HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Kathleen A. Mussatto Robert D.B. Jaquiss James S. Tweddell Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hoffman, G. M. Articles by Tweddell, J. S. Search for Related Content PubMed PubMed Citation Articles by Hoffman, G. M. Articles by Tweddell, J. S.

J Thorac Cardiovasc Surg 2005;130:1094-1100
© 2005 The American Association for Thoracic Surgery

Surgery for Congenital Heart Disease

Systemic venous oxygen saturation after the Norwood procedure and childhood neurodevelopmental outcome

^a Department of Pediatric Anesthesiology, Medical College of Wisconsin, Milwaukee, Wis.
^b Department of Cardiology, Medical College of Wisconsin, Milwaukee, Wis.
^c Department of Cardiovascular Surgery, Medical College of Wisconsin, Milwaukee, Wis.
^d Department of Critical Care Medicine, Medical College of Wisconsin, Milwaukee, Wis.
^e Department of Pediatric Psychology, Medical College of Wisconsin, Milwaukee, Wis.
^f Children's Hospital of Wisconsin, and the Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wis.
^g Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis.
^h Department of Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, Wis.

Presented in part at the annual meeting of the American Society of Anesthesiologists, Las Vegas, Nevada, October 2004.

Received for publication May 12, 2005; revisions received June 16, 2005; accepted for publication June 28, 2005.

^_* Address for reprints: George M. Hoffman, MD, Anesthesiology and Pediatrics, Children's Hospital of Wisconsin, 9000 W Wisconsin Ave, Milwaukee, WI 53226. (Email: ghoffman{at}mcw.edu).

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
OBJECTIVE: Neonates with hypoplastic left heart syndrome have impaired systemic oxygen delivery and also have a high risk of hypoxic ischemic brain injury with resultant neurodevelopmental impairment. We hypothesized that decreased postoperative oxygen delivery, as measured on the basis of systemic venous oxyhemoglobin saturation, would be related to persistent neurodevelopmental abnormality assessed in childhood.

METHODS: Early perioperative hemodynamic data, prospectively acquired from neonates undergoing staged palliation of hypoplastic left heart syndrome by using deep hypothermic circulatory arrest with uniform perioperative management, were tested for relationship to later neurodevelopmental outcome assessed at age 4 years.

RESULTS: Complete hemodynamic and neurodevelopmental data were available in 13 patients aged 7 ± 8 days at the time of the Norwood procedure and aged 4.5 ± 0.7 years at follow-up assessment. The subjects scored significantly below the population mean for motor, visual-motor integration, and composite neurodevelopmental outcomes. The 5 (38%) patients with abnormal outcomes had significantly lower postoperative systemic venous oxygen saturation values than those with normal outcomes (46% ± 8% vs 56% ± 6%, P = .024). Standard hemodynamic parameters did not differentiate patient outcomes. The risk of abnormal outcome increased with increasing time at a systemic venous oxygen saturation of less than 40% (P < .001). A multivariate model of deep hypothermic circulatory arrest time, systemic venous oxygen saturation, blood pressure, and carbon dioxide tension accounted for 79% of the observed variance (P < .001).

CONCLUSIONS: Decreased systemic oxygen delivery in the neonatal postoperative period is associated with hypoxic-ischemic brain injury and childhood neurodevelopmental abnormality. Measures of systemic oxygen delivery should be used to guide perioperative strategies to reduce the risk of hypoxic-ischemic brain injury.

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Children with congenital heart disease are at increased risk for neurodevelopmental impairment. Causes of reduced neurodevelopmental outcome include genetic factors, abnormalities of the aortic arch (including hypoplastic left heart syndrome [HLHS]), ¹ hypoxic-ischemic injury, genetic predisposition, ² and complex environmental factors. ^3-5 Perioperative events are commonly identified as potential causes of hypoxic-ischemic injury, ^6-8 particularly prolonged periods of circulatory arrest ⁹ and other cardiopulmonary bypass (CPB) support strategies that reduce oxygen delivery, such as anemia ¹⁰ and alkalosis. ^11,12 However, intraoperative factors do not adequately explain all adverse outcomes. ^5,8,13-15

