Caffeine Therapy for Apnea of Prematurity in Preterm Infants
For apnea of prematurity in preterm infants, caffeine citrate should be administered with a loading dose of 20 mg/kg (equivalent to 10 mg/kg caffeine base) followed by a maintenance dose of 5-10 mg/kg/day, with serum levels monitored to maintain concentrations between 5-20 mg/L. 1, 2, 3
Dosage Regimen
Initial Loading Dose
- Loading dose: 20 mg/kg caffeine citrate IV (equivalent to 10 mg/kg caffeine base) 2, 4
- Administer intravenously over 30 minutes to minimize side effects
Maintenance Dosing
- Standard maintenance: 5 mg/kg/day caffeine citrate (2.5 mg/kg/day caffeine base) 2
- Higher maintenance: 7-10 mg/kg/day caffeine citrate for infants with inadequate response 5
- Route: Can be administered either intravenously or orally once enteral feeds are established 2
- Timing: Begin maintenance dose 24 hours after loading dose
Therapeutic Monitoring
- Target serum concentration: 5-20 mg/L 1
- First level check: 24-48 hours after loading dose
- Subsequent monitoring: Only necessary if:
- Ongoing apnea despite therapy
- Signs of toxicity
- Significant hepatic or renal dysfunction
- Routine monitoring is not required in most infants 24-35 weeks gestational age with normal renal and hepatic function 3
Duration of Therapy
- Continue therapy until:
- Infant reaches 34-35 weeks postmenstrual age
- Infant has been apnea-free for 5-7 days
- At least 1 week before anticipated discharge
Clinical Efficacy
Caffeine therapy has been shown to:
- Reduce frequency of apnea episodes by at least 50% within 3-6 days 2
- Eliminate apnea episodes completely in many infants within 5 days 2
- Promote successful extubation from mechanical ventilation 3
- Decrease the incidence of bronchopulmonary dysplasia 3, 5
- Reduce the risk of extubation failure, particularly in extremely premature infants ≤28 weeks 5
Dosing Considerations
Higher vs. Standard Dosing
- Higher maintenance doses (7-7.5 mg/kg/day) have shown:
- Significantly fewer apnea episodes
- Lower extubation failure rates
- Reduced incidence of moderate/severe BPD
- Particularly beneficial in extremely premature infants ≤28 weeks 5
- However, higher doses are associated with increased side effects 5
Special Populations
- Extremely premature infants (≤28 weeks) may benefit more from higher maintenance doses (7-7.5 mg/kg/day) 5
- Early initiation is particularly important in this population
Adverse Effects
Common side effects include:
- Tachycardia
- Gastroesophageal reflux
- Altered sleep and behavior patterns
- Feeding difficulties 1
More severe but less common effects at higher doses:
- Jitteriness
- Irritability
- Seizures (rare)
Practical Considerations
- Caffeine citrate is preferred over other methylxanthines (theophylline) due to:
- Wider therapeutic window
- Once-daily dosing
- Fewer side effects 6
- Caffeine can be administered with intravenous lipid emulsions to reduce peroxidation and limit vitamin loss 1
- Ensure proper monitoring of vital signs during administration
Pitfalls and Caveats
- Avoid exceeding serum levels of 20 mg/L to prevent toxicity 1
- Do not confuse caffeine base with caffeine citrate dosing (caffeine citrate contains 50% caffeine base)
- Recognize that caffeine has a long half-life in neonates, which may lead to accumulation
- Be aware that caffeine may increase metabolic rate and caloric requirements
- Consider that extremely preterm infants may require higher maintenance doses for optimal effect 5