524469 research-article2014
PRF0010.1177/0267659114524469PerfusionNaik et al.
Original Paper
The impact of cerebral embolization during infant cardiac surgery on neurodevelopmental outcomes at intermediate follow-up
Perfusion 2014, Vol. 29(5) 443–449 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0267659114524469 prf.sagepub.com
RJ Naik,1 JB Wagner,1 D Chowdhury,1 ML Barnes,2 DS Wagner,3 KC Burson,3 PJ Eslinger1,3 and JB Clark1,4
Abstract Cerebral embolization during pediatric cardiac surgery may be an underappreciated source of subsequent neurodevelopmental impairment. Transcranial Doppler ultrasound is a neuromonitoring tool that can provide intraoperative surveillance for cerebral embolization. We hypothesized that increased cerebral embolic signals detected during infant cardiac surgery would be associated with worse neurodevelopmental outcomes at follow-up. A study group of 24 children who underwent infant cardiac surgery with transcranial Doppler detection of cerebral embolic signals returned at intermediate follow-up for standardized neurodevelopmental assessment. The children were evaluated using two neurocognitive tests and the parents completed two questionnaires regarding observed behavior. Statistical analysis assessed for correlation between the number of cerebral embolic signals at surgery and the results of the neurodevelopmental assessment. Of the 67 test parameters analyzed, five showed a significant association with the number of embolic signals, yet, all in the contrary direction of the clinical hypothesis, likely representing a Type I error. Thus, in this small cohort of patients, the number of cerebral embolic signals detected during infant cardiac surgery was not shown to be associated with worse neurodevelopmental outcomes at intermediate follow-up. A larger study is probably necessary to ascertain the potential influence of cerebral embolic signals on eventual neurologic outcomes in children. The clinical relevance of cerebral embolic signals during pediatric cardiac surgery remains undetermined and deserves further investigation. Keywords congenital; pediatric; brain; embolization; neurodevelopmental; neuromonitoring; transcranial Doppler
Introduction Congenital heart disease is the most common birth defect, with an incidence of nearly 1%1 and is the most common cause of first-year mortality related to birth defects.2 The definitive therapy for the majority of these defects is an operative repair with the support of cardiopulmonary bypass. Overall hospital mortality rates for pediatric heart surgery have declined to near 4% with
advances in surgical technique and perioperative management.3 As mortality rates have decreased, attention has increasingly focused on minimizing the morbidity associated with these operations. The incidence of neurologic morbidity associated with pediatric heart surgery remains significant, with acute stroke reported in 0.5-10% of patients,4,5 neurode-
1Department
500 University Drive, H085 Hershey, PA 17033 USA. Email: [email protected]
of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania, USA 2Impulse Monitoring Inc., Columbia, Maryland, USA 3Department of Neurology, Penn State College of Medicine, Hershey, Pennsylvania, USA 4Department of Surgery, Penn State College of Medicine, Hershey, Pennsylvania, USA Corresponding author: Joseph B. Clark, MD Penn State College of Medicine
Dr. Naik is currently a faculty member of Le Bonheur Children’s Hospital, University of Tennessee College of Medicine, Memphis, Tennessee. Dr. Wagner is currently a faculty member of Children’s Mercy Hospitals, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri. Dr. Chowdhury is currently a faculty member at Lancaster General Health, Lancaster, Pennsylvania.
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Perfusion 29(5)
velopmental disability in up to 50% of patients6,7 and decreased performance on late neurocognitive tests in up to 70% of patients.8 Although the etiology of such neurological dysfunction is multifactorial, intraoperative cerebral embolization of particulate or gaseous material may play an important and underappreciated role in the development of neurologic morbidity associated with pediatric cardiac surgery. The pathologic consequences of cerebral embolization are believed to manifest predominantly as global and diffuse chronic neurologic injury, rather than as acute and recognizable focal deficits.9–12 While cerebral embolization associated with cardiac surgery in adults has been shown to be a risk factor for adverse neurologic outcomes,13–17 this correlation has not been conclusively demonstrated in children. Surveillance for cerebral embolization can be performed during cardiac surgery, using transcranial Doppler ultrasound.18 As part of a multi-modality brain monitoring protocol, the use of transcranial Doppler during pediatric heart surgery has been shown to reduce acute neurologic events by facilitating corrective interventions in response to adverse neuromonitoring parameters consistent with malperfusion and cerebral embolism.19 We hypothesized that increased cerebral embolic signals detected by transcranial Doppler during infant cardiac surgery would be associated with worse neurodevelopmental outcomes at intermediate followup. The objective of this study was to assess for a correlation between the number of embolic signals at surgery and subsequent neurologic outcome in a small cohort of pediatric patients.
