title: Increasing cumulative exposure to volatile anesthetic agents is associated with poorer neurodevelopmental outcomes in children with hypoplastic left heart syndrome.
abstract: 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.
authors.affiliation: Department of Anesthesia and Critical Care Medicine, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Diaz
authors.affiliation: Division of Pediatric Cardiothoracic Surgery, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa. Electronic address: gaynor@email.chop.edu.
authors.forename: J William
authors.initials: JW
authors.lastname: Gaynor
authors.affiliation: Division of Pediatric Cardiothoracic Surgery, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa.
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Koh
authors.affiliation: Division of Biostatistics and Epidemiology, Cincinnati Children's Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ittenbach
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa.
authors.forename: Marsha
authors.initials: M
authors.lastname: Gerdes
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa.
authors.forename: Judy C
authors.initials: JC
authors.lastname: Bernbaum
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa.
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Clancy
authors.affiliation: Department of Anesthesia and Critical Care Medicine, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Rehman
authors.affiliation: Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Pennington
authors.affiliation: Division of Pediatric Cardiothoracic Surgery, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa.
authors.forename: Nancy
authors.initials: N
authors.lastname: Burnham
authors.affiliation: Division of Pediatric Cardiothoracic Surgery, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Spray
authors.affiliation: Department of Anesthesia and Critical Care Medicine, The Children's Hospital of Philadelphia, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pa.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Nicolson
mesh_terms: D000367:Age Factors; D000769:Anesthesia, Inhalation / Q000009:adverse effects*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000009:adverse effects*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D002652:Child Behavior / Q000187:drug effects*; D002657:Child Development / Q000187:drug effects*; D002675:Child, Preschool; D016208:Databases, Factual; D002658:Developmental Disabilities / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D056344:Executive Function; D005260:Female; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D007360:Intelligence; D016014:Linear Models; D008297:Male; D008499:Medical Records; D009420:Nervous System / Q000187:drug effects* / Q000254:growth & development; D009483:Neuropsychological Tests; D012189:Retrospective Studies; D012307:Risk Factors; D014705:Verbal Behavior
chemical_list: D018685:Anesthetics, Inhalation
keywords: anesthesia; congenital heart surgery; neurodevelopment; neurotoxicity