We have previously identified a higher risk of reduced systemic oxygen delivery by using continuous systemic venous oxygen saturation (SvO ₂) monitoring and reduced cerebral oxygen saturation by using near-infrared spectroscopy (NIRS) in the early postoperative period in neonates undergoing the Norwood procedure. ^15-17 Positing that impaired neurodevelopmental outcome might be a late manifestation of postoperative hypoxic-ischemic injury, we examined the relationship between neonatal perioperative hemodynamics and school-age neurodevelopmental outcome in survivors of staged palliation of HLHS. The primary hypothesis was that inadequate postoperative oxygen delivery, assessed by measuring SvO ₂ after neonatal stage 1 repair, would be a predictor of poor neurocognitive function at age 4 years.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patients
All neonates undergoing staged palliation of HLHS since 1996 have had neonatal perioperative hemodynamics maintained in a database. All survivors have been offered enrollment in a neurodevelopmental outcome study after achieving acceptable hemodynamics for completion of the Fontan procedure and attaining a minimum age of 3.5 years. Because perioperative management strategies have evolved over the past decade in ways that might affect hypoxic-ischemic injury, we limited this analysis to patients who had undergone a modified Norwood procedure for stage 1 palliation (S1P) of HLHS or a single-ventricle variant with deep hypothermic circulatory arrest (DHCA) after achievement of synthetic opioid-based perioperative anesthesia, as previously described. ^16,18 Cooling to 18°C to 20°C was achieved with a high-flow modified pH-stat strategy with a minimum cooling time of 25 minutes, ¹⁹ followed by a shift to alpha-stat blood gas management just before circulatory arrest. ²⁰ All patients had continuous superior vena caval (SVC) SvO ₂ monitoring to guide an aggressive inodilator strategy with an SvO ₂ target of 50%. ^16,18,21

Of 43 sequential patients who had S1P performed from 1996 through 1999 by using this standardized perioperative management strategy, 30 were alive at the time of this cross-sectional study. Three were excluded because of coexisting anomalies or extreme prematurity thought to independently affect neurodevelopmental performance. Parents of the 27 eligible patients were invited to participate in this study. Responses were obtained from 21 families, and neurodevelopmental testing was completed in 13. Distance greater than 100 miles from the testing center was the primary reason for nonresponse or noncompletion of testing. All patients who had completed neurodevelopmental assessment by September 2004 were included in this analysis.

Neurodevelopment Assessment
A comprehensive test battery was administered by a single developmental psychologist (CLB) under controlled conditions and with institutional review board approval. Individual tests included in this analysis were the McCarthy Scale of Children's Abilities–Motor and the McCarthy Scale of Children's Abilities–General Cognitive, the Beery Test of Visual-Motor Integration, and Achenbach's Child Behavior Checklist. These 4 individual test scores were normalized to an average score of 100 and standard deviation (SD) of 15 and summed to generate a composite outcome score. These tests measure a range of basic and higher-level integrative motor, cognitive, and psychosocial skills, representing areas of function that are at risk for impairment in children with complex congenital heart disease. ^9,11,22,23 A cutoff of greater than –2 SD from the population mean was used to classify test results as abnormal.

Hemodynamic Assessment
Perioperative hemodynamic indices were recorded prospectively for the first 48 hours after neonatal S1P, including arterial oxygen saturation (SaO ₂), SVC SvO ₂, mean arterial blood pressure (MABP), central venous pressure (CVP), heart rate (HR), hemoglobin concentration, PaCO ₂, base excess, and pH and derived parameters of arteriovenous oxygen saturation difference (Sa-vO ₂) and arteriovenous oxygen content difference (Ca-vO ₂). Intraoperative parameters included duration of support (DHCA time and CPB time) and use of phenoxybenzamine.

Statistical Analysis
Data were expressed as means ± SD for descriptive statistics and as means ± standard error for estimated statistics, with 95% confidence intervals as appropriate. The differences in early hemodynamic parameters between patients with normal or abnormal outcomes were assessed by means of one-way analysis of variance for mean values or by using the Fisher exact test for proportions. The relationship between late outcome and early hemodynamic parameters was assessed by means of multivariate, generalized, least-squares (GLS) time-series regression with correction for autocorrelation and by means of repeated-measures analysis of variance for nonlinear models. Continuous values for hemodynamic parameters were divided into clinically appropriate strata to assess the risk of abnormal outcome at key thresholds by means of binomial odds ratios and time-series logistic regression. The cutoff for significance was a P value of less than .05 after multiple comparison correction with the Tukey honestly significant difference or the Bonferroni method when applicable. All calculations were performed with Stata Version 8 (Stata Corporation, College Station, Tex).

