title: Reperfusion pulmonary edema in children with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries undergoing unifocalization procedures: A pilot study examining potential pathophysiologic mechanisms and clinical significance.
abstract: OBJECTIVE
  Children with tetralogy of Fallot (TOF), pulmonary atresia (PA), and major aortopulmonary collateral arteries (MAPCAs) are at risk for reperfusion pulmonary edema (RPE) after unifocalization procedures to reconstruct the central pulmonary arteries. The purpose of this study was to determine the incidence of RPE, describe the clinical course of patients with RPE, and explore the mechanism of RPE in this population by measuring plasma biomarkers of alveolar epithelial and endothelial injury and lung inflammation.
  
  
  METHODS
  Levels of plasma receptor for advanced glycation end products (RAGE), intercellular adhesion molecule 1 (ICAM-1), and interleukin 6 (IL-6) were measured at baseline and postoperative day (POD) 0, 1, and 2 after unifocalization. A pediatric radiologist reviewed chest radiographs from the same time points and scored each lung segment for the degree of pulmonary edema. A pediatric interventional cardiologist reviewed the preoperative angiograms for each patient and determined the degree of stenosis for each aortopulmonary collateral vessel. RPE was defined as localized pulmonary edema with a pulmonary edema score of at least 2 occurring in the lung segment demonstrating the greatest degree of angiographic stenosis within the first 48 hours after surgery and with resolution by discharge.
  
  
  RESULTS
  Thirty-five patients who underwent 37 unifocalization procedures were enrolled, and 32 patients were included in the analysis. Of these, 16 of 32 (50%) demonstrated evidence of RPE based on our defined criteria. There was no significant difference in RAGE (P=.60), ICAM-1 (P=.34), or IL-6 (P=.31) levels between those with and without RPE at any time point. The mean duration of mechanical ventilation in patients with RPE versus those without was not significantly different (5.1±4.2 vs 5.6±4.5 days, respectively; P=.57).
  
  
  CONCLUSIONS
  Fifty percent of children with TOF/PA/MAPCAs undergoing unifocalization surgery developed RPE. Levels of plasma biomarkers of alveolar epithelial and endothelial injury and lung inflammation were not increased in patients with RPE compared with those without RPE. The presence of RPE did not affect the duration of respiratory failure and mechanical ventilation. The process of RPE is clinically self-limited and seems unlikely to be associated with vascular changes.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, Calif. Electronic address: rasija@stanford.edu.
authors.forename: Ritu
authors.initials: R
authors.lastname: Asija
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, Calif.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Roth
authors.affiliation: Division of Pediatric Cardiothoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Palo Alto, Calif.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Hanley
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, Calif.
authors.forename: Lynn
authors.initials: L
authors.lastname: Peng
authors.affiliation: Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California San Francisco, San Francisco, Calif.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Liu
authors.affiliation: Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California San Francisco, San Francisco, Calif.
authors.forename: Jason
authors.initials: J
authors.lastname: Abbott
authors.affiliation: Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California San Francisco, San Francisco, Calif.
authors.forename: Hanjing
authors.initials: H
authors.lastname: Zhuo
authors.affiliation: Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California San Francisco, San Francisco, Calif.
authors.forename: Michael
authors.initials: M
authors.lastname: Matthay
mesh_terms: D015415:Biomarkers / Q000097:blood; D003097:Collateral Circulation; D017023:Coronary Angiography; D005260:Female; D006343:Heart Septal Defects / Q000000981:diagnostic imaging / Q000601:surgery*; D006801:Humans; D015994:Incidence; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D011183:Postoperative Complications / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology*; D018633:Pulmonary Atresia / Q000000981:diagnostic imaging / Q000601:surgery*; D011654:Pulmonary Edema / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood; D015427:Reperfusion Injury / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology*; D012121:Respiration, Artificial; D013771:Tetralogy of Fallot / Q000000981:diagnostic imaging / Q000601:surgery*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D018799:Intercellular Adhesion Molecule-1