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Ann Thorac Surg 2002;73:1752-1758
© 2002 The Society of Thoracic Surgeons

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Original article: cardiovascular

Current incidence of acute neurologic complications after open-heart operations in children

^a Department ofNeurology, Boston, Massachusetts, USA
^b Department ofCardiology, Boston, Massachusetts, USA
^c Department ofCardiovascular Surgery, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

Accepted for publication February 15, 2002.

* Address reprint requests to Dr du Plessis, Department of Neurology, Children’s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
e-mail: adre.duplessis{at}tch.harvard.edu

	Abstract

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Background. Previously, neurologic dysfunction was estimated to complicate 25% or less of pediatric open-heart operations. We sought to determine the current incidence and spectrum of early postoperative neurologic complications.

Methods. We undertook a retrospective review of all patients undergoing open heart operations in 1 year at our institution with the goal to identify all neurologic complications occurring in the early postoperative period.

Results. Open-heart operations were performed in 706 children. Sixteen children (2.3%) had neurologic complications develop, including 9 (1.3%) with definite clinical seizures, 1 with suspected seizures and bilateral subdural hemorrhage, 2 with coma after cardiac arrest, 2 with transient mild choreoathetosis, 1 with facial palsy, and 1 with persistent irritability. Causes of seizure were cyclosporin A toxicity posttransplant (4), cerebral ischemia post cardiac arrest (3), and unknown (2). In infants less than 1 year of age, the incidence of seizures was 1.2%.

Conclusions. This review suggests a decrease in acute neurologic morbidity after pediatric open heart operation. Clinical seizures remain the most common complication. Posttransplant, cyclosporin-associated seizures have emerged as an important etiologic category, coincident with an increase in cardiac transplantation in children.

	Introduction

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Advances in cardiac operations during the last 25 years, including deep hypothermic circulatory arrest and corrective operations in early life, have markedly increased the survival of children with congenital heart disease and reduced brain injury caused by chronic hypoxia or cyanosis. However, surgical approaches have been associated with other neurologic complications, including seizures, choreoathetosis, ischemic lesions, and encephalopathy [1–4]. Ten years before the current survey, neurologic dysfunction was estimated to complicate as many as 25% of pediatric open-heart operations in some centers [2], with seizures constituting the most common postoperative complication [1, 3, 5]. In these earlier reports, as many as two thirds of postoperative seizures in infants were of unknown cause. Previously these cryptogenic or "postpump" seizures were considered benign [1, 2], but in long-term follow-up they have been associated with significant cognitive sequelae [6, 7].

As a consequence of these trends, prevention of neurologic morbidity has become a major focus of research over the past decade in pediatric cardiac surgical centers, including our own. Because recent improvements in intraoperative neuroprotective strategies and critical care management have been instituted, we sought to define the current incidence and cause of acute neurologic complications after open-heart operations in children in a retrospective review at a tertiary center undertaking pediatric heart operations.

	Material and methods

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Subjects
In our institution, all patients who have open heart operations return to a single cardiac intensive care unit where the recognition of neurologic complications has been of particular clinical and research focus. All neurologic concerns, such as seizures, impaired level of consciousness, or motor disturbances, are addressed promptly by a dedicated neurology critical care team and are entered into a prospective database in which they are categorized into different clinical types by predetermined criteria (see Appendix).

Patients are discharged from the intensive care unit to the dedicated cardiac ward by a joint decision made by the cardiac intensivists and cardiac surgeons. The cardiac ward is staffed by specialists (cardiac nurses working together with attending cardiologists and cardiac surgeons as well as cardiology and cardiac surgery residents). The specific guidelines for discharge from the cardiac intensive care unit are as follows: "A cardiac intensive care unit patient who has recovered from his or her illness to such a degree that he or she no longer suffers from, or is at risk for, life-threatening organ system failure will be discharged from the cardiac intensive care unit. General discharge criteria include physiologic stability and the ability of the patient to protect their own airway. Specific criteria include a stable heart rate, rhythm, blood pressure, respiratory rate, and pattern. The patient should no longer require continuous nursing observation. The patient should no longer require invasive pressure monitoring." If a patient has an acute new neurologic finding develop on the cardiac ward, they are usually transferred back to the cardiac intensive care unit for full assessment.