	Results

Top Abstract Introduction Methods Results Discussion References

 
Complete hemodynamic and outcome assessment was available in 13 patients for this analysis. The cohort had S1P at 7 ± 8 days (median, 4 days) at a weight of 3.3 ± 0.7 kg. The duration of DHCA was 62 ± 8 minutes, and the duration of CPB was 128 ± 50 minutes. The postoperative hemodynamic profile was analyzed from a complete set of 624 hours of data. This profile showed a mean SaO ₂ of 77% ± 5%, SvO ₂ of 52% ± 11%, Sa-vO ₂ of 25% ± 9%, hemoglobin concentration of 15 ± 1.5 g/100 mL, Ca-vO ₂ of 4.9 ± 1.8 mL/dL, MABP of 52 ± 5 mm Hg, CVP of 11 ± 3 mm Hg, HR of 168 ± 18 min^–1, base excess of 3 ± 4 mEq/L, and PaCO ₂ of 41 ± 6 mm Hg. No patients required postoperative mechanical circulatory support.

At the time of neurodevelopment assessment, patients were 4.5 ± 0.7 years of age and ambulatory after completion of the Fontan operation. The study population performed below the population mean on a number of domains. The McCarthy Scale of Children's Abilities–Motor (42 ± 10 vs 50 ± 10, P = .01), Beery Test of Visual-motor Integration (87 ± 14 vs 100 ± 15, P = .006), and composite scores (352 ± 66 vs 400 ± 60, P = .03) were significantly below normal in the cohort. Five (38%; 95% confidence interval, 14%-68%) patients had at least one clearly abnormal score at least 2 SDs below the mean (Table 1).

View larger version (20K): [in this window] [in a new window]   Figure 1. Distributions of systemic venous oxygen saturation (Sv O 2 ), arterial oxygen saturation (Sa O 2 ), and arteriovenous oxygen saturation difference (Sa-v O 2 ) over the first 48 postoperative hours in the 2 subgroups of patients. Patients with abnormal outcomes had lower systemic venous oxygen saturation (*P = .012), arterial oxygen saturation (*P = .036), and higher arteriovenous oxygen saturation difference (*P = .039) values.

View larger version (21K): [in this window] [in a new window]   Figure 2. Forty-eight-hour distributions of arteriovenous oxygen content difference (Ca-vO 2), PaCO 2, and mean arterial blood pressure (MABP) were not different in patients with normal versus abnormal outcomes.

View larger version (21K): [in this window] [in a new window]   Figure 3. The composite outcome score was modeled as a function of hourly hemodynamic data and cardiopulmonary bypass parameters (arterial oxygen saturation, systemic venous oxygen saturation [SvO 2], mean arterial blood pressure, central venous pressure, PaCO 2, cardiopulmonary bypass time, and deep hypothermic circulatory arrest time). The model reveals the effect of systemic venous oxygen saturation on outcome, with a break point of a systemic venous oxygen saturation of less than 40% (*P < .05, analysis of variance [ANOVA]). Adjustment for other parameters did not change the main model effect but increased the power (from R 2 = 0.49 to 0.63). CI, Confidence interval.

View larger version (25K): [in this window] [in a new window]   Figure 4. The interaction between prolonged deep hypothermic circulatory arrest (DHCA) time and postoperative hemodynamics is shown in a predictive model. Patients undergoing prolonged deep hypothermic circulatory arrest had significantly lower composite outcome scores at low systemic venous oxygen saturation (SvO 2; P < .05, analysis of variance post-tests), and prolonged deep hypothermic circulatory arrest reduced neurodevelopmental outcome for any systemic venous oxygen saturation (*P < .05, analysis of variance). Adjustment for other parameters did not change the main or interaction model effects but increased the power (from R 2 = 0.49 to 0.58). CI, Confidence interval.

View larger version (39K): [in this window] [in a new window]   Figure 5. The interaction between postoperative PaCO 2 and systemic venous oxygen saturation (SvO 2) is shown in a predictive model. Patients with lower postoperative PaCO 2 had poorer outcome at lower systemic venous oxygen saturation compared with that of patients with higher PaCO 2 (*P < .05, analysis of variance). Adjustment for other parameters did not change the main or interaction model effects but increased the power (from R 2 = 0.52 to 0.64). CI, Confidence interval.

	Discussion

Top Abstract Introduction Methods Results Discussion References

The strength of the association between factors related to hypoxic injury and late outcome in this relatively small study results partly from the wide range of performance and frequency of poor performance observed in the subjects' neurodevelopmental testing. The expected probability of 5 abnormal test results in this sample size would be no greater than 1% if drawn from a normal sample. The possibility of selection bias in subjects' participation in neurodevelopmental assessment might contribute to the incidence of abnormality, but this high incidence is consistent with other reports. ^1,3,5,6,23 Although the absolute risk of abnormal outcome could only be estimated by a prospective study with complete ascertainment, the association between low postoperative SvO ₂ and poor outcome is not likely to be influenced by ascertainment bias in this sample population. The perioperative demographic and hemodynamic profile of the tested cohort was not different from that of the entire contemporaneously operated S1P population (n = 43, data not shown).

