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Journal Article•DOI•

Perioperative amplitude-integrated EEG and neurodevelopment in infants with congenital heart disease

Julia K. Gunn1, John Beca2, Rodney W. Hunt3, Rodney W. Hunt1, Monika Olischar1, Monika Olischar4, Lara S. Shekerdemian5, Lara S. Shekerdemian2 •
Royal Children's Hospital1, Boston Children's Hospital2, University of Melbourne3, Medical University of Vienna4, Baylor College of Medicine5
01 Jun 2012-Intensive Care Medicine (Springer-Verlag)-Vol. 38, Iss: 9, pp 1539-1547
TL;DR: Perioperative seizures were common in this cohort of infants but did not impact on 2-year neurodevelopmental outcome, and delayed recovery in aEEG background was associated with increased risk of early mortality and worse neurodevelopment.
Abstract: Purpose Perioperative brain injury is common in young infants undergoing cardiac surgery. We aimed to determine the relationship between perioperative electrical seizures, the background pattern of amplitude-integrated electroencephalography (aEEG) and 2-year neurodevelopmental outcome in young infants undergoing surgery for congenital heart disease.

Summary (3 min read)

Jump to: [Introduction] – [Participants] – [Amplitude-integrated EEG] – [Neurodevelopmental Assessment] – [Statistical analysis] – [Two-year neurodevelopment] – [Seizures] – [Discussion] – [Post-operative aEEG] – [Limitations] and [Conclusions]

Introduction

  • Brain injury is a potentially devastating complication of congenital heart disease (CHD) requiring surgery during the newborn period [1, 2].
  • Amplitude-integrated EEG (aEEG) is used in neonatal intensive care for assessment of seizures and background cerebral activity in high-risk neonates [4-9].
  • AEEG has also been studied in infants undergoing extracorporeal membrane oxygenation (ECMO) and in infants after the arterial switch operation [3, 11, 12].
  • Thus, the findings of historical studies should only be applied with caution in the current era.
  • The aims of this study were to ascertain the typical period of aEEG recovery in young infants following a range of cardiac operations, to determine the incidence of peri-operative seizures using continuous 2-channel aEEG before, during and for 72 hours after surgery for CHD and to relate these findings to two-year neurodevelopmental outcome.

Participants

  • Between 2005 and 2008, 150 full-term infants scheduled to undergo surgery for CHD before 2 months of age, were enrolled into a prospective study of brain injury in CHD, at The Royal Children’s Hospital, Melbourne (Centre 1) and Starship Children’s Hospital, Auckland (Centre 2).
  • Infants were excluded for the following reasons: 1) gestational age of <36 weeks; 2) a genetic abnormality independently associated with impaired neurodevelopment; or 3) the need for preoperative ECMO.
  • The study was approved by both hospitals’.
  • Human Research and Ethics Committees and parents of participants consented to their inclusion.

Amplitude-integrated EEG

  • AEEG monitoring was performed on each participant using the BRM2 cerebral monitor (BrainZ Instruments, Auckland, New Zealand).
  • The time taken for the aEEG to ‘recover’ to continuous background activity (regardless of sleepwake-cycling (SWC)) and to SWC were documented for each patient (up to 72 post-operative hours).
  • Suspected seizures on the amplitude-integrated component were confirmed on the raw EEG and considered by a second blinded assessor.
  • For the infants undergoing CPB, the perfusion strategy included continuous full-flow CPB at 150mL/kg/min with a procedure-specific target temperature during CPB of 22-34°C.
  • Post-operative analgesia and sedation were achieved with continuous infusions of morphine (10-40mcg/kg/hr) and midazolam (1-3mcg/kg/min).

Neurodevelopmental Assessment

  • Survivors underwent a neurodevelopmental assessment by a paediatrician and/or psychologist at two years, using the Bayley Scales of Infant Development (3 rd Edition) (BSID-3) for which the normative mean equates to a score of 100 ± 15.
  • Severe neurodevelopmental delay for a given domain (cognitive, language or motor) was defined as a score more than two standard deviations (SD) below the normative mean (<70).

Statistical analysis

  • Parametric and non-parametric data are reported using mean ± SD or median (interquartile range) respectively.
  • AEEG background recovery was analysed as both a continuous variable and dichotomous variable (recovery to a continuous background by 48 hours).
  • Wilcoxon rank-sum tests and linear regression were used for analysis of continuous variables.

Two-year neurodevelopment

  • Five (4%) were lost to follow-up and 125 children (96% of survivors) underwent neurodevelopmental evaluation.
  • Mean scores were significantly lower than the normative mean in all domains (cognitive and language p<0.0001; motor p=0.01).

Seizures

  • Peri-operative seizures were observed in 30% of their cohort.
  • This phenomenon has been reported as rare during adult cardiac surgery, but has rarely been studied in infants [20].
  • And anaesthetic management included routine administration of thiopentone at the nadir of body temperature (10mg/kg), which could suppress intra-operative electrical activity.
  • Post-operative electrical seizures were identified in 19% of their participants.
  • Immature brains are less likely to exhibit clinical manifestations of seizures despite their increased frequency [25].

