Hemodynamic effects of caffeine administration in premature infants

Caffeine citrate is widely used as first-line therapy for the treatment or the prevention of apnea of prematurity. The efficacy of caffeine in this therapeutic context has been shown in randomized and observational trials. However, it is largely known that caffeine stimulates the central nervous system and the cardiovascular system, increasing catecholamine secretion and basal metabolic rate. Moreover, caffeine acts at a pharmacological level blocking adenosine receptors A1 and A2a, increasing cyclic 3,5-adenosine monophosphate production and translocating intracellular calcium. These pharmacologic effects are likely to interact with the regulation of systemic hemodynamics and thus influence heart rate, stroke volume, cardiac output and vascular resistance. Some small studies have investigated the effects of caffeine on systemic blood pressure, cardiac output and vascular resistance, reporting different results. However, until today no large study has looked systematically at the acute hemodynamic effects of caffeine in premature infants.
An American group have conducted a prospective observational study to investigate the hemodynamic effects of intravenous caffeine administration in premature infants who received this drug to treat or prevent apnea of prematurity. Caffeine was administered over 15-20 min at a dosage of 5, 10 or 20 mg/Kg.
In total, 31 infants were included in the study. After intravenous caffeine, cardiac index increased in all babies, by an average of 14.6±16.3%; stroke volume increased in 24 of 31 trials, by 7.8±12.2%; heart rate increased in 28 of 31 trials by 7.7±7.2 beats per minute; and blood pressure increased in 25 of 31 trials, by 4.1±5.8mmHg (all p>0.001 vs baseline). Statistical analysis disclosed no significant effect of dose, birth weight, gestational age or postnatal age on these outcomes.
This study was the largest available describing the acute hemodynamic effects of intravenous caffeine in premature infants. Overall, the results indicate that intravenous caffeine administration appears to increase significantly all the examined cardiac parameters in normotensive premature infants. This effect appears to be reliable and to be insensitive to variations in birth weight, gestational age, chronologic age and dose. However, even if the statistical significance of the hemodynamic impact of caffeine is clear, the exact clinical meaning remains uncertain. However, these observations lead to an intriguing hypothesis: may the effect of caffeine on cardiac parameters and blood pressure suggest a potential role of this drug in improving hemodynamics in sick neonates?

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