We performed a retrospective review of our neurology database and the medical records for the calendar year 1998. We included all patients less than 21 years old who had an open heart operation performed in our hospital during this 1-year period, who presented with acute postoperative neurologic complications (ie, stroke, seizures, choreoathetosis, or coma). Patients were excluded if they had cardiac operations without cardiopulmonary bypass, or if the acute neurologic complications arose after an open heart operation that was performed at an outside hospital.

Seizures
A clinical seizure was defined as either focal motor, generalized, or subtle (constituted by a sudden and paroxysmal increase in blood pressure, heart rate, or pupil size, unexplained by medication changes, pain, or hemodynamic modifications, in a paralyzed and intubated child whose movements would be impossible to observe). Patients were classified as having postoperative clinical seizures if the neurologist witnessed the seizure, or if the description of the seizure fitted pre-established criteria such as persistence of clonic movements despite passive restraint, or criteria for subtle seizures. Criteria used for diagnosis of neurologic complications are shown in the Appendix.

Extracorporeal perfusion
Many modifications of our technique of extracorporeal perfusion support have been introduced over the last 5 to 10 years. After the results of our prospective randomized trial of circulatory arrest versus low flow bypass, the use of circulatory arrest was reduced and the duration of circulatory arrest was also decreased. In 1996 the results of a prospective randomized trial of pH strategy at Children’s Hospital Boston suggested that we should change our pH strategy to pH stat. During the current study all patients undergoing cardiopulmonary bypass with a core temperature below 30°C were cooled using the pH stat strategy. Specifically the patient’s pH as read from a blood gas analyzer at 37°C was adjusted using a nomogram to be 7.40 at the patient’s tympanic membrane temperature. This necessitated the addition of CO₂ to the ventilating gas of the oxygenator during cooling and low flow bypass. During rewarming when the patient reached 30°C, alpha stat management was instituted. Patients were rewarmed to a rectal temperature of at least 35°C before the cessation of bypass. Other changes that occurred have included the more aggressive use of conventional ultrafiltration during cardiopulmonary bypass as well as use of a hematocrit greater than 20%. A membrane oxygenator with arterial line filter was used for all patients.

	Results

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During 1998, 706 children underwent open-heart operations at our hospital. Of these operations, 122 were performed with deep hypothermic circulatory arrest of variable duration. At the time of operation, 336 children were younger than 1 year of age, of whom 130 were less than 1 month old. Fifteen patients underwent heart transplants (Table 1).

Among the 9 patients with seizures (see Table 3), the cause was cryptogenic in 2, cerebral ischemia in 3, and cyclosporin A (CsA) toxicity in 4. Status epilepticus occurred only in the 3 patients with ischemic lesions. The incidence of seizures in infants younger than 1 year of age was 1.2% (4 of 336). Seizures were most frequent in the acute period after heart transplantation, constituting a seizure rate of 26% in these patients (4 of 15). All transplant patients had clinical characteristics compatible with seizures caused by CsA neurotoxicity [8]; none had ischemic lesions. Three patients had additional exacerbating factors (high blood pressure [n = 2] and minimal subdural hemorrhage [n = 1]). The CsA levels were elevated in 2 patients and were within the therapeutic range in another 2.

With regard to the other acute neurologic complications (Table 4), our review demonstrated 2 patients with mild choreoathetosis, 1 in a heart transplant patient. Neither occurred after use of deep hypothermic circulatory arrest. Both patients improved during their intensive care unit stay. Among the 122 patients whose operation was performed using some period of deep hypothermic circulatory arrest, only 2 (1.6%) had acute neurologic complications (Tables 5 and 6). Of the 16 patients with acute postoperative neurologic injury in our study, 5 had these complications develop after a preoperative (n = 1) or postoperative (n = 4) cardiac arrest. The acute neurologic manifestations in these patients were coma (n = 2), coma with seizures (n = 1), and strokes with seizures (n = 2). All 3 patients who had coma develop after cardiac arrest died before hospital discharge.

