Increasing cumulative exposure to volatile anesthetic agents is associated with poorer neurodevelopmental outcomes in children with hypoplastic left heart syndrome

Abstract Objectives Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their neurodevelopmental (ND) outcomes. Previous studies have identified patient factors, such as prematurity and genetic syndromes, to be associated with wor...

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Published inThe Journal of thoracic and cardiovascular surgery Vol. 152; no. 2; pp. 482 - 489
Main Authors Diaz, Laura K., MD, Gaynor, J. William, MD, Koh, Shannon J., BA, Ittenbach, Richard F., PhD, Gerdes, Marsha, PhD, Bernbaum, Judy C., MD, Zackai, Elaine H., MD, Clancy, Robert R., MD, Rehman, Mohamed A., MD, Pennington, Jeffrey W., BS, Burnham, Nancy, MSN, Spray, Thomas L., MD, Nicolson, Susan C., MD
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.08.2016
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Abstract Abstract Objectives Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their neurodevelopmental (ND) outcomes. Previous studies have identified patient factors, such as prematurity and genetic syndromes, to be associated with worse ND outcomes. However, no consistent relationships have been identified among modifiable management factors, including cardiopulmonary bypass strategies, and ND outcomes after cardiac surgery in infancy. Studies in immature animals, including primates, have demonstrated neurodegeneration and apoptosis in the brain after certain levels and extended durations of anesthetic exposure. Retrospective human studies have also suggested relationships between adverse ND effects and anesthetic exposure. Methods Cumulative minimum alveolar concentration hours (MAC-hrs) of exposure to volatile anesthetic agents (VAA) (desflurane, halothane, isoflurane, and sevoflurane) were collected from an anesthetic database and medical record review for 96 patients with HLHS or variants. ND testing was performed between ages 4 and 5 years, including full-scale IQ, verbal IQ, performance IQ, and processing speed. Four generalized linear modes were hypothesized a priori and tested using a Gaussian (normal) distribution with an identity link. Results Cumulative VAA exposure ranged from 0 to 35.3 MAC-hrs (median 7.5 hours). Using specified covariates identified previously as significant predictors of ND outcomes, statistically significant relationships were identified between total MAC-hrs exposure and worse full-scale IQ and verbal IQ scores ( P 's < .05) alone and after adjusting for relevant covariates. Conclusions Increased cumulative MAC-hrs exposure to VAA is associated with worse ND outcomes in certain domains in children with HLHS and variants.
AbstractList Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their neurodevelopmental (ND) outcomes. Previous studies have identified patient factors, such as prematurity and genetic syndromes, to be associated with worse ND outcomes. However, no consistent relationships have been identified among modifiable management factors, including cardiopulmonary bypass strategies, and ND outcomes after cardiac surgery in infancy. Studies in immature animals, including primates, have demonstrated neurodegeneration and apoptosis in the brain after certain levels and extended durations of anesthetic exposure. Retrospective human studies have also suggested relationships between adverse ND effects and anesthetic exposure. Cumulative minimum alveolar concentration hours (MAC-hrs) of exposure to volatile anesthetic agents (VAA) (desflurane, halothane, isoflurane, and sevoflurane) were collected from an anesthetic database and medical record review for 96 patients with HLHS or variants. ND testing was performed between ages 4 and 5 years, including full-scale IQ, verbal IQ, performance IQ, and processing speed. Four generalized linear modes were hypothesized a priori and tested using a Gaussian (normal) distribution with an identity link. Cumulative VAA exposure ranged from 0 to 35.3 MAC-hrs (median 7.5 hours). Using specified covariates identified previously as significant predictors of ND outcomes, statistically significant relationships were identified between total MAC-hrs exposure and worse full-scale IQ and verbal IQ scores (P's < .05) alone and after adjusting for relevant covariates. Increased cumulative MAC-hrs exposure to VAA is associated with worse ND outcomes in certain domains in children with HLHS and variants.
