High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial
- P Steer1,
- V Flenady1,
- A Shearman1,
- B Charles2,
- P H Gray1,
- D Henderson-Smart3,
- G Bury4,
- S Fraser5,
- J Hegarty1,
- Y Rogers1,
- S Reid3,
- L Horton4,
- M Charlton4,
- R Jacklin5,
- A Walsh5,
- (The Caffeine Collaborative Study Group Steering Group)
- 1Department of Neonatology and Centre for Clinical Studies, University of Queensland, Mater Health Services, South Brisbane, Queensland, Australia
- 2Australian Centre for Paediatric Pharmacokinetics, School of Pharmacy, University of Queensland
- 3Neonatal Medicine, Royal Prince Alfred Hospital and Centre for Perinatal Health Services Research, University of Sydney, New South Wales, Australia
- 4Royal Hobart Hospital, Hobart, Tasmania. Australia
- 5Mercy Hospital for Women, Melbourne, Victoria, Australia
- Correspondence to:
Centre for Clinical Studies, Mater Health Services, Raymond Terrace, South Brisbane, Queensland, Australia 4101;
- Accepted 12 May 2004
Objective: To compare two dosing regimens for caffeine citrate in the periextubation period for neonates born at less than 30 weeks gestation in terms of successful extubation and adverse effects.
Design: A multicentre, randomised, double blind, clinical trial.
Setting: Four tertiary neonatal units within Australia.
Patients: Infants born less than 30 weeks gestation ventilated for more than 48 hours.
Interventions: Two dosing regimens of caffeine citrate (20 v 5 mg/kg/day) for periextubation management. Treatment started 24 hours before a planned extubation or within six hours of an unplanned extubation.
Main outcome measure: Failure to extubate within 48 hours of caffeine loading or reintubation and ventilation or doxapram within seven days of caffeine loading.
Results: A total of 234 neonates were enrolled. A significant reduction in failure to extubate was shown for the 20 mg/kg/day dosing group (15.0% v 29.8%; relative risk 0.51; 95% confidence interval (CI) 0.31 to 0.85; number needed to treat 7 (95% CI 4 to 24)). A significant difference in duration of mechanical ventilation was shown for infants of less than 28 weeks gestation receiving the high dose of caffeine (mean (SD) days 14.4 (11.1) v 22.1 (17.1); p = 0.01). No difference in adverse effects was detected in terms of mortality, major neonatal morbidity, death, or severe disability or general quotient at 12 months.
Conclusions: This trial shows short term benefits for a 20 mg/kg/day dosing regimen of caffeine citrate for neonates born at less than 30 weeks gestation in the periextubation period, without evidence of harm in the first year of life.