Methods Internal Review Board approval was obtained. Inclusion criteria included the absence of genetic syndromes or preoperative neurologic abnormalities, cardiac surgery at age less than one year with transcranial Doppler ultrasound monitoring and age 3-6 years at follow-up. Candidates were identified from a surgical database and the parents were solicited for voluntary participation. Consent for study participation was provided.
Neuromonitoring data Our multi-modality neuromonitoring protocol for pediatric cardiac surgery has been previously described.20 Several surveillance technologies are routinely used, including near-infrared spectroscopy, transcranial Doppler ultrasound, electroencephalography and somatosensory-evoked potentials. This study focused specifically on cerebral embolic signals detected by transcranial Doppler. The right middle cerebral artery is located through insonation and the probe is secured in place for the duration of the operation (Figure 1). The probe provides continuous surveillance of the blood
Figure 1. Surveillance for cerebral embolization during pediatric cardiac surgery, using transcranial Doppler ultrasound. (A) Insonation of the middle cerebral artery. (B) Probe placement during surgery.
velocity in the middle cerebral artery and detects highintensity transient signals (HITS) consistent with intravascular emboli. Intraoperative monitoring data for each operation is captured and stored to a computer database.
Neurodevelopmental testing Neurodevelopmental testing of the study participants was performed by an expert examiner, with a supervising neuropsychologist, using two instruments: the Neuropsychological Assessment Second Edition (NEPSY-II, Pearson Education, Inc., San Antonio, TX) and the Kiddie Continuous Performance Test (K-CPT, Multi-Health Systems, Inc., North Tonawanda, NY). The NEPSY-II test is a comprehensive and standardized neurocognitive assessment of children, validated for ages 3-16 years.21 The assessment yields standard scores, process scores and combined scores across six major domains of neurocognitive development: attention and executive functioning, language, learning and memory, sensorimotor functioning, visual-spatial cognition and social perception. The NEPSY-II has been shown to provide valid assessment in mild intellectual disorders, attention deficit hyperactivity disorder, autism spectrum, reading, language and math disorders and emo-
Downloaded from prf.sagepub.com at CALIF STATE POLY UNIV LIBRARY on March 18, 2015
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Naik et al.
tional disorders. The K-CPT is an interactive computer program for children, designed to measure attention disorders. Pictures of familiar objects are presented onscreen and the children are tasked to push the space bar for every picture except for a particular target stimulus (e.g., a picture of a ball). A practice administration is provided to ensure that respondents are adequately facile with the keyboard before completing the task. This test assesses timing accuracy, speed and accuracy of response, omissions and perseverations.
Parental questionnaires Parental perception of multiple aspects of their child’s neurodevelopmental performance was assessed using two instruments: the Adaptive Behavioral Assessment System, Second Edition (ABAS-II, Pearson Education Inc., San Antonio, TX), and the Behavior Assessment System for Children, Second Edition (BASC-2, Pearson Education Inc.,). The ABAS-II assesses dimensions of conceptual development (including communication and self-direction), social development (including leisure and social interactions) and practical development (including self-care and health and safety issues). The BASC-2 evaluates areas of personality, emotion and behavior.
Statistical analysis Statistical analyses were used to examine the relationship between the cerebral embolization results from surgery (i.e., number of HITS per patient operation) and the results of neuropsychological testing (NEPSY-II and K-CPT) and parental questionnaire scores (ABAS-II and BASC-2). Bivariate correlation was computed on each variable within the neurodevelopmental subtests. In each case, the null hypothesis was a “no relationship” statement and a p-value of
PRF0010.1177/0267659114524469PerfusionNaik et al.
