From the Guidelines
Apnea of prematurity is primarily treated with caffeine citrate, which is the first-line pharmacological therapy. The recommended dosing is a loading dose of 20 mg/kg followed by maintenance doses of 5-10 mg/kg once daily. Caffeine works by stimulating the respiratory center in the brain, increasing respiratory drive, and improving diaphragmatic function, as noted in the treatment of infants with chronic lung disease of infancy and childhood 1. It also reduces the threshold for hypercapnic arousal. Before starting medication, it's essential to rule out other causes of apnea such as infection, anemia, hypoglycemia, or temperature instability. Non-pharmacological interventions include:
- Proper positioning (prone or side-lying)
- Maintaining a neutral thermal environment
- Ensuring adequate oxygenation Continuous positive airway pressure (CPAP) at 4-6 cmH2O may be used for infants who don't respond adequately to caffeine. In severe cases that don't respond to these measures, mechanical ventilation may be necessary. Caffeine therapy is typically continued until the infant reaches 34-35 weeks postmenstrual age and has been apnea-free for 5-7 days, though some clinicians extend treatment until 36-37 weeks for extremely premature infants. Regular monitoring of heart rate, respiratory rate, and oxygen saturation is crucial throughout treatment. The use of caffeine is preferred over other bronchodilators due to its efficacy and safety profile in this population, as well as its additional benefits in improving pulmonary function in infants with chronic lung disease of infancy and childhood 1.
From the FDA Drug Label
Caffeine citrate injection and caffeine citrate oral solution are indicated for the short term treatment of apnea of prematurity in infants between 28 and <33 weeks gestational age. The treatment of apnea of prematurity is with caffeine citrate.
- The indication is for infants between 28 and <33 weeks gestational age.
- Caffeine citrate should be used with caution in infants with seizure disorders, cardiovascular disease, or impaired renal or hepatic function.
- The duration of treatment in the placebo-controlled trial was limited to 10 to 12 days 2.
- Serum concentrations of caffeine may need to be monitored periodically throughout treatment to avoid toxicity 2.
From the Research
Treatment of Apnea of Prematurity
- Apnea of prematurity is a common condition in preterm infants, characterized by pauses in breathing that can lead to hypoxia and other complications 3.
- Various treatment options are available, including caffeine citrate, nasal continuous positive airway pressure (NCPAP), and nasal intermittent positive pressure ventilation (NIPPV) 3, 4.
Caffeine Citrate Treatment
- Caffeine citrate is a widely used treatment for apnea of prematurity, with studies suggesting that higher maintenance doses (10-20 mg/kg daily) may be more effective than lower doses (5-10 mg/kg daily) in reducing the frequency and duration of apnea 5, 6.
- However, higher doses of caffeine citrate may also be associated with a higher incidence of side effects, such as tachycardia 5.
- A study comparing high-dose and standard-dose caffeine citrate regimens found that high-dose strategies may have little or no effect on mortality prior to hospital discharge, but may reduce the rate of bronchopulmonary dysplasia 7.
Non-Invasive Ventilation
- NCPAP and NIPPV are non-invasive ventilation techniques that can be used to support preterm infants with apnea of prematurity 4.
- A systematic review and meta-analysis found that NIPPV may be a useful method of augmenting the beneficial effects of NCPAP in preterm infants with apnea, but additional safety and efficacy data are required before recommending NIPPV as standard therapy 4.
Comparison of Treatment Options
- A study comparing the effectiveness and safety of different doses of caffeine citrate found that a therapeutic regimen consisting of a loading dose of 20 mg/kg and maintenance dose of 15 mg/(kg·d) could improve treatment effects and maintain safety for primary apnea in preterm infants 6.
- Another study found that high-dose caffeine strategies may have little or no effect on reducing mortality prior to hospital discharge or side effects, but may reduce the rate of bronchopulmonary dysplasia 7.