Discussion

  • This is the first cohort study to report on peri-operative aEEG monitoring across a range of congenital heart lesions.
  • Moreover, this is the first study which links post-operative aEEG recovery with neurodevelopmental performance in this population.
  • Sub-clinical peri-operative seizures were common during the peri-operative period, but these were not related to two-year outcome.
  • Post-operative aEEG recovery time was related both to impaired neurodevelopment and increased mortality.

Post-operative aEEG

  • Failure of the aEEG background to recover to a continuous pattern within 48 hours after CPB was highly correlated with increased mortality and worse two-year neurodevelopment in survivors.
  • In the Boston cohort, background EEG had not yet returned to baseline at 48 hours in the study participants, which may reflect a difference in anaesthetic and post-operative strategies.
  • The authors have previously reported an association between delayed post-operative aEEG recovery and motor delay in a sub-group of these infants undergoing the Norwood procedure [30].
  • Importantly, their findings are consistent with studies of neonatal encephalopathy, in which time to recovery of aEEG background, and return of SWC, is correlated with outcome [7, 31].
  • It may also reflect the nature of cerebral injury in this population, namely the dominance of white matter injury rather than localized cortical injury, which is more likely to present with seizures.

Limitations

  • The first, and probably most important limitation to their study, relates to their modality of cerebral monitoring.
  • The authors applied two-channel aEEG during the study, and did not have access to continuous conventional multichannel EEG monitoring for the extensive period of monitoring.
  • The investigator assigned to interpretation of the aEEG was experienced in this, having been trained by colleagues who have extensively published in the field [34-37].
  • All infants in their study received weaning doses of morphine and midazolam during the postoperative period, which could influence aEEG recovery, particularly as the sickest infants are more likely to require longer periods of such agents.
  • Finally, inclusion of a control group with this cohort would have strengthened the assessment of neurodevelopmental impact on these children.

Conclusions

  • Electrical seizures are common in young infants undergoing surgery for CHD, both during and after surgery, but do not predict two-year neurodevelopmental outcomes.
  • A prolonged aEEG recovery phase after surgery is associated with both increased mortality and impaired neurodevelopment in all domains at two years of age in survivors.
  • Peri-operative neuromonitoring is essential in these high risk infants.
  • Further follow-up will determine the longer-term significance of these findings.

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Figures (5)