Abstract Objectives Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their neurodevelopmental (ND) outcomes. Previous studies have identified patient factors, such as prematurity and genetic syndromes, to be associated with worse ND outcomes. However, no consistent relationships have been identified among modifiable management factors, including cardiopulmonary bypass strategies, and ND outcomes after cardiac surgery in infancy. Studies in immature animals, including primates, have demonstrated neurodegeneration and apoptosis in the brain after certain levels and extended durations of anesthetic exposure. Retrospective human studies have also suggested relationships between adverse ND effects and anesthetic exposure. Methods Cumulative minimum alveolar concentration hours (MAC-hrs) of exposure to volatile anesthetic agents (VAA) (desflurane, halothane, isoflurane, and sevoflurane) were collected from an anesthetic database and medical record review for 96 patients with HLHS or variants. ND testing was performed between ages 4 and 5 years, including full-scale IQ, verbal IQ, performance IQ, and processing speed. Four generalized linear modes were hypothesized a priori and tested using a Gaussian (normal) distribution with an identity link. Results Cumulative VAA exposure ranged from 0 to 35.3 MAC-hrs (median 7.5 hours). Using specified covariates identified previously as significant predictors of ND outcomes, statistically significant relationships were identified between total MAC-hrs exposure and worse full-scale IQ and verbal IQ scores ( P 's < .05) alone and after adjusting for relevant covariates. Conclusions Increased cumulative MAC-hrs exposure to VAA is associated with worse ND outcomes in certain domains in children with HLHS and variants.
Author Pennington, Jeffrey W., BS
Ittenbach, Richard F., PhD
Bernbaum, Judy C., MD
Koh, Shannon J., BA
Nicolson, Susan C., MD
Diaz, Laura K., MD
Clancy, Robert R., MD
Spray, Thomas L., MD
Burnham, Nancy, MSN
Gaynor, J. William, MD
Gerdes, Marsha, PhD
Rehman, Mohamed A., MD
Zackai, Elaine H., MD
AuthorAffiliation 4 Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA
2 Division of Pediatric Cardiothoracic Surgery, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA
1 Department of Anesthesia and Critical Care Medicine, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA
5 Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania
3 Division of Biostatistics and Epidemiology, Cincinnati Children's Medical Center, University of Cincinnati School of Medicine, Cincinnati OH
AuthorAffiliation_xml – name: 3 Division of Biostatistics and Epidemiology, Cincinnati Children's Medical Center, University of Cincinnati School of Medicine, Cincinnati OH
– name: 1 Department of Anesthesia and Critical Care Medicine, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA
– name: 5 Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania
– name: 4 Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA
– name: 2 Division of Pediatric Cardiothoracic Surgery, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA
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Issue 2
Keywords BSID-II
SES
NP
hypoplastic left heart syndrome
full-scale IQ
WPPSI-III
deep hypothermic circulatory arrest
CNS
general anesthesia
neurodevelopmental
anesthesia
AUC
AIMS
neurotoxicity
neurodevelopment
FSIQ
Apolipoprotein E
verbal IQ
cardiopulmonary bypass
GA
intensive care unit
APOE
performance IQ
minimum alveolar concentration hours
volatile anesthetic agents
HLHS
central nervous system
Wechsler Preschool and Primary Scale of Intelligence, 3rd edition
LOS
CPB
congenital heart surgery
ND
VAA
length of stay
PIQ
ICU
MAC-hrs
Bayley Scales of Infant Development-II
HC
head circumference
DHCA
socioeconomic status
Anesthesia Information Management System
area-under-the-curve
CHD
nasopharyngeal
congenital heart defects
VIQ
Language English
License This article is made available under the Elsevier license.
Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
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Snippet Abstract Objectives Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their...
Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their neurodevelopmental (ND)...
SourceID pubmedcentral
crossref
pubmed
elsevier
SourceType Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage 482
SubjectTerms anesthesia
Cardiothoracic Surgery
congenital heart surgery
neurodevelopment
neurotoxicity
Title Increasing cumulative exposure to volatile anesthetic agents is associated with poorer neurodevelopmental outcomes in children with hypoplastic left heart syndrome
URI https://www.clinicalkey.es/playcontent/1-s2.0-S0022522316301192
https://dx.doi.org/10.1016/j.jtcvs.2016.03.095
https://www.ncbi.nlm.nih.gov/pubmed/27183886
https://pubmed.ncbi.nlm.nih.gov/PMC5662941
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