title: Optimizing exchange transfusion for severe unconjugated hyperbilirubinemia: studies in the Gunn rat.
abstract: BACKGROUND
  Severe unconjugated hyperbilirubinemia carries the risk of neurotoxicity. Phototherapy (PT) and exchange transfusion (ET) are cornerstones in the treatment of unconjugated hyperbilirubinemia. Studies to improve ET efficacy have been hampered by the low application of ET in humans and by the lack of an in vivo model. The absence of an appropriate animal model has also prevented to determine the efficacy of adjunct or alternative treatment options such as albumin (Alb) administration.
  
  
  OBJECTIVE
  To establish an in vivo model for ET and to determine the most effective treatment (combination) of ET, PT and Alb administration.
  
  
  METHODS
  Gunn rats received either PT, PT+Alb, ET, ET+PT, ET+PT+Alb or sham operation (each n = 7). ET was performed via the right jugular vein in ≈ 20 min. PT (18 µW/cm(2)/nm) was started after ET or at T0. Albumin i.p. injections (2.5 g/kg) were given after ET or before starting PT. Plasma unconjugated bilirubin (UCB), plasma free bilirubin (Bf), and brain bilirubin concentrations were determined.
  
  
  RESULTS
  We performed ET in 21 Gunn rats with 100% survival. At T1, ET was profoundly more effective in decreasing both UCB -44%, p<0.01) and Bf -81%, p<0.05) than either PT or PT+Alb. After 48 h, the combination of ET+PT+Alb showed the strongest hypobilirubinemic effect (-54% compared to ET).
  
  
  CONCLUSIONS
  We optimized ET for severe unconjugated hyperbilirubinemia in the Gunn rat model. Our data indicate that ET is the most effective treatment option, in the acute as well as the follow-up situation.
authors.affiliation: Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, Beatrix Children's Hospital - University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Schreuder
authors.forename: Jana
authors.initials: J
authors.lastname: Vanikova
authors.forename: Libor
authors.initials: L
authors.lastname: Vitek
authors.forename: Rick
authors.initials: R
authors.lastname: Havinga
authors.forename: Charles E
authors.initials: CE
authors.lastname: Ahlfors
authors.forename: Christian V
authors.initials: CV
authors.lastname: Hulzebos
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D005078:Exchange Transfusion, Whole Blood / Q000379:methods*; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051381:Rats; D011911:Rats, Gunn; D013997:Time Factors
chemical_list: D001663:Bilirubin