title: Effects of a divided high loading dose of caffeine on circulatory variables in preterm infants.
abstract: BACKGROUND
  A single high loading dose of 25 mg/kg caffeine has been shown to be effective for the prevention of apnoea, but may result in considerable reductions in blood flow velocity (BFV) in cerebral and intestinal arteries.
  
  
  OBJECTIVE
  To assess the effects of two loading doses of 12.5 mg/kg caffeine given four hours apart on BFV in cerebral and intestinal arteries, left ventricular output (LVO), and plasma caffeine concentrations in preterm infants.
  
  
  METHODS
  Sixteen preterm neonates of <34 weeks gestation were investigated one hour after the first oral dose and one, two, and 20 hours after the second dose by Doppler sonography.
  
  
  RESULTS
  The mean (SD) plasma caffeine concentrations were 31 (7) and 29 (7) mg/l at two and 20 hours respectively after the second dose. One hour after the first dose, none of the circulatory variables had changed significantly. One hour after the second caffeine dose, mean BFV in the internal carotid artery and anterior cerebral artery showed significant reductions of 17% and 19% (p = 0.01 and p = 0.003 respectively). BFV in the coeliac artery and superior mesenteric artery, LVO, PCO2, and respiratory rate had not changed significantly. Total vascular resistance, calculated as the ratio of mean blood pressure to LVO, had increased significantly one and two hours after the second dose (p = 0.049 and p = 0.023 respectively).
  
  
  CONCLUSIONS
  A divided high loading dose of 25 mg/kg caffeine given four hours apart had decreased BFV in cerebral arteries after the second dose, whereas BFV in intestinal arteries and LVO were not affected.
authors.affiliation: Division of Neonatology, Department of Paediatrics, University of Heidelberg, Heidelberg, Germany. c_hoecker@hotmail.com
authors.forename: C
authors.initials: C
authors.lastname: Hoecker
authors.forename: M
authors.initials: M
authors.lastname: Nelle
authors.forename: B
authors.initials: B
authors.lastname: Beedgen
authors.forename: J
authors.initials: J
authors.lastname: Rengelshausen
authors.forename: O
authors.initials: O
authors.lastname: Linderkamp
mesh_terms: D020771:Anterior Cerebral Artery / Q000187:drug effects / Q000502:physiology; D001049:Apnea / Q000517:prevention & control; D001783:Blood Flow Velocity / Q000187:drug effects; D002110:Caffeine / Q000097:blood / Q000494:pharmacology*; D002343:Carotid Artery, Internal / Q000187:drug effects / Q000502:physiology; D002445:Celiac Artery / Q000187:drug effects / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000097:blood / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004334:Drug Administration Schedule; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D007422:Intestines / Q000098:blood supply*; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine