Caffeine therapy in preterm infants

Table 2 Recommended caffeine doses

Trial	Design	Population	Intervention	Outcomes	Main results
Scanlon et al[48] United Kingdom	Prospective, randomized, controlled trial	44 preterm infants less than 31 wk gestation	High (loading 25 mg/kg and maintenance 6 mg/kg per day) vs low (loading 12.5 mg/kg and maintenance 3 mg/kg per day) caffeine citrate given 24 h prior to extubation	Frequency of apnea	High dose caffeine significantly decreased the frequency of apnea
Steer et al[52] Australia	Prospective, randomized, blinded, controlled trial	127 preterm infants less than 32 wk gestation	Three dosing regimens of caffeine citrate (3, 15 and 30 mg/kg) for peri-extubation management of ventilated preterm infants	Successful extubation defined as staying off ventilation for 7 d post-extubation	No statistically significant difference in the incidence of successful extubation however, infants in the two higher dose groups had statistically significantly less documented apnea
Steer et al[53] Australia	Prospective, randomized, blinded, controlled trial	234 preterm infants less than 30 wk gestation on mechanical ventilation	High (loading 80 mg/kg and maintenance 20 mg/kg per day) vs low (loading 20 mg/kg and maintenance 5 mg/kg per day) caffeine citrate given 24 h prior to extubation	Primary: Successful extubation of mechanically ventilated infants Secondary: Frequency of apnea	High dose caffeine significantly increased the chance for successful extubation, decreased the frequency of apnea and shortened the duration of respiratory support
Shah et al[54] Singapore	Prospective, case control trial	Preterm infants less than 34 wk gestation	High (loading 20 mg/kg and maintenance 5 mg/kg per day) vs low (loading 10 mg/kg and maintenance 2.5 mg/kg per day) caffeine citrate	Primary: Frequency of apnea, desaturation, and shallow breathing Secondary: Side effect of caffeine, BPD, and ROP	High-dose caffeine significantly reduced episodes of apnea and shallow breathing without side effects
Gray et al[125] Australia	Prospective, randomized, blinded, controlled trial	287 preterm infants less than 30 wk gestation exhibit AOP or require mechanical ventilation	Loading dose of 40 mg/kg followed by two maintenance doses of either 20 or 5 mg/kg per day	Primary: Cognitive development at 1 yr of age on the Griffiths Mental Development Scales Secondary: Neonatal morbidity, death and disability, temperament at 1 yr and behavior at 2 yr of age	High maintenance dose was associated with borderline benefit in cognitive outcome without increasing morbidity, temperament or behavior disorders
Mohammed et al[55] Egypt	Prospective, randomized, blinded, controlled trial	120 preterm infants less than 32 wk gestation exhibit AOP or require mechanical ventilation	High (loading 40 mg/kg and maintenance 20 mg/kg per day) vs low (loading 20 mg/kg and maintenance 10 mg/kg per day) caffeine citrate	Primary: Successful extubation of mechanically ventilated infants Secondary: Frequency and documented days of apnea	High dose caffeine significantly increased the chance for successful extubation, decreased frequency of apnea

BPD: Bronchopulmonary; ROP: Retinopathy of prematurity; AOP: Apnea of prematurity.