Caffeine Use in Neonates: Indications, Pharmacokinetics, Clinical Effects, Outcomes

Caffeine is commonly prescribed in the NICU to treat apnea of prematurity. This review is an update based on current knowledge of the mechanisms of action, pharmacologic properties, clinical effects, and safety of caffeine in the neonatal population. Recent studies of caffeine in the neonatal population confirm its efficacy in treating apnea-related symptoms and reveal additional significant benefits with minimal short-term, and no long-term, adverse effects. Objectives After completing this article, readers should be able to: 1. Describe the mechanisms of action of caffeine. 2. Summarize the pharmacokinetics of caffeine treatment. 3. List the established and possible benefits of caffeine therapy in neonates. 4. Describe the short-term adverse effects associated with caffeine use. 5. Summarize the potential incremental benefits of early initiation of caffeine on a prophylactic basis. Introduction Initial studies documenting the efficacy of methylxanthines (aminophylline, theophylline, caffeine) for apnea of prematurity (AOP) were published more than 30 years ago. (1) The clinical effects of these methylxanthines are equivalent, and caffeine has now largely replaced aminophylline and theophylline for routine treatment because of its wider therapeutic index and longer half-life that allows oncedaily administration. (2) Exclusive use of caffeine in very low birthweight (VLBW) infants increased from 26% of all methylxanthine use in 1997 to 96% in 2010. (3) Caffeine is now one of the most commonly prescribed drugs in the NICU, and has appropriately been described as a “silver bullet” in neonatology. (1) Several reviews of caffeine therapy in neonates have been published recently. (1)(2) Recent data indicate that initiation of caffeine treatment Abbreviations AOP: apnea of prematurity BPD: bronchopulmonary dysplasia CAP: Caffeine for Apnea of