The postoperative hemodynamic parameter most variable in this patient population was SvO ₂, but the overall hemodynamic profiles were otherwise distinctly unremarkable. The children with poorer outcomes were specifically not hypotensive, acidotic, or subject to extreme arterial hypoxemia, conditions that have been associated with early postoperative changes on magnetic resonance imaging. ^6,25 They received similar levels of inotropic support and had no requirement for cardiopulmonary resuscitation. The results of their management strategy simply failed to achieve the target SvO ₂ for a greater period of time. Postoperative mechanical circulatory support was not used on an emergency basis or electively to maintain organ perfusion. ²⁶

Because standard monitoring modalities did not discriminate patients with abnormal outcomes, we believe that measurements of organ oxygen economy by means of SvO ₂ or potentially NIRS should be used to characterize the circulatory vulnerability in these patients and to guide therapy. After S1P, patients are at high risk of inadequate organ oxygen delivery and low SvO ₂ because of the superimposition of low SaO ₂, low systemic blood flow, and increased oxygen consumption. ^16,18 However, hypoxic-ischemic organ injury can result from inadequate oxygen delivery from a wide range of conditions, and we believe the relationship between SvO ₂ and neurodevelopmental outcome is generalizable to many high-risk populations.

In this relatively small sample, the effect of prolonged DHCA was highly collinear with mild hypocapnia, such that each term had univariate significance, but neither added power to the multivariate model. This finding makes physiologic sense in that prolonged DHCA causes prolonged impairment in cerebrovascular resistance, such that oxygen uptake and carbon dioxide production from the brain are reduced after CPB. ²⁷ The data also support the speculation that a hypercapnic management strategy might improve cerebral blood flow after DHCA through reduction of cerebrovascular resistance. ^17,28 The break point for poorer outcome in our sample was DHCA time of greater than 60 minutes compared with the 45-minute break point from the Boston Circulatory Arrest Study. ⁹ Our CPB strategy maintained a higher PCO ₂ and hemoglobin concentration than that in the Boston Circulatory Arrest Study analysis. Strategies that include a higher hemoglobin concentration ¹⁰ and a higher PaCO ₂ ¹¹ have been shown to improve outcome from DHCA, and thus our data are consistent with a variable dose-dependent injury related to DHCA, ^9,22,29 which can be affected by parameters related to cerebral oxygen delivery, such as PaCO ₂ and hemoglobin concentration.

In patients with parallel circulation, reduction in systemic vascular resistance can improve systemic flow by reducing and stabilizing the pulmonary/systemic flow ratio. ^30,31 In patients with limited cardiac output, reduction in systemic vascular resistance might divert blood flow away from the cerebral circulation. ^17,32 Theoretic objections to the use of afterload reduction in this patient population stem partly from this concern. ³³ In this study we found no evidence that the use of phenoxybenzamine impaired neurologic outcome.

The postoperative parameter most strongly related to outcome was SvO ₂. Because SvO ₂ is the flow-weighted average of regional venous saturations and because the cerebral blood contributes significantly to SVC venous blood in the resting and sedated patient, SvO ₂ will be strongly influenced by cerebral oxygen economy. ^15,34 The SvO ₂ might thus be closely related to whole-brain oxygen saturation in this analysis, and other measures of brain oxygen status, such as NIRS, might more directly reflect conditions of cerebral hypoxia related to adverse outcome. ^15,24,35,36

The hemodynamic vulnerability detected by decreased postoperative SvO ₂ reflects impaired oxygen delivery to metabolism balance. This impairment of oxygen economy in the early postoperative period was related to later neurocognitive disability, presumably through the development of hypoxic brain injury. Although low SvO ₂ tended to improve over the first 48 postoperative hours, the underlying circulatory vulnerability might persist, and those patients demonstrating late outcome impairment might have recurrent hypoxic injury beyond the acute perioperative period. ⁵ Strategies to improve SvO ₂ and brain oxygenation in the perioperative period and beyond are likely to reduce the occurrence of hypoxic brain injury in high-risk patient populations.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Mahle WT, Wernovsky G. Neurodevelopmental outcomes in hypoplastic left heart syndrome. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2004;7:39-47.[Medline]
   
