Periextubation caffeine in preterm neonates: a randomized dose response trial

J Paediatr Child Health. 2003 Sep-Oct;39(7):511-5. doi: 10.1046/j.1440-1754.2003.00207.x.


Objective: To compare the effectiveness of three dosing regimens of caffeine for preterm infants in the periextubation period.

Methods: A randomized double-blind clinical trial of three dosing regimens of caffeine citrate (3, 15 and 30 mg/kg) for periextubation management of ventilated preterm infants was undertaken. Infants born <32 weeks gestation who were ventilated for>48 h were eligible for the study. Caffeine citrate was given as a once daily dose for a period of 6 days commencing 24 h prior to a planned extubation, or within 6 h of an unplanned extubation. The primary outcome measure was extubation failure, defined as neonates who were unable to be extubated within 48 h of caffeine loading or who required reventilation or doxapram dose within 7 days of caffeine loading. Continuous recordings of oxygen saturation and heart rate were undertaken in a subgroup of enrolled infants.

Results: A total of 127 babies were enrolled into the study (42, 40, 45, in the 3, 15, and 30 mg/kg groups, respectively). No statistically significant difference was demonstrated in the incidence of extubation failure between dosing groups (19, 10, and 11 infants in the 3, 15, and 30 mg/kg groups, respectively), however, infants in the two higher dose groups had statistically significantly less documented apnoea than the lowest dose group. Of the 37 neonates with continuous pulse oximetry recordings, those on higher doses of caffeine recorded a statistically significantly higher mean heart rate, oxygen saturations and less time with oxygen saturations <85%.

Conclusions: This trial indicated there were short-term benefits of decreased apnoea in the immediate periextubation period for ventilated infants born <32 weeks gestation receiving higher doses of caffeine. Further studies with larger numbers of infants assessing longer-term outcomes are necessary to determine the optimal dosing regimen of caffeine in preterm infants.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Apnea / blood
  • Apnea / prevention & control*
  • Caffeine / blood
  • Caffeine / therapeutic use*
  • Central Nervous System Stimulants / therapeutic use*
  • Citrates / blood
  • Citrates / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Doxapram / therapeutic use
  • Drug Combinations
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Intubation, Intratracheal*
  • Male
  • Respiratory System Agents / therapeutic use
  • Ventilator Weaning / methods


  • Central Nervous System Stimulants
  • Citrates
  • Drug Combinations
  • Respiratory System Agents
  • Caffeine
  • Doxapram
  • caffeine citrate