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Ann Thorac Surg 2001;71:877-880
© 2001 The Society of Thoracic Surgeons
a Department of Pediatric Cardiology, Aachen University of Technology, Aachen, Germany
b Department of Thoracic and Cardiovascular Surgery, Aachen University of Technology, Aachen, Germany
Accepted for publication August 21, 2000.
Address reprint requests to Dr Sigler, Klinik für Kinderkardiologie, Pauwelsstr 30, D-52057 Aachen, Germany
e-mail: matthias.sigler{at}post.rwth-aachen.de
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Abstract |
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 Top Abstract IntroductionMaterial and methodsResultsCommentReferences |
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Methods. Cranial ultrasound was performed prospectively in 35 neonates with transposition of the great arteries before the operation as well as 4 hours, 1, 2, and 3 days, and 1 and 2 weeks postoperatively. Blood levels of neuron-specific enolase, a marker of cerebral cell damage, were determined before, during, and 4 and 24 hours postoperatively.
Results. In 17 of 35 neonates (49%), early postoperative cranial ultrasound revealed abnormalities indistinguishable from intraventricular hemorrhage. In 11 neonates findings were transient and were normalized 2 weeks postoperatively, whereas in the remaining 6 neonates there was evidence of resolving hemorrhage. In all neonates there was a rise in neuron-specific enolase blood concentrations during and 4 hours after extracorporal circulation without correlation to sonographic findings.
Conclusions. Enhanced echogenicity of the choroid plexus or dilatation of the cerebral ventricular system is a frequent early postoperative finding that may be caused by transient plexus edema rather than intraventricular hemorrhage and is not related to cerebral cell damage.
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Introduction |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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Material and methods |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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Operation
Conventional general anesthesia was performed. Dexamethasone (3 mg/m2 body surface area) given for prophylaxis of cerebral edema was administered before sternotomy. Arterial switch operation was performed under a combined low-flow cardiopulmonary bypass and hypothermic circulatory arrest (minimal nasopharyngeal temperature 15°C), using pH-stat strategy. For vasodilation in the cooling and rewarming periods, all neonates received a continuous infusion of sodium nitroprusside (0.5 to 2.3 µg/kg per minute; median, 1 µg/kg per minute).
Clinical evaluation of cerebral seizures
Seizures were diagnosed when the patient developed focal or generalized tonic-clonic movements.
Cranial ultrasound
Cranial ultrasound was performed before the operation as well as 4 hours, 1, 2, and 3 days, and 1 and 2 weeks postoperatively using a 7.5-MHz transducer. Using the anterior fontanelle as a window, standardized views of the brain were documented. Sonographic signs of enhanced intracranial echogenicity were graded in four categories (grade I = subependymal hemorrhage; II = intraventricular hemorrhage [IVH] without widening of the ventricles; III = IVH with widening of the ventricles; IV = parenchymal bleeding with or without IVH) according to the classification of intraventricular hemorrhage (IVH) in premature neonates by Papile and colleagues [2].
Blood samples
Venous blood was collected before and during the operation as well as 4 and 24 hours after the end of cardiopulmonary bypass in tubes containing EDTA. The samples were immediately centrifuged for 3 minutes (3,000 rpm), and the plasma was stored at -70°C until analysis. Neuron-specific enolase was determined by a commercially available enzyme-linked immunosorbent assay kit (Pharmacia AB, Uppsala, Sweden) and expressed in micrograms per liter. Values greater than 11.4 µg/L were considered elevated in healthy neonates [3]. Serum levels of lactate dehydrogenase were determined as a marker of hemolysis by a commercially available ultraviolet test (optimized standard method by Boehringer Mannheim SA, Germany) and expressed in units per liter.
Statistical analysis
Results are expressed by median and quartiles assuming not normal distribution of the data. For intergroup comparison of clinical and of biologic variables at specific sample times, the nonparametric Mann-Whitney U test was used. The Spearman rank correlation coefficient was assessed for correlation of independent variables, and the Fischer’s exact test was used for the analysis of contingency tables. Probability values less than 0.05 were considered significant. Alpha adjustment for multiple comparisons was performed according to Bonferroni-Holm.
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Results |
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After the operation, 17 neonates (49%) showed signs of enhanced echogenicity in the choroid plexus or in the lateral ventricles not distinguishable from IVH at this time and interpreted as IVH-like findings. Distribution and time course of the different grades of these IVH-like findings are shown in Table 1. Five patients exhibited grade III at most, and no case of parenchymal involvement (grade IV) was observed. The highest grade of IVH-like findings in individual patients was found not later than 2 days after the operation.