2. Gaynor JW, Gerdes M, Zackai EH, Bernbaum J, Wernovsky G, Clancy RR, et al. Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery. J Thorac Cardiovasc Surg 2003;126:1736-1745.[Abstract/Free Full Text]
   
3. Limperopoulos C, Majnemer A, Shevell MI, Rohlicek C, Rosenblatt B, Tchervenkov C, et al. Predictors of developmental disabilities after open heart surgery in young children with congenital heart defects. J Pediatr 2002;141:51-58.[Medline]
   
4. Fallon P, Aparicio JM, Elliott MJ, Kirkham FJ. Incidence of neurological complications of surgery for congenital heart disease. Arch Dis Child 1995;72:418-422.[Abstract/Free Full Text]
   
5. Wernovsky G, Shillingford AJ, Gaynor JW. Central nervous system outcomes in children with complex congenital heart disease. Curr Opin Cardiol 2005;20:94-99.[Medline]
   
6. Mahle WT, Tavani F, Zimmerman RA, Nicolson SC, Galli KK, Gaynor JW, et al. An MRI study of neurological injury before and after congenital heart surgery. Circulation 2002;106(suppl I):I109-I114.[Medline]
   
7. du Plessis AJ. Cerebral hemodynamics and metabolism during infant cardiac surgery. Mechanisms of injury and strategies for protection. J Child Neurol 1997;12:285-300.[Abstract/Free Full Text]
   
8. Trittenwein G, Nardi A, Pansi H, Golej J, Burda G, Hermon M, et al. Early postoperative prediction of cerebral damage after pediatric cardiac surgery. Ann Thorac Surg 2003;76:576-580.[Abstract/Free Full Text]
   
9. Wypij D, Newburger JW, Rappaport LA, duPlessis AJ, Jonas RA, Wernovsky G, 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 2003;126:1397-1403.[Abstract/Free Full Text]
   
10. Jonas RA, Wypij D, Roth SJ, Bellinger DC, Visconti KJ, du Plessis AJ, et al. The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass. results of a randomized trial in infants. J Thorac Cardiovasc Surg 2003;126:1765-1774.[Abstract/Free Full Text]
    
11. Bellinger DC, Wypij D, du Plessis AJ, Rappaport LA, Riviello J, Jonas RA, et al. Developmental and neurologic effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg 2001;121:374-383.[Medline]
    
12. Priestley MA, Golden JA, O'Hara IB, McCann J, Kurth CD. Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs. J Thorac Cardiovasc Surg 2001;121:336-343.[Medline]
    
13. du Plessis AJ. Neurologic complications of cardiac disease in the newborn. Clin Perinatol 1997;24:807-826.[Medline]
    
14. Mahle WT, Lundine K, Kanter KR, Forbess JM, Kirshbom P, Tosone SR, et al. The short term effects of cardiopulmonary bypass on neurologic function in children and young adults. Eur J Cardiothorac Surg 2004;26:920-925.[Abstract/Free Full Text]
    
15. Hoffman GM. Detection and prevention of neurologic injury inn the intensive care unit. Cardiol Young 2005;15(suppl 1):149-153.[Medline]
    
16. Tweddell JS, Hoffman GM, Fedderly RT, Ghanayem NS, Kampine JM, Berger S, et al. Patients at risk for low systemic oxygen delivery after the Norwood procedure. Ann Thorac Surg 2000;69:1893-1899.[Abstract/Free Full Text]
    
17. Hoffman GM, Stuth EA, Jaquiss RD, Vanderwal PL, Staudt SR, Troshynski TJ, 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 2004;127:223-233.[Abstract/Free Full Text]
    
18. Hoffman GM, Ghanayem NS, Kampine JM, Berger S, Mussatto KA, Litwin SB, et al. Venous saturation and the anaerobic threshold in neonates after the Norwood procedure for hypoplastic left heart syndrome. Ann Thorac Surg 2000;70:1515-1521.[Abstract/Free Full Text]
    
19. Kern FH, Ungerleider RM, Schulman SR, Meliones JN, Schell RM, Baldwin B, et al. Comparing two strategies of cardiopulmonary bypass cooling on jugular venous oxygen saturation in neonates and infants. Ann Thorac Surg 1995;60:1198-1202.[Abstract/Free Full Text]
    
20. Skaryak LA, Chai PJ, Kern FH, Greeley WJ, Ungerleider RM. Blood gas management and degree of cooling. effects on cerebral metabolism before and after circulatory arrest. J Thorac Cardiovasc Surg 1995;110:1649-1657.[Abstract/Free Full Text]
    