Original Paper
The impact of cerebral embolization during infant cardiac surgery on neurodevelopmental outcomes at intermediate follow-up
Perfusion 2014, Vol. 29(5) 443–449 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0267659114524469 prf.sagepub.com
RJ Naik,1 JB Wagner,1 D Chowdhury,1 ML Barnes,2 DS Wagner,3 KC Burson,3 PJ Eslinger1,3 and JB Clark1,4
Abstract Cerebral embolization during pediatric cardiac surgery may be an underappreciated source of subsequent neurodevelopmental impairment. Transcranial Doppler ultrasound is a neuromonitoring tool that can provide intraoperative surveillance for cerebral embolization. We hypothesized that increased cerebral embolic signals detected during infant cardiac surgery would be associated with worse neurodevelopmental outcomes at follow-up. A study group of 24 children who underwent infant cardiac surgery with transcranial Doppler detection of cerebral embolic signals returned at intermediate follow-up for standardized neurodevelopmental assessment. The children were evaluated using two neurocognitive tests and the parents completed two questionnaires regarding observed behavior. Statistical analysis assessed for correlation between the number of cerebral embolic signals at surgery and the results of the neurodevelopmental assessment. Of the 67 test parameters analyzed, five showed a significant association with the number of embolic signals, yet, all in the contrary direction of the clinical hypothesis, likely representing a Type I error. Thus, in this small cohort of patients, the number of cerebral embolic signals detected during infant cardiac surgery was not shown to be associated with worse neurodevelopmental outcomes at intermediate follow-up. A larger study is probably necessary to ascertain the potential influence of cerebral embolic signals on eventual neurologic outcomes in children. The clinical relevance of cerebral embolic signals during pediatric cardiac surgery remains undetermined and deserves further investigation. Keywords congenital; pediatric; brain; embolization; neurodevelopmental; neuromonitoring; transcranial Doppler
Introduction Congenital heart disease is the most common birth defect, with an incidence of nearly 1%1 and is the most common cause of first-year mortality related to birth defects.2 The definitive therapy for the majority of these defects is an operative repair with the support of cardiopulmonary bypass. Overall hospital mortality rates for pediatric heart surgery have declined to near 4% with
advances in surgical technique and perioperative management.3 As mortality rates have decreased, attention has increasingly focused on minimizing the morbidity associated with these operations. The incidence of neurologic morbidity associated with pediatric heart surgery remains significant, with acute stroke reported in 0.5-10% of patients,4,5 neurode-
1Department
500 University Drive, H085 Hershey, PA 17033 USA. Email: [email protected]
of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania, USA 2Impulse Monitoring Inc., Columbia, Maryland, USA 3Department of Neurology, Penn State College of Medicine, Hershey, Pennsylvania, USA 4Department of Surgery, Penn State College of Medicine, Hershey, Pennsylvania, USA Corresponding author: Joseph B. Clark, MD Penn State College of Medicine
Dr. Naik is currently a faculty member of Le Bonheur Children’s Hospital, University of Tennessee College of Medicine, Memphis, Tennessee. Dr. Wagner is currently a faculty member of Children’s Mercy Hospitals, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri. Dr. Chowdhury is currently a faculty member at Lancaster General Health, Lancaster, Pennsylvania.
Downloaded from prf.sagepub.com at CALIF STATE POLY UNIV LIBRARY on March 18, 2015
444
Perfusion 29(5)
velopmental disability in up to 50% of patients6,7 and decreased performance on late neurocognitive tests in up to 70% of patients.8 Although the etiology of such neurological dysfunction is multifactorial, intraoperative cerebral embolization of particulate or gaseous material may play an important and underappreciated role in the development of neurologic morbidity associated with pediatric cardiac surgery. The pathologic consequences of cerebral embolization are believed to manifest predominantly as global and diffuse chronic neurologic injury, rather than as acute and recognizable focal deficits.9–12 While cerebral embolization associated with cardiac surgery in adults has been shown to be a risk factor for adverse neurologic outcomes,13–17 this correlation has not been conclusively demonstrated in children. Surveillance for cerebral embolization can be performed during cardiac surgery, using transcranial Doppler ultrasound.18 As part of a multi-modality brain monitoring protocol, the use of transcranial Doppler during pediatric heart surgery has been shown to reduce acute neurologic events by facilitating corrective interventions in response to adverse neuromonitoring parameters consistent with malperfusion and cerebral embolism.19 We hypothesized that increased cerebral embolic signals detected by transcranial Doppler during infant cardiac surgery would be associated with worse neurodevelopmental outcomes at intermediate followup. The objective of this study was to assess for a correlation between the number of embolic signals at surgery and subsequent neurologic outcome in a small cohort of pediatric patients.