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Age at operation, sex, ventricular septal defect in addition to transposition, and incidence of seizures were not significantly related to the occurrence of IVH-like findings. The same was true for epinephrine requirement after operation. Dosage of sodium nitroprusside was significantly lower 24 hours postoperatively (p = 0.025) in patients with enhanced echogenicity or dilatation of cerebral ventricles. Table 2 summarizes comparative clinical data of patients with and without IVH-like findings at any time during the study.
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Laboratory tests
Neuron-specific enolase plasma levels increased intraoperatively compared with preoperative values, reaching peak levels 4 hours after termination of cardiopulmonary bypass. Twenty-four hours postoperatively, NSE levels reached preoperative levels (Fig 1). Neuron-specific enolase levels were not significantly different in patients with or without IVH-like findings, in patients with transient IVH-like findings versus patients with persistent IVH, and in patients with or without postoperative seizures. There was no correlation between NSE and lactate dehydrogenase plasma levels. Thus, an influence of hemolysis as a cause for increased NSE levels in our patients was excluded.
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Comment |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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In the present study, 49% of our patients exhibited areas of enhanced echogenicity of the choroid plexus or dilatation of the cerebral ventricular system within 24 hours postoperatively. So far, these sonographic findings in the choroid plexus and the cerebral ventricles have usually been interpreted as signs of IVH, indicating an increased risk for cerebral cell damage and early childhood developmental or neuromotor handicaps [6]. However, the early complete resolution of these findings within 2 weeks in the majority of our affected patients suggests that in these patients, true IVH was not present. This statement is supported by the fact that in true IVH, resolution of enhanced echogenicity of the choroid plexus or dilatation of the cerebral ventricles or development of cysts or reduced focal echogenicity is described as occurring only after several weeks [7]. It was, therefore, the time course of sonographic findings that allowed us to retrospectively exclude true IVH in case of normalization of the findings within 2 weeks without residual lesions.
The sonographic feature of transient IVH-like findings shortly postoperatively may be caused by plexus edema. The choroid plexus acts as intracranial lymphatic system and could be overburdened with the resorption of cerebrospinal fluid whose amount may be increased owing to the systemic inflammatory reaction that takes place during cardiac operations and leads to capillary leak syndrome particularly in neonates [8].
The fact that patients without IVH-like findings in cranial ultrasound received a higher dosage of sodium nitroprusside 24 hours postoperatively suggests a beneficial effect of sodium nitroprusside with regard to the occurrence of plexus edema. Indeed, sodium nitroprusside has been shown to have some antiinflammatory properties by releasing nitric oxide, which is an inhibitor of complement activation [9] and reduces endothelium-leukocyte interactions [10].
Capillary leak syndrome is related to increased microvascular permeability [11]. Increased permeability of cerebral cell membranes, although not demonstrated so far, is likely to develop in the setting of cardiac operations in neonates. This could be the reason for the increase of NSE blood levels we observed in all patients without any correlation to cranial ultrasound findings.
In our study, NSE levels and occurrence of seizures were not correlated. Another study from our group showed no correlation between perioperative NSE release and midterm neurodevelopmental outcome after arterial switch operation (8 patients were common to both study groups) [12]. Thus, NSE cannot be regarded as a reliable marker for neuronal cell damage related to cardiac operations in neonates.
The only clinical indicator for brain damage in our study was the occurrence of seizures in the early postoperative period. Four of 35 of our patients (11%) experienced seizures. Miller and coworkers [13] reported an incidence of 15% in a group of 91 infants under the age of 6 months after open heart surgery. Newburger and associates [14] found clinical seizures in 11% and electrical seizures (with continuous electroencephalographic monitoring) in 26% of neonates after arterial switch operation for transposition. In our study, occurrence of seizures was not correlated with findings in cranial ultrasound.
In conclusion, the present study demonstrates a high incidence of IVH-like abnormal findings in cranial ultrasound in neonates having undergone an arterial switch operation. In the majority of patients, these findings are transient, suggesting plexus edema rather than true IVH as the underlying cause. This should be kept in mind when withdrawal from supportive therapy after cardiac operation in neonates is considered because of sonographic signs of IVH.
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References |
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This article has been cited by other articles:
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  H H Hovels-Gurich, K Konrad, M Wiesner, R Minkenberg, B Herpertz-Dahlmann, B J Messmer, and G von Bernuth Long term behavioural outcome after neonatal arterial switch operation for transposition of the great arteries Arch. Dis. Child., December 1, 2002; 87(6): 506 - 510. [Abstract] [Full Text] [PDF]
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 H. H. Hovels-Gurich, M.-C. Seghaye, R. Schnitker, M. Wiesner, W. Huber, R. Minkenberg, F. Kotlarek, B. J. Messmer, and G. von Bernuth Long-term neurodevelopmental outcomes in school-aged children after neonatal arterial switch operation J. Thorac. Cardiovasc. Surg., September 1, 2002; 124(3): 448 - 458. [Abstract] [Full Text] [PDF]
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