title: The effect of caffeine citrate on neural breathing pattern in preterm infants.
abstract: BACKGROUND
  Caffeine citrate is widely used to prevent and treat prematurity-associated apnea.
  
  
  OBJECTIVE
  The aim of this study was to characterize the effect of caffeine citrate on the neural control of breathing, especially central apnea, in premature infants.
  
  
  METHODS
  Preterm infants were evaluated for 30min before and 30min after caffeine citrate loading (20mg/kg). A feeding tube including miniaturized sensors was used to measure the diaphragm electrical activity (Edi) waveform. Central apnea was defined as any period where the Edi waveform was flat for >5s.
  
  
  METHODS
  Seventeen preterm infants with a mean age of three days and mean birth weight of 900 grams were evaluated.
  
  
  METHODS
  In addition to central apnea, several parameters including neural inspiratory time, neural respiratory rate, peak Edi, delta inspiratory change in Edi (phasic Edi) and minimum Edi on exhalation were measured.
  
  
  RESULTS
  The majority of the apnea were short (5 to 10s) and the number of apnea correlated with birth weight (p=0.039). Caffeine citrate reduced significantly the number of 5-to-10-second-long central apnea during the 30-minute periods (12±11 to 7±7; p=0.02). Caffeine citrate increased both peak and phasic Edi leading to a significant increase in the diaphragm energy expenditure.
  
  
  CONCLUSIONS
  Edi signal can be reliably measured and processed to study changes in premature infants' neural breathing. The beneficial effect of caffeine citrate on the reduction of the number of apnea is mediated through stimulated neural breathing increasing the diaphragm energy expenditure.
authors.affiliation: Department of Pediatrics, Turku University Hospital, University of Turku, Turku, Finland. Electronic address: vilpar@utu.fi.
authors.forename: Vilhelmiina
authors.initials: V
authors.lastname: Parikka
authors.affiliation: Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada; Department of Critical Care, St. Michael's Hospital, Toronto, Canada; Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Beck
authors.affiliation: Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhai
authors.affiliation: Department of Pediatrics, Turku University Hospital, University of Turku, Turku, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Leppäsalo
authors.affiliation: Department of Pediatrics, Turku University Hospital, University of Turku, Turku, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Lehtonen
authors.affiliation: Department of Pediatrics, Turku University Hospital, University of Turku, Turku, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Soukka
mesh_terms: D001049:Apnea / Q000188:drug therapy; D002110:Caffeine / Q000494:pharmacology* / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000494:pharmacology* / Q000627:therapeutic use; D002951:Citrates / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D012119:Respiration / Q000187:drug effects*
chemical_list: D000697:Central Nervous System Stimulants; D002951:Citrates; D002110:Caffeine; C026189:caffeine citrate
keywords: Apnea; Diaphragm electrical activity; NAVA; Neurally adjusted ventilation