21. Tweddell JS, Hoffman GM, Mussatto KA, Fedderly RT, Berger S, Jaquiss RD, et al. Improved survival of patients undergoing palliation of hypoplastic left heart syndrome. lessons learned from 115 consecutive patients. Circulation 2002;106(suppl I):I82-I89.[Medline]
    
22. Bellinger DC, Jonas RA, Rappaport LA, Wypij D, Wernovsky G, Kuban KC, et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med 1995;332:549-555.[Medline]
    
23. Mahle WT, Wernovsky G. Long-term developmental outcome of children with complex congenital heart disease. Clin Perinatol 2001;28:235-247.[Medline]
    
24. Austin 3rd EH, Edmonds Jr HL, Auden SM, Seremet V, Niznik G, Sehic A, et al. Benefit of neurophysiologic monitoring for pediatric cardiac surgery. J Thorac Cardiovasc Surg 1997;114:707-717.[Abstract/Free Full Text]
    
25. Galli KK, Zimmerman RA, Jarvik GP, Wernovsky G, Kuypers MK, Clancy RR, et al. Periventricular leukomalacia is common after neonatal cardiac surgery. J Thorac Cardiovasc Surg 2004;127:692-704.[Abstract/Free Full Text]
    
26. Ungerleider RM, Shen I, Yeh T, Schultz J, Butler R, Silberbach M, et al. Routine mechanical ventricular assist following the Norwood procedure—improved neurologic outcome and excellent hospital survival. Ann Thorac Surg 2004;77:18-22.[Abstract/Free Full Text]
    
27. Greeley WJ, Kern FH, Meliones JN, Ungerleider RM. Effect of deep hypothermia and circulatory arrest on cerebral blood flow and metabolism. Ann Thorac Surg 1993;56:1464-1466.[Medline]
    
28. Sakamoto T, Kurosawa H, Shin'oka T, Aoki M, Isomatsu Y. The influence of pH strategy on cerebral and collateral circulation during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease. results of a randomized trial and real-time monitoring. J Thorac Cardiovasc Surg 2004;127:12-19.[Abstract/Free Full Text]
    
29. Ungerleider RM, Shen I. Optimizing response of the neonate and infant to cardiopulmonary bypass. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2003;6:140-146.[Medline]
    
30. Tweddell JS, Hoffman GM, Fedderly RT, Berger S, Thomas Jr JP, Ghanayem NS, et al. Phenoxybenzamine improves systemic oxygen delivery after the Norwood procedure. Ann Thorac Surg 1999;67:161-168.[Abstract/Free Full Text]
    
31. Hoffman GM, Tweddell JS, Ghanayem NS, Mussatto KA, Stuth EA, Jaquis RD, et al. Alteration of the critical arteriovenous oxygen saturation relationship by sustained afterload reduction after the Norwood procedure. J Thorac Cardiovasc Surg 2004;127:738-745.[Abstract/Free Full Text]
    
32. Hoffman GM, Ghanayem NS, Tweddell JS. Noninvasive assessment of cardiac output. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2005;8:12-21.
    
33. Wernovsky G, Hoffman GM, Stuth EA, Jaquiss RD, Vanderwal PL, Staudt SR, Troshynski TJ, 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. 2004;127:223-233.[Abstract/Free Full Text]
    
34. Weiss M, Dullenkopf A, Kolarova A, Schulz G, Frey B, Baenziger O. Near-infrared spectroscopic cerebral oxygenation reading in neonates and infants is associated with central venous oxygen saturation. Paediatr Anaesth 2005;15:102-109.[Medline]
    
35. Abdul-Khaliq H, Schubert S, Troitzsch D, Huebler M, Boettcher W, Baur MO, et al. Dynamic changes in cerebral oxygenation related to deep hypothermia and circulatory arrest evaluated by near-infrared spectroscopy. Acta Anaesthesiol Scand 2001;45:696-701.[Medline]
    
36. Abdul-Khaliq H, Troitzsch D, Schubert S, Wehsack A, Bottcher W, Gutsch E, et al. Cerebral oxygen monitoring during neonatal cardiopulmonary bypass and deep hypothermic circulatory arrest. Thorac Cardiovasc Surg 2002;50:77-81.[Medline]
    

This article has been cited by other articles:

				J. A. Feinstein, D. W. Benson, A. M. Dubin, M. S. Cohen, D. M. Maxey, W. T. Mahle, E. Pahl, J. Villafane, A. B. Bhatt, L. F. Peng, et al. Hypoplastic left heart syndrome current considerations and expectations. J. Am. Coll. Cardiol., January 3, 2012; 59(1 Suppl): S1 - S42. [Abstract] [Full Text] [PDF]

