title: An exploratory study with an adaptive continuous intravenous furosemide regimen in neonates treated with extracorporeal membrane oxygenation.
abstract: BACKGROUND
  The objective of the present study was to explore a continuous intravenous furosemide regimen that adapts to urine output in neonates treated with extracorporeal membrane oxygenation (ECMO).
  
  
  METHODS
  Seven neonates admitted to a paediatric surgical intensive care unit for ECMO therapy were treated with a furosemide regimen consisting of a loading bolus (1-2 mg/kg) followed by a continuous infusion at 0.2 mg/kg per hour, which was adjusted according to the target urine production of 6 ml/kg per hour. Therapeutic drug monitoring for furosemide concentrations in blood was performed.
  
  
  RESULTS
  The mean +/- standard deviation furosemide dose was 0.17 +/- 0.06 mg/kg per hour, 0.08 +/- 0.04 mg/kg per hour and 0.12 +/- 0.07 mg/kg per hour, respectively, on the first day, second day and third day of the study. The median (range of the urine production of the study subjects) urine production over the consecutive study days was 6.8 (0.8-8.4) mg/kg per hour, 6.0 (4.7-8.9) mg/kg per hour and 5.4 (3.4-10.1) ml/kg per hour. The target urine production was reached after a median time of 7 (3-37) hours. The regimen was haemodynamically well tolerated and the median furosemide serum concentration was 3.1 (0.4-12.9) mug/ml, well below the toxic level.
  
  
  CONCLUSIONS
  The evaluated furosemide infusion appears an effective means to reduce volume overload in neonates treated with ECMO. The data of this preliminary study suggest that the starting dose of furosemide was too high, however, because the urine output was excessive and required frequent adaptations. The results of this study therefore indicate that a novel pharmacokinetic/pharmacodynamic model needs to be developed for neonates treated with ECMO.
authors.affiliation: Centre for Human Drug Research, Leiden, The Netherlands.
authors.forename: Maria M J
authors.initials: MM
authors.lastname: van der Vorst
authors.forename: Jan
authors.initials: J
authors.lastname: den Hartigh
authors.forename: Enno
authors.initials: E
authors.lastname: Wildschut
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Jacobus
authors.initials: J
authors.lastname: Burggraaf
mesh_terms: D000471:Alkalosis / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004232:Diuretics / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D005665:Furosemide / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D012709:Serum Albumin / Q000187:drug effects; D014556:Urine; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D004232:Diuretics; D012709:Serum Albumin; D005665:Furosemide; D003404:Creatinine