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Ann Thorac Surg 2003;76:576-580
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

Early postoperative prediction of cerebral damage after pediatric cardiac surgery

^a Department of Neonatology and Pediatric Critical Care, PICU, Vienna, Austria
^b ECMO Project, Vienna, Austria
^c Department of Cardiac Surgery, Vienna, Austria
^d Department of Medical Computer Sciences, University of Vienna, Vienna, Austria

Accepted for publication February 27, 2003.

^* Address reprint requests to Dr Trittenwein, Pediatric Intensive Care Unit, University Children’s Hospital Vienna, Waehringerguertel 18-20, A-1090, Wien, Austria.
e-mail: g.trittenwein{at}a1.net

	Abstract

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BACKGROUND: Cerebral damage is a serious complication of pediatric cardiac surgery. Early prediction of actual risk can be useful in counseling of parents, and in early diagnosis and rehabilitation therapy. Also, if all children at risk could be identified therapeutic strategies to limit perioperative cerebral damage might be developed. The aim of this study is to create a mathematical model to predict risk of neurologic sequelae within 24 hours after surgery using simple and readily available clinical measurements.

METHODS: The hospital records of 534 children after cardiac surgery were reviewed. Variables examined were age at operation, diagnosis, use of cardiopulmonary bypass, arterial and central venous oxygen saturation, serum glucose, lactate and creatine kinase, mean arterial pressure, and body temperature. The endpoint for each study patient was the occurence or lack of occurence of seizures, movement or developmental disorders, cerebral hemorrhage, infarction, hydrocephalus, or marked cerebral atrophy. Univariate and multivariate regression analyses were used to evaluate the predictive power of the investigated factors as well as to create a predictive model.

RESULTS: In 6.26% of children symptoms of cerebral damage were found. Significant risk factors were age at surgery, more complex malformations, metabolic acidosis, and increased lactate (odds ratio: age, 0.882/yr [0.772–1.008]; complex malformations, 10.32 [1.32–80.28]; arterial pH more than 7.35 to 0.4 [0.18–0.89]; lactate -1.018 per mg/dL [1.006–1.03]).

CONCLUSIONS: It is possible to quantify the risk of appearance of symptoms of cerebral damage after cardiac surgery within 24 hours using simple and readily available clinical measurements.

	Introduction

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Postoperative cerebral dysfunction is a serious complication of pediatric cardiac surgery that may result in adverse surgical outcome and prolonged hospitalization [1, 2].

Early detection of postoperative neurologic impairment enables prompt institution of therapy and appropriate counseling of parents, which may result in earlier rehabilitation. In addition, if children at risk could be identified, new strategies to reduce neurologic impairment after cardiac surgery might be developed.

Diagnostic tests to identify impaired cerebral function after cardiac surgery have been reported. Elevation of protein S-100 or of neuronospecific enolase in the serum of patients after surgery, as well as alterations of the electroencephalogram or of evoked potentials, were described to verify cerebral damage [3–7]. Additional costs and technical support prohibit their routine use in all pediatric intensive care units (PICU). We report here our study of readily available clinical variables in the prediction of risk of neurologic sequelae after pediatric cardiac surgery.

	Material and methods

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Measurements
The hospital records of 543 children who underwent cardiac surgery between 1994 and 1999 were reviewed retrospectively. Diagnostic subgroups were as follows: Group S comprised children with simple atrial or ventricular septal defects; Group RVO comprised children with right ventricular outflow obstruction (pulmonary stenosis, pulmonary atresia, tetralogy of Fallot, or tricuspid atresia); Group LVO comprised children with left ventricular outflow obstruction, including aortic stenosis or coarctation; and Group C comprised children with complex malformations, such as double outlet right ventricle, transposition of the great arteries, atrioventricular canal, total anomalous pulmonary venous drainage, or hypoplastic left heart syndrome.

Variables assessed were age at operation, use of cardiopulmonary bypass, arterial and central venous oxygen saturation, arterial pH, arterial or central venous glucose, lactate and creatine kinase, mean arterial blood pressure, and body temperature. For purposes of statistical evaluation we used values for each factor that differed most from normal range during the first 24 hours postoperatively.

Positive endpoints were clinical or morphologic findings of postoperative cerebral impairment [2]. Clinical symptoms include seizures, pareses, choreoathetosis, or impairment of cognitive or statomotoric development. The latter impairment was thought present if already learned abilities disappeared after surgery or if no further development could be recognized after surgery. This defintion resulted in our inclusion of children with preexisting neurologic impairment or chromosomal abnormalities like trisomy 21. Findings occuring after pediatric cardiac surgery and indicative for perioperative cerebral damage were cerebral infarction, cerebral hemorrhage, hydrocephalus or marked cerebral atrophy diagnosed by cat scan, magnetic resonance tomography, or autopsy.

Statistics
Values for arterial pH, arterial and central venous oxygen saturation, and mean arterial blood pressure were categorized as normal or abnormal for ease of clinical application of this model. Lactate was recorded as a continuous as well as a categorized variable.

Association between categorical variables was evaluated using the ² test and the Fischer’s exact test. Linear correlation between continuous variables was evaluated by the Pearson correlation coefficient. In order to assess the prognostic value of variables, simple and multiple logistic regression models were fitted to the observed data with neurologic findings as the dependent variable. Measurements were estimated by the maximum likelihood method and p values referred to Wald ² statistics. To assess the predictive ability of the fitted logistic model, a receiver operating characteristic (ROC) curve was constructed. This curve is a plot of the sensivity (or true-positive rate) to the false-positive rate and is commonly used to demonstrate the accuracy of a diagnostic measure.