Content maybe subject to copyright    Report

1
Peri-operative amplitude-integrated EEG and neurodevelopment in infants with congenital
heart disease
Julia K Gunn PhD
a,b
, John Beca MBChB
c
, Rodney W Hunt PhD
a,b,d
, Monika Olischar MD
a,e
,
Lara S Shekerdemian MB, MD
f
From the
a
Department of Neonatal Medicine, Royal Children’s Hospital and the
b
Neonatal
Research Group, Murdoch Children’s Research Institute,
Melbourne Australia,
c
Paediatric
Intensive Care Unit, Starship Children’s Hospital, Auckland New Zealand,
d
Department of
Paediatrics, The University of Melbourne, Melbourne Australia,
e
The Medical University of
Vienna, Vienna Austria and
f
Intensive Care Services, Texas Children’s Hospital, Houston USA.
Key words:
Congenital heart disease; Pediatrics; Brain; Follow-up studies; Cardiac Surgery
Abbreviations:
aEEG = amplitude-integrated electroencephalography
CHD = congenital heart disease
CPB = cardiopulmonary bypass
ECMO = extra corporeal membrane oxygenation
EEG = electroencephalography
HLHS = hypoplastic left heart syndrome
SWC = sleep wake cycling
Address for correspondence:
Lara Shekerdemian, MB, MD, FRACP, FCICM, FAAP
Section Head of Critical Care & Professor of Pediatrics
Texas Children's Hospital & Baylor College of Medicine
6621 Fannin Street, WT6-006
Houston, Texas 77030
Tel: 832-826-6297
Email: lssheker@texaschildrens.org
The authors have no financial disclosures nor conflicts of interest to declare.
2
Abstract
Purpose
Peri-operative brain injury is common in young infants undergoing cardiac surgery. We aimed to
determine the relationship between peri-operative electrical seizures, the background pattern of
amplitude-integrated electroencephalography (aEEG) and two-year neurodevelopmental
outcome in young infants undergoing surgery for congenital heart disease.
Methods
150 newborn infants undergoing cardiac surgery underwent aEEG monitoring prior to and during
surgery, and for 72 hours post-operatively. Two blinded assessors reviewed the aEEGs for
seizure activity and background pattern. Survivors underwent neurodevelopmental outcome
assessment using the Bayley Scales of Infant Development (3
rd
Edition) at two years.
Results
The median age at surgery was seven days (IQR 4-11). Cardiopulmonary bypass was used in
83%. Peri-operative electrical seizures occurred in 30%, of whom ¼ had a clinical correlate, but
were not associated with two-year outcome. Recovery to a continuous background occurred at a
median 6 (3-13) hours and sleep-wake-cycling recovered at 21 (14-30) hours. Prolonged aEEG
recovery was associated with increased mortality and worse neurodevelopmental outcome.
Failure of the aEEG to recover to a continuous background by 48 post-operative hours was
associated with impairment in all outcome domains (p<0.05). Continued abnormal aEEG at
seven post-operative days was highly associated with mortality (p<0.001).
Conclusions
Peri-operative seizures were common in this cohort of infants but did not impact on two-year
neurodevelopmental outcome. Delayed recovery in aEEG background was associated with
increased risk of early mortality and worse neurodevelopment. Ongoing monitoring of the
survivors is essential to determine the longer-term significance of these findings.
1
Introduction
Brain injury is a potentially devastating complication of congenital heart disease (CHD)
requiring surgery during the newborn period [1, 2]. The developing white matter is particularly
vulnerable to acute changes in cerebral perfusion and oxygenation which are typical during the
peri-operative period in young infants with complex CHD. Continuous electroencephalography
(EEG) provides a real-time picture of the brain’s surface electrical activity and therefore offers a
time-sensitive method of detecting brain injury.[3]
Amplitude-integrated EEG (aEEG) is used in neonatal intensive care for assessment of seizures
and background cerebral activity in high-risk neonates [4-9]. As well as providing real-time
continuous bedside monitoring, time-compressed background aEEG patterns have been shown to
correlate with magnetic resonance imaging changes [5] and neurodevelopmental outcome in
neonatal encephalopathy [7-10]. aEEG has also been studied in infants undergoing
extracorporeal membrane oxygenation (ECMO) and in infants after the arterial switch operation
[3, 11, 12]. We recently reported an association between adverse outcomes (death or impaired
neurodevelopment) and peri-operative aEEG abnormalities in a subgroup of these infants
undergoing Norwood-type palliations [13].
Post-operative clinical and electrical seizures, on conventional EEG monitoring, have been
shown to correlate with impaired early neurodevelopment in cohorts of young infants before and
after cardiac surgery [14-16]. Refinements in perfusion techniques, anaesthetic regimes and
surgical approaches, as well as perinatal and post-operative care have together contributed to
improved survival in recent years. Thus, the findings of historical studies should only be applied
with caution in the current era.
2
The aims of this study were to ascertain the typical period of aEEG recovery in young infants
following a range of cardiac operations, to determine the incidence of peri-operative seizures
using continuous 2-channel aEEG before, during and for 72 hours after surgery for CHD and to
relate these findings to two-year neurodevelopmental outcome.
Patients and Methods
Participants
Between 2005 and 2008, 150 full-term infants scheduled to undergo surgery for CHD before 2
months of age, were enrolled into a prospective study of brain injury in CHD, at The Royal
Children’s Hospital, Melbourne (Centre 1) and Starship Children’s Hospital, Auckland (Centre
2). Infants were excluded for the following reasons: 1) gestational age of <36 weeks; 2) a genetic
abnormality independently associated with impaired neurodevelopment; or 3) the need for pre-
operative ECMO. The study was approved by both hospitals’ Human Research and Ethics
Committees and parents of participants consented to their inclusion.
Amplitude-integrated EEG
aEEG monitoring was performed on each participant using the BRM2 cerebral monitor (BrainZ
Instruments, Auckland, New Zealand). A two-channel recording of electrical activity was
collected from scalp electrodes positioned in the C3, P3, C4, P4 positions of the international
10-20 EEG system. The monitor used a computer generated algorithm to filter and compress raw
data for each cerebral hemisphere. Data were considered acceptable for analysis according to the
following criteria: impedance of less than 10kΩ, absence of movement or electrocardiographic
artefact on the raw trace, and absence of interference from diathermy or other electrical devices.
3
A neonatologist experienced in aEEG interpretation, and blinded to clinical information,
analysed all de-identified aEEG recordings offline. The complete compressed background
recording and the intra-operative raw trace were assessed. Background traces were classified
according to the dominant pattern at the following pre-defined phases:
Phase 1 – One hour pre-operative aEEG.
Phase 2 – Intra-operative aEEG: a) from commencement of anaesthesia; b) during
cooling and maintenance of the target hypothermic temperature; c) during rewarming and
d) after cardiopulmonary bypass (CPB) until surgery was completed (or from the time
normothermia was reached if CPB not used).
Phase 3 – Post-operative aEEG: hourly for six hours then six hourly until 72 hours after
the cessation of CPB (or one hour post-CPB when CPB was not utilised).
Phase 4 – One hour late post-operative aEEG seven days following surgery.
Background aEEG activity was classified as continuous (normal), discontinuous or suppressed
(burst suppression, low voltage or flat trace), based on a previously described system.[5, 17] The
time taken for the aEEG to ‘recover’ to continuous background activity (regardless of sleep-
wake-cycling (SWC)) and to SWC were documented for each patient (up to 72 post-operative
hours). This was then classified as normal (continuous) or abnormal at 48 hours. Seizures were
defined as repetitive waveforms evolving over a minimum of ten seconds on either hemisphere.
Suspected seizures on the amplitude-integrated component were confirmed on the raw EEG and
considered by a second blinded assessor. Seizures identified acutely were managed at the
discretion of the treating clinical team. A seizure detection algorithm was not utilised.
Operative Management
Citations
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Journal Article•DOI•
D-transposition of the great arteries: the current era of the arterial switch operation.

[...]