	Comment

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Our review showed a current incidence of seizures of 1.2% in infants who underwent open heart operations compared with 9% to 32% in earlier retrospective series [1, 3, 5]. In prospective trials at our own institution, the incidence of early postoperative clinical seizures was 6.5% in 1988 [9] and 3.3% in 1996 [10], despite limiting inclusion in these trials to lower-risk neonates and young infants undergoing two-ventricle repair. Although we ascertained clinical seizures through retrospective review in the current series, diagnostic criteria for clinical seizures applied by bedside nurses and physicians were identical to those used in previous prospective studies. Nurses in our intensive care unit have been trained in the recognition of clinical seizures as part of their involvement in clinical trials that have been ongoing since 1988 [9]. Our cardiac intensive care unit uses a dedicated team of critical care neurologists for all neurologic consultations. Furthermore, it is the policy in our cardiac intensive care unit to obtain neurologic consultation in every child with suspected neurologic complications in the early postoperative period. The decision to obtain neurodiagnostic studies or EEGs is determined in consultation with the child neurologist.

The causes of postoperative seizures are multifactorial. Experimental studies have suggested that, under deep hypothermia, duration of circulatory arrest of more than 40 minutes carries increasing risk of neurologic injury [9, 11–13]. Both longer duration of total circulatory arrest and occurrence of perioperative seizures are independent risk factors for worse neurodevelopmental outcomes at ages 1 and 4 years [6, 7, 14]. A possible mechanism for postcirculatory arrest brain injury is suggested by experimental reports showing that the release of excitatory neurotransmitters such as glutamate seem to be responsible for delayed cell death [15].

Dissemination of both macroemboli and microemboli (gaseous or particulate) may also cause brain injury; indeed, one pediatric study found that 14% of patients with d-transposition of the great arteries had magnetic resonance imaging evidence 1 year postoperatively of cerebral infarction, usually very small, after the arterial switch operation [6]. In this retrospective series of neurologic complications in the early postoperative period, we cannot assess the overall prevalence of embolic infarction. Furthermore, the definitive imaging technique (ie, brain magnetic resonance imaging), often is not possible in the early postoperative period because of concerns relating to overheating of fresh sternal wires. We speculate, however, that the potential for embolic brain injury has decreased with introduction of smaller infant bypass circuits that reduce the interface between blood and foreign material, the use of arterial filtration in the bypass circuit, and replacement of bubble oxygenators by membrane oxygenators. Other variables that may influence the risk of brain injury include the duration of total support, the depth of hypothermia, the rate and duration of core cooling [16, 17], the degree of hemodilution, and other aspects of the biochemical milieu [18, 19].

The clinical spectrum of CsA-related neurotoxicity is broad [8, 20, 21]. However, as was the case in our study, seizures are by far the most common manifestation. Indeed, one quarter of all patients undergoing cardiac transplantation suffered with postoperative seizures. CsA-related seizures usually manifest after several weeks [8] but can occur more acutely, even at the very onset of treatment, as seen in our 4 patients. Various manifestations of CsA neurotoxicity can complicate up to 40% of organ transplants [20]; seizures have been reported in up to 36% of children [22] who have undergone heart transplantation, with a variable proportion attributed to CsA. CsA-induced seizures most often occur in association with high drug levels, but also can be observed with levels within the therapeutic range [8], as it occurred in 2 of our patients. These CsA-related seizures are often associated with features of posterior leukoencephalopathy on magnetic resonance imaging scan, and persistence of these imaging abnormalities after the acute period have been identified as a risk factor for later seizure recurrence [8], as seen in 1 of our patients.

The mechanisms of CsA neurotoxicity are poorly understood and likely multifactorial [23–26]. Likewise the interaction between CsA levels and known associated disturbances in blood pressure and magnesium remains unclear. Paradoxically, recent data suggest a potential neuroprotective role for CsA against hypoxic-ischemic brain injury [27].

The results of our study should be viewed in the light of the limitations of a retrospective study. It is possible, although unlikely, that clinical complications, such as seizures or mild changes in mental status, were missed because of the retrospective design of the study. However, subtle complications such as clinical occult electrographic seizures are necessarily understated in this report, because it is logistically unrealistic to perform continuous EEG monitoring on every patient. In fact, data from prospective trials [9, 10] have demonstrated that clinical seizures are detected in only one third to one half the neonates in whom EEG seizures are recorded by continuous monitoring. Also, the presence of subtle preoperative or postoperative neurologic abnormalities cannot be ruled out without a prospective design. Because this study was retrospective and performed in a tertiary center, only partial information was available regarding the occurrence of later neurologic complication, because for most patients follow-up is performed in their primary hospital.

