Interventions for apnoea of prematurity: an expert view

Apnoea of prematurity (AOP) is a widespread disorder in very preterm infants and can cause serious problems, including potential neurodevelopmental impairment. Dr. Poets has recently reviewed the available evidence on the different therapeutic strategies used in the treatment of AOP, according to current literature and his personal experience. Interventions have been grouped into those beneficial to improve AOP and those where the effect may be questionable and/or needs further study. Among proven-effective strategies, only prone head-elevated positioning, respiratory support, and caffeine have been included.
The prone position stabilizes the chest wall, reduces thoraco-abdominal asynchrony, and was shown to reduce apnoea rate in preterm infants in several studies. An extension of the prone position is the prone head-elevated tilt position which gives better reduction in the frequency of desaturation and bradycardia. However, this effect of head-up positioning may be less pronounced in infants already receiving other treatments for AOP, like respiratory support or caffeine.
Continuous positive airway pressure (CPAP) reduces extubation failure in preterm infants and application via (bi-)nasal prongs should be preferred since it is associated with lower reintubation rates. Studies were performed to compare CPAP with nasal intermittent positive pressure ventilation (N-IPPV) to understand which technique provides higher effectiveness. Preliminary evidence suggests that the key to success for nasal ventilatory support resides in the reduction of work of breathing, which can be achieved via either synchronized N-IPPV or variable flow CPAP devices.
Methylxanthines increase chemoreceptor sensitivity as well as respiratory drive and can also improve diaphragmatic function. Among the substances available, caffeine has a wider therapeutic range and fewer side effects than theophylline. The results of the Caffeine for Apnea of Prematurity (CAP) study have shown that caffeine reduces death or disability at a corrected age of 18 months. In particular, caffeine appears to be the only drug identified so far to reduce cerebral palsy. Moreover, caffeine reduces the incidence of bronchopulmonary dysplasia, symptomatic patent ductus arteriosus, and retinopathy of prematurity. Clinical results of a recent randomized controlled trial indicate that clinicians should consider starting caffeine at the standard dose of 10 mg / kg loading, 5 mg / kg / day maintenance (doses expressed as caffeine base), but to switch to a higher dose if AOP persists.
Based on the clinical evidence currently available, it is suggested that treatment strategies for AOP should follow an incremental approach, starting with positioning, followed by caffeine (for which a first-line treatment should be considered in infants <1250 g), and respiratory support via systems that reduce work of breathing. From a research point of view, data on the frequency and severity of bradycardia and intermittent hypoxia that can be tolerated without putting an infant at risk of impaired development or retinopathy of prematurity are urgently required.

Top