Juan Villafane1, M. Regina Lantin-Hermoso2, Ami B. Bhatt3, James S. Tweddell4, Tal Geva5, Meena Nathan5, Martin J. Elliott6, Victoria L. Vetter7, Stephen M. Paridon8, Lazaros K. Kochilas9, Kathy J. Jenkins5, Robert H. Beekman10, Gil Wernovsky11, Jeffrey A. Towbin10 •
University of Kentucky1, Baylor College of Medicine2, Harvard University3, Children's Hospital of Wisconsin4, Boston Children's Hospital5, Great Ormond Street Hospital for Children NHS Foundation Trust6, Children's Hospital of Philadelphia7, University of Pennsylvania8, University of Minnesota9, Cincinnati Children's Hospital Medical Center10, FIU Herbert Wertheim College of Medicine11
05 Aug 2014-Journal of the American College of Cardiology
TL;DR: The arterial switch operation (ASO) has replaced atrial switch procedures for D-loop transposition of the great arteries (D-TGA) in the current surgical era, and 90% of patients now reach adulthood.
Abstract: This paper aims to update clinicians on "hot topics" in the management of patients with D-loop transposition of the great arteries (D-TGA) in the current surgical era. The arterial switch operation (ASO) has replaced atrial switch procedures for D-TGA, and 90% of patients now reach adulthood. The Adult Congenital and Pediatric Cardiology Council of the American College of Cardiology assembled a team of experts to summarize current knowledge on genetics, pre-natal diagnosis, surgical timing, balloon atrial septostomy, prostaglandin E1 therapy, intraoperative techniques, imaging, coronary obstruction, arrhythmias, sudden death, neoaortic regurgitation and dilation, neurodevelopmental (ND) issues, and lifelong care of D-TGA patients. In simple D-TGA: 1) familial recurrence risk is low; 2) children diagnosed pre-natally have improved cognitive skills compared with those diagnosed post-natally; 3) echocardiography helps to identify risk factors; 4) routine use of BAS and prostaglandin E1 may not be indicated in all cases; 5) early ASO improves outcomes and reduces costs with a low mortality; 6) single or intramural coronary arteries remain risk factors; 7) post-ASO arrhythmias and cardiac dysfunction should raise suspicion of coronary insufficiency; 8) coronary insufficiency and arrhythmias are rare but are associated with sudden death; 9) early- and late-onset ND abnormalities are common; 10) aortic regurgitation and aortic root dilation are well tolerated; and 11) the aging ASO patient may benefit from "exercise-prescription" rather than restriction. Significant strides have been made in understanding risk factors for cardiac, ND, and other important clinical outcomes after ASO.

197 citations

Journal Article•DOI•
Brain Injury and Neurodevelopmental Outcome in Congenital Heart Disease: A Systematic Review

[...]

Mirthe J Mebius1, Elisabeth M. W. Kooi1, Catherina M. Bilardo1, Arend F. Bos1•
University Medical Center Groningen1
01 Jul 2017-Pediatrics
TL;DR: Prenatal and postnatal preoperative abnormal cerebral findings might play an important role in neurodevelopmental impairment in infants with CHD, and increased awareness of the vulnerability of the young developing brain of an infant withCHD among caregivers is essential.
Abstract: CONTEXT: Brain injury during prenatal and preoperative postnatal life might play a major role in neurodevelopmental impairment in infants with congenital heart disease (CHD) who require corrective or palliative surgery during infancy. A systematic review of cerebral findings during this period in relation to neurodevelopmental outcome (NDO), however, is lacking. OBJECTIVE: To assess the association between prenatal and postnatal preoperative cerebral findings and NDO in infants with CHD who require corrective or palliative surgery during infancy. DATA SOURCES: PubMed, Embase, reference lists. STUDY SELECTION: We conducted 3 different searches for English literature between 2000 and 2016; 1 for prenatal cerebral findings, 1 for postnatal preoperative cerebral findings, and 1 for the association between brain injury and NDO. DATA EXTRACTION: Two reviewers independently screened sources and extracted data on cerebral findings and neurodevelopmental outcome. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Abnormal cerebral findings are common during the prenatal and postnatal preoperative periods. Prenatally, a delay of cerebral development was most common; postnatally, white matter injury, periventricular leukomalacia, and stroke were frequently observed. Abnormal Doppler measurements, brain immaturity, cerebral oxygenation, and abnormal EEG or amplitude-integrated EEG were all associated with NDO. LIMITATIONS: Observational studies, different types of CHD with different pathophysiological effects, and different reference values. CONCLUSIONS: Prenatal and postnatal preoperative abnormal cerebral findings might play an important role in neurodevelopmental impairment in infants with CHD. Increased awareness of the vulnerability of the young developing brain of an infant with CHD among caregivers is essential.

113 citations

Journal Article•DOI•
Subclinical seizures identified by postoperative electroencephalographic monitoring are common after neonatal cardiac surgery

[...]