				M. Y. Naim, A. A. Topjian, and V. M. Nadkarni CPR and E-CPR: What is New? World Journal for Pediatric and Congenital Heart Surgery, January 1, 2012; 3(1): 48 - 53. [Abstract] [Full Text] [PDF]

				M. S. Khan and C. D. Fraser Neonatal Brain Protection in Cardiac Surgery and the Role of Intraoperative Neuromonitoring World Journal for Pediatric and Congenital Heart Surgery, January 1, 2012; 3(1): 114 - 119. [Abstract] [Full Text] [PDF]

				J. Simons, E. D. Sood, C. D. Derby, and C. Pizarro Predictive value of near-infrared spectroscopy on neurodevelopmental outcome after surgery for congenital heart disease in infancy J. Thorac. Cardiovasc. Surg., January 1, 2012; 143(1): 118 - 125. [Abstract] [Full Text] [PDF]

				S. B. Iyer, J. B. Anderson, J. Slicker, R. H. Beekman III, and C. Lannon Using Statistical Process Control to Identify Early Growth Failure Among Infants With Hypoplastic Left Heart Syndrome World Journal for Pediatric and Congenital Heart Surgery, October 1, 2011; 2(4): 576 - 585. [Abstract] [Full Text] [PDF]

				J. Lemson, A. Nusmeier, and J. G. van der Hoeven Advanced Hemodynamic Monitoring in Critically Ill Children Pediatrics, September 1, 2011; 128(3): 560 - 571. [Abstract] [Full Text] [PDF]

				J. M. Costello, P. S. McQuillen, E. C. Claud, and R. H. Steinhorn Prematurity and Congenital Heart Disease World Journal for Pediatric and Congenital Heart Surgery, July 1, 2011; 2(3): 457 - 467. [Abstract] [Full Text] [PDF]

				M. E. Kleinman, L. Chameides, S. M. Schexnayder, R. A. Samson, M. F. Hazinski, D. L. Atkins, M. D. Berg, A. R. de Caen, E. L. Fink, E. B. Freid, et al. Part 14: Pediatric Advanced Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Circulation, November 2, 2010; 122(18_suppl_3): S876 - S908. [Full Text] [PDF]

				M. E. Kleinman, A. R. de Caen, L. Chameides, D. L. Atkins, R. A. Berg, M. D. Berg, F. Bhanji, D. Biarent, R. Bingham, A. H. Coovadia, et al. Pediatric Basic and Advanced Life Support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Pediatrics, November 1, 2010; 126(5): e1261 - e1318. [Full Text] [PDF]

				M. E. Kleinman, L. Chameides, S. M. Schexnayder, R. A. Samson, M. F. Hazinski, D. L. Atkins, M. D. Berg, A. R. de Caen, E. L. Fink, E. B. Freid, et al. Pediatric Advanced Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Pediatrics, November 1, 2010; 126(5): e1361 - e1399. [Full Text] [PDF]

				M. E. Kleinman, A. R. de Caen, L. Chameides, D. L. Atkins, R. A. Berg, M. D. Berg, F. Bhanji, D. Biarent, R. Bingham, A. H. Coovadia, et al. Part 10: Pediatric Basic and Advanced Life Support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Circulation, October 19, 2010; 122(16_suppl_2): S466 - S515. [Full Text] [PDF]

				B. D. Kussman, D. Wypij, P. C. Laussen, J. S. Soul, D. C. Bellinger, J. A. DiNardo, R. Robertson, F. A. Pigula, R. A. Jonas, and J. W. Newburger Relationship of Intraoperative Cerebral Oxygen Saturation to Neurodevelopmental Outcome and Brain Magnetic Resonance Imaging at 1 Year of Age in Infants Undergoing Biventricular Repair Circulation, July 20, 2010; 122(3): 245 - 254. [Abstract] [Full Text] [PDF]

				J. A. Ballweg, R. F. Ittenbach, J. Bernbaum, M. Gerdes, T. E. Dominguez, E. H. Zackai, R. R. Clancy, and J. W. Gaynor Hyperglycaemia after Stage I palliation does not adversely affect neurodevelopmental outcome at 1 year of age in patients with single-ventricle physiology Eur J Cardiothorac Surg, October 1, 2009; 36(4): 688 - 693. [Abstract] [Full Text] [PDF]

				Q. Chen and A. J. Parry The current role of hybrid procedures in the stage 1 palliation of patients with hypoplastic left heart syndrome Eur J Cardiothorac Surg, July 1, 2009; 36(1): 77 - 83. [Abstract] [Full Text] [PDF]

