Carbon dioxide sensitivity and caffeine therapy in the prematurely born infant

Abstract

Background: Caffeine therapy is used in the treatment of apnoea, yet the mechanism by which it reduces apnoea remains unclear. It has been suggested carbon dioxide (CO₂) chemosensitivity may be enhanced by caffeine therapy, but this has not been assessed in infants.

Aims and objectives: To determine the effect of caffeine on the ventilatory response to hypercarbia in prematurely born infants.

Methods: Infants <34 weeks gestation not requiring respiratory support were recruited on the first day after birth. A steady state hypercarbic challenge was delivered via an open circuit, consisting of a non-return valve, a capnograph and a pneumotachograph. Gas at 4 litres/minute was supplied to a nasal mask. In the supine position, baseline ventilation was measured for 5 minutes with the infant breathing air. The ventilatory response to either 2% or 4% CO₂ enriched air was then measured for 5 minutes. Following 5 minutes recovery the infant was then exposed to the alternative CO₂ level. The order of gas exposure was randomised. Mean minute volume was calculated for the final minute of exposure at each level and CO₂ sensitivity calculated as the gradient of the line of best fit. The study was repeated weekly until discharge.

Results: Fourteen infants (8 received caffeine) were recruited with a median gestational age 32 (range 31-33) weeks and birth weight 1.71 (1.19-2) kg. Multivariate linear regression with CO₂ sensitivity as dependent variable demonstrated a significant increase in CO₂ sensitivity with caffeine therapy (p=0.013) and increasing corrected gestational age (p=0.001).

Conclusion: Caffeine therapy increases the ventilatory response to hypercarbia, this may be a mechanism by which it reduces apnoea.