Maryam Y. Naim1, J. William Gaynor1, Jodi Chen1, Susan C. Nicolson1, Stephanie Fuller1, Thomas L. Spray1, Dennis J. Dlugos1, Robert R. Clancy1, Livia Vianez Costa1, Daniel J. Licht1, Rui Xiao1, Heather Meldrum1, Nicholas S. Abend1 •
University of Pennsylvania1
01 Jul 2015-The Journal of Thoracic and Cardiovascular Surgery
TL;DR: Continuous electroencephalographic monitoring identified seizures in 8% of neonates after cardiac surgery with cardiopulmonary bypass, a marker of greater illness severity and increased mortality.
Abstract: Objectives The American Clinical Neurophysiology Society recommends continuous electroencephalographic monitoring after neonatal cardiac surgery because seizures are common, often subclinical, and associated with worse neurocognitive outcomes. We performed a quality improvement project to monitor for postoperative seizures in neonates with congenital heart disease after surgery with cardiopulmonary bypass. Methods We implemented routine continuous electroencephalographic monitoring and reviewed the results for an 18-month period. Clinical data were collected by chart review, and continuous electroencephalographic tracings were interpreted using standardized American Clinical Neurophysiology Society terminology. Electrographic seizures were classified as electroencephalogram-only or electroclinical seizures. Multiple logistic regression was used to assess associations between seizures and potential clinical and electroencephalogram predictors. Results A total of 161 of 172 eligible neonates (94%) underwent continuous electroencephalographic monitoring. Electrographic seizures occurred in 13 neonates (8%) beginning at a median of 20 hours after return to the intensive care unit after surgery. Neonates with all types of congenital heart disease had seizures. Seizures were electroencephalogram only in 11 neonates (85%). Status epilepticus occurred in 8 neonates (62%). In separate multivariate models, delayed sternal closure or longer deep hypothermic circulatory arrest duration was associated with an increased risk for seizures. Mortality was higher among neonates with than without seizures (38% vs 3%, P Conclusions Continuous electroencephalographic monitoring identified seizures in 8% of neonates after cardiac surgery with cardiopulmonary bypass. The majority of seizures had no clinical correlate and would not have been otherwise identified. Seizure occurrence is a marker of greater illness severity and increased mortality. Further study is needed to determine whether seizure identification and management lead to improved outcomes.

107 citations

Cites background or methods from "Perioperative amplitude-integrated ..."

  • ...Likewise, a study of a heterogeneous CHD cohort of neonates and infants reported perioperative (preoperative, intraoperative, and postoperative) electrographic seizures in 30% of neonates, of which 16% were electroclinical.(19) In comparison, Andropoulos and associates(20) examined the occurrence of preoperative and postoperative seizures in neonates undergoing surgery with CBP and found that only 1 patient with a single ventricle had an EEG seizure, leading to an overall incidence of 1....

    [...]

  • ...Study Limitations First, we did not monitor patients preoperatively or intraoperatively, as has been done in previous reports.(19,20) Second, we did not evaluate neurodevelopmental outcomes and thus cannot determine whether seizure occurrence was associated with adverse neurodevelopmental outcomes among survivors....

    [...]

  • ...The operative strategy consisted primarily of antegrade cerebral perfusion at one center for all patients; in the second center, DHCAwas used with only brief periods (median duration, 8 minutes [IQR 5-17]) in patients with biventricular circulation during arch reconstruction and during surgery to the atrial septum.(19) In this study, on univariable analysis, seizures occurred more often in neonates who were younger at the time of surgery compared with those who were older (aged 3 vs 5 days)....

    [...]

  • ...The Journal of Thoracic and Ca have reported the highest seizure incidence in patients with 2-ventricle defects with aortic arch obstruction.(19) In addition,we found that increasingDHCAduration predicted seizure occurrence....

    [...]

Journal Article•DOI•
Australian Clinical Consensus Guideline: The diagnosis and acute management of childhood stroke.

[...]

Tanya L Medley1, Christina Miteff2, Ian Andrews3, Tyson L Ware4, Michael Cheung1, Michael Cheung5, Paul Monagle5, Paul Monagle1, Simone Mandelstam5, Simone Mandelstam1, Alison Wray1, Clair Pridmore2, Christopher Troedson6, Russell C. Dale6, Michael C Fahey2, Adriane J Sinclair7, Peter Walsh2, Belinda Stojanovski1, Belinda Stojanovski5, Mark T Mackay1, Mark T Mackay5 •
University of Melbourne1, Boston Children's Hospital2, University of New South Wales3, Royal Hobart Hospital4, Royal Children's Hospital5, Children's Hospital at Westmead6, University of Queensland7
01 Jan 2019-International Journal of Stroke
TL;DR: The Australian Clinical Consensus Guideline for the Diagnosis and Acute Management of Childhood Stroke was developed to minimize unwarranted variations in care and document best evidence on the risk factors, etiologies, and conditions mimicking stroke that differ from adults.
Abstract: Stroke is among the top 10 causes of death in children and survivors carry resulting disabilities for decades, at substantial cost to themselves and their families. Children are not currently able to access reperfusion therapies, due to limited evidence supporting safety and efficacy and long diagnostic delays. The Australian Clinical Consensus Guideline for the Diagnosis and Acute Management of Childhood Stroke was developed to minimize unwarranted variations in care and document best evidence on the risk factors, etiologies, and conditions mimicking stroke that differ from adults. Clinical questions were formulated to inform systematic database searches from 2007 to 2017, limited to English and pediatric studies. SIGN methodology and the National Health and Medical Research Council system were used to screen and classify the evidence. The Grades of Recommendation, Assessment, Development, and Evaluation system (GRADE) was used to grade evidence as strong or weak. The Guideline provides more than 60 evidence-based recommendations to assist prehospital and acute care clinicians in the rapid identification of childhood stroke, choice of initial investigation, to confirm diagnosis, determine etiology, selection of the most appropriate interventions to salvage brain at risk, and prevent recurrence. Recommendations include advice regarding the management of intracranial pressure and congenital heart disease. Implementation of the Guideline will require reorganization of prehospital and emergency care systems, including the development of regional stroke networks, pediatric Code Stroke, rapid magnetic resonance imaging and accreditation of primary pediatric stroke centers with the capacity to offer reperfusion therapies. The Guideline will allow auditing to benchmark timelines of care, access to acute interventions, and outcomes. It will also facilitate the development of an Australian childhood stroke registry, with data linkage to international registries, to allow for accurate data collection on stroke incidence, treatment, and outcomes.

