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Editor
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.
Perioperative stroke in infants undergoing open heart operations for congenital heart disease.
Ann Thorac Surg 2009; 88:823-9
Review by Mark D. Twite MA, MB, BChir, MRCPCH
The objectives of this prospective, observational study were to determine the prevalence of stroke as assessed by postoperative brain MRI and identify risk factors for its development in infants undergoing surgery for congenital heart disease (CHD).
The study was conducted at The Children’s Hospital of Philadelphia. Patients 6 months or younger undergoing cardiopulmonary bypass (CPB) with or without deep hypothermic circulatory arrest (DHCA), for repair of CHD were eligible. Patients were recruited from two ongoing studies; the first study evaluated apolipoprtein genotype as a risk factor for neurodevelopmental dysfunction and the second study assessed the role of cytokine gene polymorphisms in perioperative brain injury. The study authors acknowledge that this study design may have resulted in selection bias because not all patients from the ongoing studies had post-operative MRIs either because they had been discharged or were too unstable to undergo a MRI. The study otherwise had appropriate exclusion criteria, all patients were accounted for and statistical methods were correct.
Brain MRI was performed in 122 infants 3 to 14 days after cardiac operation. Two types of stroke were identified: focal arterial ischemic and vascular watershed. The timing of the stroke in relationship to the operation was determined from the date of operation relative to the date of the MRI and estimated radiologic maturity of the infarct as acute, subacute or chronic. An infarct was judged to be preoperative if the radiologic appearance was subacute or chronic and the MRI was obtained within 7 days after the operation. An infarct was judged to be possibly intraoperative or postoperative if the radiologic appearance was acute and the MRI was obtained within 7 days after the operation. Preoperative, intraoperative, and postoperative data were collected. Risk factors were tested by logistic regression for univariate and multivariate associations with stroke.
Stroke was identified in 12 of 122 patients (10%). Strokes were possibly preoperative in 6 patients and intra- or post-operative in the other 6 patients. Strokes were clinically silent in all patients except for one who had clinical seizures. There were no significant differences in cardiac anatomy, type of operation, intracardiac shunting or prostaglandin use between patients with or without stroke. Arterial-occlusive and watershed infarcts were identified with equal distribution in both hemispheres suggesting a multifactor mechanism that may include thromboembolism and hypoperfusion. Multivariate analysis identified lower birth rate, preoperative intubation, lower intraoperative hematocrit after hemodilution on CPB (26% in the stroke group vs 28% in the no stroke group), and higher blood pressure at admission to the cardiac intensive care unit (CICU) postoperatively as significant factors associated with stroke. Aside from the initial systolic blood pressure upon admission to the CICU, there was no difference in blood pressure for the next 48 hours between patients with and without strokes. Prematurity, younger age at operation, duration of CPB, and use of DHCA were not significantly associated with stroke.
In addition to the limitation of the study design already mentioned, this study is also limited by the lack of pre-operative MRIs. This precludes definitive identification of the timing of occurrence of stroke and limits the interpretation of cause and effect among potential risk factors.
The results of this study contrast to the other study from the same CHOP group reviewed in this newsletter. In the other study the authors conclude that infants with complex CHD have immature brains that makes them more vulnerable to injury from hypoxia and hypotension resulting in an increased incidence of perioperative PVL. However, in this study, hypoxemia and hypotension were not associated with an increased risk of stroke, including watershed infarcts. This suggests that there are different mechanisms underlying cerebral injury in infants with CHD. With a 10% incidence of perioperative stroke, future studies are required to elucidate the mechanisms of cerebral injury and to investigate the effect of stroke on short and long term neurodevelopmental outcomes. As with the other study reviewed, this raises the issue of whether structural and functional brain imaging pre and post operatively should be performed in all infants with complex CHD, and it emphasizes the importance of long term multidisciplinary follow-up.
Brain maturation is delayed in infants with complex congenital heart defects.
J Thorac Cardiovasc Surg 2009; 137:529-37
Review by Mark D. Twite MA, MB, BChir, MRCPCH
This prospective, observational study utilizing historical controls tested the hypothesis that brain development is structurally delayed in infants with complex congenital heart disease (CHD).
The study was conducted at The Children’s Hospital of Philadelphia. Patients recruited into the study were ‘healthy’ term infants (gestational age > 37 weeks) with either hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA). The study had appropriate exclusion criteria, all patients were accounted for and statistical methods were correct. Outcome measures were head circumferences and the total maturation score (TMS) on MRI. TMS is a semiquantitative scoring system developed and validated in healthy preterm infants to assess whole brain maturity.
A total of 42 patients were included in the analysis, 29 with HLHS and 13 with TGA. The mean gestational age was 38.9 ± 1.1 weeks. Mean head circumference was 1 standard deviation below normal. The mean TMS for the cohort was 10.15 ± 0.94, significantly lower than reported normative data in infants without congenital heart defects, corresponding to a delay of 1 month in structural brain development. In addition, immature brain development was also seen on MRI as the incomplete closure of the cerebral operculae in 90% of infants studied. The operculum comprises an area of fronto-parietal brain that includes the sensory motor cortical representation of buccal, glottic, and esophageal structures, as well as receptive and expressive language. Bilateral abnormalities in the cerebral operculum have been linked to feeding and language delays.
This structurally immature brain in infants with complex CHD may be more vulnerable to hypoxia and ischemia, resulting in injury to the white matter located in the vascular watershed zone adjacent to the lateral ventricles and the subsequent development of periventricular leukomalacia (PVL). In this study cohort PVL was identified in 20% of patients pre-surgery and 50% post-surgery, suggesting that peri-operative hypotension and hypoxemia are important factors.
Low TMS scores, small head circumferences, a high prevalence of open operculae, and an increased and ongoing risk for PVL collectively suggest that in utero brain development is impaired in this population. The study authors suggest that in the fetus without CHD the normal fetal circulation results in preferential streaming of blood with higher oxygen content from the placenta to the brain whereas this pattern is not present in TGA or in HLHS. This hypoxic cerebral environment in the fetus with TGA or HLHS may predispose the brain to PVL at an age that it would not otherwise be expected.
School aged children with complex CHD who have undergone surgical repair in infancy have significant neurodevelopmental delays. Interestingly, their neurodevelopmental profiles are similar to that of premature infants without CHD, with relatively preserved intelligence but a higher than expected frequency of deficits in attention, executive function, language, fine and gross motor coordination and visual-motor integration. The common neuropathology is PVL. Well-designed studies of neurodevelopmental outcomes of infant heart surgery have focused on intra-operative strategies but have failed to show long-term benefit. This suggests it is the underlying brain substrate in CHD that contributes more to longer-term outcomes that changes in intra-operative techniques.
This study raises management issues for all health professionals involved in the care of children with complex CHD. Should children with prenatally diagnosed complex CHD be carried to 40 weeks gestation or even post-term? Are families able to move close to a tertiary care hospital while waiting for a natural labor? Are the health care systems of these hospitals able to optimally manage newborns with complex CHD at all hours regardless of the day of the week? Is it justifiable to suggest that the ideal practice for newborns with complex CHD requiring surgery should include pre and post operative neurologic imaging, perioperative neurologic monitoring, and long term neurodevelopmental assessment by a multidisciplinary team? With the advent of potential neuroprotective strategies the importance of collecting baseline data on the brain substrate will also become critical to enable meaningful data interpretation.
Dr. Mark D. Twite MA MB BChir MRCPCH
Director of Pediatric Cardiac Anesthesia
The Children's Hospital &
University of Colorado, Denver
13123 East 16th Avenue, B090
Aurora, CO 80045
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