Treatment of apnea in neonates

Reduction of the work of breathing

• maintaining the prone position: in this position, the chest wall is stable and the thoraco-abdominal asynchrony is reduced
• CPAP or nasal intermittent positive pressure ventilation (NIPPV): generally with a peak inspiratory pressure (PIP) of 15-20 cm H2 O, positive end-expiratory pressure (PEEP) of 5-6 cm H2 O the extent of desaturation can be reduced by up to 50%

Increased respiratory drive

• low flow oxygen : reduces the degree of hypoxia and apnea. However, considering the O2 toxicity there is an ideal level of O2 that may be recommended
• increase in inspired CO2 : the increase of the concentration of CO2 in the inspired air of 0.8% for 2 hours is able to reduce the amount of apneas
• transfusion of red blood cells : which causes an increase in tissue oxygenation
• use of methylxanthines: increase the sensitivity of chemoreceptors and then the respiratory drive and can also increase the contractility of the diaphragm. Caffeine has a better therapeutic range and fewer side effects of theophylline
• doxapram: this drug stimulates the peripheral chemoreceptors in low doses and the central ones in high doses. Its effect is dose-dependent

Dosing

• Dosing may be different between several guidelines. Do double check with available guidelines and hospital practices.

Theophylline

• The loading dose of intravenous aminophylline is 5 to 6 mg/kg, followed by 1.5 to 3 mg/kg every 8 to 12 hours. Oral theosphylline can be administered once the infant becomes stable in the same dose
• Recommended therapeutic levels is 5 to 10 μg/ml for aminophylline
• Aminophylline should be continued till 34 weeks corrected gestational age and stopped thereafter if no episodes of apnea have occurred in the last 7 days.
• Aminophylline initiated in order to facilitate extubation may be stopped after 7 days

Caffeine

• A typical loading dose of 20 mg/kg caffeine citrate is followed in 24 hours by 5 to 8 mg/kg per dose, administered once every 24 hours
• Recommended therapeutic levels is 8 to 20 μg/ml for caffeine
• Xanthine therapy should be discontinued at least 1 to 2 weeks prior to discharge, a guideline that is especially relevant for caffeine because of its longer half-life

Doxapram

• indications for doxapram include failure to respond to both methylxanthine and CPAP therapy
• Doxapram infusion is started at 0.5 mg/kg/hour and increased gradually to a maximum of 2-2.5 mg/kg/hr
• Doxapram may be tried for a period of 48 hours before weaning the drug
• Methylxanthine therapy should be continued during doxapram infusion

References:

1. Apnea in Newborn (2007). http://www.newbornwhocc.org/pdf/Apnea_new_170108.pdf
2. Neonatal Resource Services Apnea and Bradycardia April 2013
3. Apnea of prematurity. Journal of Pediatric and Neonatal Individualized Medicine 2013;2(2)