64 citations

Journal Article•DOI•
Perioperative risk factors for impaired neurodevelopment after cardiac surgery in early infancy

[...]

Julia K. Gunn1, Julia K. Gunn2, John Beca3, Rodney W. Hunt1, Rodney W. Hunt2, Michelle Goldsworthy3, Christian P. Brizard1, Kirsten Finucane3, Susan Donath2, Lara S. Shekerdemian3 •
Royal Children's Hospital1, University of Melbourne2, Boston Children's Hospital3
06 Jun 2016-Archives of Disease in Childhood
TL;DR: In the modern era of infant cardiac surgery and perioperative care, children continue to demonstrate neurodevelopmental delays and the use of updated assessment tools has revealed early language dysfunction and relative sparing of motor function.
Abstract: Objective Historical cohort studies have reported adverse neurodevelopment following cardiac surgery during early infancy. Advances in surgical techniques and perioperative care have coincided with updating of neurodevelopmental assessment tools. We aimed to determine perioperative risk factors for impaired neurodevelopment at 2 years following surgery for congenital heart disease (CHD) in early infancy. Design and patients We undertook a prospective longitudinal study of 153 full-term infants undergoing surgery for CHD before 2 months of age. Infants were excluded if they had a genetic syndrome associated with neurodevelopmental impairment. Outcome measures Predefined perioperative parameters were recorded and infants were classified according to cardiac anatomy. At 2 years, survivors were assessed using the Bayley Scales of Infant Development-III. Results At 2 years, 130 children (98% of survivors) were assessed. Mean cognitive, language and motor scores were 93.4±13.6, 93.6±16.1 and 96.8±12.5 respectively (100±15 norm). Twenty (13%) died and 12 (9%) survivors had severe impairment (score <70), mostly language (8%). The lowest scores were in infants born with single ventricle physiology with obstruction to the pulmonary circulation who required a neonatal systemic-to-pulmonary artery shunt. Additional risk factors for impairment included reduced gestational age, postoperative elevation of lactate or S100B and repeat cardiac surgery. Conclusions In the modern era of infant cardiac surgery and perioperative care, children continue to demonstrate neurodevelopmental delays. The use of updated assessment tools has revealed early language dysfunction and relative sparing of motor function. Ongoing follow-up is critical in this high-risk population.

64 citations

References
More filters
Journal Article•DOI•
Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial

[...]

Peter D. Gluckman1, John S. Wyatt2, Denis Azzopardi3, Roberta A. Ballard4, A. David Edwards3, Donna M. Ferriero5, Richard A. Polin6, Charlene M.T. Robertson7, Marianne Thoresen8, Andrew Whitelaw8, Alistair J. Gunn1 •
University of Auckland1, University College London2, Imperial College London3, Children's Hospital of Philadelphia4, University of California, San Francisco5, Columbia University6, University of Alberta7, University of Bristol8
19 Feb 2005-The Lancet
TL;DR: Induced head cooling is not protective in a mixed population of infants with neonatal encephalopathy, but it could safely improve survival without severe neurodevelopmental disability in infants with less severe aEEG changes.
Abstract: Summary Background Cerebral hypothermia can improve outcome of experimental perinatal hypoxia-ischaemia. We did a multicentre randomised controlled trial to find out if delayed head cooling can improve neurodevelopmental outcome in babies with neonatal encephalopathy. Methods 234 term infants with moderate to severe neonatal encephalopathy and abnormal amplitude integrated electroencephalography (aEEG) were randomly assigned to either head cooling for 72 h, within 6 h of birth, with rectal temperature maintained at 34–35°C (n=116), or conventional care (n=118). Primary outcome was death or severe disability at 18 months. Analysis was by intention to treat. We examined in two predefined subgroup analyses the effect of hypothermia in babies with the most severe aEEG changes before randomisation—ie, severe loss of background amplitude, and seizures—and those with less severe changes. Findings In 16 babies, follow-up data were not available. Thus in 218 infants (93%), 73/110 (66%) allocated conventional care and 59/108 (55%) assigned head cooling died or had severe disability at 18 months (odds ratio 0·61; 95% CI 0·34–1·09, p=0·1). After adjustment for the severity of aEEG changes with a logistic regression model, the odds ratio for hypothermia treatment was 0·57 (0·32–1·01, p=0·05). No difference was noted in the frequency of clinically important complications. Predefined subgroup analysis suggested that head cooling had no effect in infants with the most severe aEEG changes (n=46, 1·8; 0·49–6·4, p=0·51), but was beneficial in infants with less severe aEEG changes (n= 172, 0·42; 0·22–0·80, p=0·009). Interpretation These data suggest that although induced head cooling is not protective in a mixed population of infants with neonatal encephalopathy, it could safely improve survival without severe neurodevelopmental disability in infants with less severe aEEG changes.

