Treatment of Apnea of Prematurity

Abstract

In the last decade, knowledge regarding the neurodevelopment and functional aspects of the respiratory centers during postnatal maturation has increased substantially. However, an increase in such knowledge has not provided a basis for change in practice. The diagnosis of apnea of prematurity (AOP) is one of exclusion. All causes of secondary apnea must be ruled out before initiating treatment for AOP. Treatment will depend on the etiology as well as effectiveness and tolerability of the treatment by the patient. The primary goal of any treatment of AOP is to prevent the frequency of apnea lasting >20 seconds, and/or those that are shorter, but associated with cyanosis and bradycardia. The clinical management of AOP is not much different today than it was two decades ago, with pharmacologic and nonpharmacologic treatment options remaining the mainstay of therapy. Methylxanthines are still the most widely used pharmacologic agents. Due to the wider therapeutic index of caffeine and ease of once daily administration, it should be the preferred agent. Doxapram, or nonpharmacologic treatment measures such as nasal continuous positive airway pressure, may be considered in infants who are unresponsive to methylxanthine treatment alone. Treatment should be continued until there is complete resolution of apnea, and for some time thereafter. The choice of method for weaning treatment remains one of individual physician preference. Discharge from hospital after apnea requires close monitoring and some infants will require home apnea monitors. The decision to provide a home apnea monitor should be individualized for each patient, depending on the effectiveness of treatment and clinical response.

Tripartite Purinergic Modulation of Central Respiratory Networks during Perinatal Development: The Influence of ATP, Ectonucleotidases, and ATP Metabolites

“…It also has implications for apnea of prematurity in which a premature, ADO-sensitive respiratory network is a hypothesized contributor to respiratory instability (Barrington and Finer, 1991). In fact, despite ongoing debate as to whether the beneficial effects of caffeine are attributable to A 1 receptor antagonism, caffeine administration is a primary therapy for apnea of prematurity (Hascoet et al, 2000;Bhatt-Mehta and Schumacher, 2003;Schmidt, 2005;Schmidt et al, 2006).…”

“…ADO is a P1R agonist whose actions are unclear, but, in premature and neonatal mammals, it is primarily reported to inhibit breathing (Herlenius et al, 1997(Herlenius et al, , 1999(Herlenius et al, , 2002. It is also implicated in apnea of prematurity (Bhatt-Mehta and Schumacher, 2003).…”

Caffeine impairs gastrointestinal function in newborn rats

“…Theophylline, another methylxanthine, is equally as effective as a respiratory stimulant in neonates, but its use is associated with more cardiovascular and central nervous system side effects, as compared with caffeine (4,26).…”

“…The drug belongs to the methylxanthine family and stimulates breathing via its effector role in the brain medullary respiratory center (2)(3)(4). The respiratory stimulation properties of the drug depend on the central nervous system adenosine inhibitory effect (5,6).…”

Sequential Updating of a New Dynamic Pharmacokinetic Model for Caffeine in Premature Neonates

“…Since sampling blood causes trauma on such fragile infants, the number of blood samples is limited. Therefore, it is not possible to collect extensive information on caffeine concentration time course in a given patient and pediatricians refer to a standard protocol of administration [13,14] . In doing so, they control treatments or times to sample ``on average" in the patients' population.…”