Caffeine Treatment for Apnea of Prematurity
Caffeine citrate is the first-line treatment for apnea of prematurity because it stimulates the respiratory center, increases minute ventilation, decreases threshold to hypercapnia, and improves diaphragmatic function, resulting in reduced mortality and improved neurodevelopmental outcomes. 1, 2
Mechanism of Action
Caffeine, a methylxanthine, works through several mechanisms to treat apnea of prematurity:
- Antagonism of adenosine A1 and A2 receptors 2
- Stimulation of the respiratory center
- Increased minute ventilation
- Decreased threshold to hypercapnia
- Increased response to hypercapnia
- Increased skeletal muscle tone
- Decreased diaphragmatic fatigue
- Increased metabolic rate
Dosing Protocol
The recommended dosing regimen for caffeine citrate is:
- Loading dose: 20 mg/kg (equivalent to 10 mg/kg caffeine base)
- Maintenance dose: 5-10 mg/kg/day 1
Higher maintenance doses (7-7.5 mg/kg/day) may benefit extremely premature infants (≤28 weeks) 1.
Administration and Monitoring
- Can be administered intravenously or orally once enteral feeds are established
- Target serum concentration: 5-20 mg/L
- Monitor serum levels 24-48 hours after loading dose
- Further monitoring only needed if:
- Ongoing apnea
- Signs of toxicity
- Significant hepatic or renal dysfunction 1
Duration of Treatment
Caffeine therapy should be continued until:
- Infant reaches 34-35 weeks postmenstrual age
- Has been apnea-free for 5-7 days
- At least 1 week before anticipated discharge 1
Benefits Beyond Apnea Treatment
Caffeine therapy has shown several important benefits:
- Reduced bronchopulmonary dysplasia (BPD) 3
- Neurodevelopmental benefits, though the exact mechanism is not fully defined 4
- Facilitation of extubation in mechanically ventilated preterm infants 3
- Decreased duration of oxygen therapy and respiratory support 5
Prophylactic vs. Therapeutic Use
Prophylactic caffeine (administered in the first 72 hours of life) compared to therapeutic caffeine (only when apnea occurs) has been shown to:
- Decrease duration of oxygen therapy
- Reduce duration of respiratory support
- Lower incidence of mild to moderate BPD
- Shorten length of hospital stay 5
Side Effects and Precautions
Common side effects include:
- Tachycardia
- Gastroesophageal reflux
- Altered sleep patterns
- Feeding difficulties
More severe but less common effects at higher doses:
- Jitteriness
- Irritability
- Seizures (rare) 1
Clinical Considerations
- Caffeine has a long half-life in neonates (3-4 days) due to immature hepatic function 2
- Use with caution in preterm neonates with impaired renal or hepatic function 2
- Caffeine may increase metabolic rate and caloric requirements 1
- Higher doses may reduce BPD but require careful monitoring for side effects 3
Caffeine is preferred over other methylxanthines due to its wider therapeutic window, once-daily dosing, and fewer side effects 1.