1,863 citations

Journal Article•DOI•
A Comparison of the Perioperative Neurologic Effects of Hypothermic Circulatory Arrest versus Low-Flow Cardiopulmonary Bypass in Infant Heart Surgery

[...]

Jane W. Newburger1, Richard A. Jonas, Gil Wernovsky, David Wypij, Paul R. Hickey, Karl C.K. Kuban, David M. Farrell, Gregory L. Holmes, Sandra L. Helmers, Jules Constantinou, Enrique Carrazana, John K. Barlow, Amy Z. Walsh, Kristin C. Lucius, Jane Share, David L. Wessel, Frank L. Hanley, John E. Mayer, Aldo R. Castaneda, James H. Ware •
Boston Children's Hospital1
07 Oct 1993-The New England Journal of Medicine
TL;DR: This randomized, single-center trial compared the incidence of perioperative brain injury after deep hypothermia and support consisting predominantly of total circulatory arrest with the incidence after deep Hypothermic Circulatory arrest in a randomized,single- center trial.
Abstract: Background Hypothermic circulatory arrest is a widely used support technique during heart surgery in infants, but its effects on neurologic outcome have been controversial. An alternative method, low-flow cardiopulmonary bypass, maintains continuous cerebral circulation but may increase exposure to known pump-related sources of brain injury, such as embolism or inadequate cerebral perfusion. Methods We compared the incidence of perioperative brain injury after deep hypothermia and support consisting predominantly of total circulatory arrest with the incidence after deep hypothermia and support consisting predominantly of low-flow cardiopulmonary bypass in a randomized, single-center trial. The criteria for eligibility included a diagnosis of transposition of the great arteries with an intact ventricular septum or a ventricular septal defect and a planned arterial-switch operation before the age of three months. Results Of 171 patients with D-transposition of the great arteries, 129 (66 of whom were assign...

638 citations

Journal Article•DOI•
Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial.

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David C. Bellinger1, David C. Bellinger2, David Wypij, Adre J. duPlessis1, Adre J. duPlessis2, Leonard Rappaport2, Leonard Rappaport1, Richard A. Jonas1, Richard A. Jonas2, Gil Wernovsky1, Gil Wernovsky2, Jane W. Newburger1, Jane W. Newburger2 •
Harvard University1, Boston Children's Hospital2
01 Nov 2003-The Journal of Thoracic and Cardiovascular Surgery
TL;DR: Although mean scores on most outcomes were within normal limits, neurodevelopmental status in the cohort as a whole was below expectation in many respects, including academic achievement, fine motor function, visual-spatial skills, working memory, hypothesis generating and testing, sustained attention, and higher-order language skills.
Abstract: Objectives Our goal was to determine which of the two major methods of vital organ support used in infant cardiac surgery, total circulatory arrest and low-flow cardiopulmonary bypass, results in better neurodevelopmental outcomes at school age. Methods In a single-center trial, infants with dextrotransposition of the great arteries underwent the arterial switch operation after random assignment to either total circulatory arrest or low-flow cardiopulmonary bypass. Developmental, neurologic, and speech outcomes were assessed at 8 years of age in 155 of 160 eligible children (97%). Results Treatment groups did not differ in terms of most outcomes, including neurologic status, Full-Scale or Performance IQ score, academic achievement, memory, problem solving, and visual-motor integration. Children assigned to total circulatory arrest performed worse on tests of motor function including manual dexterity with the nondominant hand ( P = .003), apraxia of speech ( P = .01), visual-motor tracking ( P = .01), and phonologic awareness ( P = .003). Assignment to low-flow cardiopulmonary bypass was associated with a more impulsive response style on a continuous performance test of vigilance ( P P = .05). Although mean scores on most outcomes were within normal limits, neurodevelopmental status in the cohort as a whole was below expectation in many respects, including academic achievement, fine motor function, visual-spatial skills, working memory, hypothesis generating and testing, sustained attention, and higher-order language skills. Conclusions Use of total circulatory arrest to support vital organs during heart surgery in infancy is generally associated with greater functional deficits than is use of low-flow cardiopulmonary bypass, although both strategies are associated with increased risk of neurodevelopmental vulnerabilities.

609 citations

"Perioperative amplitude-integrated ..." refers background in this paper

  • ...8 years [15, 28, 29], we did not demonstrate a relationship...

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Journal Article•DOI•
Neurodevelopmental outcome and lifestyle assessment in school-aged and adolescent children with hypoplastic left heart syndrome.

