18)
The highest level of evidence that a new monitoring modality is standard of care would be multiple, prospective randomized controlled trials demonstrating that using the monitor and successfully treating abnormal values results in meaningful improvements in outcome, i.e. mortality or short and long term neurological morbidity. To date, this level of evidence for NIRS in pediatric cardiac surgery does not exist. However, there are important recent adult cardiac surgery studies that provide this evidence. Murkin et al (19) studied 200 patients undergoing CABG, randomized to either intraoperative rSO2 monitoring with active intervention, vs. blinded rSO2 monitoring. For the intervention group, the goal was to keep rSO2 above 75% of the baseline value. If rSO2 was below 75% of baseline a prioritized intervention protocol was instituted, including checking for head and facial plethora and adjusting head position or venous cannula; increasing PaCO2 to 40 mm Hg or more whether on or off CPB; increasing mean arterial pressure to greater than 60 mm Hg if low with phenylephrine; decreasing jugular venous pressure to less than 10 mm Hg if elevated; increasing CPB flow or cardiac output; increasing hematocrit if below 20%; increasing FiO2, or administering propofol to increase depth of anesthesia. Primary outcome was a composite of postoperative complications as defined by the Society of Thoracic Surgeons, and included new Q wave myocardial infarction; clinical stroke confirmed by CT scan; prolonged ventilation of greater than 24 and 48 hours; dialysis depended renal failure; reoperation or reexploration for bleeding; arrthymia requiring treatment; wound infection; readmission; or death. Fewer patients in the monitoring and intervention group experienced major organ morbidity or mortality as defined above; 3 patients vs. 11 patients, p=0.048. Additionally, severe cerebral desaturation, defined as rSO2 <70% of baseline for greater than 150 minutes intraoperatively, was seen in no monitor/intervention patient, vs. 6 blinded control patients (p=0.014). Finally, in a prospective, randomized trail in 265 adult CABG patients, prolonged low rSO2 was associated with early postoperative cognitive decline on neuropsychiatric testing (p=0.024), and threefold increased risk of prolonged hospital stay >6 days (p=0.007).(20)
Another potential benefit of routine NIRS monitoring is to avert the rare but very real and devastating potential neurological disaster from cannulation problems, where rSO2 declines dramatically from cannula malposition and cerebral arterial or venous obstruction, yet all other bypass parameters are normal. This has been described for both aortic cannula malposition (21), and SVC obstruction (22) during cavopulmonary anastomosis, where low rSO2 alerted the anesthesiologist and surgeon to these problems, which likely would have resulted in acute neurological injury if left untreated.
Prospective randomized trials in infants and children are confounded by the duration of follow up that is required and the multifactorial etiology contributing to adverse neurological outcomes. Unlike adults who can easily undergo pre- and postoperative neuropsychiatric testing, this is impossible in young children. It also may be difficult for these studies to be performed due to lack of equipoise for many centers who already use NIRS, and the complexity and cost of conducting trials requiring large sample sizes to achieve adequate statistical power to detect a difference in the incidence of relative rare events. However, acute studies of early outcomes such as mortality, need for ECMO, or prolonged ICU stay are more easily performed and should be done. Even though very large studies of changes in outcome through the use of pulse oximetry have never clearly demonstrated benefit, we would not practice without it.(23)
Conclusion: NIRS Should Become a Standard of Care for Pediatric Cardiac Surgery with CPB In summary, there is strong and increasing evidence that routine use of NIRS for cardiopulmonary bypass surgeries in pediatric patients will improve outcomes. However, because of the lack of the gold standard of multiple randomized controlled trials showing benefit, this author’s position is that NIRS monitoring, although not at this point in time a REQUIRED standard of care, SHOULD become a standard of care in the future. In the author’s institution NIRS has been our standard for almost a decade.
References:
1. www.ASAhq.org; accessed November 25, 2009.
2. Kurth CD, Steven JM, Nicolson SC, et al. Kinetics of cerebral deoxygenation during deep hypothermic circulatory arrest in neonates. Anesthesiology 1992;77: 656-661.
3.Yoshitani K, Kawaguchi M, Tatsumi K, et al. A comparison of the INVOS 4100 and the NIRO 300 near infrared spectrophotometers. Anesth Analg 2002;94: 586-570.
4. Kurth CD, Steven JL, Montenegro LM. Cerebral oxygen saturation before congenital heart surgery. Ann Thorac Surg 2001; 72: 187-192.
5. Jobsis FF. Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 1977;198:1264-67.
6. Kurth CD, Levy WJ, McCann J. Near-infrared spectroscopy cerebral oxygen saturation thresholds for hypoxia-ischemia in piglets. J Cereb Blood Flow Metab 2002;22:335-341.
7. Hou X, Ding H, Teng Y, et al. Research on the relationship between brain anoxia at different regional oxygen saturations and brain damage using near-infrared spectroscopy. Physiol Meas 20076;28:1251-65.
8. Kurth CD, McCann JC, Wu J, et al. Cerebral oxygen saturation-time threshold for hypoxic-oschemic injury in piglets. Anesth Analg 2009;108:1268-77.
9. Hoskote A, Li J, Hickey C, et al. The effects of carbon dioxide on oxygenation and systemic, cerebral, and pulmonary vascular hemodynamics after the bidirectional superior cavopulmonary anastomosis. J Am Coll Cardiol. 2004;44:1501-9.
10. Andropoulos DB, Stayer SA, Diaz LK, et al. Neurological monitoring for congenital heart surgery. Anesth Analg. 2004;99:1365-75.
11. Madsden PL, Skak C, Rasmussen A, Secher NH. Interference of cerebral near infrared oximetry in patients with icterus. Anesth Analg 2000;90:489-93.
12. Abdul-Khaliq H, Troitzsch D, Berger F, Lange PE. 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) 2000;45: 328-332.
13. Chatterjee K. The Swan-Ganz catheters: past, present, and future. A viewpoint. Circulation. 2009;119:147-52.
14. Phelps HM, Mahle WT, Kim D, et al. Postoperative cerebral oxygenation in hypoplastic left heart syndrome after the Norwood procedure. Ann Thorac Surg. 2009 May;87(5):1490-4.
15. 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 2006;131:190-197.
16. McQuillen PS, Barkovich AJ, Hamrick SE, et al. Temporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects. Stroke 2007;38 [part 2]:736-41.
17. Austin EH, III, Edmonds HL, Jr., Auden SM. Benefit of neurophysiologic monitoring for pediatric cardiac surgery. J Thorac Cardiovasc Surg 1997;114: 707-15, 717.
18. Hoffman GM, Mussatto KM, Brosig CL, et al. Cerebral oxygenation and neurodevelopmental outcome in hypoplastic left heart syndrome. Anesthesiology 2008;109:A7 (Abstract)
19. Murkin JM, Adams SJ, Novick RJ, et al. Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study. Anesth Analg 2007;104:51-8.
20. Slater JP, Guarino T, Stack J, et al. Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg. 2009;87:36-44.
21. Gottlieb EA, Fraser CD, Andropoulos DB, Diaz LK. (2006) Bilateral monitoring of cerebral oxygen saturation results in recognition of aortic cannula malposition during pediatric congenital heart surgery. Paediatr Anaesth 2006;16:787-9.
22. Ing RJ, Lawson DS, Jaggers J, et al. Detection of unintended partial superior vena cava occlusion during a bidirectional cavopulmonary anastomosis. J Cardiothorac Vasc Anesth 2004;18:472-74.
23. Pedersen T, Pedersen BD, Moller AM. Pulse oximetry for perioperative monitoring. Cochrane Database Syst Rev 2003;2: CD002013.
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