Dose & administration
Loading dose 20 mg/kg of caffeine citrate (corresponding to 10 mg/kg of caffeine base), intravenously over 30 minutes. Maintenance dose 5-10 mg/kg once daily, intravenously over 10 minutes or by oral administration, 24 h after the loading dose. A higher maintenance dose can be considered but the possibility of accumulation should be taken into account.
Can be discontinued when the infant has been free from significant apneas 5-7 days.
Can be diluted in sterile solutions for infusion with glucose 50 mg/ml or sodium chloride 9 mg/ml.
Apnea of prematurity. BPD prevention.
Contraindications and special considerations
Apnea of prematurity is a diagnosis of exclusion. Always consider other possible causes of instable breathing.
Caffeine stimulates the CNS and the cardiovascular system, and should be used cautiously in infants with seizure disorders and congenital heart defects.
Caffeine increase metabolism which may result in higher energy and nutrition requirements during therapy.
Measurement of plasma levels of caffeine is possible. A range of 8-30 mg/l has been associated with clinical benefit and levels above 50 mg/l could be regarded as elevated.
Infusion site phlebitis
Exacerbation of gastro-esophageal reflux
Caffeine acts by antagonism of adenosine receptors and act as a CNS stimulant. Several mechanisms have been proposed for its effect on apnea of prematurity, such as respiratory center stimulation, increased minute ventilation, decreased threshold to hypercapnia, and increased response to hypercapnia.
Onset of action is within minutes after intravenous infusion and after oral administration the peak concentration is reached in 30-120 minutes.
Elimination is predominantly by renal clearance and to some extent by hepatic clearance (Cytochrome P450 1A2). Mean half-life (T1/2) are inversely related to gestational / postmenstrual age. In newborn infants, the T1/2 is approximately 3-4 days but increases over time. By 9 months of age, caffeine metabolism approximates that of adults (T1/2 = 5 hours).
The pharmacokinetics in newborn infants with hepatic or renal insufficiency have not been studied. Infants with significant renal impairment may risk accumulation. Cholestasis may also prolong half-life.
European Medicines Agency. European public assessment report (EPAR) for Peyona. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/001014/human_med_000940.jsp
Schmidt. Caffeine Therapy for Apnea of Prematurity. N Engl J Med 2006;354:2112-21. PMID 16707748.
Schmidt. Long-Term Effects of Caffeine Therapy for Apnea of Prematurity. N Engl J Med 2007;357:1893-1902. PMID 17989382.
Eichenwald. Apnea of prematurity. Pediatrics 2016:e20153757. PMID 26628729.
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Created 2016-05-15 / Stefan Johansson