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Apnea in the premature infant can be caused by decreased central respiratory drive, inability to maintain airway patency, inadequate function of the respiratory muscles; these conditions often co-exist. Central apnea is treated with caffeine and NCPAP is used to treatment upper airway obstruction and to support inadequate function of respiratory muscles. Caffeine is a methylxanthine that acts as a central nervous system stimulant. The effects are mediated by its antagonism of the actions of adenosine at cell surface receptors in the medulla. It increases chemoreceptor sensitivity to CO and the neurological output of the respiratory center in the medulla.

Drug information Caffeine Citrate:

Loading dose 20 to 40 mg/kg
Maintenance dose: 5 to 10 mg/kg q 24 hours.
Monitoring: Clinical response; consider holding dose if HR >180
Adverse Effects: Tachycardia, restlessness, vomiting, decrease seizure threshold.

Indications to start caffeine:

A. Intubated premature infants less than 32 weeks with plans for extubation in the next 24 hours:
1. ≤ 28 weeks: Load 2 hours prior to planned extubation and continue maintenance therapy.
2. 29-32 weeks: Consider a load of caffeine prior to extubation. Discuss with attending/fellow the need for maintenance therapy.

B. If patient is having apnea, is not intubated and is less than 28 weeks:
1. Load patient with caffeine & continue with maintenance for any one of the following:

- >2 episodes requiring PPV

- >6 total episodes requiring any stimulation - >8 total episodes (including self-resolving)

2. Consider starting or increasing the amount of positive pressure support (NCPAP or HFNC)

C. If patient is having apnea, is not intubated and >28 and <32 weeks:
1. Consider starting or increasing the amount of positive pressure support (NCPAP or HFNC), if that is ineffective then,

2. Load patient with caffeine & continue with maintenance for any one of the following:

- >2 episodes requiring PPV
- >6 total episodes requiring any stimulation - >8 total episodes (including self-resolving)

D. Prophylactic Caffeine:
1. If patient is ≤28weeks and not yet displaying apnea, consider the use of prophylactic caffeine. Prior to starting, discuss with attending/fellow on service.

Maintenance dosing adjustments:

A. Indications to reload (10mg/kg) and increase maintenance (8 mg/kg/day or 10 mg/kg/day):
1. If positive pressure support is escalated without improvement in apnea within 12 hours. 2. If no improvement in frequency or severity of apnea after initiation of caffeine.

B. Adjust maintenance dosing for weight Monday & Thursday as needed.

End point for caffeine therapy:

A. 32 weeks adjusted age and 5 days without apnea in patients between > 28 weeks and
at birth.
B. 34 weeks adjusted age in patients ≤ 28 weeks GA at birth (use with discretion as ELBW's may have symptoms past 34 weeks).

Apnea Countdown:

A. If on caffeine: Stop Caffeine and wait 3 days to start an 8 day apnea countdown (total of 11 days). B. If not on caffeine: The apnea countdown is 8 days long.

< 32 weeks GA

References
1. Schmidt B, Roberts RS, Davis P, Doyle LW, Barington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trail Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18; 354 (20):2112-21.

2. Darnall RA, Kattwinkel J, Nattie C, Robinson M. Margin of safety for discharge after apnea in preterm infants. Pediatrics. 1997 Nov; 100 (5 ):795-801.

3. Henderson-Smart DJ, Davis PG. Prophylactic methylxanthines for extubation in preterm infants. Cochrane Database Syst Rev. 2003; (1):CD000139. Review.

Created: Grebe and Johnson 07/08
Last Revised: Aliaga and Laughon 02/10