Finally, the derived mathematical model was applied to two virtual patients and depicted on a graph to demonstrate clinical application.

	Results

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The median age at surgery of the 543 children was 16 months old (range 0 to 286 months old), and 409 patients underwent procedures using cardiopulmonary bypass; 143 patients belonged to group S, 111 patients to group LVO, 99 patients to group RVO, and 190 patients to group C.

Thirty-four children exhibited one or more of the above described clinical or morphologic findings that indicated neurologic impairment (6.26%). Table 1 illustrates age at surgery, diagnoses, operation, and neurologic findings in those children. Table 2 demonstrates the result of univariate analysis comparing the values of investigated variables to predict the appearance of perioperative cerebral damage. There was a strong correlation between high glucose and high lactate values, but we could not find a significant predictive value for glucose. Table 3 depicts the mathematical model created by multiple regression and the odds ratio of the included parameters. The included parameters were found to be independently predictive. Figure 1 depicts the ROC curve demonstrating the predictive value of the derived mathematical model. Figure 2 illustrates the graphical application of the predictive model in two virtual patients. First is a neonate with a complex cardiac malformation (eg, transposition of great arteries) with increasing lactate values during the first 24 hours after cardiac surgery. The effect of lactate values on the risk of appearance of postoperative neurologic symptoms is depicted. The other virtual patient, an 18 year old, is depicted during the first 24 hours after correction of a ventricular septal defect. Again, the correlation between increasing lactate values and the risk for neurologic sequelae is demonstrated.

View larger version (12K): [in this window] [in a new window]   Fig 1. Receiver operating characteristic (ROC) curve of the predictive mathematical model for prediction of cerebral damage. The area under the ROC curve is 0.82; logistic regression was used.

View larger version (10K): [in this window] [in a new window]   Fig 2. Application of the predictive model. Estimated risk of appearance of neurologic symptoms is demonstrated in two virtual patients experiencing postoperative metabolic acidosis. The increasing serum lactate levels during the first 24 hours postoperatively are illustrated, and the effect of lactate values on the risk of appearance of postoperative neurologic symptoms (predicted probability) is depicted. Predicted probability is derived following the mathematical model described in Table 3. (Straight line = a 3-day-old neonate after correction of transposition of great arteries; dotted line = an 18-year-old patient after ventricular septal defect closure.)

	Comment

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Specific methods for detection of perioperative cerebral damage as electroencephalography or investigation of biochemical markers like protein S-100 have been described [3–7]. The additional costs and needed technical support prohibit their routine use in all patients and restrict their use to those with suspected cerebral damage. In many cases, however, it is difficult to estimate hypoxic cerebral damage, for example, after short periods of low arterial oxygen saturation or depressed arterial pressure, small air emboli, short periods of low cardiac output after weaning from bypass, or insufficient cooling particulary of the head during bypass. A simple method to routinely assess the postoperative risk of hypoxic neurologic damage in all operated children would be very helpful and might lead to development of strategies to diminish impairment after intraoperative hypoxic cerebral damage. These include prolonged postoperative hypothermia, prolonged sedative analgesia, and paralysis to reduce oxygen demand or aggressive use of mechanical circulatory support in cases of prolonged low cardiac output.

The significant predictors in our study were lower age at surgery, complex cardiac malformations, metabolic acidosis, and increased lactate level. These predictors are plausible because during the first year of life rapid brain growth makes it susceptible to hypoxic damage. Particulary in neonates, lactate accumulation is described to be of high predictive power for hypoxic brain damage [8]. Complex congenital heart defects require more difficult surgery, which may carry a higher risk of intraoperative complications; although this may vary greatly among various cardiac surgical centers [9].

We did not find use of cardiopulmonary bypass to be a significant predictor of cerebral damage in uinivariate analysis. This is understandable realizing that children with and without bypass may experience marked arterial desaturation, for example, during a Blalock-Taussing shunt procedure without bypass or cardiac arrest while preparing for or after bypass.

The value of our study is limited by its retrospective design and underestimation of sequelae cannot be ruled out. The endpoint of the study is not specific and we used the detection of each of the described findings indicative for perioperative hypoxic damage, which may underestimate neurologic sequelae. Volpe feels there is no specific test for postoperative hypoxic damage [10], and commonly used developmental tests are not specific [11]. Another limitation of our study is the short 6-month follow-up time that may also result in lack of recognition of neurologic symptoms in some patients.

In summary, it seems possbile to quantify the risk of appearance of symptoms of cerebral damage after cardiac surgery within 24 hours using readily available clinical measurments. This may be helpful in informing parents, and it may allow for earlier therapeutic interventions. Our findings imply that neonates who undergo surgery for complex cardiac malformation and experience postoperative metabolic acidosis with lactate levels above 100 mg/dL have a greater than 30% risk of developing symptoms of postoperative brain damage.

	Acknowledgments

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This article is presented on behalf of the "Verein zur Durchführung wissenschaftlicher Forschung auf dem Gebiet der Neonatologie und Pädiatrischen Intensivmedizin," Vienna, Austria. The authors thank S. Bert Litwin, MD, for his help with language editing this manuscript.

	References

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8. Cheung P.Y., Robertson C.M.T., Finer N.N. Plasma lactate as a predictor of early childhood neurodevelopmental outcome of neonates with severe hypoxiemia requiring ECMO. Arch Dis Child 1996;74:F47-F50.
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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): Gregor Wollenek Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Trittenwein, G. Articles by Wollenek, G. Search for Related Content PubMed PubMed Citation Articles by Trittenwein, G. Articles by Wollenek, G. Related Collections Cerebral protection