Methods Internal Review Board approval was obtained. Inclusion criteria included the absence of genetic syndromes or preoperative neurologic abnormalities, cardiac surgery at age less than one year with transcranial Doppler ultrasound monitoring and age 3-6 years at follow-up. Candidates were identified from a surgical database and the parents were solicited for voluntary participation. Consent for study participation was provided.
Neuromonitoring data Our multi-modality neuromonitoring protocol for pediatric cardiac surgery has been previously described.20 Several surveillance technologies are routinely used, including near-infrared spectroscopy, transcranial Doppler ultrasound, electroencephalography and somatosensory-evoked potentials. This study focused specifically on cerebral embolic signals detected by transcranial Doppler. The right middle cerebral artery is located through insonation and the probe is secured in place for the duration of the operation (Figure 1). The probe provides continuous surveillance of the blood
Figure 1. Surveillance for cerebral embolization during pediatric cardiac surgery, using transcranial Doppler ultrasound. (A) Insonation of the middle cerebral artery. (B) Probe placement during surgery.
velocity in the middle cerebral artery and detects highintensity transient signals (HITS) consistent with intravascular emboli. Intraoperative monitoring data for each operation is captured and stored to a computer database.
Neurodevelopmental testing Neurodevelopmental testing of the study participants was performed by an expert examiner, with a supervising neuropsychologist, using two instruments: the Neuropsychological Assessment Second Edition (NEPSY-II, Pearson Education, Inc., San Antonio, TX) and the Kiddie Continuous Performance Test (K-CPT, Multi-Health Systems, Inc., North Tonawanda, NY). The NEPSY-II test is a comprehensive and standardized neurocognitive assessment of children, validated for ages 3-16 years.21 The assessment yields standard scores, process scores and combined scores across six major domains of neurocognitive development: attention and executive functioning, language, learning and memory, sensorimotor functioning, visual-spatial cognition and social perception. The NEPSY-II has been shown to provide valid assessment in mild intellectual disorders, attention deficit hyperactivity disorder, autism spectrum, reading, language and math disorders and emo-
Downloaded from prf.sagepub.com at CALIF STATE POLY UNIV LIBRARY on March 18, 2015
445
Naik et al.
tional disorders. The K-CPT is an interactive computer program for children, designed to measure attention disorders. Pictures of familiar objects are presented onscreen and the children are tasked to push the space bar for every picture except for a particular target stimulus (e.g., a picture of a ball). A practice administration is provided to ensure that respondents are adequately facile with the keyboard before completing the task. This test assesses timing accuracy, speed and accuracy of response, omissions and perseverations.
Parental questionnaires Parental perception of multiple aspects of their child’s neurodevelopmental performance was assessed using two instruments: the Adaptive Behavioral Assessment System, Second Edition (ABAS-II, Pearson Education Inc., San Antonio, TX), and the Behavior Assessment System for Children, Second Edition (BASC-2, Pearson Education Inc.,). The ABAS-II assesses dimensions of conceptual development (including communication and self-direction), social development (including leisure and social interactions) and practical development (including self-care and health and safety issues). The BASC-2 evaluates areas of personality, emotion and behavior.
Statistical analysis Statistical analyses were used to examine the relationship between the cerebral embolization results from surgery (i.e., number of HITS per patient operation) and the results of neuropsychological testing (NEPSY-II and K-CPT) and parental questionnaire scores (ABAS-II and BASC-2). Bivariate correlation was computed on each variable within the neurodevelopmental subtests. In each case, the null hypothesis was a “no relationship” statement and a p-value of