				H. M. Phelps, W. T. Mahle, D. Kim, J. M. Simsic, P. M. Kirshbom, K. R. Kanter, and K. O. Maher Postoperative Cerebral Oxygenation in Hypoplastic Left Heart Syndrome After the Norwood Procedure Ann. Thorac. Surg., May 1, 2009; 87(5): 1490 - 1494. [Abstract] [Full Text] [PDF]

				J. Li, G. Zhang, H. Holtby, B. Bissonnette, G. Wang, A. N. Redington, and G. S. Van Arsdell Carbon dioxide-a complex gas in a complex circulation: Its effects on systemic hemodynamics and oxygen transport, cerebral, and splanchnic circulation in neonates after the Norwood procedure. J. Thorac. Cardiovasc. Surg., November 1, 2008; 136(5): 1207 - 1214. [Abstract] [Full Text] [PDF]

				R. G. Ohye, J. W. Gaynor, N. S. Ghanayem, C. S. Goldberg, P. C. Laussen, P. C. Frommelt, J. W. Newburger, G. D. Pearson, S. Tabbutt, G. Wernovsky, et al. Design and rationale of a randomized trial comparing the Blalock-Taussig and right ventricle-pulmonary artery shunts in the Norwood procedure. J. Thorac. Cardiovasc. Surg., October 1, 2008; 136(4): 968 - 975. [Abstract] [Full Text] [PDF]

				S. Tabbutt, A. S. Nord, G. P. Jarvik, J. Bernbaum, G. Wernovsky, M. Gerdes, E. Zackai, R. R. Clancy, S. C. Nicolson, T. L. Spray, et al. Neurodevelopmental Outcomes After Staged Palliation for Hypoplastic Left Heart Syndrome Pediatrics, March 1, 2008; 121(3): 476 - 483. [Abstract] [Full Text] [PDF]

				J. Li, G. Zhang, H. Holtby, A.-M. Guerguerian, S. Cai, T. Humpl, C. A. Caldarone, A. N. Redington, and G. S. Van Arsdell The influence of systemic hemodynamics and oxygen transport on cerebral oxygen saturation in neonates after the Norwood procedure J. Thorac. Cardiovasc. Surg., January 1, 2008; 135(1): 83 - 90. [Abstract] [Full Text] [PDF]

				O. J. Liakopoulos, J. K. Ho, A. Yezbick, E. Sanchez, C. Naddell, G. D. Buckberg, R. Crowley, and A. Mahajan An Experimental and Clinical Evaluation of a Novel Central Venous Catheter with Integrated Oximetry for Pediatric Patients Undergoing Cardiac Surgery Anesth. Analg., December 1, 2007; 105(6): 1598 - 1604. [Abstract] [Full Text] [PDF]

				S. P Miller and P. S McQuillen Neurology of congenital heart disease: insight from brain imaging Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2007; 92(6): F435 - F437. [Full Text] [PDF]

				J. S. Tweddell, N. S. Ghanayem, K. A. Mussatto, M. E. Mitchell, L. J. Lamers, N. L. Musa, S. Berger, S. B. Litwin, and G. M. Hoffman Mixed Venous Oxygen Saturation Monitoring After Stage 1 Palliation for Hypoplastic Left Heart Syndrome Ann. Thorac. Surg., October 1, 2007; 84(4): 1301 - 1311. [Abstract] [Full Text] [PDF]

				A. R. Joffe, C. M.T. Robertson, A. Nettel Aguirre, I. M. Rebeyka, R. S. Sauve, and The Western Canadian Complex Pediatric Therapies P Mortality after neonatal cardiac surgery: Prediction from mean arterial pressure after rewarming in the operating room J. Thorac. Cardiovasc. Surg., August 1, 2007; 134(2): 311 - 318. [Abstract] [Full Text] [PDF]

				M. A. Padula and A. M. Ades Neurodevelopmental Implications of Congenital Heart Disease NeoReviews, July 1, 2006; 7(7): e363 - e369. [Full Text] [PDF]

				G. M. Hoffman Neurologic Monitoring on Cardiopulmonary Bypass: What Are We Obligated to Do? Ann. Thorac. Surg., June 1, 2006; 81(6): S2373 - S2380. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Kathleen A. Mussatto Robert D.B. Jaquiss James S. Tweddell Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hoffman, G. M. Articles by Tweddell, J. S. Search for Related Content PubMed PubMed Citation Articles by Hoffman, G. M. Articles by Tweddell, J. S.