Nevertheless, the aim of this study was to characterize the current incidence of acute clinically evident neurologic complications of open heart operations in a tertiary hospital. Although acute neurologic morbidity appears to be appreciably lower than in the past at our institution, definitive conclusions cannot be drawn because the patient populations used in the earlier studies were highly selected. Inclusion in the current series of all infants undergoing open heart operations, including the Norwood Stage 1 procedure, however, should have biased our recent results toward a higher rather than a lower rate of infant seizures. Furthermore there has been a trend toward a shorter duration of sedation and paralysis ("fast tracking"), which should have also biased the results towards more complete identification of seizures. Our cardiac intensive care nursing staff and the cardiac medical intensive care staff are highly attuned to observe unanticipated changes in heart rate or other hemodynamic findings as a marker of seizure activity. Finally, even assuming that neurologic morbidity has been reduced in the current era, we cannot determine the exact mechanisms by which this reduction has been achieved using a descriptive study design.

In conclusion, over the past decade the preservation of neurologic function has been a major focus in the management of infants and children undergoing open-heart operations.

This review suggests that the incidence of acute, clinically evident neurologic sequelae is lower in the current era than reported in the past. Furthermore, the etiologic profile of postoperative seizures appears to have shifted, with fewer cryptogenic or "postpump" seizures and a relative increase in symptomatic seizures, particularly those related to CsA toxicity after cardiac transplantation. The decrease in cryptogenic seizures over time highlights the importance of identifying modifiable underlying causes of postoperative neurologic complications. Future observations will demonstrate whether this low incidence of postoperative neurologic complications can be sustained or even further reduced.

	Acknowledgments

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Dr Menache was supported by a grant from Fondation Carlos et Elsie de Reuter, Geneva, Switzerland. He also received the Outstanding Junior Member Award from the Child Neurology Society for this study.

	Appendix

 
Common indications for neurologic consultation in the intensive care unit
Seizures
Clinical seizures are suspected when paroxysmal, stereotypic, repetitive motor behaviors (tonic, clonic, or myoclonic) cannot be suppressed by passive restraint, repositioning, or stimulation of the infant. These events may be accompanied by alterations in awareness. In the postoperative period, sedating and paralyzing medications may confine seizure manifestations to autonomic paroxysms, such as sudden unexplained increases in blood pressure and heart rate, often accompanied by pupillary dilation. In our intensive care unit, the diagnosis of seizures requires unequivocal clinical motor manifestations or confirmation by electroencephalogram of more subtle clinical changes.

Weakness
Neurologic consultation was requested for any patients with a new onset (focal, lateralized, or diffuse) that was clearly of a new onset. Depending on the accompanying clinical features, these infants are investigated further by neuroimaging techniques, nerve conduction velocities, or peripheral nerve stimulation.

Unexplained altered mental state
Neurologic consultation was requested in cases where recovery of consciousness in the postoperative period could not be explained by persistent sedating or paralyzing effects of medications. Other alterations of mental state included severe irritability, insomnia, or agitation not responsive to appropriate doses of analgesic or sedating medication.

Choreoathetosis
Involuntary movement disorders, or dyskinesias, were suspected if children had irrepressible movements develop that were either irregular, nonrepetitive and nonrhythmic (chorea) or continuous slow, writhing movements of the extremities, face, and trunk (athetosis), or sustained tortional muscular contractions (dystonia). When mixed features of the first two conditions occur, the term choreoathetosis is used.

Abnormal ultrasound studies
Certain high-risk newborn infants undergo routine preoperative cranial ultrasound examinations, including infants born prematurely with birth weight under 1500 grams, infants with coagulation disturbances, or hemodynamic instability causing significant metabolic acidosis. In addition all infants requiring extracorporeal membrane oxygenation, and infants with certain high-risk cardiac diagnoses, such as hypoplastic left heart syndrome and coarctation of the aorta, undergo preoperative cranial ultrasound. Any abnormalities on these studies elicit a neurology consultation.

Potentially significant ischemic insults
Any child with acute onset sustained hypotension or cardiac arrest that is successfully resuscitated, is evaluated and followed clinically by the neurology consult team. This includes all infants and children requiring a period of extracorporeal membrane oxygenation support.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

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