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William T. Mahle1, Robert R. Clancy2, Edward Moss, Marsha Gerdes1, David R. Jobes3, Gil Wernovsky •
Children's Hospital of Philadelphia1, University of Pennsylvania2, Hospital of the University of Pennsylvania3
01 May 2000-Pediatrics
TL;DR: Although the majority of school-aged children with HLHS had IQ scores within the normal range, mean performance for this historical cohort of survivors was lower than that in the general population.
Abstract: OBJECTIVES The purposes of this study are to describe the quality of life and cognitive function in school-aged children who have undergone staged palliation for hypoplastic left heart syndrome (HLHS), and to identify factors that are predictive of neurodevelopmental outcome in this population. METHODS School-aged survivors with HLHS who had undergone palliative surgery at our institution were identified and mailed a questionnaire to assess subjectively quality of life, school performance, and incidence of medical complications. A subgroup of local patients underwent standardized testing of cognitive function and neurologic examination. These patients were compared with the larger (remote) group of questionnaire respondents to determine whether results may be generalizable to the entire HLHS population. Potential predictors of neurologic and cognitive outcome were tested for their association with test scores using multivariate regression analysis. RESULTS Questionnaire results were obtained from 115 of 138 eligible children (83%; mean age: 9.0 +/- 2.0 years). Standardized testing was performed in 28 of 34 (82%) eligible local patients (mean age: 8.6 +/- 2.1 years). The majority of parents or guardians described their child's health as good (34%) or excellent (45%) and their academic performance as average (42%) or above average (42%). One third of the children, however, were receiving some form of special education. Chronic medication usage was common (64%); the incidence of medical complications was comparable to that previously reported in children with Fontan physiology. Cognitive testing of the local group demonstrated a median full scale IQ of 86 (range: 50-116). Mental retardation (IQ: <70) was noted in 18% of patients. In multivariate analysis, only the occurrence of preoperative seizures predicted lower full scale IQ. CONCLUSIONS Although the majority of school-aged children with HLHS had IQ scores within the normal range, mean performance for this historical cohort of survivors was lower than that in the general population.

444 citations

Journal Article•DOI•
Underestimation of developmental delay by the new Bayley-III Scale.

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Peter J. Anderson, Cinzia R. De Luca1, Cinzia R. De Luca2, Esther Hutchinson2, Esther Hutchinson1, Gehan Roberts3, Gehan Roberts1, Lex W. Doyle2, Lex W. Doyle1 •
Royal Women's Hospital1, University of Melbourne2, Royal Children's Hospital3
05 Apr 2010-JAMA Pediatrics
TL;DR: The Bayley-III scale seriously underestimates developmental delay in 2-year-old Australian children.
Abstract: Objective To assess the ability of the third edition of the Bayley Scales of Infant and Toddler Development (Bayley-III) to detect developmental delay in 2-year-old children who were extremely preterm and those carried to term. Design Prospective cohort study. Setting The state of Victoria, Australia. Participants Subjects were consecutive surviving children who were born either at less than 28 weeks' gestational age (extremely preterm) or with less than 1000 g birth weight (extremely low-birth-weight; n = 221) in the state of Victoria, Australia, in 2005 and randomly selected controls who were both carried to term and of normal birth weight (n = 220). Main Outcome Measure Children were assessed by psychologists blinded to knowledge of group at 2 years of age, corrected for prematurity with the new Bayley-III scale. Results Follow-up rates of both cohorts were high (>92%). Mean values for all composite and subtest scores for the extremely preterm/extremely low-birth-weight group were significantly below those of the control group ( P Conclusion The Bayley-III scale seriously underestimates developmental delay in 2-year-old Australian children.

430 citations

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20 Sep 2011-Circulation
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Bradley S. Marino, Paul H. Lipkin, Jane W. Newburger, Georgina Peacock, Marsha Gerdes, J. William Gaynor, Kathleen A. Mussatto, Karen Uzark, Caren S. Goldberg, Walter H. Johnson, Jennifer S. Li, Sabrina E. Smith, David C. Bellinger, William T. Mahle 
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05 Mar 2013-Circulation
John Beca, Julia K. Gunn, Lee Coleman, Ayton Hope, Peter W. Reed, Rodney W. Hunt, Kirsten Finucane, Christian P. Brizard, Brieana Dance, Lara S. Shekerdemian 
Developmental and Neurologic Status of Children after Heart Surgery with Hypothermic Circulatory Arrest or Low-Flow Cardiopulmonary Bypass

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02 Mar 1995-The New England Journal of Medicine
David C. Bellinger, Richard A. Jonas, Leonard Rappaport, David Wypij, Gil Wernovsky, Karl C.K. Kuban, Patrick D. Barnes, Gregory L. Holmes, Paul R. Hickey, R D Strand 
Brain maturation is delayed in infants with complex congenital heart defects

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01 Mar 2009-The Journal of Thoracic and Cardiovascular Surgery
Daniel J. Licht, David Shera, Robert R. Clancy, Gil Wernovsky, Lisa M. Montenegro, Susan C. Nicolson, Robert A. Zimmerman, Thomas L. Spray, J. William Gaynor, Arastoo Vossough 
Frequently Asked Questions (1)
Q1. What are the contributions mentioned in the paper "Aeeg and ndo in chd" ?

In this paper, a 2-channel Amplitude-Integrated EEG ( aEEG ) is used in neonatal intensive care for assessment of seizures and background cerebral activity in high-risk infants.